Quantifying the uncertainty of deep learning-based computer ...

Quantifying the uncertainty of deep learning-based computer-aided diagnosis for patient safety Max-Heinrich Laves, Institute of Mechatronic Systems, Leibniz Universität Hannover, Hannover, Germany, [email protected] Sontje Ihler, Institute of Mechatronic Systems, Leibniz Universität Hannover, Hannover, Germany, [email protected] Lüder A. Kahrs, Institute of Mechatronic Systems, Leibniz Universität Hannover, Hannover, Germany, [email protected] Tobias Ortmaier, Institute of Mechatronic Systems, Leibniz Universität Hannover, Hannover, Germany, [email protected] In recent years, deep learning methods have received significant attention for computer-aided diag-nosis in a variety of fields of medical imaging. They outperform former methods in capability and accuracy. However, deep models trained for diagnosis of specific cases currently lack the ability to say "I don't know" for ambiguous or unknown cases. Therefore, this work proposes the integration of prediction uncertainties into diagnostic classifiers to increase patient safety in deep learning. We train the ResNet-34 image classifier on a dataset of 84.484 optical coherence tomographies showing four different retinal conditions. Monte Carlo sampling is applied with dropout at test time for uncertainty estimation. Dropout with p=0.5 is added before the last fully connected layer, creat-ing a probabilistic classifier. In Monte Carlo experiments, 100 forward passes are performed to get a posterior distribution of the class labels. The variance of the posterior is used as metric for the uncertainty. A study is performed to show if false predictions of a deep model correlate to high pre-diction uncertainty. Our results shown that cases in which the network predicts incorrectly correlate with a higher un-certainty. Mean uncertainty of incorrectly diagnosed cases was 8.7 times higher than mean uncer-tainty of correctly diagnosed cases. In addition, it was observed that a higher prevalence of a disease in the data set correlates with a lower mean uncertainty. The findings were even stronger when training the classifier with smaller data sets. Modeling of the prediction uncertainty in computer-aided diagnosis with deep learning yields more reliable results and is therefore anticipated to increase patient safety. This can help to transfer such systems into clinical routine and to increase the acceptance of physicians and patients for machine learning in diagnosis. In future work, the uncertainties can be used to further increase classification accuracy.

S111Abstracts – BMT 2019 – Frankfurt am Main, September 25–26 • DOI 10.1515/bmt-2019-6023 Biomed. Eng.-Biomed. Tech. 2019; 64(s2): S111–S271 • © by Walter de Gruyter • Berlin • Boston

Using Deep Correlation Features to define the Meta Style of Cells for Classifica-tion Simon Grützmacher, Dept. of Informatics, Reutlingen University, Reutlingen, Germany, [email protected] Ralf Kemkemer, Dept. of Applied Chemistry, Reutlingen University & Max Planck Institute for Medical Research, Heidelberg, Germany, [email protected] Cristóbal Curio, Dept. of Informatics, Reutlingen University, Reutlingen, Germany, [email protected]

Digital light microscopy techniques are among the most widely used methods in cell biology and medical research. De-spite that, automated classification of objects such as cells or specific parts of tissues is difficult. We present an ap-proach to classify confluent cells in microscopy images by learnt deep correlation features using deep neural networks. These deep correlation features are generated through the use of gram-based correlation features and given to a neural network for learning the correlation between them. This approach has proven to be suitable for the classification of art-works in respect of their artistic period. The method generates images that contain recognizable characteristics of a spe-cific cell type, for example the average size and the ordered pattern, but lack in artifacts that occur randomly in the orig-inal image. An advantage of our approach is the achieved robustness as well as transfer the learned deep correlation fea-tures to similar cell types where not much ground data is available.


Computer Aided Detection of Polyps in White-light-Colonoscopy Images using

Deep Neural Networks

Pascal Zobel, Fraunhofer IIS, Erlangen, Germany, [email protected] Magnus Rathke, Fraunhofer IIS, Erlangen, Germany, [email protected] Steffen Mühldorfer, Klinikum Bayreuth, Germany, [email protected] Thomas Wittenberg, Fraunhofer IIS, Erlangen, Germany, [email protected] Early detection and removal of neoplastic lesions in the form of polyps is one central goal of colonoscopic screening programs. Screening colonoscopy is currently the “gold-standard” for the examination of the colon. Using a video endo-scope, the surface and tissue of the colon's tissue is examined for conspicuous regions. In order to possibly support gas-troenterologists during this examination process, convolutional deep neural networks can be applied for computer-assisted detection of neoplastic lesions. As image data for the experiments, 2484 still HD images from routine colonosocpy examinations (Olympus system) were extracted and manually labelled. In total 2513 polyps were delineated (data set A). This data collection was split up in three disjunct subsets for training (65%), validation (20%) and testing (15%). From the MICCAI 2015 polyp detection challenge two further data sets were used for testing [Bernal et al, 2017]. Data set B (CVC-ClinicDB) incorporates 612 SD images (Pentax system), while data set C (ETIS-LaribPolypDB) includes 196 HD colonoscopy frames (Olympus system). For the automated detection of polyps in colonoscopy white light images, a Mask R-CNN architecture (a convolutional deep neural network for instance segmentation) was examined. As the available data sets were relatively small for the complex network architecture, a transfer learning approach was employed. The network was pretrained on the MS-COCO image data collection with over 200,000 images and 91 classes from street-life. Then, the network was forced to a two-class problem, consisting of foreground (“polyp”) and background (“non-polyp”). Training was done in different stages, starting from training only the fully connected network head to fine tuning all forward layers. As the available training data (from data set A) is quite sparse, image augmentation (flipping, rotation, down-scaling) was used during training. After the learning process, results on the validation data set A were achieved in the range from recall = 0.9, precision = 0.64, F1 = 0.75 to rec = 0.86, prec = 0.81, F1 = 0.83, depending on the selected confidence thresholds. Results on the corresponding validation test data set A were rec = 0.88, prec = 0.83, F1 = 0.85. On test set B results in the range from rec = 0.85, prec = 0.66, F1 = 0.74 to rec = 0.81, prec = 0.79, F1 = 0.80 were obtained. On test set C results in the range from rec = 0.83, prec = 0.66, F1 = 0.73 to rec = 0.78, prec = 0.81, F1 = 0.79 could be obtained. Compared to the 2017 published values of the MICCAI challenge’s winner, our results are considerably better on data set C. Nevertheless, for real clinical value, still too many false positives areas are detected and some false negatives are missed. One explanation for the currently achieved values is the small training data set, as it is known from literature that more and diverse training data will provide better results. Thus, we are currently extending our training data set in order to achieve better results.


3D print of heart rhythm model with cryoballoon catheter ablation of pulmonary vein Sandra Wehsener, University of Applied Science, Offenburg, Germany, [email protected] Robin Müssig, University of Applied Science, Offenburg, Germany, [email protected] Matthias Heinke, University of Applied Science, Offenburg, Germany, [email protected] Stefan Junk, University of Applied Science, Offenburg, Germany, [email protected] Johannes Hörth, University of Applied Science, Offenburg, Germany, [email protected] Steffen Schrock, University of Applied Science, Offenburg, Germany, [email protected] The visualization of heart rhythm disturbance and atrial fibrillation therapy allow the optimization of new cardiac catheter ablations. With the simulation software CST (Computer Simulation Technology, Darmstadt) electromagnetic and thermal simulations can be carried out to analyze and optimize different heart rhythm disturbance and cardiac catheters for pulmonary vein isolation. Another form of visualization is provided by haptic, three-dimensional print models. These models can be produced using an additive manufacturing method, such as a 3D printer. The aim of the study was to produce a 3D print of the Offenburg heart rhythm model with a representation of an atrial fibrillation ablation procedure to improve the visualization of simulation of cardiac catheter ablation. The basis of 3D printing was the Offenburg heart rhythm model and the associated simulation of cryoablation of the pulmonary vein. The thermal simulation shows the pulmonary vein isolation of the left inferior pulmonary vein with the cryoballoon catheter Arctic Front AdvanceTM from Medtronic. After running through the simulation, the thermal propagation during the procedure was shown in the form of different colors. The three-dimensional print models were constructed on the base of the described simulation in a CAD program. Four different 3D printers are available for this purpose in a rapid prototyping laboratory at the University of Applied Science Offenburg. Two different printing processes were used: 1. a binder jetting printer with polymer gypsum and 2. a multi-material printer with photopolymer. A final print model with additional representation of the esophagus and internal esophagus catheter was also prepared for printing. With the help of the thermal simulation results and the subsequent evaluation, it was possible to make a conclusion about the propagation of the cold emanating from the catheter in the myocardium and the surrounding tissue. It could be measured that already 3 mm from the balloon surface into the myocardium the temperature drops to 25 °C. The simulation model was printed using two 3D printing methods. Both methods as well as the different printing materials offer different advantages and disadvantages. While the first model made of polymer gypsum can be produced quickly and cheaply, the second model made of photopolymer takes five times longer and was twice as expensive. On the other hand, the second model offers significantly better properties and was more durable overall. All relevant parts, especially the balloon catheter and the conduction, are realistically represented. Only the thermal propagation in the form of different colors is not shown on this model. Three-dimensional heart rhythm models as well as virtual simulations allow a very good visualization of complex cardiac rhythm therapy and atrial fibrillation treatment methods. The printed models can be used for optimization and demonstration of cryoballoon catheter ablation in patients with atrial fibrillation.


An Implementation of Neural Network on FPGA for Real-Time Grasp Recogni-tion based on sEMG Ivan Potapov, RWTH Aachen, Aachen, Germany, [email protected] Dmitry Amelin, Fraunhofer IBMT, Sulzbach, Germany, [email protected] Josep Cardona Audí, Fraunhofer IBMT, Sulzbach, Germany, [email protected] Roman Ruff, Fraunhofer IBMT, Sulzbach, Germany, [email protected] Klaus-Peter Hoffmann, Fraunhofer IBMT, Sulzbach, Germany, [email protected] Patients with bilateral loss of grasping function caused by cervical spinal cord injury suffer from an inability to lead a full life. More than half of them still have residual muscle functions. Targeted electrical stimulation can be used to replace lost functionality artificially. This method is investigated in BMBF funded research project INTAKT coordinated by Fraunhofer Institute for Biomedical Engineering. One of the INTAKT project goals is to restore grasping activities by means of neuroprosthesis using miniature active implants, which implement both measurement and stimulation. For effi-ciently real-time pattern classification of electromyogram (EMG) machine learning techniques, such as artificial neural networks (ANN), is proposed as an intention classifier. To overcome typical limitations of that method, a field-program-mable gate array (FPGA) was used to perform complex computational operations in parallel. The proposed approach enables the achievement of form factors suitable for wearable computing architectures. Based on researches a multilayer perceptron (MLP) was selected as ANN type. By varying hyperparameters, such as a number of neurons, signal frame width, and input features, ANNs were trained and tested in MATLAB to find out the best proportion of accuracy to performance. The dataset contains 8-channels differential surface EMG recorded from a healthy subject. The key features used to accelerate computations on FPGA were fixed-point data representation, appli-cation of parallel matrices multiplication and substitution of activation functions for lookup tables. Developed feature extraction module calculates the root mean square values (RMS) from each channel in a parallel way for the ANN input. The threshold level of the overall RMS value determines the start of the movement. MLP instance with 60 and 30 neurons in the first and second hidden layers respectively was implemented on FPGA. Ten day-to-day grasps (such as palmar, open hand, lateral, clench, etc.) were recognized with a mean accuracy of 97,14% (maximum 99,65%; minimum 94,54%; the standard deviation is 1,55%) for 50 ms signal frame in MATLAB. On FPGA mean accuracy of 95,84% (maximum is 99,72%; minimum is 90,94%; the standard deviation is 3,11%) was reached without signal preprocessing. Single feedforward calculation takes 45 µs. For the introduced ANN the accuracy mostly depends on the frame width which is used to calculate input features. Having an overall limitation of 100 ms for real-time recognition and computation duration about tens of µs the frame width be-comes the most significant parameter.


OmniPD: One-Step Person Detection in Top-View Omnidirectional Indoor Scenes Jingrui Yu, Faculty of Electrical Engineering and Information Technology, TU Chemnitz, Chemnitz, Germany, [email protected] Roman Seidel, Faculty of Electrical Engineering and Information Technology, TU Chemnitz, Chemnitz, Germany, [email protected] Gangolf Hirtz, Faculty of Electrical Engineering and Information Technology, TU Chemnitz, Chemnitz, Germany, [email protected] We propose a one-step person detector for top-view omnidirectional indoor scenes based on convolutional neural net-works (CNNs). While state of the art person detectors reaches competitive results on perspective images, missing CNN architectures as well as training data that follows the distortion of omnidirectional images makes current approaches not applicable to our data. The method predicts bounding boxes of multiple persons directly in omnidirectional images without perspective transformation, which reduces overhead of pre- and post-processing and enables real-time perfor-mance. The basic idea is to utilize transfer learning to fine-tune CNNs trained on perspective images with data augmen-tation techniques for detection in omnidirectional images. We fine-tune two variants of Single Shot MultiBox detectors (SSDs). The first one uses Mobilenet v1 FPN as feature extractor (moSSD). The second one uses ResNet50 v1 FPN (resSSD). Both models are pre-trained on Microsoft Common Objects in Context (COCO) dataset. We fine-tune both models on Pascal VOC07 and VOC12 datasets, specifically on class “person”. Random 90-degree rotation and random vertical flipping are used for data augmentation in addition to the methods proposed by original SSD. We reach an av-erage precision (AP) of 67.2% with moSSD and 75.5% with resSSD on the evaluation dataset. To enhance the fine-tuning process, we add a subset of HDA Person dataset and a subset of PIROPO database and reduce the number of perspective images to Pascal VOC07. The AP rises to 83.2% for moSSD and 86.3% for resSSD, respectively. The aver-age inference speed is 28 ms per image for moSSD and 38 ms per image for resSSD using Nvidia Quadro P6000. Our Method is applicable to other CNN-based object detectors and can potentially generalize for detecting other objects in omnidirectional images.


Assessment of 4D Ultrasound Systems for Image-guided Radiation Therapy – Image Quality, Framerates and CT Artifacts Svenja Ipsen, Institute for Robotics and Cognitive Systems, University of Lübeck, Germany, [email protected] Ralf Bruder, Institute for Robotics and Cognitive Systems, University of Lübeck, Germany, [email protected] Verónica García-Vázquez, Institute for Robotics and Cognitive Systems, University of Lübeck, Germany, [email protected] Achim Schweikard, Institute for Robotics and Cognitive Systems, University of Lübeck, Germany, [email protected] Floris Ernst, Institute for Robotics and Cognitive Systems, University of Lübeck, Germany, [email protected] 4D ultrasound (4DUS) is gaining relevance as a tracking method in radiation therapy as modern matrix array probes offer new possibilities for real-time target detection. For clinical implementation, however, image quality, volumetric framerate and artifacts caused by the probe’s presence during planning and/or setup CT must be quantified. We compared three 4DUS systems (GE Vivid7 with 3V probe, E95 with 4V and 4Vc, Philips Epiq7 with X6-1) using a commercial wire phantom to measure spatial resolution and a torso phantom to measure speckle signal-to-noise ratio (SSNR) and contrast-to-noise ratio (CNR). CT artifacts (Somatom DefinitionAS, 0.9x0.9x1mm³ voxel size) were quantified in the torso phan-tom by calculating the total variation (TV) and percentage of affected voxels ( HU>25) between a reference scan and scans with probes in place. At 15cm depth, covering an area of 122x84mm², the framerates were 13.8Hz (Vivid7), 20.9Hz (E95) and 8Hz (Epiq7). The mean wire resolution was 3.1mm (Vivid7), 2.8mm (E95) and 3.0mm (Epiq7). Epiq7 showed superior SSNR through-out all experiments while CNR was higher for E95 and Vivid7 in a kidney tumor of the phantom. In CT, axial slices intersecting the probes showed artifacts in all cases, with TV increase between 1.9% (4Vc) and 4.6% (X6-1) over the entire CT scan. This was most pronounced directly below the probes, ranging from 166% (4Vc) to 390% (X6-1). At 15cm depth, this reduced to between 10% (4Vc) and 41% (3V). 6.5cm away from the probes, TV increase was between 0.1% (4Vc) and 3.6% (3V). The percentage of affected voxels ranged from 13.9% (4Vc) to 22.1% (3V). This shows that state-of-the-art 4DUS systems with small probes can fit inside the CT bore and cause less metal artifacts than larger probes. Volume sizes and framerates are much higher than commercially used systems, warranting further investigation regarding their clinical performance for image guidance.


Preliminary Study on 3D Printing of PEGDA Hydrogels for Frontal Sinus Im-

plants using Digital Light Processing (DLP)

Robert Mau, Microfluidics, University of Rostock, Germany, [email protected]

Jamal Nazir, Microfluidics, University of Rostock, Germany, [email protected]

Samuel John, HörSys GmbH, Hannover, Germany, [email protected]

Hermann Seitz, Microfluidics, University of Rostock, Germany, [email protected]

Digital Light Processing (DLP) enables high precision 3D-printing of photopolymers and holds promising potentials for

patient-specific implant solutions. Poly(ethylene glycol) diacrylate (PEGDA) has emerged as an interesting biomaterial

for the use in biomedical applications. This study shows preliminary results of processing PEGDA hydrogels using

DLP. Photocurable PEGDA-solutions were prepared by mixing PEGDA of low molecular weight (Mn of 700) with dis-

tilled water (90, 70, 50, 30, 10 % w/w and no water content) and the photoinitiator lithium phenyl-2,4,6-trimethyl

benzoyl phosphinate (LAP, 0.05 % w/w regarding the mass of PEGDA in solution). For 3D-printing investigations, a

DLP-device VIDA (Envisiontec, Germany) was used.

First, for each PEGDA-solution DLP-3D-printing investigations were performed by printing simple rectangular test

samples (one Shore A hardness test sample of 40 mm x 40 mm x 7 mm and two flat test samples of

54 mm x 10 mm x 2 mm) placed next to each other on the build platform (spacing 3 mm). An exposure time per layer

of 20 seconds and a layer height of 100 µm were used. Contour sharpness, as well as Shore A hardness, were investi-

gated to evaluate the printed PEGDA-hydrogel specimens. The results show that PEGDA hydrogel could be

successfully processed via DLP. Contour sharpness and Shore A hardness increases with decreasing proportions of wa-

ter. However, for dilutions of lower than 30 % w/w of water, no significant influence on the test parameters were found.

Second, the feasibility of printing a patient individual frontal sinus implant prototype was tested by using PEGDA-

hydrogel (30 % w/w of water). For comparison reasons, the frontal sinus implant prototype was also printed using the

acrylate polymer E-Model light (Envisiontec). The results show that the contour sharpness of the PEGDA-hydrogel-

protoype is acceptable. However, overhanging structures could not be realised yet. Further investigations utilizing UV

absorbers will be conducted to optimise printing quality.


Development and manufacturing of a custom made implant regarding the new

European Medical Device Regulation (MDR)

Mareike Schonhoff, Frankfurt University of Applied Science, Frankfurt am Main, Germany, [email protected]

Astrid Heinze, Frankfurt University of Applied Science, Frankfurt am Main, Germany, [email protected]

Juliette Carrillo, Frankfurt University of Applied Science, Frankfurt am Main, Germany, [email protected]

Annika Lopinski, Frankfurt University of Applied Science, Frankfurt am Main, Germany, [email protected]

Damian Großkreutz, Frankfurt University of Applied Science, Frankfurt am Main, Germany, [email protected]

Stefan Hanusek, Frankfurt University of Applied Science, Frankfurt am Main, Germany, [email protected]

New technologies are great opportunities for personalized medicine. Custom made implants can be very helpful for pa-

tients with severe bone defects or in case of bone tumor. Through the European Union it is regulated how many possi-

bilities and restrictions all medical devices have. Because of critical vulnerabilities a new European Medical Device

Regulation (MDR) was published in May 2017 and it will enter into force in May 2020. For the manufacturers of cus-

tomized products it will change the documentation of the manufacturing and tracking of serious incidents.

Patients with a pelvis defect of Paprosky IIb and higher can benefit from a cutom made pelvis implant, because all

planning steps according to biomechanic and bone contact to the implant can be designed and proofed during a recon-

struction process. With regular modular implant systems, it probably can be a trial and error procedure during the sur-

gery according to biomechanic and a stable position of the implant.

Based on the 3D-Reconstruction of CT-Scans of a patient with a Paprosky IIb pelvis defect, a personalized acetabulum

implant was designed. To maintain as much bone as possible, the implant was shaped to the remaining pelvic bone

stock. Additive manufacturing gives the opportunity to produce custom made single items even in a quality that fulfills

the requirements of the MDR. Modern Selective Laser Melting (SLM) and Electron Beam melting (EBM) Systems are

able to produce Titanium or CoCr parts in the ISO standards for Implants (ISO 5832 ff).

In this study the process chain, starting from the reconstruction, to the design and the production of a custom made ace-

tabulum cup was run through on an exemplary CT-Data of one patient. We could show, that it is possible to establish a

process, that is able to address surgical needs for patients that benefit from those techniques.


mailto:[email protected]






Combined adaptive load and displacement controlled knee simulator

Hans-Reiner Ludwig, Personalized Biomedical Engineering Lab, Frankfurt University of Applied Sciences, Frankfurt am

Main, Germany, [email protected]

Peter Weimar, Personalized Biomedical Engineering Lab, Frankfurt University of Applied Sciences, Frankfurt am Main,

Germany, [email protected]

Markus Auermann, Frankfurt Universtity of Applied Sciences, Frankfurt, Germany, [email protected]

Christopher Blase, Personalized Biomedical Engineering Lab, Frankfurt University of Applied Sciences, Frankfurt am

Main, Germany, [email protected]

Degenerative joint disease or traumatic processes lead to damaging of articular cartilage in the knee joint, which is treated

by partial or total knee arthroplasty. Implants for knee arthroplasty currently use stiff materials, like titanium or ceramics.

In the case of local endoprotheses, which are used in the treatment of localized cartilage defects, these stiff materials

interact directly with the articulating cartilage which might lead to increased wear and secondary damage to the cartilage.

Materials for implants or surface coatings of implants, whose (visco-) elastic properties are better matched to articular

cartilage might be better suited for the creation of small, local endoprotheses.

We have developed a test rig for tribology and wear testing of knee implants, in accordance with ISO 14243. Testing is

performed with a combined displacement and load controlled approach. In the case of soft, viscoelastic implant materials,

however, synchronisation of load and displacement control of several axes is too slow to be performed in real-time, e.g.

with a simulated gait cycle of 1 Hz. Therefore we are developing a new control system for the adaptive load and displace-

ment control for viscoelastic materials.



Mobile System for the Prevention, Diagnosis, and Personalized Treatment of Neck Pain Under a Patients Everyday Life Circumstances Puian Tadayon, Research Center for BioMedical Technology (BMT), University of Applied Sciences and Arts, Dort-mund, Germany, [email protected] Thomas Felderhoff, Research Center for BioMedical Technology (BMT), University of Applied Sciences and Arts, Dortmund, Germany, [email protected] Andreas Knopp, Chair of Signal Processing (EIT 3.2), Munich University of the Bundeswehr, Neubiberg, Germany, [email protected] Gerhard Staude, Chair of Signal Processing (EIT 3.2), Munich University of the Bundeswehr, Neubiberg, Germany, [email protected] Chronicle or recurring neck pain is a serious and widespread disease with major restrictions for the affected patients: in 2005 about 21% of the population in Germany suffered from shoulder and neck pain, approximately every 3rd case of absence from work origins from neck pain. The main reasons for neck pain lie in the lack of movement and rigid neck posture in monotonous activities e.g. during work with computers and the prolonged use of smartphone or tablets. However, currently no technical devices exist which provide the acquisition of a persons’ neck posture and movement under conditions of daily life in order to aid health professionals in the diagnosis and treatment of neck pain causes. Therefore, in the research project MEDITHENA funded by the German Federal Ministry of Education and Research (BMBF), a new interactive and personalizable system for the prevention, diagnosis, and therapy of neck pain is pro-posed. The system consists of two wearable measurement devices and a smartphone device for personalized patient in-teraction and enables mobile long-term acquisition of both rotatory and translatory neck movements in a person’s eve-ryday life environment. The wearable measurement devices are worn at the persons’ head and torso respectively and provide the posture and movement of the head in relation to the torso based on a novel motion capture method employing inertial and magnetic field sensors and a single coil for magnetic field generation. The devices are battery driven and communicate with each other and the smartphone via Bluetooth. The measured motion data is processed in real-time to enable biofeedback (e.g. via smartphone vibration) in case of rig-id neck posture to prevent the emerging of neck pain. The system also provides interactive mentoring in therapeutic ex-ercises chosen and configured individually by the treating physiotherapist. Furthermore, the long-term data is trans-ferred to a cloud server to provide diagnostic support of the individual causes of neck pain based on offline analysis of the data.


Robust contactless optical heart rate acquisition - measuring human perception in minimal invasive settings Weißkopf, Peter; Koch, Robert; Haßlmeyer, Erik; Hauenstein, Thomas; Wagner, Eugen; Lang, Nadine; Garbas, Jens-Uwe; Wittenberg, Thomas; Struck, Matthias Fraunhofer Institute of Integrated Circuits IIS, Division of Smart Sensing and Electronics, Erlangen, Germany, Corresponding author: [email protected] The continuous long-term observation of the heart-rate (HR) is essential in various clinical and home-care-scenarios. Additional scenarios include psychological research where reactions to the exposure of sensory stimuli, including visual or acoustical signals as well as odors or tastes are observed and correlated. In current clinical and experimantal meas-urement setups, patients and test subjects are exposed to stimuli and asked post-experimental, how they felt. However, it is known that the questionnaire itself influences the subjects’ answers and only provides subjective impressions to the stimuli. In order to understand how sensory stimuli may influence the human status, subconscious as well as conscious reactions need to be measured. One of the most analyzed signals is the electrodermal activity (EDA), which together with the heart rate (HR), can show subconscoius reactions on external stimuli. Nevertheless, wire-bound ECG ap-proaches for heart-rate assessment are partially limited due the need of electrodes, the wiring, as well as their influence on subjects. To cope with this limitation, systems have been developed, which can derive the HR contactless in realtime. Those systems are based on RGB-cameras, measuring a slight shift in skin colour, which changes with every heart beat, when blood is pumped through the blood vessels. This colour-shift, invisible for the human eye, follows the same rate as the heart rate. Despite their obvious advantages, they also have drawbacks, like the susceptibility to move-ment and poor lighting. We set up a contactless HR-detection system which is currently able to operate robustly, despite movement and changing lighting, in a laboratory as well as in an office environment, addressing exactly these draw-backs. In independent studies including over 30 subjects, the quality of the system was evaluated by comparing the de-rived HR with a gold standard ECG signal. It was shown, that the usage of such a system is feasible in multiple en-vorinments, and may help to analyse human perception and reactions to stimuli in a more natural setting. Moreover, preliminary results suggest it might be possible, at least with corresponding conditions, to additionally analyze the heart rate variabiltity (HRV).


Neue Methoden zur Identifikation und Ueberwachung von autonomen und

sensorischen Beckennerven: Eine praeklinische Studie an Schweinen zum

intraoperativen pelvinen Neuromonitoring

M.Sc. Ramona Schuler, FuE, Dr. Langer Medical GmbH, Waldkirch, Deutschland, [email protected]

Dr.-Ing. Andreas Langer, FuE, Dr. Langer Medical GmbH, Waldkirch, Deutschland, [email protected]

PD Dr. med. Matthias Goos, Chefarzt Allgemein- und Viszeralchirurgie, Helios Klinik Müllheim; wissenschaftlich für

die Klinik für Allg. – und Viszeralchirurgie des Universitätsklinikum Freiburg und das Center for Experimental Models

and Transgenic Service Freiburg i. Br., Deutschland, [email protected]

Priv. Doz. Dr. med. univ. Marko Konschake, Facharzt für Anatomie, Sektion für Klinisch-funktionelle Anatomie,

Medizinische Universität Innsbruck, Innsbruck, Österreich, [email protected]

Das Risiko einer Schädigung von autonomen, sensorischen und motorischen Beckennerven ist während Operationen im

Bereich des Beckens sehr hoch und bringt stark einschränkende Folgen für die Lebensqualität der Patienten mit sich. Die

Folgen von Schädigungen der Beckennerven sind postoperativ auftretende Funktionsstörungen der Beckenorgane wie

Harninkontinenz, Stuhlinkontinenz und sexuelle Funktionsstörungen. Das Nervengeflecht des Beckens ist hochkomplex,

seine Ausprägung ist äußerst filigran und die Lage der Nerven ist interindivudell verschieden. Die Methoden des in-

traoperativen Neuromonitorings aus anderen chirurgischen Fachbereichen lassen sich deshalb nur schwer auf Becken-

nerven übertragen.

In einer präklinischen Studie mit 10 weiblichen Schweinen, genehmigt vom Regierungspräsidium Freiburg (35-

9185.81/G-16/27), wurden zwei neue Messmethoden zur intraoperativen Identifikation und Überwachung von autonomen

und sensorischen Beckennerven evaluiert. Der chirurgische Zugang in das Abdomen erfolgte durch Längslaparotomie.

Nach Darstellung der Ureteren, Harnblase, Urethra und Vagina folgte die Darstellung des Plexus hypogastricus, dann

schrittweise der weiteren peripheren Nerven und die Durchführung des Neuromonitorings.

Die intraoperative Funktionskontrolle viszeraler aufsteigender Bahnen wurde durch Stimulation des unteren Harntrakts

und des Rektums während der Ableitung kortikaler evozierter Potenziale an den Punkten Fz-Cz durchgeführt. Die Stim-

ulationselektroden wurden am unteren Harntrakt auf Höhe der Mm. sphincter urethrae und im Rektum ca. 5 cm proximal

des Anus positioniert. Es konnten abhängig von der Stimulationsfrequenz und -position, reproduzierbare kortikale Poten-

ziale abgeleitet werden.

Die intraoperative Identifikation und Funktionskontrolle viszeraler absteigender Nervenbahnen im Situs wurde durch

direkte Nervstimulation mit einer Handsonde und simultaner Messung der Gewebeimpedanzänderung am glatten Muskel

der Harnblase und des Rektums durchgeführt. Die direkte Nervstimulation evozierte eine makroskopische Kontraktion

der glatten Muskulatur der leeren Harnblase und/oder des Rektums, die reproduzierbar mittels Messung einer Gewebeim-

pedanzänderung erfasst werden konnte. Damit ist erstmals eine intraoperative Messung der Blasenkontraktion an der

leeren Harnblase möglich. Durch Einspeichsung eines Wechselstroms im µA-Bereich, wird die verursachte Spannungsän-

derung zwischen zwei Messelektroden am Zielorgan gemessen und als Änderung der Gewebeimpedanz graphisch

dargestellt. Es wurden unterschiedliche Stimulationsparameter, Elektrodenarten und Elektrodenanordnungen zur Imped-

anzmessung analysiert.

Ebenso wurden Gewebeproben zur histologischen Analyse entnommen, die intraoperativ als autonomes Nervengewebe

durch direkte Stimulation und Impedanzmessung identifiziert wurden. Mittels Immunhistochemie konnten sympathische

und parasympathische Nervenfasern in den Proben nachgewiesen werden, wodurch die Richtigkeit der Ergebnisse

bestätigt wurde.

Die direkte Nervstimulation mit Impedanzmessung und die Ableitung viszeraler evozierter Potenziale sind neue erfolgs-

versprechende Methoden im intraoperativen pelvinen Neuromonitoring. Weitere Studien zur Übertragbarkeit auf den

Menschen und Einführung in die klinische Routine sind in geplant.










Optimized indium tin oxide (ITO) multielectrode arrays for combined opto-bioelectronic monitoring Sabine Schmidt, Heinz-Georg Jahnke, Ronny Frank, Winnie Weigel, Christoph Prönnecke and Andrea A. Robitzki University of Leipzig, Center for Biotechnology and Biomedicine (BBZ), Molecular biological-biochemical Processing Technology, Deutscher Platz 5, 04103 Leipzig, Germany Highly conductive and biocompatible electrodes materials like gold and platinum are preferred for bioelectronic sensors in diverse applications and assays. While these materials offers superior electrochemical characteristics, their opaque nature prohibits combination with microscopic monitoring as well as other optical analysis. This drawback can be overcome with transparent electrode materials like indium tin oxide (ITO). ITO has the same biocompatible characteristics compared with gold and platinum. Thus, it is suitable for the use in combination especially with cells and tissues. Only its semiconducting property that results in a clearly lowered conductivity of two to three magnitudes is a disadvantage of the material. In this context, we analyzed the achievable signals of cells cultured on multielectrode arrays (MEAs) and calculated the signal-to noise ratios. Especially, when ITO is used for large scale electrodes a dramatically signal loss occurs. To optimize MEAs for minimized signal loss, we used finite element method (FEM) simulations to identify the influence of electrode geometry and material characteristic. As a result of these simulations we developed a multi composite MEA that combines the excellent transparent properties of ITO electrodes and offers sufficient conductivity for good signal-to-noise ratios.


Noninvasive Blood Glucose Monitoring (GluMo) Navid Shaghaghi, Faculty (Departments of Math & Computer Science and Computer Science & Engineering, Santa Clara University), Santa Clara, USA, [email protected] Zhiwen Zhang, Chair (Department of Bio Engineering, Santa Clara University), Santa Clara, USA, [email protected] For millions of patients suffering from diabetes around the world the repeated task of pricking their fingertip in order to check their glucose level is a painful and sometimes messy fact of daily life. In an effort to change that for the better, we envisioned, designed, and prototyped a portable noninvasive glucose monitoring medical instrument which we have dubbed as GluMo. In place of a drop of blood we use Infrared (IR) light emitters and sensors as part of a small form factor Internet of Things (IoT) medical instrument which calculates the amount of the voltage drop across a finger's soft tissue due to the IR wave’s interaction with glucose molecules within the blood stream. The information is then wirelessly transmitted to an online database for tracking, history building, and data visualization for the patient (and potentially the patient’s doctor and/or medical facility staff if authorized) through a web application. A mobile application is also possible but we found that a web interface is both more accessible and easier to prototype. A further market imposed requirement for GluMo’s prototype is low cost as current single droplet blood glucose monitors are attainable as cheap as $10 USD. In order to satisfy this requirement by keeping GluMo’s cost under $100 USD without diminishing the accuracy of the reading outside of an acceptable bounds, Near Infrared (NIR/IR-A DIN) emitters at the 1300 nanometer (nm) wavelength and corresponding receivers were chosen for the porotype. The choice of 1300nm NIR/IR-A comes from the fact that 60% of human blood is water (H2O) and 1300nm NIR/IR-A has the largest positive difference between its absorbance in glucose and its absorbance in water among the other wavelengths of IR in the NIR/IR-A range. Our initial test results have yielded a 99.2% level of accuracy for normal range blood glucose levels and the main effort of the research is now on increasing the accuracy for the edge cases of the glucose bell-shaped distribution curve as well as the reduction of the instrumentation’s size to pocket size; utilizing the smallest off the shelf microcontroller, sensor, and other components as well as a 3D-printed instrumentation casing. Another change to the design of GluMo’s Minimum Viable Product (MVP) under research and development is the utilization of Short-Wavelength Infrared (SWIR/IR-B DIN) at 1550nm instead of the current 1300nm Near Infrared (NIR/IR-A DIN) due to it having an even larger difference between its absorbance in glucose and in water. The higher cost of 1550nm IR emitters and corresponding receivers will thus result in a more than $100 USD initial cost for the future pocket-sized GluMo MVP until economies of scale can cause a reduction in its production costs. A future goal is the design and production of a system on a chip solution addable to existing wearables for continued monitoring of blood glucose levels for diabetics. This will even further reduce the cost thus making GluMo even more affordable and accessible to patients and medical facilities with all levels of economic background and purchasing power.


Patient-Specific Identification of Atrial Flutter Vulnerability–A Computational Approach to Reveal Latent Reentry Pathways Axel Loewe (1), Emanuel Poremba (1), Tobias Oesterlein (1), Armin Luik (2), Claus Schmitt (2), Gunnar Seemann (1,3,4), and Olaf DDlssel (1) (1) Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany (2) Medizinische Klinik IV, St( 2dtisches Klinikum Karlsruhe, Karlsruhe, Germany (3) Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg Bad Krozingen, Freiburg, Germany (4) Faculty of Medicine, Albert-Ludwigs University, Freiburg, Germany [email protected] Atypical atrial flutter (AFlut) is a reentrant arrhythmia, which patients frequently develop after ablation for atrial fibrilla-tion (AF). Indeed, substrate modifications during AF ablation can increase the likelihood to develop AFlut and it is clin-ically not feasible to reliably and sensitively test if a patient is vulnerable to AFlut. Here, we present a novel method based on personalized computational models to identify pathways along which AFlut can be sustained in an individual patient. We build a personalized model of atrial excitation propagation considering the anatomy as well as the spatial distribution of anisotropic conduction velocity and repolarization characteristics based on a combination of a priori knowledge on the population level and information derived from measurements performed in the individual patient. The fast marching scheme is employed to compute activation times for stimuli from all parts of the atria. Potential flutter pathways are then identified by tracing loops from wave front collision sites and constricting them using a geometric snake approach under consideration of the heterogeneous wavelength condition. In this way, all pathways along which AFlut can be sustained are identified. Flutter pathways can be instantiated by using an eikonal-diffusion phase extrapolation approach and a dynamic multifront fast marching simulation. In these dynamic simulations, the initial pattern eventually turns into the one driven by the dominant pathway, which is the only pathway that can be observed clinically. We assessed the sensi-tivity of the flutter pathway maps with respect to conduction velocity and its anisotropy. Moreover, we demonstrate the application of tailored models considering disease-specific repolarization properties (healthy, AF-remodeled, potassium channel mutations) as well as applicabilty on a clinical dataset. Finally, we tested how AFlut vulnerability of these sub-strates is modulated by exemplary antiarrhythmic drugs (amiodarone, dronedarone). Our novel method allows to assess the vulnerability of an individual patient to develop AFlut based on the personal anatomical, electrophysiological, and pharmacological characteristics. In contrast to clinical electrophysiological studies, our computational approach provides the means to identify all possible AFlut pathways and not just the currently dominant one. This allows to consider all relevant AFlut pathways when tailoring clinical ablation therapy in order to reduce the development and recurrence of AFlut.


Comparison and Implementation of Open Source Face Detection and Tracking Systems on mobile Android Devices for use in home-based Speech Therapy Ahamad Hassan Mirza, Research Center for BioMedical Technology, University of Applied Sciences and Arts, Dort-mund, Germany, [email protected] Dominik Fromme, Research Center for BioMedical Technology, University of Applied Sciences and Arts, Dortmund, Germany, [email protected] Stefan Patzke, Research Center for BioMedical Technology, Universityof Applied Sciences and Arts, Dortmund, Ger-many, [email protected] Jörg Thiem, Research Center for BioMedical Technology, Univerity of Applied Sciences and Arts, Dortmund, Germany, [email protected] Digitalization in the health system enables many new possibilities with regard to therapies and care for patients. At the same time, new interdisciplinary fields of research are opening up. In particular, due to the widespread use of mobile devices and their increasing performance, new possibilities of home therapy are offered by computer-aided systems. For example, the great advances in audiovisual speech recognition of recent years can be used to support speech therapy by evaluating the home exercises through an automatic speech recognition system which detects speech disorders. The best recognition rates in the field of automatic speech recognition can be achieved by merging audio and visual infor-mation, since this way the advantages of both systems can be combined. An important component of an audiovisual speech recognition system is the face detection and facial-landmark detec-tion. For example, in visual speech recognition, facial-landmarks describe the position of the mouth, lips and chin in an image. Landmarks can be used to selectively cut out regions of interest for further processing and subsequent feature extraction, or can be used as a feature themself. In order to be able to use audiovisual speech recognition in home therapy, the latency time between a spoken word and the response of the speech recognizer should be as low as possible for a seamless user experience. This can only be en-sured if the individual algorithms, e.g. landmark-detection, can be performed in real-time on a mobile device. Conse-quently, this paper examines the speed of face detection and facial landmark detection of different open scource software with different image resolutions on mobile android devices and implements and evaluates a real-time face tracking. There-fore, the openCV face detection, Dlib toolkit, which allows detection of 68 facial landmarks and the Mobile Visi-on API from Google will be discussed.


Validation System for Digital Stethoscopes Michael Klum, Chair of Electronics and Medical Signal Processing, Technische Universität Berlin, Berlin, Germany, [email protected] Julian Jakob Stehling, Chair of Electronics and Medical Signal Processing, Technische Universität Berlin, Berlin, Ger-many, [email protected] Alexandru-Gabriel Pielmus, Chair of Electronics and Medical Signal Processing, Technische Universität Berlin, Berlin, Germany, [email protected] Timo Tigges, Chair of Electronics and Medical Signal Processing, Technische Universität Berlin, Berlin, Germany, [email protected] Reinhold Orglmeister, Chair of Electronics and Medical Signal Processing, Technische Universität Berlin, Berlin, Ger-many, [email protected] The stethoscope is a widely used, inexpensive diagnostic device. The conventional stethoscope however, was already deemed obsolete due to observation bias and the availability of more advanced, yet more expensive methods. The de-velopment of digital stethoscopes and advances in auscultatory sound analysis led to on objectification and increased the interest in the field. Applications include respiratory flow and heart stroke volume estimation as well as asthma and COPD diagnostics. While handheld digital stethoscopes are available, the integration of this additional diagnostic di-mension in wearable patient monitoring has yet to come. When characterizing digital stethoscopes, most researchers focus on the electronic filtering. The acoustical transfer function of the stethoscope however, has a large impact on the overall frequency response as well and should not be ignored. We developed a cost efficient method to characterize the acoustic transfer function of digital stethoscopes using a gel phantom. Applying a structure-borne sound converter con-nected to a PVC assembly embedded into the gel, the excitation of the phantom was realized. A highly linear accel-erometer was used to record a reference to which the stethoscope transfer function was calculated. A pressure sensor was embedded into the system in order to account for different transfer functions at different mechanical pressure levels applied to the stethoscope. The frequency response of the phantom was flattened by modulating the amplitude of the excitatory signal. Using the presented system, the frequency range between 40 Hz and 2.5 kHz can be characterized. With the dominant frequency of heart sounds located at 48 Hz and respiratory sounds ranging up to 2.5 kHz, we are able to cover the full relevant spectrum. The proposed design was evaluated using a commercially available digital stethoscope. We conclude that the presented system can be used to characterize acoustical properties of digital stetho-scopes in a cost efficient manner.


A Piezoelectric Flexural Plate Wave (FPW) Bio-MEMS Sensor with Improved Molecular Mass Detection for Point-of-Care Diagnostics

Christian Walk, Fraunhofer-Institut für Mikroelektronische Schaltungen und Systeme (IMS), Duisburg, Germany, [email protected] Matthias Wiemann, Fraunhofer-Institut für Mikroelektronische Schaltungen und Systeme (IMS), Duisburg, Germany, [email protected] Michael Görtz, Fraunhofer-Institut für Mikroelektronische Schaltungen und Systeme (IMS), Duisburg, Germany, [email protected] Jens Weidenmüller, Fraunhofer-Institut für Mikroelektronische Schaltungen und Systeme (IMS), Duisburg, Germany, [email protected] Andreas Jupe, Fraunhofer-Institut für Mikroelektronische Schaltungen und Systeme (IMS), Duisburg, Germany, Andreas.Jupe @ims.fraunhofer.de Karsten Seidl, Fraunhofer-Institut für Mikroelektronische Schaltungen und Systeme (IMS), Duisburg, Germany, Universität Duisburg-Essen, Elektronische Bauelemente und Schaltungen, Duisburg, Germany Karsten.Seidl @ims.fraunhofer.de The Respiratory Syncytial Virus (RSV) is responsible or a high rate of post-neonatal deaths. A fast and early diagnosis with accurate detection is vital for an effective treatment. Common diagnostics for the identification of unknown patho-gens require large sample volumes and are time consuming. In this work, a piezoelectric flexural plate wave (FPW) Bio-MEMS sensor has been developed. The detection is based on the frequency shift of a FPW membrane due to bind-ing of an additional mass depending on the applied functionalisation treatment. There are many acoustic sensors for molecular mass detection. However, the operating frequencies of sensors, such as shear horizontal surface acoustic wave (SH-SAW), surface transverse wave (STW) are usually larger than 100 MHz, which substantially complicates the readout electronics and increases the overall device costs. Only flexural plate wave (FPW) sensors have lower operating frequencies, allow for high mass sensitivity, and their phase velocity is less than the sound velocity in liquid, thus resulting only in minor energy dissipation into a testing liquid. A piezoelectric FPW-sensor with multiplexing capability has been developed for a point of care device in this work. The FPW-sensor consists of an electrode configuration termed as an interdigital transducer (IDT) placed on a mem-brane. An input IDT excites and an output IDT detects the propagating acoustic waves through a PZT layer. Design optimizations and fabrication improvements of the FPW sensor led to significantly reduced attenuation of the wave signal and the damping of the propagating waves between the IDTs. While a frequency shift of about 350 Hz was detected for design A, about 7 kHz can be measured with the improved sensor design B. Thus the resolution was signif-icantly improved from 0.7 Hz/nM to 14 Hz/nM chemokine in complex solution.


Microphysiological system for heart tissue – going from 2D to 3D culture – tech-nological challenges and tissue integration concepts Mathias Busek, TU Dresden, Chair of Microsystems, Dresden, Germany, [email protected] Mario Schubert, Kaomei Guan, TU Dresden, Institute of Pharmacology and Toxicology, Dresden, Germany Florian Schmieder, Frank Sonntag, Fraunhofer IWS Dresden, Dresden, Germany Uwe Marschner, Andreas Richter, TU Dresden Chair of Microsystems, Dresden, Germany Recently we developed a microphysiological system (MPS) with an integrated peristaltic micro pump, micro channels, tissue chambers and an oxygen exchange membrane. Together with a smart controlling unit, fluid flow and oxygen rates can be controlled and maintained at physiological levels. Moreover, pathological processes like hypoxia, ischemia or hypertension can be modelled by varying the process parameters or geometry of the MPS. Due to the low circulating volume of the MPS (70 µL) tissue interactions can be easily observed as secreted proteins and biomarkers are reperfused from one tissue model to the other. First experiments on human cardiomyocytes differentiated from induced pluripotent stem cells (iPSC-CMs) revealed significant improvements of the maturation state of cells cultivated in our MPS which might be caused by this physiolog-ical and periodic hemodynamic stimulation. Improved maturation comes in line with morphological changes of the cells like an increased sarcomere length, denser mitochondria network and more elongated cell shape as well as changes in the beating pattern (better aligned beating motion and increased amplitude) which has been successfully proven via video analysis and finally changes in the gene expression profile. Currently the used organ model is 2D-based, meaning the cells are seeded at the bottom of the culture chamber. As we already investigated improvements in maturation state of the perfused 2D-culture implementing a 3D-heart tissue would drive this maturation process even further. Therefore, we aim for integrating small heart muscle strings in our MPS. This study presents concepts for tissue integration, different chamber layouts and manufacturing technologies to implement flexible pacing electrodes and posts to hold the muscle string in place. Finally, first cell cultivation results are presented and the deflection of the muscle string is evaluated via video-based analysis.


Auditory nerve implants: Surgical access and implantation procedure or flexible foil-based electrode arrays Thomas Stieglitz, Laboratory for Biomedical Microtechnology-IMTEK, BrainLinks-BrainTools, Bernstein Center Frei-burg, Albert-Ludwig-University of Freiburg, Freiburg, Germany, e-mail: [email protected] Paul Čvančara, Laboratory for Biomedical Microtechnology-IMTEK, Albert-Ludwig-University of Freiburg, Freiburg, Germany, e-mail: [email protected] Thomas Lenarz, Department of Otolaryngology, Head & Neck, Hannover Medical School & Hearing 4All , Hannover, Germany, e-mail: [email protected] Cochlear implants are state-of the-art in hearing restoration for sensorineural deafness. However, cochlear malformation or ossification after infections like encephalitis and tumor resection in neuro-fibromatosis type 2 patients requires dif-ferent anatomical levels of technical interfaces to the hearing system. Auditory brainstem (ABI) and midbrain implants (MBI) offer solutions for those patients but lack sufficient electrode numbers to deliver the same quality of speech and sound perception that can be achieved with cochlear implants. Our approach focus on the opportunities that miniaturization technologies offer to develop and evaluate flexible mi-cromachined polymer-based stimulation implants to interface with the acoustic nerve. Tonotopy, selectivity and chronic compatibility, functionality, and spatial selectivity of devices need to be investigated of such auditory nerve implants with high numbers of stimulation sites across its diameter to address all frequency areas using small size, high-density and channel count arrays and multipolar stimulation paradigms. In this pilot study, surgical techniques have been explored and developed to implant a flexible polyimide-based linear array transversally in the auditory nerve and fixate it accordingly. Electrodes with a iridium oxide coating and a diame-ter of 80 µm has been used as stimulation sites. We started with human cadaver experiments to develop a general surgi-cal technique and pulled the foil with a needle and surgical threat through the auditory nerve. Anatomical data have been derived in these studies to refine the design with respect to array dimensions, electrode size and pitch. Acute stim-ulation has been performed in a guinea pig model to evaluate stimulation thresholds measured by evoked potentials. Stimulation pulses have been well in the chemical safe charge injection range of the electrodes. Graded recruitment of acoustic nerve fibers was monitored. First results were promising. Further histological studies have to guide the engi-neering design towards arrays capable of high spatial selective stimulation.


Design of a Flow Phantom for the Evaluation of Quantitative ICG Fluorescence Angiography Ady Naber, Institute of Biomedical Engineering, Karlsruhe Institute of Technology, Karlsruhe, Germany, [email protected] Leila Meyer-Hilberg, Institute of Biomedical Engineering, Karlsruhe Institute of Technology, Karlsruhe, Germany, [email protected] Werner Nahm, Institute of Biomedical Engineering, Karlsruhe Institute of Technology, Karlsruhe, Germany, [email protected] Fluorescence video angiography is used in neurosurgery to intraoperatively monitor the vascular function, namely the blood flow. This is done by injecting the dye Indocyanine green (ICG) intravenously. After excitation by a near-infrared light source, the fluorescence signal is captured by a camera system. The recorded signal is used to qualitatively assess the vascular function during the intervention. This provides the surgeon with an immediate feedback of the quality of his surgery. Nevertheless, this qualitative assessment needs to be extended and a quantitative value should be calculated to assist the surgical staff. This step requires a standardized and validated test setup mimicking cerebral vessels for stud-ies, such as measurement of the flow and flow profile. This includes the confirmation of the suitability of the investiga-tion site in the phantom. Therefore, a flow phantom is designed according to the requirements and set up. The require-ments include a variable diameter of the vessel mimicking tubes, variable flow range within the clinical relevant range, a handy and precise injection system with an initial ICG concentration which minimizes quenching effects, a non-toxic and low cost blood analogue with similar viscosity as human blood and finally a last requirement which need more ex-planation. Real blood should not be used due to the contamination of the pump, so water is used as flow media. But the ICG is dissolved in a protein solution and should be surrounded by a protein solution to ensure mixing and diffusion into the same solution media, so the ICG should not get into touch with the flow media water. The investigation sites are given in the ranges which are confirmed to be suitable. The flow phantom provides a consistent testing environment and will be used to conduct studies analyzing the suitability of different methods to assess the flow by fluorescence im-aging.


An Evaluation of Image Feature Detectors Based on Spatial Density and Tem-poral Robustness in Microsurgical Image Processing Konstantin Sieler, Institute of Biomedical Engineering, Karlsruhe Institute of Technology, Karlsruhe, Germany, [email protected] Ady Naber, Institute of Biomedical Engineering, Karlsruhe Institute of Technology, Karlsruhe, Germany, [email protected] Werner Nahm, Institute of Biomedical Engineering, Karlsruhe Institute of Technology, Karlsruhe, Germany, [email protected] Image processing applied during neurosurgery can uncover information not visible to the human eye. Based on video streams of surgical microscopes, models can be computed that provide real-time support for surgeries and potentially assist the surgical staff in decision making. Inaccurate results can be caused by motion artefacts, induced by the cameras or the patients movement, like brain-movement through the pulse or a change in the mass of the liquor. One option to reduce these inaccuracies is feature detection and spatial allocation. This can result in more precise temporal illustration and application of models and structures. The goal of this project was to evaluate different feature detectors based on density and robustness over a representative sequence of video frames. Feature detectors included corner-, blob- and scale-space-detectors. From the microscope’s RGB channels the grayscale images were extracted and the region of in-terest was set to the area of clear focus. For each feature detector the features of each frame were extracted and features of consecutive frame pairs were matched. Starting with the initial feature set of the first frame in the sequence, features were accepted if they could be matched to the consecutive frame and if their location shift was in a specified range. Fi-nally, factors such as the feature density, minimum-, maximum- and mean number of features in the region of interest were evaluated. Feature detectors with promising high feature densities in single frames proved to have a low persis-tence of features lasting for 5 frames and no strong robustness was found throughout more than 3 frames. KAZE proved to be the best feature detector in density and robustness.


A modular monitoring system for decubitus prophylaxis (DekuProSys) Simon Gallinger, Fachgebiet Medizintechnik Technische Universität Berlin, Berlin, Germany, [email protected] Natalie Jankowski, Fachgebiet Medizintechnik Technische Universität Berlin, Berlin, Germany, [email protected] In the DekuProSys project, bedding systems for children and adolescents in palliative care are equipped with an innovative monitoring system for decubitus prophylaxis. With the aim of improving care and relieving caregivers, passive and active repositioning and risk factors for tissue damage are recorded and transferred to the care assessment. The modular moni-toring system has a wireless sensor network, a central unit with powerful database and evaluation functions and various user interfaces. Interdisciplinary cooperation, user-centered development and continuous consideration of the ELSI as-pects are paramount. Patients in palliative care must be cared for closely due to the limited general condition and the specific underlying dis-eases in order to prevent complications due to bed rest. The development of skin lesions and pressure sores (decubitus) depends on various individual risk factors and represents a serious impairment. The body tissue may be susceptible to ulceration due to intrinsic parameters if dehydration, malnutrition or metabolic disorders impair blood circulation. Un-derweight or overweight, sensitivity disorders, incontinence or existing skin irritations can also promote the development of decubitus. The microclimate on the body surface, friction and shear forces, mobility, positioning techniques and body hygiene must be considered as external risk factors. The development of the monitoring system is based on a user-centered approach. Challenges and solutions are discussed in an interdisciplinary manner. The derived requirements are translated into functional models and iteratively optimized with users. The modular design includes climate and acceleration sensors and enables adaption to the specific care and risk situation. Decubitus-relevant factors are recorded objectively, control and documentation are ensured. The data can be transferred to various information systems available in different care settings, including mobile devices and vital mon-itoring systems. Adaptive algorithms are used to detect deviating data patterns, so the system can automatically issue warnings and notes for preventive measures.


Calibration and Control of a Gait Simulator for lower limb exoprostheses Simon Gallinger, Fachgebiet Medizintechnik Technische Universität Berlin, Berlin, Germany, [email protected] Peter Seufert, Fachgebiet Medizintechnik Technische Universität Berlin, Berlin, Germany, [email protected] The gait simulator is a hydraulic test bench for lower limb exoprostheses. It is currently being developed at the Department of Biomedical Engineering of the Technische Universität Berlin and is meant for comprehensive functional and fatigue testing of modern prosthetic knee joints, including microprocessor controlled knees. Technological advances in exopros-thetics lead to an increase in the mobility of amputees. The resulting and partially complementary demands on the pros-theses concerning low weight, high functional capability, and improved strength result in complex designs which are optimized to the individual needs of their users. To determine if and to what extent these prostheses meet their demands, it is necessary to perform tests under realistic operating conditions. The current standard tests described in DIN EN ISO 10328 and DIN EN ISO 22675 are not able to address this requirement as the amount of loading and the number of cycles does not comply with field studies. In contrast, the gait simulator is able to apply real time series of multi-axis loads like they occur in the actual use of prostheses. Compared to tests with human subjects, it is possible to perform test scenarioswith a very high reproducibility and from an objective point of view. Especially the influence of test subjects concerning inter-individual and day-to-day variability, as well as accommodation time on different prostheses set ups can becompletely eliminated. Particularly, the simulator is suited for measurements which are usually not possible due to ethical restrictions or excessive stress for the subjects, such as simulations of falls and stumbles.The reproduction of these highly dynamic processes poses high re-quirements on the control of the hydraulic actuators of the gait simulator. This article will illustrate the calibration and the control algorithms of two main testing parameters during normal gait, the vertical ground reaction force and the sagittal hip moment.


Shoe integrated power measurement for cycling Diana Völz, Frankfurt Universtity of Applied Sciences, Frankfurt, Germany, [email protected] Markus Auermann, Frankfurt Universtity of Applied Sciences, Frankfurt, Germany, [email protected] Sebastian Pohl, Frankfurt Universtity of Applied Sciences, Frankfurt, Germany, [email protected] Christopher Blase, Frankfurt Universtity of Applied Sciences, Frankfurt, Germany, [email protected] Andreas Wittek, Frankfurt Universtity of Applied Sciences, Frankfurt, Germany, [email protected] Cycling is one of the most popular sports, because the exercises and the equipments are very simple and therefore can be done by everyone. Due to joint-gentle exercises, cycling is suitable exspecially for beginners in sports. As a result, cycling has become a proven medical way to increase fitness for patients, too, e.g. after serious injuries in rehabilitation programs. One reason is that the exercises can be easily integrated into day-to-day life. In order to be able to control the changing fitness level, technical subjects must be equipped with monitoring systems. This is not new, but existing systems are very expensive and mostly realized as a fixed installation at the pedal bearing, used in professional sports. Changing the power meter from bicycle to bicycle is complex and uncomfortable. For rehabilitation patients, it would be useful to have a portable measurement system, independent of the bicycle. A market, literature and patent research have shown that such a system does not yet exist. Thus this project aims to develop a portable power meter for cycling which is fixed to the shoe. A first concept was developed, consisting of a strain gauge on a flexible beam for measuring force, a magnet which produces a reference and a gyroscope for detecting the pedal direction. The control unit is located on the shoe as well and connected by cable to the measuring head. The system connects to the smartphone via Bluetooth. This concept was real-ized as a first prototype especially to tackle the challenge to calibrate the system for measuring on different bicycles. Next step will be to investigate piezo technology and consolidate and evaluate data at an Internet of Things platform. As a result, cyclists and rehabilitation patients can easily track their performance data in cycling, independent of the bicycle and/or home trainer.


Investigation of action forces of patient hoists according to DIN EN ISO 10535:2007 and Mital Cedric Mester, Lorenz Müller, Saskia Sobkowicz, Niels Hinricher, Claus Backhaus

Caregivers suffer significantly more from musculoskeletal diseases than other occupational groups due to the physically very strenuous mobilization of patients. One way of reducing the stress of patient mobilization is to use patient hoists. The maximum action forces during the handling of patient hoists are specified in the norm DIN EN ISO 10535:2007. Those differ markedly from the Mital acceptance values for pulling loads with the fingers. This study investigated whether these psychophysical acceptance values were also adhered to during the handling of patient hoists. Therefor the 12 most in Germany used patient hoists have been tested. The tests were carried out with a patient doll weighing 120 kg. The wheels have an angle of 180° to the intended direction of movement, the lifting arm is adjusted to the maximum range and the undercarriage is not spread. The action forces are measured with three- dimensional force measuring grips from Kistler (type 9809A) with the WIDAAN software. The force is measured on a flat linoleum floor where the patient hoists are moved over a distance of 5 metres at a constant running speed of approximately 1 meter per second. The measurement is repeated five times per hoist for pulling and pushing. The initial force results from the 95th percentile, the constant force from the 50th percentile of the recorded force values. All hoists tested conform to the limit values of DIN EN ISO 10535:2006 of 160 N for the initial force and 85 N for the constant force. The highest recorded initial force was 133 N, the lowest 83 N. The highest measured constant force was 56 N, the lowest 25 N. The psychophysical limit according to Mital for pulling with the fingers is 50 N. During product trainings it is necessary to point out that caregivers handle the patient hoists with closure of fist.


Automated detection of bone splinters in DEXA phantoms using deep neural networks Steffen Rüger, Fraunhofer EZRT, Fürth, Germany, [email protected] Markus Firsching, Fraunhofer EZRT, Fürth, Germany, [email protected] Julija Lucic, Fraunhofer EZRT, Fürth, Germany, [email protected] Alexander Ennen, Fraunhofer EZRT, Fürth, Germany, [email protected] Norman Uhlmann, Fraunhofer EZRT, Fürth, Germany, [email protected] Thomas Wittenberg, Fraunhofer IIS, Erlangen, Germany, [email protected] In the past, dual energy radiographic imaging has been proven to be a good method to provide material information in X-ray images and can be used to differentiate between various soft and hard tissue types in the human body. Typical appli-cations for the use of dual energy CT (DECT) are e.g. abdominal imaging, differentiation of kidney stones, or the analysis of lung perfusion, whereas dual energy X-ray absorption (DEXA) can be applied for the assessment of osteoporosis, measurement of breast density, or bone analysis of fractures. In order to support radiologists and physicians with the assessment of DECT or DEXA images, various machine learning approaches have been proposed and evaluated in the past. Nevertheless, recently novel methods such as convolutional deep neural networks (CNNs) have been available for large-scale medical image analysis, which can be applied for the automated assessment of dual energy imaging. In order to evaluate such CNN approaches for the automated detection of bone splinters after fractions in DEXA phantom images, a deep neural network architecture and the related hyperparameter-space are explored. For the automated detection of bone splinters, artificial deep neural networks (ADNNs) are used. As image data, 47 phan-toms with (35) and without (12) bone splinters have been scanned using a dual energy device, providing a low and a high energy channel image. From these, basis material decomposition and energy weighting was applied resulting in two ad-ditional image channels. Due to the limited number of samples, the available image data was extended using data aug-mentation techniques. First, the images were divided into small patches of 15x15 pixels. Further augmentation was achieved by rotation and mirroring. The resulting patches were labeled weather they contain bone pieces or not. Different patch sizes (30x30 and 60x60 pixels) were evaluated as well. The proposed ADNN architecture consists of seven distinct computational layers, which can be divided into the “feature-extraction” and the “decision-making” parts. The feature-extraction part uses three double-layers, each consisting of a convolution followed by a max pooling operation to reduce the spatial dimension. The decision-making part incorporates a fully connected network providing a binary decision (bone present or absent). The available data was split up in three disjunct sets for training, validation and testing. As result a classification rate of 90% in regions with, and 99% in regions without bone splinters was achieved, using only the two DEXA-channels as input and a patch size of 60x60. The impact of variation of training hyperparameters for the ADNNs will be presented and discussed.


Integrating Label Uncertainty in Ultrasound Image Classification using Weighted Support Vector Machines Jannis Hagenah, Institute for Robotics and Cognitive Systems, University of Lübeck, Lübeck, Germany, [email protected] Sascha Leymann, Institute for Robotics and Cognitive Systems, University of Lübeck, Lübeck, Germany, [email protected] Floris Ernst, Institute for Robotics and Cognitive Systems, University of Lübeck, Lübeck, Germany, [email protected] Inference from medical image data using machine learning still suffers from the disregard of label uncertainty. Usually, medical images are labelled by multiple experts. However, the uncertainty of this training data, assessible as the unity of opinions of observers, is neglected as training is commonly performed on binary decision labels. In this work, we pre-sent a novel method to incorporate this label uncertainty into the learning problem using weighted Support Vector Ma-chines (wSVM). The idea is to assign an uncertainty score u to each data point. The score is between 0 and 1 and is cal-culated based on the unity of opinions of all observers, where u=1 if all observers have the same opinion and u=0 if the observers opinions are exactly 50/50, with linear interpolation in between. This score is integrated in the Support Vector Machine (SVM) optimization as a weighting of errors made for the corresponding data point. For evaluation, we asked 15 observers to label 48 2D ultrasound images of aortic roots addressing whether the images show a healthy or a patho-logically dilated anatomy, where the ground truth was known. As the observers were not trained experts, a high diversi-ty of opinions were present in the data set (amount of observers that share the same opinion: 74.9+/-15.1%). We used a pre-trained convolutional neural network for feature extraction and then performed image classification using both ap-proaches, i.e. classical SVM and wSVM with integrated uncertainty weighting, utilizing 5-fold Cross Validation, re-spectively (linear kernel, C=7). By incorporating the observer uncertainty, the classification accuracy could be im-proved by 3.1 percentage points (SVM: 83.5%, wSVM: 86.6%). This indicates that integrating information on the ob-servers’ unity of opinions increases the generalization performance of the classifier and that uncertainty weighted wSVM could present a promising method for machine learning in the medical domain.


Prediction of Surgery Duration from Laparoscopic Videos using Recurrent neu-ral network Tamer Abdulbaki Alshirbaji, Institute of Technical Medicine, Furtwangen University, Villingen-Schwenningen, Ger-many, e-Mail: [email protected] Nour Aldeen Jalal, Institute of Technical Medicine, Furtwangen University, Villingen-Schwenningen, Germany, e-Mail: [email protected] Knut Möller, Institute of Technical Medicine, Furtwangen University, Villingen-Schwenningen, Germany, e-Mail: [email protected] Estimating surgery duration based on preoperative information is a challenging problem because of unpredicted or ad-verse circumstances occurring during operations. Therefore, optimizing operating room (ORs) planning and scheduling requires predicting the duration of surgical procedures intraoperatively. By accurate estimation of remaining time of the ongoing operation, this would contribute in the development of aware operating rooms through improving patient care (i.e. by reducing the anesthesia duration), optimizing OR resources and supporting clinicians inside and outside the OR. In this work, predicting the remain intervention time in colorectal surgeries is studied using convolutional neural net-work (CNN) and long short-term memory (LSTM) recurrent neural network. A CNN model is firstly pretrained to per-form phase recognition in cholecystectomy procedure using Chlec80 dataset which contains 80 cholecystectomy videos with phase annotations. Then, the trained CNN model is combined with a LSTM recurrent layer. Finally, the CNN-LSTM model is trained to perform the remaining time estimation of surgery from laparoscopic videos without manual annotations. The model was evaluated on a dataset of 26 colorectal videos, namely of type sigmoid resection, rectal re-section and proctocolectomy. The experimental results show that the overall mean error is approximately 40%.


Virtual Reality Feedback Creation for Assisted Motion Control Lars Lehmann, Professur Digital- und Schaltungstechnik, Technische Universität Chemnitz, Chemnitz, Germany, [email protected] Gangolf Hirtz, Professur Digital- und Schaltungstechnik Technische Universität Chemnitz, Chemnitz, Germany, [email protected] In medical training therapy (MTT), the precise execution of the training exercises developed by a therapist is of decisive importance for the success of the therapy. Currently, a therapist must treat up to 15 patients simultaneously on an outpa-tient basis. The consequences of demographic change and increasing cost pressure in the health sector will further exac-erbate this problem. At the TU Chemnitz an assistance system was developed, which can evaluate both quantity and quality of the accomplished movement on the basis a purposeful model and can give by means of feedback directly to the patient recommendations for action. An avatar in traffic light colours signals in which body region an error has oc-curred. The problem with a static feedback display is that the body position and viewing direction change for each exer-cise change. In order to ensure a conformal execution of the exercise, the feedback display would have to be positioned differently each time. This is not realistic in practice and limits its applicability. As a solution we suggest the use of VR glasses (HTC Vive) in the MTT as feedback, as this allows adequate feedback to be given in every training situation. A further advantage is that the virtual training environment always adapts to its current visual field and thus suboptimal visual coverage is avoided. Since only the patient moves and the environment remains static, cyber sickness is avoided. The virtual training environment was developed with Qt (C++), SDL, OpenGL and GLSL. Valves free OpenVR API was used as interface to the glasses. In order to improve motivation, we suggest an individual adaptation of the VR environment to the respective person as well as an individual design of the avatars, which is reflected in improved training performance. Further work will investigate further positive motivational and learning effects.


Catheter pose-dependent virtual angioscopy images visualized on augmented re-ality glasses Felix von Haxthausen, Institute for Robotics and Cognitive Systems, University of Lübeck, Lübeck, Germany, [email protected] Sonja Jäckle, Fraunhofer MEVIS – Institute for Digital Medicine, Lübeck, Germany, [email protected] Floris Ernst, Institute for Robotics and Cognitive Systems, University of Lübeck, Lübeck, Germany, [email protected] Verónica García-Vázquez, Institute for Robotics and Cognitive Systems, Lübeck, Germany, [email protected] Endovascular aortic repair (EVAR) procedures are commonly guided using fluoroscopy, causing radiation exposure. Previous studies proposed potential radiation-sparing guidance by means of an electromagnetically (EM) tracked cathe-ter in combination with preoperative computed tomography (CT) scans. Augmented reality (AR) glasses can provide an intuitive 3D visualization of the virtual aorta and the catheter. For additional guidance, we propose to also display virtu-al angioscopy images (VAIs) based on the current pose of the tracked catheter. In addition, this study assessed the la-tency of displaying VAIs on the AR glasses. The catheter tip was tracked with an EM tracking system (Aurora Mini 6DOF and Tabletop Field Generator, Northern Digital Inc.). A landmark-based registration allowed computing EMTCT (rigid transformation from the EM to the CT co-ordinate system). An open-source software (Plus Toolkit) sent the current pose of the catheter tip from the EM tracking system to MeVisLab software (MeVis Medical Solutions AG). Thereafter, each pose was transformed to the CT coor-dinate system by applying EMTCT. Every pose-dependent VAI (JPEG image format) was created in MeVisLab from an aorta segmentation of a previously obtained CT scan. Each image was then sent to the AR glasses (Microsoft HoloLens) via Wi-Fi using a remote procedure call (gRPC) and then displayed on a virtual 2D panel within the HoloLens applica-tion developed with Unity 2018.2.8f1. The latency evaluation was performed on HoloLens by calculating the interval between requesting an image (matrix size 512x512) and displaying it. The proposed system was capable of streaming the VAI corresponding to the catheter tip pose to HoloLens. The latency was 89±12 ms (mean±standard deviation, 574 images sent), thus within real-time perception (threshold 100 ms). Future work will focus on reducing this latency and using intraoperative imaging for updating the current anatomy. Our ap-proach may add valuable additional information for guidance in EVAR procedures.


Towards High-Quality 3-D Reconstructions with Omnidirectional Stereo Vision Systems Julian Seuffert, Faculty of Electrical Engineering and Information Technology, Chemnitz University of Technology, Chemnitz, Germany, [email protected] Pavan Deshpande, Faculty of Electrical Engineering and Information Technology, Chemnitz University of Technology, Chemnitz, Germany, [email protected] Since the mid-twentieth century, the world population has been experiencing significant aging. This process not only yields a drastic increase of the total number of elderly people but reinforces also the lack of free spaces in care facilities. The field of Ambient Assisted Living addresses this issue. AAL focuses on age-appropriate smart home systems. By assisting elderly people in their daily routines at home, such systems can reduce the need of care attendants as well as care facilities. Based on three-dimensional reconstructions of indoor scenes, modern AAL systems can detect accidents and inform a physician automatically. Omnidirectional stereo vision cameras embedded in such systems allow to recon-struct the flat of elderly people with only few sensors and enable localization as well as action recognition of care recip-ients. Evidently, three-dimensional object and person detection rely on a high-quality reconstruction of the scene. We therefore determine the influence of two extrinsic camera parameters on the reconstruction quality: The baseline (dis-tance between two cameras in the stereo system) and the viewing direction of the cameras. The alignment (same view-ing direction) of cameras is widely used in perspective stereo vision systems and improves the point-wise stereo corre-spondence matching. However, this alignment yields an unequal distribution of reconstructed world points. Therefore, we simulate differing (not aligned) viewing directions and evaluate the influence of an increasing angle between the camera orientations on the 3-D model quality. We show that a careful choice of the aforementioned extrinsic parameters can significantly improve the reconstruction quality and hence a subsequent action recognition of people in need of care.


Temperature controlled and monitored Ex Vivo Lung Perfusion setup for research and training purposes Christina Pongratz, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany, [email protected] Jens Ziegle, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany, [email protected] Helena Linge, Department of Thoracic Surgery, University Clinic for Cardiac and Thoracic Surgery, Otto-von-Guericke University, Magdeburg, Germany, [email protected] Axel Boese, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany, [email protected] Thorsten Walles, Department of Thoracic Surgery, University Clinic for Cardiac and Thoracic Surgery, Otto-von-Gue-ricke University, Magdeburg, Germany, [email protected] Michael Friebe, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany, [email protected] Ex vivo lung perfusion (EVLP) is a preservation method for donor lungs, which keeps lungs viable in a physiological environment outside of a body for a short period of time. Other applications of EVLP are in research of e.g. lung cancer, stem cell therapy or in thoracic surgery. For preservation, a lung is placed in an organ chamber with under-inflation and perfused with a solution called perfusate through the pulmonary artery. A ventilation system adapted to the primary bronchus repetitively inflates the lung and provides air. In this work we introduce a thermoregulation system for an EVLP system that shall be used for clinicoradiological and lung cancer research as well as for training medical students using porcine lungs. A thermoregulation of a lung (initial temperature 4°C) is necessary to achieve body temperature and to realistically sustain lung tissue. The perfusate is warmed to 37°C which is achieved through counterflow tubes, where caloric is transferred from heated water (outer tube) from a thermostat to the perfusate (inner tube). Initially, the perfusate cools down due to heat transfer from the perfusion solution into the lung and to the other components of the setup. The EVLP system must be thermically insulated, so loss of caloric is avoided. For monitoring, temperature sensors are inte-grated within the lung, in the organ chamber and in the afferent perfusate tube, whereby the measured values determine the thermoregulation. Initial tests using thermal packs (cooled to 4-6°C) placed on a heating mat, as a part of the perfusion circuit, showed that the perfusate temperature falls to 34°C, but restores after approximately 60 minutes (36.5°C), whereby the thermal pack is warmed. With this setup, future tests using porcine lungs are planned, assuming to generate longer perfusion times than without thermoregulation due to normothermic perfusion of the lung.


Cytotoxicity and Sterilization Resistance of Electronic Components for Disposa-ble Smart Biomedical Devices Valerie M. K. Werner, Institute of Medical and Polymer Engineering, Technical University of Munich, Garching, Ger-many, [email protected] Daniel Stroemsdoerfer, Institute of Medical and Polymer Engineering, Technical University of Munich, Garching, Ger-many, [email protected] Viet Nga Bui, Institute of Medical and Polymer Engineering, Technical University of Munich, Garching, Germany, [email protected] Niklas von Wittenburg, Institute of Medical and Polymer Engineering, Technical University of Munich, Garching, Ger-many, [email protected] Markus Eblenkamp, Institute of Medical and Polymer Engineering, Technical University of Munich, Garching, Germany, [email protected] The design of Smart Biomedical Devices will be a defining element of future research in the context of intelligent medical devices for the Internet of Medical Things (IoMT). Prerequisite for serving the disposable market is the use of low-cost electronic components. In addition to this economic aspect, the highest reliability of the developed products with regard to biocompatibility and bioprotection is at the forefront. These include the sterilization resistance by various methods and in particular the protection of electronic components to prevent cytotoxicity. In the study, four types of resistors as well as capacitors and three photodiodes, different in their materials and construction forms, were examined. The selected types represented electronic components as they are commonly installed on electronic system from the segment of low-cost standard components. These were subjected to steam sterilization with up to 50 cycles, gamma sterilization with a dose of 25 kGy, and a CCK-8 assay to test in vitro cytotoxicity. We found out that in general the electronic components were not significantly damaged functionally by steam sterilization with 50 cycles. The percentage change was less than 0.5 % of the initial values. However, optical changes could already be observed after one steam sterilization cycle. Gamma sterilization of resistors did not lead to significant changes in resistance values. Capacitors with the dielectric barium titanate, on the other hand, were found to be highly susceptible to gamma radiation as a high decrease of the capacitance values was measurable. A complete functional failure could not be determined for any component. In addition, non-cytotoxic electronic components could be identified. The results show that certain electronic standard components are suitable for the realization of disposable Smart Biomedical Devices. Thus, cost-intensive special components can be avoided, especially for medical devices in the lower price segment and lower risk classes.


Chitosan as matrix for inner ear neurite regeneration Jana Schwieger, Department of Otolaryngology, Hannover Medical School, Hannover, Germany, [email protected] Noushin Kakuan, Department of Otolaryngology, Hannover Medical School, Hannover, Germany, [email protected] Anayancy Osorio-Madrazo, Department of Microsystems Engineering, University of Freiburg, Freiburg, Germany, [email protected] Thomas Lenarz, Department of Otolaryngology, Hannover Medical School, Hannover, Germany, [email protected] Verena Scheper Department of Otolaryngology, Hannover Medical School, Hannover, Germany, [email protected] The nerve-electrode-interaction of a cochlear implant may be improved by bridging the gap between the primary auditory neurons, the spiral ganglion neurons (SGN), and the electrodes. For a direct coupling between electrode-contacts and neurites a neurite growth through the fluid-filled scala tympani has to be induced, guided and structurally supported. Chitosan (CHI) in combination with neurotrophic factors (NF) was tested as growth matrix. CHI is produced by N-deacetylation of chitin, mainly extracted from crustacean. The co-polysaccharide consists of (1,4)-linked D-glucosamine and N-acetyl D-glucosamine. The degree of acetylation (DA) and the polymer molecular

weight are the most important CHI parameters, defining its physico-chemical and bioactive properties. Different concentrations (0.7-2%) of a highly-deacetylated CHI (DA: 2.5%) with high molecular weight (Mw: 4.1 x 105 g/mol (± 6.4%)) and low polydispersity index (Ip = 1.49 ( ± 11.6%) were tested. CHI-stability was observed in PBS, culture medium and artificial perilymph and CHI was investigated in vitro as growth matrix for SGN-neurites. SGN-explants of neonatal rats were harvested and cultured for 5 days on 0.7%, 1%, 1.3% or 2% CHI, followed by analysis of number and length of regenerated neurites. A combination of 50 ng/ml brain-derived neurotrophic factor and 100 ng/ml ciliary-neurotrophic factor (NF) in the cell culture medium was compared to 10% serum (positive control) and no additives (negative control). CHI was stabile for the time of cultivation. SG-explants were rounded and neurite regeneration was not supported on 2% CHI. The addition of serum and NF significantly increased the neurite regeneration on 1% and 1.3% CHI while 0.7% CHI was less supportive. Around the grown neurites, rarely non-neuronal cells were detected and the neurite terminals entered the CHI. CHI, especially when combined with NF, shows a promising potential as neurite growth matrix to bridge the gap between CI-electrode and SGN.


A convenient method using live cell imaging to track cell adhesion on transpar-ent biocompatible materials Richard Schmid, (Institute of Medical and Polymer Engineering, Technical University of Munich), Garching, Germany, [email protected], Sepent Oh, (Institute of Medical and Polymer Engineering, Technical University of Munich), Garching, Germany, [email protected], Martin Woywod (innoME GmbH), Espelkamp, Germany, [email protected], Eike Kottkamp (innoME GmbH), Espelkamp, Germany, [email protected], Markus Eblenkamp, (Institute of Medical and Polymer Engineering, Technical University of Munich), [email protected] Recent advances in live cell imaging enable convenient methods for the observation of cell attachment as a method of material testing towards transparent, biocompatible materials and allow to draw a correlation between the relative time of cell adhesion and the contact angle of biocompatible surfaces. We developed a novel method with use of a 24-channel digital microscope suitable for live cell imaging inside the incubator, adjusted our additive manufactured sam-ples with different contact angles below 90 ° by plasma treatment and quantified the relative attachment speed of cells on the polymer surface via microscopy. The samples made from biocompatible, transparent acrylate polymer were addi-tive manufactured using digital light processing and were seeded with a cell line for a comparable growth behavior study. A microscope image was taken every 10 minutes of each sample at a fixed position. The cell adherence of all our observed samples showed a negative logarithmic trend curve, meaning a relative high number of cells adhered shortly after seeding while the time for other cells to adhere was higher. This non-destructive method allows to track cell adhe-sion over time and enables to correlate the relative adhesion time to the contact angle of plasma treated biocompatible surfaces. Further it is a simple technique to observe in situ cell growth on biocompatible materials on multiple samples simultaniously.


Immobilization of rh BMP-2 and rhVEGF on Electrospun PDLLA-Scaffolds

for Sequential Release

Andrea Sowislok and Herbert P. Jennissen Institute of Physiological Chemistry, Biochemical Endocrinology Group, University of Duisburg-Essen, 45147

Essen, Germany

The aim of this work is to synthesize scaffolds from poly (D,L-lactide) (PDLLA) nanofibers loaded with rhBMP-2 and/ or VEGF for tissue engineering in vitro and for stimulating bone formation in vivo. The effective osteoinductive dose of rhBMP-2 in humans is ca. 100-1000-fold higher than in animals. These unphysiologically high doses in humans have led to side effects and serious complications in spine fusion surgery. Therefore we have proposed synthesizing biohybrid scaffolds capable of sequential growth factor release, in this case releasing rhVEGF165 for blood vessel formation first followed by the release of rhBMP-2 for bone formation. In the present work, electrospun PDLLA-nanofibers were therefore functionalized, by protein adsorption on the surface of PDLLA nanofibers. Bioactive rhBMP-2 and rhVEGF165 were obtained form Morphoplant GmbH and for adsorption and release work labeled with 125I. For transmission electron microscopic (TEM) investigations the rhBMP-2 and rhVEGF adsorbates on the nanofibers were stained with OsO4, with ferritin taken as an unstained control. Adsorption of rhBMP-2 and rhVEGF from a solution was carried out at pH 4.5 and pH 7.4 respectively leading to 0 = 8-10 mg/g. Desorption kinetics were measured in continuous-flow chambers in sterile PBS and fitted to a two phase exponential decay. It was found that rhVEGF165 (t1/2 ~ 19 days) was released at an 11-fold higher rate, than the sustained release of adsorbed rhBMP-2 (t1/2 ~ 209 days). In TEM pilot experiments of electrospun nanofibers a visualization ferritin and stained rhBMP-2 and rhVEGF165 nanoparticles will be further investigated. Supplementary adsorption and desorption experiments with mixtures of radiolabelled rhBMP-2 and rhVEGF165 are planned for synthesizing a bimodal release nanofiber biohybrid scaffold (supported by DFG JE 84/15-3).


Aspects of Multimodal Biohybrid Scaffolds

Herbert P. Jennissen

Institute of Physiological Chemistry, University of Duisburg-Essen, Universitätsklinkum Essen, D-45122 Essen, Germany

[email protected]

Immobilizing a single growth factor such as human bone morphogenetic protein 2 (rhBMP-2) on Implant materials, i.e. monomodal bioactive implants, can significantly increase the integration of implants into bone in animals. However this technology fails in humans, because humans are refractory to their own growth factor BMP-2. The application of unphysiologically high doses in humans cause side effects and serious complications in spine fusion surgery. In physiological secondary bone healing at least 10 different growth and differentiation factors are involved in the first two healing phases leading to a callus and/or woven bone. It is therefore hypothesized that the mandatory 10-100-fold dose reduction for physiological rhBMP-2 applications on implants in humans can only be achieved by a combination of rhBMP-2 with a second or third essential mediator such as vascular endothelial growth factor (rhVEGF165) or stromal cell-derived factor 1 (SDF1 ). To this end a new generation of bi- or multimodal bioactive hybrid carriers with specific spatio-temporal release kinetics for each factor is indispensable. Such carriers are engineered e.g. to release rhVEGF with a shorter half-life than rhBMP-2 based on the physiological bone healing time-scale. A versatile material for developing such a carrier is poly-(D,L)-lactide (PDLLA), where a growth factor can either be immobilized on the surface or inside the bulk material e.g. by foaming technologies. rhBMP-2 containing foamed tablets show a sustained release of rhBMP-2 with half-lives ranging between 85 and 350 days depending on the temperature and are bioactive in vitro and in vivo. Another technology, allowing the simultaneous separate immobilization of multiple proteins, which is in a successful collaborative development, consists of electrospinning PDLLA nanofibers to a bioactive fleece with bi- multimodal mediator release properties. Such multikomponent electrospun scaffolds are in preparation (supported by DFG JE 84/15-3).


Superparamagnetic Ironoxide Nanoparticles An Evaluation of the Sonochemi-cal Synthesis Process Zuzana Penxová, Institut für Medizintechnik, Universität zu Lübeck, Lübeck, Germany, [email protected] Kerstin Lüdtke-Buzug, Institut für Medizintechnik, Universität zu Lübeck, Lübeck, Germany, [email protected] The direct detection of the spatial distribution of superparamagnetic ironoxide nanoparticles (SPIONs) as a tracer for Magnetic Particle Imaging (MPI) enables three-dimensional functional images with high spatial and temporal resolu-tion. The commercially available tracers have not been developed primarily for MPI. Therefore, they do not sufficiently contribute to the desired image quality. Hence, optimizing the SPIONs during the production process is of interest. A peculiarity of the here presented synthesis method the alkaline coprecipitation of Iron salts in the presence of Dextran as a coating material is its process under ultrasound control. The use of ultrasound creates extraordinary reaction con-ditions through sonochemical phenomena, such as formation, growth and implosive collapse of cavitation bubbles with-in a liquid. In addition, the ultrasonic waves and the oscillation of the medium improve the mixing process and thus en-sure the homogenization during the synthesis. The object of this study is the variation of ultrasonic frequencies and the type of used Dextran. The goal of the optimization is to provide SPIONs with better performance for MPI and more suitable properties for in vivo application. The optimization potential is based on the magnification of the magnetite cores while reducing the hydrodynamic size. The experiments have shown that both the ultrasound frequency and the molecular weight of used Dextran influence the properties of the SPIONs.


Impact of platinum nanoparticles on the organ of Corti cell line HEI-OC1 and on spiral ganglion neurons Kirsten Wissel, Department of Otolaryngology, Hannover Medical School, Germany, [email protected] Gudrun Brandes, Institute of Neuroanatomy and Cell Biology, Hannover Medical School, Germany [email protected] Gerrit Paasche, Department of Otolaryngology, Hannover Medical School, Germany, [email protected] Thomas Lenarz, Department of Otolaryngology, Hannover Medical School, Germany, [email protected] Martin Durisin, Department of Otolaryngology, Hannover Medical School, Germany, [email protected] Despite the technological progress made with cochlear implants (CI), impedances and their modula-tions remain in the focus of interest. Increases in impedance have been related to technical defects of the electrode as well as inflammatory reactions and/or fibrosis along the electrode. Some studies have demonstrated highly increased impedances as the result of corroded platinum (Pt) electrode contacts. However, composition of the resulting Pt compounds as well as possible formation of particular Pt as the consequence of electrical stimulation remains to be elucidated. So far, a cell culture model was established to characterize the cytotoxicity of both ionic and particular Pt in the human neuroblastoma cell line (SH-SY5Y) following electrical stimulation in vitro. In this study, potential Pt nanoparticle toxicity was investigated in cultures of the organ of Corti cell line (HEI-OC1) and in cultures of spiral ganglion neurons (SGN) dissociated from postnatal rats. For this purpose, both cell types were exposed to Pt nanoparticles (Pt-NP, 3 nm) with varying concentra-tions. The biological activity of the HEI-OC1 cells was demonstrated by the fluorescence activity of the resazurin assay showing strong resistance to Pt-NP intoxication up to 100 µg/ml. However, scan-ning electron microscopy revealed discrete morphological changes and induction of apoptosis with 75 µg/ml and 100 µg/ml Pt-NP. Primary SGN exhibited decreased survival rates in a concentration dependent manner between 20 and 100 µg/ml as demonstrated by immunocytochemical staining of neuronal filaments, thus indicating higher sensitivity to Pt-NP exposure in comparison to the HEI-OC1 cell line. The present study shows for the first time a direct toxic effect of Pt-NP on a cultured organ of Corti cell line as well primary sensory neurons. Further investigations are necessary to reveal the cellular mechanism of the responsible agents, nanoparticles and/or cationic Pt.


Covalent coupling of polymers as drug delivery coatings on silicone surfaces for future applications Katharina Wulf, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, Germany, [email protected] Michael Teske, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, Germany, [email protected] Daniela Arbeiter, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, Germany, [email protected] Thomas Eickner, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, Germany, [email protected] Gerrit Paasche, Department of Otorhinolaryngology, Head and Neck Surgery, Hannover Medical School, Hannover, Germany, [email protected] Thomas Lenarz, Department of Otorhinolaryngology, Head and Neck Surgery, Hannover Medical School, Hannover, Germany, [email protected] Niels Grabow, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, Germany, [email protected] Insertion of a cochlear implant (CI) into the scala tympani evokes electrode insertion trauma that can result in mechani-cal damage of the lateral and medial wall and most adversely in ingrowth of fibrous tissue on the implant surface. Thus, not only the impedance at the electrode–tissue interface is increased and higher power is needed to ensure CI perfor-mance, also selective neuronal stimulation for discrimination between different sound frequencies is disturbed. In con-sequence, it is of great clinical interest to modify the silicone surface of CI’s in order to inhibit and minimize the over-growth by connective tissue. The covalent coupling of biofunctional polymers on common CI silicone surfaces is a versatile method to influence the implant cell interaction, but is still a challenge due to the chemically unreactive properties of silicone. In this investiga-tion, we present a sophisticated method to apply a biodegradable polymer coating, such as polylactide or polyhydroxy-butyrate, on silicone surfaces to generate a drug delivery system using a covalently bound intermediate layer. The adhe-sive drug delivery coatings with different drug concentrations were applied via spray- and spincoating processes with high adherence to the intermediate layer. Coatings were analyzed by scanning electron microscopy, infrared spectros-copy and contact angle measurements. Furthermore, the adhesive strength of the applied degradable drug layer was ana-lyzed with preliminary tests. Changes in morphology were visible by comparison of pure silicone and coated silicone and specific polymer bands were detected by IR, indicating a complete coating with polylactide or polyhydroxybutyrate. Furthermore for all coated silicone samples the contact angles changed towards contact angles as known for the presence of a polymer coating. The results confirm the presented method as a versatile tool for the coating of silicone CI electrodes with degradable polymer layers demonstrating high morphologic homogeneity and durability.


Controlled biodegradation of metallic biomaterials by plasma polymer coatings

using hexamethyldisiloxane and allylamine monomers

Michael Teske, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, Germany,

[email protected]

Joschka Fink, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, Germany,

[email protected]

Thomas Eickner, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, Germany,

[email protected]

Daniela Arbeiter, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, Germany,

[email protected]

Volkmar Senz, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, Germany,

[email protected]

Niels Grabow, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, Germany,

[email protected]

Sabine Illner, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, Germany,

[email protected]

Plasma enhanced chemical vapor deposition is a promising process for the generation of tailor-made polymer coatings

on medical devices in order to improve their implant/ host interaction. The ultra-thin coatings can fulfil a variety of

purposes, depending on the monomers used, the process conditions and the location of the coated implants in the human

body. In addition, even complex geometries can be coated easily and without the application of solvents. Extreme hy-

drophilic and hydrophobic plasma polymer coatings can improve biocompatibility, especially in blood contact.

Furthermore, the selection of the monomers used enables the generation of specific functional groups for further surface

immobilization of drugs, such as proteins, by chemical crosslinking. The release of toxic residues from polymeric

implants, such as monomers, additives or degraded components, can also be avoided. The aim of our investigation was

the generation of plasma polymer films, their characterization and application as coatings for biodegradable metallic

biomaterials in order to retard the degradation process. Metallic biomaterials, in various forms are frequently used in

orthopaedics, dentistry, cardiovascular and neurosurgical equipment, because of their tensile strength, fracture

toughness, fatigue strength and electrical conductivity.

Plasma polymerization was performed with the monomers hexamethyldisiloxane and allylamine. A radio frequency

(13.56 MHz) glow plasma at low pressure and temperature was used. After determining suitable process parameters, the

plasma polymer films were generated. We then analyzed mass growth over time, surface morphology via scanning

electron microscopy, chemical structure via infrared spectroscopy, biocompatibility in direct contact and eluate test with

L929 mouse fibroblasts, as well as thermal properties via differential scanning calorimetry. Plasma coated aluminum

pads were used as a model system for degradable metallic biomaterials and tested in an accelerated degradation process

to investigate retarded degradation.


Thermomechanical properties of PEGDA in combination with different photo-

curable comonomers

Natalia Rekowska, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, Germany,

[email protected]


[email protected]

Jan Konasch, Chair of Microfluidics, Rostock University, Rostock, Germany, [email protected]

Alexander Riess, Chair of Microfluidics, Rostock University, Rostock, Germany, [email protected]

Robert Mau, Chair of Microfluidics, Rostock University, Rostock, Germany, [email protected]

Thomas Eickner,, Institute for Biomedical Engineering, Rostock University Medical Center City, Rostock, Germany,

[email protected]

Hermann Seitz, Chair of Microfluidics, Rostock University, Rostock, Germany, [email protected]

Niels Grabow, Institute for Biomedical Engineering, Rostock University Medical Center City, Rostock, Germany,

[email protected]

Michael Teske, Institute for Biomedical Engineering, Rostock University Medical Center City, Rostock, Germany,

[email protected]

The technology of pharmaceutical drug delivery systems (DDS) as individual and adjustable tool for drug administra-

tion has been intensively developed in the last years. Additive manufacturing (AM) techniques, such as stereolithogra-

phy, are a promising approach towards DDS scaffold manufacturing. Stereolithography, by using layer by layer photo-

polymerisation, creates DDS scaffolds with highly controlled 3D geometry. Combined with inkjet printing it allows a

very precise positioning of the drug depot in the basic scaffold and therefore also a better control of the drug release.

Furthermore, this hybrid AM technique also allows the creation of a multi-drug DDS with a few drug depots localized

in desired positions within the scaffold. Determination of the scaffold and drug depots materials properties is one of the

initial steps for such novel DDS development. Basic characteristics, such as stiffness, elasticity or glass transition tem-

perature (Tg), are important for designing and adapting the material for biomedical application. The photosensitive

poly(ethylene glycol) diacrylate (PEGDA) can be easily formed into a desired biocompatible scaffold geometry via ste-

reolithography. In this study we have focused on the evaluation of PEGDA (Mn=700 g/mol) as a pure and copolymer

system in combination with other acrylates (butanediol diacrylate, pentaerythritol triacrylate) as possible materials for

DDS using this novel hybrid AM technique. Irgacure 2959, a biocompatible photoinitiator (PI), was used as a radical

starter for photopolymerisation. Samples varying in PI and copolymer concentration were prepared by conventional

photopolymerisation. Physico-chemical analyses of the samples were performed and several parameters, such as stiff-

ness, elongation at break and glass transition temperatures, were determined.


Formation and characterisation of hydrogel diffusion channels for directed drug delivery Thomas Eickner, Institute for Biomedical Engineering, University Medical Center Rostock, Rostock, Germany, [email protected] Stefanie Kohse, Institute for Biomedical Engineering, University Medical Center Rostock, Rostock, Germany, [email protected] Sabine Illner, Institute for Biomedical Engineering, University Medical Center Rostock, Rostock, Germany, [email protected] Stefan Oschatz, Institute for Biomedical Engineering, University Medical Center Rostock, Rostock, Germany, [email protected] Michael Teske, Institute for Biomedical Engineering, University Medical Center Rostock, Rostock, Germany, [email protected] Natalia Rekowska, Institute for Biomedical Engineering, University Medical Center Rostock, Rostock, Germany, [email protected] Volkmar Senz, Institute for Biomedical Engineering, University Medical Center Rostock, Rostock, Germany, [email protected] Klaus-Peter Schmitz, Institute for Biomedical Engineering, University Medical Center Rostock, Rostock, Germany, [email protected] Niels Grabow, Institute for Biomedical Engineering, University Medical Center Rostock, Rostock, Germany, [email protected] Drug Delivery Systems (DDS) are frequently operating in a surrounding liquid, such as blood for drug-eluting stents or perilymph for cochlear implants. However, there is also a demand for systems with sustained drug release in predomi-nantly dry environments, mostly consisting of ambient air. Examples are the treatment of diseases located in the middle ear or the paranasal sinuses. Thus, the functionality of a polymer/drug composite for a sustained drug release in such environments would be limited because of the lack of transportation media. On the other hand, these environments are generally equipped with mucus membranes. Hence, a somewhat humid surrounding is ensured. In this study, a concept of a hydrogel equipped DDS for drug delivery through the round window membrane is present-ed, addressing two objectives. First objective is to ensure the drug transport by serving as a diffusion channel. For in-stance the route to the drug target destination, the round window membrane, can be provided by a hydrogel. The second objective is to ensure the adhesion to the membrane. Two promising approaches are presented in this study: The photo induced immobilisation of PEGDA700, as well as the immobilisation of chitosan on poly(L-lactic acid) (PLLA). For both approaches PLLA specimen had to be modified with oxygen plasma followed by activation for crosslinking with subse-quent immobilisation of the hydrogel. With these methods a layer thickness of at least 5 µm was achieved. All steps were characterized with contact angle measurements. After the immobilisation of the hydrogel, the swelling factor, as well as the layer thickness was examined.


Postprocessive chemical treatment of polyimide electrospun nonwovens with diamines for biomedical applications Stefan Oschatz, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, Germany, [email protected] Daniela Arbeiter, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, Germany, [email protected] Thomas Eickner, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, Germany, [email protected] Niels Grabow, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, Germany, [email protected] Sabine Illner, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, Germany, sabine. [email protected] Polyimides (PI) are widely used in the manufacturing of biomedical devices such as tubes, catheters, the insulation or encapsulation of neuronal active implants, or as drug delivery systems. This polymer class stands out due to its biocom-patibility, mild foreign body reaction, mechanical toughness, chemical inertness and highly beneficial dielectric proper-ties paired with a low coefficient of thermal expansion. However, the generation of electrospun nonwovens from these materials remains challenging as the fibers are prone to distinct delamination, most probably due to the limiting solu-bility of PI in solvents such as DMF. This hinders partial fusion at fiber contact points and fibre mingling, preventing the formation of a stable network. In consequence, the resulting nonwoven material has particulary low structural integ-rity and follow-up treatment, such as high temperature thermal treatment, is required. In this work, we present a facile method for a postprocessive treatment to achieve a mechanically stable PI nonwoven, while maintaining the characteristic morphology of the electrospun material. The follow-up treatment was performed using various solutions of diamines in methanol at 37 °C and ambient pressure to achieve a modified inter-fiber interac-tion. FTIR spectroscopy was used to observe the reaction of the imide group with the diamines. Moreover, the effect on the morphology of the fibers was determined via SEM imaging. Overall, the developed treatment protocol opens new possibilities in the processing of PI into delamination-free electrospun nonwovens. Potential adverse effects of a high temperature thermal treatment are being avoided, and for new applications in the field of medical devices may become accessible.


The effect of diamine treatment on the physico-chemical properties of polyimide electrospun nonwovens Daniela Arbeiter, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, Germany, [email protected] Niels Grabow, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, Germany, [email protected] Sabine Illner, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, Germany, [email protected] Stefan Oschatz, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, Germany, [email protected] Polymers represent a versatile material class for medical implants in the focus of investigation for future use. Depend-ing on their target biomedical application, polymers have to show different characteristics, such as high resistance to the physicochemical environment in vivo. Therefore, a variety of chemical processes have to be explored. Electrospinning of nonwoven structures is currently being established as a promising procedure for the generation of innovative medical implant applications. These materials can be manufactured with high reproducibility, offering the potential for postpro-cessive chemical modification to alter their properties. The polymer class of polyimides (PI) has demonstrated to be a suitable material for the insulation or encapsulation of neuronally active implants. However, the generation of electrospun nonwovens from polyimides remains challenging, as the fibers show a propenstity for delamination, most probably due to solubility issues. This prevents the formation of fiber mingling at fiber contact points, thus suppressing the formation of a stable fiber network. In consequence, PI nonwovens are demanding for a suitable follow-up treatment to improve structural integrity. In this study, we investigate the morphological, mechanical and thermal properties of PI fiber nonwovens. A follow-up treatment to generate stable nonwoven structures was performed using solutions of various diamines in methanol at 37 °C and ambient pressure in order to achieve a modified inter-fiber interaction. Morphological analyses were per-formed using light microscopy. The mechanical performance of PI nonwovens was analysed with uniaxial tensile tests. Thermal properties were investigated with differential scanning calorimetry (DSC). In comparison to the mechanical properties of well-established implant materials, such as polyurethanes or silicone, the results indicate the suitability of PI nonwovens for medical applications.


Safety evaluation of resveratrol as an active compound for drug-eluting cardio-vascular implants Valeria Khaimov, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock-Warnemünde, Germany, [email protected] Thomas Reske, Institute for ImplantTechnology and Biomaterials e.V., Rostock-Warnemünde, Germany, [email protected] Niels Grabow, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock-Warnemünde, Germany, [email protected] Claudia Matschegewski, Institute for ImplantTechnology and Biomaterials e.V., Rostock-Warnemünde, Germany, [email protected] Cardiovascular disease is the leading cause of death worldwide. Stents and heart valves are medical devices that save lives by correcting structural and functional defects of the cardiovascular system. However, thrombosis, neointimal hy-perplasia, calcification and foreign body reaction are common post-implantation complications leading to implant fail-ure. Drug-eluting implants gradually release a pharmaceutical compound to counteract these side effects and support the process of tissue healing. Stilbenoids are polyphenolics synthesized in plants in response to stress with promising phar-maceutical properties. Resveratrol is a member of stilbenoids that was shown to prevent stenosis and exhibit an an-ti‑atherosclerotic effect. This hallmark makes it an extremely interesting candidate for local drug delivery to damaged tissue adjacent to the implant in order to reduce implant-related complications. For the regulatory approval drug-eluting medical devices have to be thoroughly tested for safety, efficacy and interactions with the surrounding tissue, including tests for sensitization among others. Studies for sensitization help to estimate the risk for an allergic reaction upon pro-longed exposure to a chemical compound. Due to increased social and regulatory demand for replacement of animal experiments by in vitro approaches a number of reliable predictive non-animal tests have been developed. In this study we aimed to evaluate the sensitization potential of resveratrol when used as coating for drug-eluting cardiovascular de-vices. For this purpose we have established an in chemico sensitization method, the direct peptide reactivity assay (DPRA) described in OECD 442C. DPRA was further used to test for reactivity of clinically relevant concentrations of resveratrol.


Applikation of 3R principles in small animal GLP testing of bio-materials Sabine Kischkel, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, Germany, e-mail: [email protected] Andreas Brietzke, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, Germany, e-mail: [email protected] Claudia Matschegewski, Institute for ImplantTechnology and Biomaterials e.V., Rostock, Germany, email: [email protected] Wolfram Schmidt, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, Germany, e-mail: [email protected] Thomas Eickner, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, Germany, e-mail: [email protected] Niels Grabow, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, Germany, e-mail: [email protected] On the protection of animals used for scientific purposes, the EU Parliament adopted Directive 2010/63/EU. The essen-tial factor is the 3R principle: Reduction, Refinement, Replacement. In 2013, the Third Amendment to the German An-imal Welfare Act was revised and adapted to the European directive. The majority of animals in science are used in basic research and translational, and applied research. Animal experi-mentation in medical research is conducted to clarify previously unknown life processes and basic biological relation-ships, in order to improve diagnostics and treatment of human illnesses and diseases. Before an animal experiment can be performed, it must be reported to the responsible authorities and approved. The planned research project must be justified scientifically, and it must be demonstrated that the personnel and spa-tial/technical prerequisites are in place to successfully complete the project. If all conditions are being met, the approval is being granted, wbut may be subject to conditions. The guiding principle of essentiality also affects the performance of the experiments: The number of animals used and the pain, suffering and damage caused to these animals must be limited to what is strictly essential. In this context, the 3R principle has to be applied. After careful selection of an animal model, we test e.g. in our GLP laboratory a new drug release systems for ophthal-mological applications in rabbits. Stress during animal experiments must be avoided as far as possible. Providing pain-killers and ensuring the best possible husbandry and care conditions are crucial for the animal’s wellbeing and absence of pain and anxiety. To obtain reliable results, it is essential that the laboratory animals are in a normal physiological state and free of pain and fear, if possible. Scientific interests and animal welfare are therefore not in opposition but rather mutually depend-ent.


Protein adsorption on Implants: Determination of the hip implant proteome

H.P. Jennissen1,2, M. Jäger2, M. Haversath2, A. Busch2, T. Grupp3, A. Sowislok 1,2, & M. Herten2 1 Institute of Physiological Chemistry, Work Group Biochemical Endocrinology, University of Duisburg-Essen, 45147 Essen, Germany; 2 Department of Orthopedics and Trauma Surgery, University of Duisburg-Essen, 45147 Essen, Germany; 3 Aesculap AG, Research & Development, 78532 Tuttlingen, Germany. e-Mail: [email protected] Proteins are adsorbed to surfaces with high affinity by multivalent, cooperative mechanisms involving adsorption hysteresis. In multiprotein systems the protein layer is dynamic displaying the Vroman effect and protein-protein displacement. On implants the question is "Who gets there first"? All current information on the initial protein layer has been concluded from in vitro experiments. Therefore the objective of the present study was the determination of the complete initial protein layer composition on the hip implant after placement in humans. This is possible by a proteomic analysis. In this first clinical study on an implant proteome the femoral stem prosthesis was explanted after 2 min. in situ. The stems were washed with saline, quick frozen in liquid nitrogen and stored at -80 °C. Proteins were eluted under reducing conditions with 4% SDS at room temperature and analyzed by LC-MS/MS. Under the set conditions the implant proteome was found to consist of 2802 unique proteins. Of these 77% were of intracellular origin, 9% were from the plasma proteome, 8% from bone proteome in addition to proteins from the bone marrow. The most abundant protein in the adsorbed total protein layer was hemoglobin (8-11%) followed by serum albumin (3.6-6%). The implant proteome thus had a unique unforeseen composition. This study is a major step ion understanding and predicting the implant-induced response of the osseous microenvironment, leading to enhanced healing with a reduction of postoperative surgical revisions.


Evaluation of MRI-compatible pneumatic muscle stepper motors Guthrie, Alan, Department of Medical Engineering, Otto-von-Guericke University Magdeburg, Germany,

[email protected]

Odenbach, Robert, Department of Medical Engineering, Otto-von-Guericke University Magdeburg, Germany, [email protected]

Friebe, Michael, Department of Medical Engineering, Otto-von-Guericke University Magdeburg, Germany, [email protected]

The automation of robotic devices (e.g. needle positioning robot for prostate surgery) or tools (e.g. bone drill) for appli-cation in interventional MRI (iMRI) is still challenging due to a lack of accurate, affordable and completely metal-free actuators and motors. Inspired by biological muscles, a bionic equivalent - fluid muscles - which can be operated either pneumatically or hydraulically, are well-known in the mechanical engineering industry. Fluid muscles have multiple beneficial characteristics: they are simple, self-returning, low-friction and can produce relatively high actuation forces at low diameters and pressures. However, there are no metal-free versions on the market.

In this paper we present a novel design for metal-free, pneumatic stepper motors using pneumatic air muscles (PAMs) for application in iMRI. For precise automation purposes, e.g. in robotic devices, stepper motors are desirable due to their precisely controllable rotational motion. Our stepper motors derive motive force from simple pneumatic muscles assem-bled from low-cost off-the-shelf components. Since their design is inherently air-tight (unlike pneumatic cylinders), fluid muscles are beneficial for iMRI applications since they do not exhaust potentially contaminated air to the local environ-ment, unlike some other pneumatic motor designs. Besides the pneumatic muscles, the components of the stepper motor demonstrators were 3D-printed using the stereolithographic additive manufacturing process (SLA printing).

We evaluated the effect of pneumatic muscle length on contractile force and length, and used the results to produce a functioning motor demonstrator. Our results have shown the functional feasibility of our pneumatic-muscle-powered and fully MRI-compatible stepper motor designs. In future research, we will characterize and improve the motor’s perfor-mance and reliability, and apply the stepper motors to powering a micropositioning device in iMRI-phantom tests.


Development and validation of bone models using structural dynamic measurement methods. Constanze Neupetsch, Adaptronics and Lightweight Design in Production, Technische Universität Chemnitz, Chemnitz, Germany, [email protected] Eric Hensel, Technical Acoustics, Fraunhofer Institute for Maschine Tools and Forming Technology IWU, Dresden, Germany, [email protected] Michael Werner, Medical Technology, Fraunhofer Institute for Maschine Tools and Forming Technology IWU, Dresden, Germany, [email protected] Sven Meißner, Applied plastics technologies, Fraunhofer Institute for Maschine Tools and Forming Technology IWU, Dresden, Germany, [email protected] Jan Troge, Technical Acoustics, Fraunhofer Institute for Maschine Tools and Forming Technology IWU, Dresden, Germany, [email protected] Welf-Guntram Drossel, Adaptronics and Lightweight Design in Production, Technische Universität Chemnitz, Chemnitz, Germany, [email protected] Christain Rotsch, Medical Technology, Fraunhofer Institute for Maschine Tools and Forming Technology IWU, Dresden, Germany, [email protected] Vibration measurement and signal analysis methods are common to evaluate the functionality and characteristics of technical components in different industrial and scientific areas. Modal analysis for example is a standard method to characterize the dynamic behavior of a structure and enables the development of validated models of real structures. The state of the art of analyzing bone structures does not include the modal damping, although it has a significant contribution to the dynamic characteristics.Within the presented investigations, the modal analyses were executed contactless with respect to excitation and response acquisition, which implies that there is no influences of shakers or sensor couplings. Therefore an automated impulse hammer excitation and a response detection by 3D Scannig Laser Doppler Vibrometer were used. Various supports of the test specimens, surface pretreatments, excitation points and excitation impulses were investigated to optimize the measurement setup with a suitable test program, which determined the process chain. Experimental modal analysis data were analyzed by curve fittig methods to determine the modal parameters. To evaluate different structures and effects of damping, 3D printed artificial bones and animal in vitro bones were used to perform the measurements. To produce the cortical layer of the artificial bone models, volume models were generated based on medical image data and printed by polyamide based selective laser sintering. The cancellous bone was represented by different foam fillings for the artificial bones. Thereby, the variation of the porosity was achieved by using different mixing ratios of the polyurethane foam and the hardnener. Furthermore the modal damping paramters were determined from the measurement on animal bones. The measurement time was optimized during the practical implementation of the parameter determination to mimimize the influence of drying and decomposition processes on the measurement results.


Kinematics of the Lumbo–Pelvic Complex under Different Loading Conditions Martin Weidling, Center for Research on Musculoskeletal Systems (ZESBO), Faculty of Medicine, University of Leipzig, Leipzig, Germany, [email protected] Christian Voigt, Center for Research on Musculoskeletal Systems (ZESBO), Faculty of Medicine, University of Leipzig, Leipzig, Germany, [email protected] Toni Wendler, Center for Research on Musculoskeletal Systems (ZESBO), Faculty of Medicine, University of Leipzig, Leipzig, Germany, [email protected] Martin Heilemann, Center for Research on Musculoskeletal Systems (ZESBO), Faculty of Medicine, University of Leipzig, Leipzig, Germany, [email protected] Michael Werner, Fraunhofer Institute for Machine Tools and Forming Technology IWU, Dresden, Germany, [email protected] Jan-Sven Jarvers, Department of Orthopaedic, Trauma and Plastic Surgery, University Hospital Leipzig, Leipzig, Germany, [email protected] Christoph-E. Heyde, Department of Orthopaedic, Trauma and Plastic Surgery, University Hospital Leipzig, Leipzig, Germany, [email protected] Implant design requires knowledge about the weight transfer from the spine to the hip region which is, therefore, a major field of biomechanical investigation. The lumbo–pelvic complex, comprised of the lumbosacral transition and the pelvic ring, is a highly complex structure including different bones, ligaments and intervertebral discs. To deepen our understanding how these components interact to transfer loads, the current study aims to identify the kinematics of the interacting bone segments under different loading conditions. A specimen of the lumbo-pelvic complex was obtained from a human body donor and tested in a self-developed test rig. The L3 was firmly embedded while the load was introduced via the acetabular voids. The experimental setup was designed to imitate extension, flexion and axial rotation to the left and to the right, repectively. Furthermore, lateral movement was simulated by a single-sided acetabular load on the right and left, respectively. Markers were attached to 15 landmarks. The markers were connected to the bone by pins to account for bone movement rather than soft tissue movement. Using a digital image correlation (DIC) system with a three-camera-setup, the 3D motion of the markers at different landmarks were measured during cyclic loading for each of the six specific loadcases. The relative movements between neighboring bone segments were calculated using a self-developed evaluation routine. Results are given in the standard body coordinate system. As results show, different loadcases generate characteristic motion patterns of the investigated bone segments. Thus, kinematic effects of six individual loadcases on the behaviour of the biomechanical system can be identified. The experimental technique enables further biomechanical studies, such as relative movements of sacroiliac and vertebral joints or deformation of sacrum and hemipelves.


Improved Acquisition of Vibroarthrographic Signals of the Knee Joint Lisa Klemm, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany, [email protected] Thomas Sühn, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany, [email protected] Moritz Spiller, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany, [email protected] Alfredo Illanes, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany, [email protected] Axel Boese, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany, [email protected] Michael Friebe, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany, [email protected] The human knee is a compound modified hinge joint, comprising the tibiofemoral and the patellofemoral joint as well as several ligaments and cartilage tissue. Due to the high complexity and to high kinetic loads, the knee is considered to be vulnerable to osteoarthritis. Sports-related knee injuries are common and related with high cost. To overcome the limita-tions of current diagnostical methods such as ultrasound and magnetic resonance based imaging or the invasive procedure of arthroscopy, the measurement of acoustic signals of the knee joint in motion is a promising approach. This method called vibroarthrography (VAG) requires a stable measurement setup to ensure a reliable auscultation and high signal quality. The attachment and interface between skin an audio sensor is a cruicial part of the acquisition. This paper presents a reliable attachment setup and movement protocol for the reproducible vibroarthrographic signal acquisition. Four dif-ferent methods for the sensor attachment to the knee were assessed with a focus on the stability and reproducibility of the measured signals. Therefore, a experimental protocol with a subject repeatedly performing a sit-to-stand movements in a steady pace was designed. Power spectral density estimates were used to compare the similarity between main compo-nents of the acquired audio signals of each movement. An analysis of the cross-correlation values was used to evaluate the stability.With a moderate average cross-correlation value of 0.42 and 0.53, two of the setups do not provide adequate and reproducible results. The remaining two setups show better results, with an average cross-correlation value of 0.66 and 0.65, respectively. The values indicate a moderate similarity between signals of repeated sit-to-stand movements. Possible explanations are the transient nature and the physiological source of the signal. Additionally, a more sophisticated processing approach such as wavelet analysis could be used to evaluate the similarities in a better way.


Determination of the hyperelastic material behavior of hydrogel specimens for expandable lens implants

Heiner Martin, Institute for Biomedical Engineering, University Medical Center Rostock, [email protected] Olga Sahmel, Institute for Biomedical Engineering, University Medical Center Rostock, [email protected] Christine Kreiner, KreCo GmbH, Hennigsdorf, [email protected] Niels Grabow, Institute for Biomedical Engineering, University Medical Center Rostock, [email protected] Thomas Eickner, Institute for Biomedical Engineering, University Medical Center Rostock, [email protected] Rudolf Guthoff, Department of Ophthalmology, University Medical Center Rostock, [email protected] The development of accommodative lenses has not achieved a sustainable success so far, though numerous concepts were developed and tested. Especially the replacement of the lens material, which is becoming harder with the age, remains still a competitive concept.

The filling of the lens capsule with curing polymer was further enhanced, however, the risk of the exact dosing of the lens content and the requirement of capsular sealing remain as well as the uncertainty of ensuring the optical quality of the lens. Therefore, an alternative concept of lens implants made of expandable biocompatible hydrogels was investigated, which allows a relatively simple implantation and an exactly defined lens shape.

An important point in this concept is to ensure the optical and mechanical material properties, which allow a deformation of the lens with accommodation. From earlier finite element investigations (e.g. by Burd et al) the required material properties of the human native lens and its capsule are approximately known.

Hence, the hyperelastic material law of hydrogel specimens for lens implants were determined with pressure tests and proven by finite element models of test specimens as well as for lenses. From the lens specimen deformation in a specially developed test device according to that by Burd et al, the accommodation ability of the lens can be determined.

The valid range of material properties for the hyperelastic material data is essential for the validation of the concept of an accommodative lens implant concepts.


Plasma Treatment of Printed Circuit Boards to Optimize Electronic Integration into Smart Medical Plastic Parts Valerie M. K. Werner, Institute of Medical and Polymer Engineering, Technical University of Munich, Garching, Ger-many, [email protected] Lingji Xu, Institute of Medical and Polymer Engineering, Technical University of Munich, Garching, Germany, [email protected] Simon Eßing, Institute of Medical and Polymer Engineering, Technical University of Munich, Garching, Germany, [email protected] Markus Eblenkamp, Institute of Medical and Polymer Engineering, Technical University of Munich, Garching, Germany, [email protected] The expansion of the Internet of Medical Things (IoMT) requires the development of systems with highly compacted communication structures to increase the network capabilities of Smart Medical Devices. Equipping plastic components with electronics holds particularly high innovation potential, because of beneficial properties of polymers in medical technology like biocompatibility. Therefore, central importance has the systematic investigation of interactions of poly-mer matrices with electronic components and recommendations for action regarding appropriate process technology. The aim of the present study was to find optimal surface conditions of electronic material surfaces for integration into plastics. Empirical basis was the influencing of the surface energy of a FR-4 Printed Circuit Board (PCB) with solder resist and with the surface finish Electroless Nickel Immersion Gold by different pretreatment measures (aqueous, alcoholic, and PCB washing agent pre-cleaning; pretempering before activation) and parameterization of atmospheric pressure plasma activation (carrier gases air and nitrogen). Pre- and post-experimental contact angle measurements were performed to quantify the surface energies. Within the scope of the work, the effectiveness of plasma treatments on the PCBs with regard to an increase of the surface energy could be demonstrated. The results showed a significantly increased wettability of the PCB surfaces after cleaning and subsequent eightfold plasma activation with nitrogen at a distance of 10 mm from the nozzle to the substrate and a translation speed of 10 m/min. An associated improved adhesion tendency could be validated in the cross-cut test with various coating materials. The present study formed the foundation for the integration of electronic components in near-contour polymer matrices under the prerequisite of optimal adhesion conditions for a composite. A major advantage of this approach is, in addition to economic aspects, the production of component combi-nations with a higher degree of integration and simultaneously increasing resistance to adverse environmental impacts.


Investigation of mechanical and magnetophoretic focusing for magnetic flow cy-

tometry

Jan Liu, Heinz-Nixdorf-Chair of Biomedical Electronics, Technical University of Munich, Munich, Germany,

[email protected]

Mathias Reisbeck, Heinz-Nixdorf-Chair of Biomedical Electronics, Technical University of Munich, Munich, Germa-

ny, [email protected]

Oliver Hayden, Heinz-Nixdorf-Chair of Biomedical Electronics, Technical University of Munich, Munich, Germany,

[email protected]

Optical flow cytometry has evolved as the gold standard for single-cell analysis since its invention around 50 years ago.

Its impact on preclinical and clinical applications requiring single cell function information for counting, subtyping and

quantification of epitope expression is still unchallenged. However, it requires significant logistical effort and special-

ized laboratories. In recent years, magnetic flow cytometry for non-optical detection of cells in whole blood samples has

emerged. It overcomes the high complexity and laborious sample preparation and is therefore more applicable for point-

of-care (POC) diagnostics, where clinically relevant decisions have to be made based on rapid results obtained at the

bedside. Especially, time-of-flight (TOF) magnetic sensing of rolling immunomagnetically labeled cells using giant

magnetoresistance sensors offers great potential for single cell analysis in POC settings. However, this method is lim-

ited due to the spatial resolution of the sensor. Here, an in-situ cell focusing approach that uses mechanical structures

and magnetophoretic forces to manipulate cell trajectories is investigated theoretically and experimentally. This method

allows the integration into a low-cost microfluidic system fabricated by injection molding or hot embossing and ensures

a resolvable spatial distance between two analytes. Based on theoretical foundations, a three-dimensional simulation

algorithm has been implemented that revealed parameters balancing hydrodynamic drag forces and magnetophoretic

forces. Additionally, physical experiments with magnetic particles and labeled erythrocytes were conducted in micro-

channels fabricated by means of rapid prototyping. The results were assessed using novel three-dimensional particle

tracking methods.


Development of low cost transparent electrode arrays for brain stimulation in large animals Sanchit Rathi, Lehrstuhl für Mikrosystemtechnik, Otto-von-Guericke-Universität, Magdeburg, Germany, [email protected] Martin Deckert, Lehrstuhl für Mikrosystemtechnik, Otto-von-Guericke-Universität, Magdeburg, Germany, [email protected] Sven Brinkhues, Lehrstuhl für Mikrosystemtechnik, Otto-von-Guericke-Universität, Magdeburg, Germany, [email protected] Markus Detert, Lehrstuhl für Mikrosystemtechnik, Otto-von-Guericke-Universität, Magdeburg, Germany, [email protected] Michael Brosch, Speziallabor Primatenneurobiologie, Leibniz-Institut für Neurobiologie, Magdeburg, Germany, [email protected] Bertram Schmidt, Lehrstuhl für Mikrosystemtechnik, Otto-von-Guericke-Universität, Magdeburg, Germany, [email protected] The aim of this work is to develop and evaluate a novel low cost, transparent electrode array for electrical brain stimulation and simultaneous optical imaging (calcium imaging, two-photon microscopy, etc.) at the same location. Commonly used, conventional opaque metal based (micro-) electrode sites prohibit the application of optical imaging methods for neuro-scientific investigations of the underlying brain structures. In this respect we explore the utility of the potentially trans-parent but conductive electrode material PEDOT:PSS. Performance evaluations during the development/testing phase were carried out on an artificial brain phantom before being used on a living macaque monkey. This combination of in vitro and in vivo testing leads to the refinement, reduction and to some extent replacement of animal tests in compliance with the 3R principles of EU guidelines on animal testing. PEDOT:PSS (Poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate)) was chosen as the material of interest due to its high charge-injection-capacity, high transparence, high mechanical durability and flexibility as well as cost effectiveness. Spin coated and cured polyimide PI-2611 (HD-MicroSystems) thin films of various thicknesses serve as substrate mate-rial. Post curing, the single layer screen printed PEDOT:PSS test structures had thicknesses of approximately 390 nm with an average impedance of 184 K measured using a 4-point probe setup. The impedance decreased to 25.37 K for six layered structures. Fabricated test structures created no artefacts during MR and X-ray imaging and, therefore, allow for the future use of X-Ray/MR imaging on animal subjects implanted with such entirely polymer based electrode arrays. As a result, the electrodes manufactured using PEDOT:PSS as the transparent conductive material along with transparent, ultra-thin polyimide substrates enable to benefit from both the spatial superiority of optical imaging as well as temporal superiority of electrophysiology.


Removal of ECG artifacts from EMG signals with different artifact magnitudes by template subtraction Lorenz Kahl, Drägerwerk AG & Co. KGaA, Lübeck, Germany, [email protected] Ulrich G. Hofmann, Section for Neuroelectronic Systems, Faculty of Medicine, University of Freiburg, Freiburg, Ger-many, [email protected] This work investigates the performance of an event-synchronous noise cancelling algorithm to separate ECG artifacts from thoracic EMG recordings. Three key components are the precise detection of heart beats, the exact time alignment of the QRS segments and the construction of a template QRS signal. A modified structural intensity (SI) approach based on the observation of extrema in low pass filtered versions of the second derivative is compared to the performance of a classical detector. The exact alignment is based on timing and magnitude of extrema in the low pass filtered signal and its first and second derivatives. One alternative calculates the exact timing by threshold intersection within the strongest slope of the QRS. A second alternative shifts the segments until the error is minimized. QRS templates are comparably constructed by alternatives to simple averaging. In order to have a clear picture of the separation results, artificial signals are utilized. They are constructed by addition of ECG signals to sEMG data from upper arm static contractions with different magnitudes. In the subsequent performance analysis the separated ECG based on the ECG only signal (without added EMG) is regarded as target. In case of higher EMG levels the detection capabilities of the modified SI is superior to the classical detector. Regarding the exact time alignment the extrema based approach and the error minimization yields better results than threshold cross-ing. The use of the mean value to construct a template from the superimposed heart beat signal segments remains the favorite choice. We show the performance of extrema based methods is similar or even better than alternatives. Further investigation is necessary to include other effects like cyclic EMG activity or irregularity in the ECG signal itself.


Electrical Dipole Source Localization using Hybrid Least Squares Method in

combination with ICA

Fars Samann, Department of Biomedical Engineering, University of Duhok, 42001 Duhok , Kurdistan Region, Iraq,

e-mail: [email protected]

Andreas Rausch, Technische Hochschule Mittelhessen (THM), FB Life Science Engineering (LSE), Institut für

Biomedizinische Technik (IBMT), Wiesenstr. 14, 35390 Gießen, Germany, e-mail: [email protected]

Thomas Schanze, Technische Hochschule Mittelhessen (THM), FB Life Science Engineering (LSE), Institut für


In biomedical engineering, dipole source localization is commonly used to identify brain activities from scalp recorded

potentials, which is known as inverse problem of Electroencephalography (EEG) source localization. However, this

problem is fundamental in biomedical engineering, medicine and neuroscience. The EEG inverse problem is non-

linear, in addition, it is ill-posed and it is unstable, i.e. the solution is non-unique and it is highly sensitive to small

changes of the measured signal (noise). For solving the EEG inverse problem iterative methods, like Levenberg-

Marquardt algorithm, are usually considered. However, these techniques require good initial values and a large number

of electrodes N, since a large redundancy supports the finding of the right solution. Therefore, in this paper, a hybrid

method of linear and non-linear modelling and least squares approach is proposed to overcome of these problems: the

solutions calculated by means of a linear approximation of EEG inverse problems serve as initial values for solving

the original non-linear models. In addition, independent component analysis (ICA) is combined with the proposed

hybrid least squares method to separate different dipole sources from multiple EEG signals. The performance of the

hybrid least squares method with and without ICA is measured in term of root mean square error. The simulated results

show that the proposed method can estimate the location of dipole source with acceptable accuracy under high noise

condition and small N comparing with linear least squares method considering larger N. Finally, it should be

mentioned that our hybrid method promises advantages in finding solutions of the EEG inverse problem effectively

and efficiently.








Multiscale Parameter Estimation (msPE) of QRS complexes distorted by magnetohydrodynamic effects at 7 Tesla Nicolai Spicher, Department of Computer Science, University of Applied Sciences and Arts Dortmund, Dortmund, Germany, [email protected] Markus Kukuk, Department of Computer Science, University of Applied Sciences and Arts Dortmund, Dortmund, Germany, [email protected] Stefan Maderwald, Erwin L. Hahn Institute for Magnetic Resonance Imaging, University of Duisburg/Essen, Essen, Germany, [email protected] Mark E. Ladd, Deutsches Krebsforschungszentrum (German Cancer Research Center, DKFZ), Heidelberg, Germany, Erwin L. Hahn Institute for Magnetic Resonance Imaging, University of Duisburg/Essen, Essen, Germany, [email protected] Ultra-high-field magnetic resonance imaging (UHF MRI) with field strengths •7T offers higher sensitivity than clinical imaging at •3T, but magnetohydrodynamic interactions distort the acquisition of electrocardiography (ECG) used for cardiac triggering and gating, resulting in image artefacts. Pulse oximetry is not equivalent due to trigger jitter, and recently proposed methods that process heart sounds or skin color require additional hardware. QRS complex detectors within the ECG signal have been proposed, with some including a learning phase outside the magnetic field. We aim to develop a QRS complex detector using our recently proposed multiscale parameter estimation method: zero-crossings from a signal’s scale-space representation are substituted into analytical expressions, allowing estimation of the parameters of a Gaussian derivative model that includes the Gaussian as a special case. In prior work, we demonstrated effectiveness in delineation of clinical QRS complexes. In this work, we process QRS complexes biased by magnetohydrodynamic effects: ECG signals (400Hz sampling rate) were acquired using vendor-provided hardware/software (MAGNETOM 7T; Siemens Healthineers) from three healthy volunteers (27-33years) with the patient table in the iso-center (7T) and in home position (•0.3T). For each experiment, 100 ECG segments (400ms duration) containing a pronounced QRS complex in terms of amplitude and positions were stored as ground truth. For each segment, msPE processed lines of scale-space zero-crossings closest to the position of maximum amplitude for estimating parameters of a Gaussian function. Positions were compared to ground truth (50ms threshold), showing that sensitivity (in percentage) and accuracy (mean±standard deviation (s.d.)) were comparable at 0.3T (Volunteer1:99%,11.5±1.8ms, V2:94%,3.4±2.0ms, V3:98%,-4.4±2.6ms) and 7T (V1:95%,-2.3±2.7ms, V2:97%,8.3±4.8ms, V3:95%,7.8±2.9ms) with slightly increased s.d. at 7T. These initial results indicate that msPE accurately estimates parameters despite magnetohydrodynamic interference when applied at the correct peak. Therefore, cardiac gating might be feasible by parameter estimation of every occurring peak combined with a self-learning classifier.


Automatic differentiation between Veress needle events in laparoscopic access

using proximally attached audio signal characterization

Anna Schaufler, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany,

[email protected]

Alfredo Illanes, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany, alfredo.il-

[email protected]

Axel Boese, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany, axel.bo-

[email protected]

Cora Wex, Medical Faculty, Otto-von-Guericke Universität, Magdeburg, Germany, [email protected]

Roland Croner, Medical Faculty, Otto-von-Guericke Universität, Magdeburg, Germany, [email protected]

Michael Friebe, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany, mi-

[email protected]

The initial phase of each laparoscopic procedure consists of placing an insufflation instrument into the abdominal cavity

and applying a pneumoperitoneum. A common insufflation instrument is the Veress needle consisting of a sharp, hollow

cannula inside in which a blunt obturator is located and is equipped with a safety mechanism. However, access phase is

a critical aspect of laparoscopic procedures that can lead to severe visceral and vascular injuries. The main objective of

this work is to demonstrate that information on intracorporeal interactions between Veress needle and tissue can be rec-

orded extracorporeally in the form of acoustic emissions (AE) and to show to which extend these records can be used to

distinguish between different events during Veress needle insertion.

A metallic Veress needle was fixed in a material testing system and inserted at constant speed into a gelatin phantom

filled with ex-vivo porcine fat tissue. The testing machine recorded the axial needle insertion force as reference. A 3D

printed adapter was plugged into the valve at the proximal end of the needle and equipped with a MEMS microphone

sensor. A video camera was placed to visualize the events occurring during the insertion. 11 experiments have been

performed and each recording was separated according to the event segment (layer puncture, fat, gelatin, Veress click).

In total, for each event, 22 signal segments were extracted. Each segment was first preprocessed and then eight time-

frequency domain features were extracted. Finally the feature space dimension was reduced to three using Principal Com-

ponent Analysis (PCA).

Result shows that clear clusters between the events are formed in the 3D scatter plot of the 3-dimensional PCA features

showing a clear potential of the use of AE for identifying puncture during needle insertions and therefore it can be used

as a technique for monitoring entry in laparoscopic procedures.


Local blood flow analysis and visualization from RGB-video sequences Benjamin Kossack, Fraunhofer Heinrich-Hertz-Institute (Computer Vision and Graphics), Berlin, Germany, [email protected] Eric L. Wisotzky, Fraunhofer Heinrich-Hertz-Institute (Computer Vision and Graphics), Berlin, Germany, [email protected] Ronny Hänsch, Technische Universität Berlin (Computer Vision & Remote Sensing), Berlin, Germany, [email protected] Anna Hilsmann, Fraunhofer Heinrich-Hertz-Institute (Computer Vision and Graphics), Berlin, Germany, [email protected] Peter Eisert, Fraunhofer Heinrich-Hertz-Institute (Computer Vision and Graphics), Berlin, Germany, [email protected] The ability to extract the heart rate and other vital parameters from video recordings of a person has attracted much at-tention over the last years. In contrast to other works that consider vital parameters only globally, we use remote photo-plethysmography (rPPG) to examine local characteristics in video recordings. These characteristics enable us to visual-ize the blood flow through the skin tissue of the human face and neck. A first step identifies the global pulse rate in RGB images using normalized green color channel intensities. We investi-gated five different signal types to locally analyze the rPPG signal and show that the local rPPG signal is best represent-ed by a chrominance based signal, revealing a time difference between distinct spatial regions. Using this information, we can extract the blood flow path through human skin tissue in the neck and face. We visualize this local blood flow by using maps of the pulse transit time and signal-to-noise ratio calculated from the extracted signal. For evaluation, we recorded a video database with 88 recordings of twelve subjects and acquired reference data using a vital sign monitor. We show that the visualization of the blood flow path follows a common pattern that corresponds to the physiologically defined path. For example, differences in blood supply between the forehead and the rest of the face as well as the position of the common carotid artery are clearly visible. Possible applications include alternative contactless and precise medical diagnostics, e.g., in image-guided surgery or for differentiation of tumorous tissue, but also in security-related applications including live detection of presentation attacks.


Evaluation of inertial sensors and optical measurement methods for head and shoulder angle motion analysis Oliver Mayr, Research Center for BioMedical Technology (BMT), University of Applied Sciences and Arts, Dortmund, Germany, [email protected] Puian Tadayon, Research Center for BioMedical Technology (BMT), University of Applied Sciences and Arts, Dort-mund, Germany, [email protected] Thomas Felderhoff, Research Center for BioMedical Technology (BMT), University of Applied Sciences and Arts, Dortmund, Germany, [email protected] Often a lack of exercise or wrong movements are the reason for pain. The real-time data acquisition, processing and analysis of such movements can help to identify the reasons for this pain. Therefore Inertial sensors or stationary camera-based systems are used. For real-life data recording, inertial sensor-based methods have significant advantages, e.g. small size, light weight or low power requirements. They are suitable for mobile, portable and non stationary systems. i.e. for mobile long-term moni-toring of human body movement under everyday conditions. But inertial sensor-based methods also have some limita-tions. In this paper the advantages and disadvantages of both measuring methods are examined and compared to the detection of head and shoulder angles. For this purpose 3 ExG inertial sensor modules from Shimmer Sensing and a Kinect 2 camera system are used. The recorded data of both systems are converted into a comparable form. The recording and evaluation of the head and shoulder movements are accomplished with the help of two developed C# applications. The first application records the motion of the head from both, the Kinect and inertial sensor data. Addition-ally it calculates a graphic motion pattern for a 3D model of a human head. The motion pattern allows a real-time visual-ization of the motion while recording. For the inertial sensor-based determination of rotational movements quaternions are determined with a fusion of the acceleration, rotation rate and magnetic field data. The camera-based detection of the head movement by the Kinect 2 is realized by using the Microsoft Kinect SDK 2.0. Based on the existing joint points, new reference points are calculated to allow the detection of rotational and translational head movements. The second application focuses on rotational shoulder movements. In addition, it allows a live visualization of the rec-orded scene in form of a schematic 3D motion representation of the shoulder for both sensor systems. Based on an evaluation of the recorded measurement data, the inertial sensor and the camera-based methods are compared with regard to their suitability for detecting movements in the head and shoulder area. The results show how the data from both measurement systems can be optimally combined to improve the accuracy and reliability of the resulting motion detection.


Foetal heart rate assessment by empirical mode decomposition and spectral analysis Patricio Fuentealba, Otto-von-Guericke University, Magdeburg, Germany, [email protected] Alfredo Illanes, Otto-von-Guericke University, Magdeburg, Germany, [email protected] Frank Ortmeier, Otto-von-Guericke University, Magdeburg, Germany, [email protected] The main aim of foetal surveillance during labour is to timely identify potential acidotic foetuses without unnecessary interventions. This operation is commonly performed by using a cardiotocograph (CTG), which provides the joint re-cording of foetal heart rate (FHR) and uterine contraction signals. Currently, the CTG assessment involves a visual analysis of several morphological FHR signal patterns based on proposed medical guidelines. However, the CTG inter-pretation by this methodology has demonstrated a wide intra- and inter-observer disagreement and poor reproducibility. Current advances in clinical research indicate that a correct identification of hypoxemia requires a good understanding of the foetal compensatory mechanisms modulated by the autonomic nervous system. Certainly, this modulation reflects variations in the beat-to-beat FHR, whose time-varying dynamics can involve significant information about the foetal condition. Considering this phenomenon, conventional methods that do not integrate these characteristics could not be appropriate for a correct CTG assessment, because they consider only a snapshot of the complete time-variant process. The main contribution of this work is to study such characteristics by combining two signal processing methods: empir-ical mode decomposition (EMD) and time-varying autoregressive (AR) modelling. The idea is to study the EMD intrin-sic mode functions (IMFs) not only in the time-domain but also in the spectral-domain in order to extract information from their frequency components over time. For this operation, first the FHR signal is decomposed into a finite number of IMFs. Then, for each IMF the time-varying AR spectrum is computed in order to investigate whether the behaviour of their spectral dynamics can help to assess the foetal condition. The proposed approach has been evaluated on real CTG data extracted from the open access CTU-UHB database. Re-sults reveal that the proposed features can help to assess the foetal condition by showing a statically significant differ-ence (p-value<0.05) between normal and acidotic cases.


Robustness of Algorithms for Describing Changes in the ST-T Segment in the ECG Due to Extracellular Calcium Concentration Changes Nicolas Pilia, María Hernández Mesa, Axel Loewe, Olaf Dössel, Institute of Biomedical Engineering, Karlsruhe Insti-tute of Technology (KIT), Karlsruhe, Germany, E-mail: [email protected] Haemodialysis patients show an increased risk of dying from sudden cardiac death (SCD). It was found that these pa-tients are often bradycardiac before dying. Moreover, a recent study revealed a connection between extracellular calci-um concentrations and bradycardia. For monitoring and preventing lethal cardiac events in patients, a continuous meth-od for estimating the calcium concentration is needed. To be able to use the ECG for monitoring the extracellular calci-um concentrations, a robust method to detect changes caused by a concentration shift is required. We already showed in a simulation study that the ST-T segment in the ECG is sensitive to changes of the calcium concentration in the extra-cellular space. To quantify the ST-T changes robustly, we compared two methods for measuring the degree of the change in this study. The first method builds on an approximation of the two halves of the T wave (including parts of ST and TP segments) using two individual model functions (ST-model). The offset difference of the estimated model functions was taken as a measure for the ST-T change. The second method used the first statistical moment of the ST-T part of the ECG (ST-moment). Both features were highly correlated with the change of the calcium concentration. To evaluate the robustness of the methods, we added noise to the simulated ECGs yielding SNR levels between 10dB and 30dB. We evaluated the mean absolute value of the relative change of the features with respect to the noise-free case. Here, ST-moment outperformed ST-model with respect to this performance features. Hence, ST-moment is a promising feature for estimating changes of the calcium concentrations using the ECG.


The effect of stray light on the electrophysiological measurement of the contrast threshold Benjamin Solf*, Institute of Biomedical Engineering and Informatics, Faculty of Computer Sciences and Automation, Technische Universität Ilmenau, Ilmenau, Germany, [email protected] Stefan Schramm, Institute of Biomedical Engineering and Informatics, Faculty of Computer Sciences and Automation, Technische Universität Ilmenau, Ilmenau, Germany, [email protected] Sascha Klee, Institute of Biomedical Engineering and Informatics, Faculty of Computer Sciences and Automation, Tech-nische Universität Ilmenau, Ilmenau, Germany, [email protected] Electrophysiological measurement can be used for objective functional diagnostics. Therefore, standardized conditions are needed. However, the influence of retinal stray light on the electrophysiological determination of the contrast sensi-tivity still needs to be investigated. We studied 10 healthy subjects (mean age 27.2 ± 5.8 years) and determined the con-trast threshold under normal conditions and in the presence of a stray light source using sweep steady state visual evoked potentials (VEP). Checkerboard stimuli (d = 7.2°) with a check size of 0.35° were presented in pattern-reversal mode (7.5 changes per second) for 8 contrast levels (98%, 50%, 25%, 12.5%, 10%, 7.5%, 5%, 2.5%) at mean luminances of 50 cd/m2 and 30 cd/m2 in a random order. The ring-shaped stray light source (r = 5 to 10°) surrounded the checkerboard and had a luminance of 350 cd/m2. The active electrode was placed at Oz, reference electrode at FCz and ground electrode at FPz. The stimulations were performed monocularly in a dimmed room. The recorded VEP were transformed using Fourier Analysis and the evoked magnitudes at stimulus frequency were plotted as a function of log contrast levels. Contrast thresholds were estimated by extrapolation of the VEP response function to zero amplitude. For statistical analysis Wil-coxon test for paired samples were used. Contrast thresholds showed significant differences (p<0.05) between normal conditions and in the presence of the stray light source (mean luminance = 50 cd/m2: from 1.3% to 1.9%, mean luminance = 30 cd/m2: from 1.9% to 2.6%). The results show an influence of retinal stray light on the determination of the contrast threshold using sweep VEP. The contrast threshold increases with increasing retinal stray light.


Improving Correlation-Based Spike Sorting by Combining Amplitudes and Time Lags of Minima and Maxima of Correlation Functions of Spike Waves Tom Juergens, IBMT, FB Life Science Engineering (LSE), Technische Hochschule Mittelhessen (THM), Giessen, Germany, [email protected] Pavel Larionov, IBMT, FB Life Science Engineering (LSE), Technische Hochschule Mittelhessen (THM), Giessen, Germany, [email protected] Thomas Schanze, IBMT, FB Life Science Engineering (LSE), Technische Hochschule Mittelhessen (THM), Giessen, Germany, [email protected] The automatic classification of waveforms is an important method in data processing, especially within the investigation of biosignals. In the past, spike sorting has gained importance, but there is still no universal solution. In addition, efficient and real-time capable methods are required. A correlation-based analysis of spikes from different neurons present in extracellular recordings allows the fast extraction of spike-wave characteristics and offers a good possibility for detection and classification of spikes. Such a correlation-based single-channel spike sorter has been the subject of our work in recent years. For this purpose, the minima and maxima were extracted from the arrays obtained from the correlations between the spike candidates and a signal-driven reference spike. However, the related data clouds correspond to the spike waves in the data. The subsequent cluster analysis of these clouds allows the assignment of the spike candidates to different classes, i.e. neuronal units. To improve the performance of the correlation-based spike-sorting algorithm, we tested whether our algorithm can achieve better classification results with a dimension increase by adding a feature. This feature is the time difference between the obtained absolute minimum and maximum of a correlation time course. This time difference was approximated by interpolation to get rid of sampling effects. With this extension of the algorithm, a three-dimensional instead of a two-dimensional clustering was performed. However, this measure is expected to improve clustering. Our results show, as expected, that this additional time-lag information yields advantages in spike sorting when minima and maxima of correlation functions between spike waves from different sources and the reference spike wave have similar amplitudes but different time lags. Simulations also indicate that the computational burden only slightly increases when time lags are additionally considered. Future work will focus on the evaluation with real data and on real-time capability.


Magnetocardiography with Optically Pumped Magnetometers Integrated in a Patient Bed

Christin Bald1, Eric Elzenheimer1, Julia Kreisel1, Nico Simoski1, Alexej Namenas1, Jens Reermann1, Thomas Demming2, Norbert Frey2, Gerhard Schmidt1 1 Digital Signal Processing and System Theory, Institute of Electrical and Information Engineering, Kiel University, Kiel, Germany, [email protected]/[email protected]/[email protected]/[email protected]/[email protected]/[email protected] 2 Department of Cardiology and Angiology, Kiel University, Kiel, Germany, [email protected]/[email protected]

Cardiologic in-hospital patients, especially in intensive care, are usually monitored continuously. After hospital discharge patient monitoring is stopped abruptly as the patient returns home or to rehabilitation. Occurrence of arrhythmic events and alteration of parameters of autonomic tone is still common in this subacute phase of cardiac diseases such as myocardial infarction. The first step for a better health control could be measuring the heart signal of a patient during the night.

Therefore, the patient bed could be equipped with several magnetic sensors so that the heart signal can be measured in any decubitus position. Optically pumped magnetometer are sensitive enough to measure the heart signal also in a certain distance and thus are suitable for this application.

In order to make the measurement robust, the best signal of the various optically pumped magnetometers has to be selected automatically depending on the respective SNR. Also a vectorized combination of the signals is possible for an enhanced output signal.

A prototype of a patient bed has been constructed in the shielded chamber of the technical faculty at Kiel university and tested with four commercially available optically pumped magnetometers. The optimal selection of the best sensor signal and a subsequent heart rate variability analysis were implemented and tested successfully.


Beamforming in Epilepsy with combined MEG&EEG Frank Neugebauer, Institute for Biomagnetism and Biosignalanalysis, University of Münster, Münster, Germany, [email protected] Stefan Rampp, Department of Neurosurgery, University Hospital Erlangen, Erlangen, Germany, [email protected] Gabriel Möddel, Department of Neurology with Institute of Translational Neurology, Epilepsy Center Münster-Osnabrück, Germany, [email protected] Carsten H. Wolters, Institute for Biomagnetism and Biosignalanalysis, University of Münster, Münster, Germany, [email protected] Epilepsy is a neuronal disease characterized by unprovoked seizures. While many cases can be treated with drugs, a substantial number of patients considers surgery as an alternative treatment. Finding the origin of the seizures in the brain is a complicated task needing many modalities like MRI, fMRI, PET, se-miology, intra-cranial EEG, EEG, and MEG. For MEG data analysis, non-seizure data is recorded and ongoing epileptic activity is marked by an epileptologist. Clas-sically, the data is then averaged and a dipole scan is performed. Beamforming is an inverse method that uses adaptive spatial filtering to estimate source location and orientation. As is does not assume a fixed number of sources across the brain, it presents an alternative to dipole scanning in epilepsy data that may reveal more information or strengthen the trust in the dipole location. We present the data of an epilepsy patient with a focal cortical dysplasia type IIb to show show how beamforming can be used to localize epileptic spikes, using MEG and EEG with a highly detailed 6 compartment (compact skull bones spongy skull bone, CSF, gray matter, and anisotropic white matter) FEM head model. Further, using a noise transformation, we combine MEG and EEG to a unit-less combined measurement. We show that this yields better results than MEG or EEG alone could produce. Results are validated using surgery results.


An efficient ECG Denoising method using Discrete Wavelet with Savitzky-

Golay filter

Fars Samann, Department of Biomedical Engineering, University of Duhok, 42001 Duhok , Kurdistan Region, Iraq,


Thomas Schanze, Technische Hochschule Mittelhessen (THM), FB Life Science Engineering (LSE), Institut für


Electrocardiogram (ECG) is a widely used tool for the early diagnosis and evaluation of cardiac disorders. The ECG

signal is usually distorted during reordering by different types of noise which may lead to incorrect diagnosis.

Therefore, clear ECG signals are required for better cardiac disorder diagnosing. In this paper, an efficient ECG

denoising method using combined discrete wavelet with Savitzky-Golay (S-G) filter is proposed. The S-G filter can

smoothen the ECG signals by keeping the properties of the original signal as possible. The performance of S-G filter

is studied in term of polynomial degree and frame size, i.e. signal section. In addition, the performance of denoising

wavelet is studied in term of mother wavelet type and wavelet order. The advantage of S-G filter is combined with

discrete wavelet denoising method to get better denoising performance. The performance of S-G filter, wavelet

denoising and proposed method are evaluated using signal to noise ratio (SNR) and percentage root mean square

difference (PRD). For this we used simulated and Gaussian white noise surrogated ECG signals. Our results show that

combined S-G and wavelet filter denoising is noticeable better than the respective individual procedures. In addition,

we found that the selection of frame size, order of the S-G filter and the wavelet type and order should be done

carefully in order to get optimal results. It also holds true for the new filter that the optimal choice of filter parameters

is a compromise between noise reduction and distortion.






Variability of pattern-reversal electroretinogram measurements using skin-electrodes Maren-Christina Blum, Institute of Biomedical Engineering and Informatics, Faculty of Computer Sciences and Automation, Technische Universität Ilmenau, Ilmenau, Germany, [email protected] Sascha Klee, Institute of Biomedical Engineering and Informatics, Faculty of Computer Sciences and Automation, Technische Universität Ilmenau, Ilmenau, Germany, [email protected] The pattern-reversal electroretinogram (PERG) is an ISCEV-standardized electrophysiological measurement method for the investigation of the retinal ganglion cell function. Consecutive measurements show intraindividual variabilities, which have not been sufficiently investigated for the use of skin electrodes up to now. This work aims to quantify these variabilities. We measured the PERG in 15 healthy eyes (10 left eyes, 5 right eyes, 5female, 10male, 30.8±4.9 years) six times in a row with a break of 90s between every measurement (n=75). The differences between two consecutive measurements for the N95 amplitude were investigated. The pattern checkerboard (d=16°), with a check size of 1°, was presented binocular with a reversal rate of 4 reversals per second for 300 times (averaged 200 sweeps) and a mean luminescence of 186cd/m². The skin-electrodes (ring shape, Ag/AgCl) were placed at the lower eyelid (active), ipsilateral earlobe (reference) and the forehead (ground). For statistical analysis we performed a confidence level analysis with Bonferroni correction. The mean value of the consecutive differences was 0,54µV with a standard deviation of 0,45µV. We found no significant effects (α =0,05) for the differences between measurements. With an increase of the measurement time, the confidence interval size raised which is an indicator for an increased variability of the PERG N95 amplitude (confidence interval size, difference 1: 0,37µV; difference 2: 0,6µV; difference 3: 0,61µV; difference 4: 0,95µV; difference 5: 0,8µV). The results show an influence of the measurement time on the variability of the PERG. Therefore, no more than four consecutive measurements should be done when using skin electrodes.


A micro physiological system to investigate the pressure dependent filtration at an artificial glomerular kidney barrier Florian Schmieder, Stephan Behrens, Nina Reustle, Nathalie Franke, Fraunhofer IWS Dresden, Dresden, Germany Jan Sradnick, Department of Internal Medicine III, University Hospital Carl Gustav Carus, Dresden, Germany Frank Sonntag Fraunhofer IWS Dresden, Dresden, Germany Chronic kidney disease (CKD) is a global health problem that affects around 11 to 13% of the world’s population and more than 18% of European citizens. Characteristic syndromes of CKD during all stages of the disease are proteinuria and ongoing glomerular dysfunction caused by cellular damages at the glomerular filtration barrier. While some rare cases of the disease are correlated to genetic depositions the majority of cases are caused by diabetes, glomerulosclero-sis, high blood pressure and glomerulonephritis. Thus, recapitulating the interplay of high blood pressure and changes at the glomerular filtration barrier in vitro seems an adequate way to mimic CKD. Here we present a micro physiological system of the glomerular filter that is capable to simulate high blood pressure at the glomerular filtration barrier in vitro. The artificial glomerular filtration barrier was formed by seeding human immortalized podocytes and human blood out-growth endothelial cells on opposite sides of a transwell membrane. Transepithelial electrical resistance (TEER) was measured daily to evaluate the barrier function of the cellular layers. To investigate the influence of high blood pressure on the in vitro-barrier a micro physiological system called ZEBRA-Chip was invented. It consists of a closed loop mi-crofluidic circuit with an integrated pneumatically driven heart like micro pump that constantly circulates the cell cul-ture media at the blood site of the glomerular barrier. The transwell insert could be reversibly integrated into a holder system that ensures the correct position of the insert within the microfluidic circuit. By using different modulations of the integrated pneumatic micro pump different physiological and pathophysiological conditions e.g. hypertonic stress, like in CKD, could be applied. The influence of hypertonic conditions on the filtration above the barrier was studied by changes of TEER values and measurement of the flux of fluorescent labelled inulin and albumin through the cellular barrier.


Generation of an azide-modified extracellular matrix by adipose-derived stem cells using metabolic glycoengineering Svenja Nellinger, Applied Chemistry, Reutlingen University, Reutlingen, Germany, [email protected] Silke Keller, Institute of Interfacial Process Engineering and Plasma Technology, University of Stuttgart, Stuttgart, Ger-many, [email protected] Alexander Southan, Institute of Interfacial Process Engineering and Plasma Technology, University of Stuttgart, Stuttgart, Germany, [email protected] Valentin Wittmann, Department of Chemistry, University of Konstanz, Konstanz, Germany, [email protected] Petra J. Kluger, Applied Chemistry, Reutlingen University, Reutlingen, Germany, [email protected] Extracellular matrix (ECM) is the natural environement of the cells of a specific tissue. It is synthesized and assembled by the resident cells of the tissue, Thus natural ECM represents an ideal biomaterial for tissue engineering and regenera-tive medicine approaches. However, there is a need for specific addressable functional groups to achieve individual chem-ical and physical properties. This was achieved by the clickECM technique using metabolic glycogenineering (MGE) with azide-modified monosaccharide derivates. In this study the existing procedure based on human fibroblasts was ado-poted to adipose-derived stem cells (ASCs) as alternative cell source for MGE. ASCs were isolated from adipose tissue obtained from patients undergoing plastic surgery. To investigate the biocompatibility of the azide-modified monosac-charide, LDH assay and resazurin assay were performed after 24h and 2 days. For generation of modified ECM, azide-modified monosaccharide derivates were added into the cell culture medium. Their incorporation efficiency into the gly-cocalyx of the ASCs and the ECM was proven by copper-catalyzed click reaction with fluorescent labeled alkyine. LDH assay and reazurin assay revealed biocompatibility of the azide-modified monosaccharides. Incorporation of the azide-modified monosaccharide into the glycocalyx and the ECM was successfully proven by click reaction with fluorescent labeld alkyne. Therefore, the used azide-modified monosaccharide derivate in combination with ASCs are suitable for clickECM technique by MGE. We successfully prove ASCs as suitable cell souce for MGE using azide-modified mono-saccharides. The glycocalyx and the ECM of ASCs was successfully modified with azide-groups, which can be addressed by molecules with alkyne-groups. With this clickECM technique the ECM of ASCs can be chemically modified e.g. with molecules enhancing cell adhesion, cell viability or cell differentiation. Further the azide-modified ECM can be used for polymerization approaches by cross-linking and adjusting of specific physical properties.


Dynamic Cooling IR thermographic imaging- an initial setup for non-invasive detection of small tumours Axel Boese, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany, [email protected] Maryam Sadeghi, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany, [email protected] Iván Maldonado, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany, [email protected] Jörg Sauerhering, Institute of Fluid Dynamics and Thermodynamics, Otto-von-Guericke University, Magdeburg, Ger-many, [email protected] Simon Schlosser, GBN Systems GmbH, Germany, [email protected] Heinrich Wehberg, Medizintechnik Wehberg GmbH, Germany, [email protected] Konrad Wehberg, Medizintechnik Wehberg GmbH, Germany, [email protected] Michael Friebe, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany, [email protected] Thermographic imaging is an approved technology to detect small temperature differences. For medical applications it was already tested to visualize blood supply, inflammatory processes and superficial or larger tumours. Therefore the patient is imaged directly after undressing and after waiting in a cool environment. The patterns of heat distribution are used for diagnosis. For detection of small tumours of the breast at early stage, contact thermography using liquid crystal foils (LCF) com-bined with short contact cooling was reported to be feasible. These tumours appear 1-4 degrees warmer than normal tis-sue due to vascularisation processes. The dynamic change of colour patterns during the re-heating process is imaged by cameras. But this method comes with a variance of potential failure sources like poor skin contact, limited temperature range or reflections and needs user experience. To overcome these issues and to develop a user friendly system for breast screening purposes, the feasibility of dynamic cooling in combination with infrared (IR) imaging was evaluated in a phantom study. A temperature-controllable gel phantom including a heating plate, a depth-adjustable heat source (2mmx1mm) mimicking a tumour and three sensors for temperature monitoring was built up. A raspberry pi serves as control unit to create a stable temperature balance comparable to a human breast. For the tests the tumour was placed in 5mm, 10mm, 15mm and 20mm depth. After cooling with an 18°C waterglas for 5-10 seconds the re-heating was imaged using an IR camera and a webcam. The experiments were conducted with and without LCF for comparison. The acquired IR sequences show a distinct pattern at the tumour area that correlates with the LCF. A pixelwise analysis of the IR data detects a higher gradient of temperature change in this region. The experi-ments demonstrated the feasibility of tumour detection based on dynamic cooling and IR imaging.


Simulation of Breathing Patterns and Classification of Sensor Data for the early detection of impending Sudden Infant Death Nicolas Wolf, University of Applied Sciences, Ulm, Germany, [email protected] Michael Munz, University of Applied Sciences, Institute of Medical Engineering and Mechatronics, Ulm, Germany, [email protected] The sudden infant death syndrome is still one of the most common causes for infants’ death. Studies show a relation be-tween different pathological breathing patterns during sleep and the sudden infant death. In this work, we present a pre-warning monitoring system able to classify different breathing patterns. In contrast to other systems, alarms are generat-ed prior to an incident. The system comprises a conductive strain fabric sensor which changes its electrical resistance when strain is applied. This sensor can easily be integrated into a baby’s sleepsuit around the chest for monitoring breathing motion. Additionally, an inertial sensor unit (IMU) was integrated near to the fabric. Data of both sensors is fused in a classification system. To validate the measurements of the conductive strain fabric, the chest movement of a subject was simultaneously measured by the sensor system and a conventional polysomnography device. Results show high correlation between the conventional polysomnography device and the sensor data of the system. For creating a dataset of sensor data comprising pathological as well as physiological breathing patterns of infants, a mechanic chest wall simulator was designed. The simulator can conduct motion of breathing patterns using a stepper motor. The motion of the chest wall simulator has been validated using a 3D motion capturing system. Multiple breathing patterns were run several times on the chest wall simulator and recorded by the sensors. Afterwards six features were extracted from sensor data over short time windows. For the classification step, an artificial neural network was trained and applied on time window of three seconds, which is fast enough for a pre-warning system. Us-ing a second stage classifier combining the results of multiple consecutive time windows, the classification rate is raised over 95%. False alarm rate and detection rate can be adjusted according to the case of application.


The AutoSon project: improvement of a neuronavigation system for neurosurgi-cal procedures Jesús Gguillermo Cabal Aragón, Innovation Center Computer Assisted Surgery (ICCAS), Leipzig, Germany, [email protected] Dirk Lindner, Department of Neurosurgery, University Hospital Leipzig, Leipzig, Germany, [email protected] Sven Arnold, Arno Schmitgen, Localite GmbH, Sankt Augustin, Germany, [email protected], [email protected] Claire Chalopin, Innovation Center Computer Assisted Surgery (ICCAS), Leipzig, Germany, [email protected] The use of intraoperative ultrasound (iUS) imaging supports the neurosurgeon during brain tumor operations. The US device can be integrated into a neuro-navigation system. Such system performs the visualization of the iUS image data overlapped on preoperative image data. However, the limitations are the lack of communication between the devices and of tools for the annotation of the image data. Therefore, the purpose of the project is the development of an im-proved neuro-navigation system. Firstly, an image based connector was developed to automatically identify the values of the US parameters set during the acquisition. These parameters, for example the probe and the image depth, are only accessible through the monitor of the US device and are variously represented using characters, digits, symbols and geometrical shapes. Secondly, semi-automatic tools were developed to segment the brain tumor, the ventricles and vascular structures in the preopera-tive MR images. Moreover, an approach to automatically enhance the brain tumor contours in the iUS data was includ-ed. It consists in registering a brain tumor model with the iUS image data. To test the demonstrator, first the live 2D iUS images of a phantom were visualized in comparison with the correspond-ing slices in the preoperative CT and 3D iUS data for a given image depth. Then the depth was modified by the user. The visualization was not correct anymore. The connector tool detected the change and communicated the new depth to the navigation system which updated the visualization. The second test consisted in segmenting the object using the tool of the research platform. The segmentation was sent to the navigation system which displayed the contours on its moni-tor. A commercial neuro-navigation system was improved by several tools facilitating the communication with the US de-vice and performing the segmentation of target structures. The next step is the evaluation in the operating room.


Predicting Surgical Phases using CNN-NARX Neural Network

Nour Aldeen Jalal, Institute of Technical Medicine, Furtwangen University, Villingen-Schwenningen, Germany, e-

Mail: [email protected]

Tamer Abdulbaki Alshirbaji, Institute of Technical Medicine, Furtwangen University, Villingen-Schwenningen, Ger-

many, e-Mail: [email protected]

Knut Möller, Institute of Technical Medicine, Furtwangen University, Villingen-Schwenningen, Germany, e-Mail:

[email protected]

Online recognition of surgical phases is essential to develop systems able to effectively conceive the workflow and

communicate relevant information to human operators during surgical procedures. These systems, known as context-

aware system (CAS), are designed to assist surgeons, improve scheduling efficiency of operating rooms (ORs) and sur-

gical team and promote a greater understanding and awareness of the OR. State-of-the-art studies for recognizing surgi-

cal phases have made use of data from different sources such as videos or binary usage signals from surgical tools. In

this work, we propose a deep learning pipeline, namely a convolutional neural network (CNN) and a nonlinear auto-

regressive network with exogenous inputs (NARX), designed to predict surgical phases from laparoscopic videos. A

convolutional neural network (CNN) is used to perform the tool classification task by automatically learning visual fea-

tures from laparoscopic videos. The output of the CNN, which represents binary usage signals of surgical tools, is pro-

vided to a NARX neural network that performs a multistep-ahead predictions of surgical phases. Surgical phase predic-

tion performance of the proposed pipeline was evaluated on a dataset of 80 cholecystectomy videos (Cholec80 dataset).

Results show that the NARX model provides a good modelling of the temporal dependencies between surgical phases.

However, more input signals are needed to improve the recognition accuracy.


A Lightweight Hybrid Mock Circulation for Control Algorithms of Ventricular Assist Devices Tobias Salesch, Institute of Automatic Control, RWTH Aachen University, Germany, [email protected] Jonas Gesenhues, Institute of Automatic Control, RWTH Aachen University, Germany, [email protected] Dirk Abel, Institute of Automatic Control, RWTH Aachen University, Germany, [email protected] Before new control strategies and control algorithms for (Left) Ventricular Assist Devices (LVADs) can be deployed in-vivo it is desirable to examine these algorithms in-vitro. Suitable test benches, also called mock circulatory loop systems (MCLs), vary in use cases and design depending on their purpose. Hardware-in-the-loop (HIL) concepts use a numerical model of the cardiovascular system to calculate flow rates and pressures for a given scenario. Thus, the mechanical com-plexity reduces while a virtual representation of the plant runs in the background. HIL concepts are state of the art in the development process of LVADs. This work deals with the design and control of a new lightweight hybrid MCL concept. The focus is set to simplify in-vitro hard- and software evaluation and testing. Thus, an absolute minimal amount of actuators is used to reduce mechan-ical, electrical and controlling complexity. Pressure cylinders with a constant amount of air are connected to both sides of the LVAD representing the left ventricular and aortic pressure. For this purpose, a high dynamic fluid gear pump varies the fluid-level and the air is compressed or expanded, respectively. A reservoir delivers the required amount of fluid. A simulation environment of this concept is provided and used to proof that the concept works in principle. In this math-ematical model the air is assumed as ideal gas and the impact of the pressure difference on the gear pump’s flow is modelled as a linear function. Furthermore, first order lag elements represent the voltage to flow transmission behaviour of the gear pumps. The simulation shows that with a suitable range of both, the amount of air and the gear pumps dynamics, the pressure cylinders can be set up for aortic and left ventricle pressure. To validate these findings, further investigations with the MCL under realistic test conditions are required.


New development approach for Cyber-Physical Systems

Josep Cardona Audí, Fraunhofer IBMT, Sulzbach, Germany, [email protected] Dmitry Amelin, Fraunhofer IBMT, Sulzbach, Germany, [email protected] Roman Ruff, Fraunhofer IBMT, Sulzbach, Germany, [email protected] Networks of distributed implantable bioelectronics, wearables or stationary diagnostic equipment will increasingly be used in biomedical fields of application in the future. These interacting devices (nodes) comprise typically of components like sensors, actuators, telemetry, and energy management and can be classified as a Cyber-Physical System (CPS). Commonly these functionalities are implemented on embedded hardware with very limited resources. One of the major challenges of engineering such systems is to manage their adaptability to modified application requirements without affecting the system reliability. Current software engineering methods, such as component-based software development and adaption models, do not cover all the needs of the system developer, as these models only deal with software implementation without considering physical constraints. In this work, we propose a new type of architecture based on Cyber-Physical Components (CPC). These components are similar to software components, but they are additionally characterized by the following metric groups:

1. Functionality metrics define the basic unit of data and the interfaces of the components. This basic unit of data is being used as a measurement unit to evaluate other metrics.

2. The hardware metrics are CPU, memory, and other peripherals usage and are restricted to the context of a single node.

3. The physical metrics are energy consumption and the response time in the context of the entire system. The implementation of the CPC allows to estimate the viability of different system compositions through the complete software engineering process, even during runtime. This improves the robustness of the system, increases the efficiency of the development process and can shorten the time-to-market.


Telemetry protocol for cyber-medical systems Fabian Schiche, Hochschule München, München, Germany, [email protected] Dmitry Amelin, Fraunhofer IBMT, Sulzbach, Germany, [email protected] Josep Cardona Audí, Fraunhofer IBMT, Sulzbach, Germany, [email protected] Roman Ruff, Fraunhofer IBMT, Sulzbach, Germany, [email protected] An increasing number of stationary diagnostic equipment, wearable devices, and even implantable bioelectronics are organized as wireless network systems. These network nodes incorporate telemetry, energy management, central proces-sors and application-specific sensor/actuator units. Getting rid of wired connections has the advantage of highly flexible network structures and promotes device independence. In a network of implanted and extracorporeal devices, secure and reliable real-time communication poses one of the major technological challenges. Furthermore, the human body is a highly inhomogeneous communication medium, therefore communication technologies must be adequately robust to ex-ternal interferences. The proposed telemetry protocol for cyber-medical systems (CMTP Cyber-Medical Telemetry Protocol) is based on the concept of “Direct Diffusion”, using weighted pathfinding to define gradients data flows along. CMTP saves weights optimized for e.g. transmission delay, data rate (bandwidth), energy efficiency, as data policies. Switching routing prior-ities is as simple as changing the data’s policy. Complete independency from global network information allows localized real-time routing, resulting in very low end-to-end transmissions delays. In our tests, CMTP transmission delays have reached values up to 5 milliseconds with a data rate of 120 kbps and a total payload of 34 bytes. Besides real-time capability, fault tolerance is another limiting factor for reliable delivery of critical data packets. Ac-cording to “Direct Diffusion” data is transmitted through all available gradient links. However, the use of multiple paths provides higher reliability but increases energy consumption at the same time. To avoid this problem, it is possible to prioritize selected gradients, reducing the number of redundant data transmissions. CMTP is also able to detect faulty nodes by exchanging low-level acknowledgments and mark them as inactive. Prolonged inactivity of communication units will trigger redirection of data through the next active gradient of the same policy. If no more gradients are available, the protocol will enter a failsafe state. Nodes can broadcast their state to neighbors, reactivating gradients lost due to non-critical transmission failures, e.g. gradients lost through high interference on the transmission medium. Moreover, CMTP allows for ad-hoc node deployment (i.e. addition or removal of nodes during runtime).


Interactive Image Segmentation for Cochlea Implant Planing based on DVT Data Nathalie Killguß1, Thomas Eixelberger1, Robin Rupp², Mathias Hofer³, Daniela Franz1 and Thomas Wittenberg1

1 Fraunhofer Institute for Integrated Circuits IIS, Erlangen, Germany, [email protected] ² Universitätsklinikum Erlangen, Erlangen, Germany ³ University of Leipzig Medical Center, Leipzig, Germany Cochlea Implant (CI) planning is usually based on preoperative obtained CT data, visualizing risk structures in the petrosal bone. In the past years, Digital Volume Tomography (DVT) has become more important in the clinical routine for otology. DVT yields smaller voxel spacings, is faster to obtain and radiation is less than normal CT. Thereby DVT is perfect for surgical planning of CI interventions, but gray levels are not normalized to Hounsfield units. In this work we propose an extension of our interactive “wizard”-guided approach for segmenting middle and inner ear structures for the use with DVT data. Different filter pipelines enable the user to segment the acoustic canal, ossicles, tympanic cavity, facial nerve, chorda tympani, round window, cochlea and semicircular canals. User interaction is only required for choosing adequate seed points for the critical structures (ossicles, nerves), and selecting the correct candidate of the round window. All others are segmented automatically and users check the results and correct them, if necessary. The system renders all structures in 3D and draws them into the built-in DICOM viewer. The approach has been evaluated on six pre-operative acquired DVT datasets by an ENT expert. The available data consist of four patients with normal ear anatomy, one with a poorly ventilated tympanic cavity and one with a tympanoplasty. Results imply that the proposed approach can handle DVT quite well and it can potentially be used for interactive OR planning. Small inaccuracies in the area of the cochlea are induced by the quantization of the data. Medical students and assistant physicians can also use the segmentation within an interactive learning software. Further work will evaluate the capability of this approach with different data such as DVT of child or special anatomies. The inaccuracies of the cochlea can further be removed by smoothing the extracted model.


Volume reconstruction of the human cornea with oscillating focus scans

Lukas Kornelius, Institute for Automation and Applied Informatics, Karlsruhe Institute of Technology (KIT), Karlsruhe,


Stephan Allgeier, Institute for Automation and Applied Informatics, Karlsruhe Institute of Technology (KIT), Karlsruhe,


Sebastian Bohn, Department of Ophthalmology, Rostock University Medical Center, Rostock, Germany,

[email protected]

Klaus-Martin Reichert, Institute for Automation and Applied Informatics, Karlsruhe Institute of Technology (KIT),

Karlsruhe, Germany, [email protected]

Karsten Sperlich, Department of Ophthalmology, Rostock University Medical Center, Rostock, Germany,

[email protected]

Oliver Stachs, Department of Ophthalmology, Rostock University Medical Center, Rostock, Germany,

[email protected]

Bernd Köhler, Institute for Automation and Applied Informatics, Karlsruhe Institute of Technology (KIT), Karlsruhe,


For corneal confocal microscopy (CCM), we use the Heidelberg Retina Tomograph (HRT) and the Rostock Cornea

Module (RCM; both Heidelberg Engineering GmbH, Heidelberg, Germany). A modification of the HRT software enables

the recording of focal image stacks by continually oscillating the focus depth within up to 80 µm. To align the CCM

images for volume reconstruction we developed special-purpose image registration algorithms, which also correct the

motion induced distortions in the CCM images.

In a first approach, a method was implemented where all image pair combinations of a recorded oscillating focus series

were registered to each other. The application of this exhaustive strategy was investigated on 40 recorded focal series

with 600 images each (focus oscillation amplitude: ±25 µm, focus difference: 0.5 µm/image). As a result, less than 19%

of the image pairs yield a valid registration result, whereas in more than 81% of the pairs no corresponding image area is

detected, mostly due to differing focal depth and the low depth of field. To accelerate the registration process, the image

pairs considered for registration can be reduced by applying a configurable threshold Δzreg for their focus depth difference.

In order to experimentally determine an optimal value Δzreg,opt for this depth-based strategy, we systematically examined

the registration results for focus depth differences in the range 1 µm < Δzreg < 20 µm. We found the value Δzreg,opt = 8 µm

to be suitable for practical application. Applied to the above-mentioned focus series, this reduces the number of processed

image pairs by approximately 70% from 7,176,000 to 2,168,160 and the runtime for registration by more than a factor of

three. Although the number of successful image pair registrations also decreases by 10.5%, no loss of quality of the

reconstructed volume images is detected.

The runtime benefit increases with the oscillation amplitude. A newly developed RCM enables recording of image stacks

with oscillation amplitudes of ±250 µm. For such focal series the estimated execution time for depth-based image

registration can be reduced by a factor of > 20 compared to the exhaustive pairwise image registration strategy.


Quantitative Imaging of the Iron-Oxide Nanoparticle-Concentration for Mag-netic Drug Targeting Employing Inverse Magnetomotive Ultrasound Michael Fink, Department of Sensor Technology, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany, [email protected] Stefan Lyer, Section of Experimental Oncology and Nanomedicine, University Hospital Erlangen, Erlangen, Germany, [email protected] Christoph Alexiou, Section of Experimental Oncology and Nanomedicine, University Hospital Erlangen, Erlangen, Germany, [email protected] Helmut Ermert, Department of Sensor Technology, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany, [email protected] Magnetic Drug Targeting is a cancer treatment technique that enables a local chemotherapy. For this purpose chemotherapeutic drugs are bound to magnetic nanoparticles and are accumulated in the tumor area by means of an external magnetic field. Hereby, a well-defined particle concentration in the cancerous tissue requires monitoring of the particle accumulation. Unfortunately, classical ultrasonic pulse-echo imaging modes are not capable to display nanoparticles due to their weak backscattering. Therefore, an alternative imaging mode called Magnetomotive Ultrasound (MMUS) has been established. MMUS visualizes particle induced tissue movements, excited by an alternating magnetic field. Although MMUS enables the ultrasound based detection of tissue, perfused by magnetic nanoparticles, a quantitative representation of the particle density distribution is not possible. Therefore, we present an enhanced MMUS mode to solve this inverse problem. Inverse MMUS is capable to detect quantitatively the concentration of iron-oxide nanoparticles in biological tissue by using additional data that are idle in conventional MMUS, like the properties of the magnetic field and of the nanoparticles. Knowing the magnetic field and the properties of the nanoparticles allows to calculate the magnetic force on the particles. By means of an assumed nanoparticle distribution and by means of approximated mechanical tissue parameters, like Young’s modulus, the resulting tissue movement is calculated, which can be compared to the measured tissue shift that results from the conventional MMUS mode. The variation of the assumed particle distribution permits an iterative adjustment between calculated and measured tissue shift values. This method enables to estimate the particle distribution and thereby the local particle concentration. We have produced and applied tissue mimicking phantoms which include areas that are perfused by different concentrations of nanoparticles. As a result, the particle loaded areas could be identified employing the inverse MMUS procedure and the magnitude of nanoparticle concentration could be determined.


Non-contact Measurement of Blood Pressure during Dialysis Christian Wiede, Professur Digital- und Schaltungstechnik, Technische Universität Chemnitz, Chemnitz, Germany, [email protected] Gangolf Hirtz, Professur Digital- und Schaltungstechnik Technische Universität Chemnitz, Chemnitz, Germany, [email protected] Many people have to undergo dialysis on a daily basis because their kidneys are no longer able to clean the blood suffi-ciently. In an outpatient treatment, the patient's blood is channeld outside the body through a semi-permeable membrane in which undesirable substances are filtered out. One treatment can take several hours until the blood is sufficiently puri-fied and must be monitored by a physician. Vital parameters, which reflect the current heatlh status well, are decisive for monitoring. One of these vital parameters is the blood pressure. The conventional measurement of blood pressure using a blood pressure cuff is not suitable during dialysis because the blood flow must not be suddenly blocked. Another meas-urement method that works without contact would be of great benefit for this application. At the TU Chemnitz, this motivation led to the development of a method based on the use of a remote optical sensor. The blood pressure is first determined using a blood pressure cuff before the measurement in order to determine the individual calibration parameters for the specific person. Subsequently, the optical sensor detects a pulse wave on two different body parts on the skin. These skin regions are called region of interest (ROI). The pulse transit time can be determined by the difference in transit time (PTT) of one and the same pulse wave. Due to the linear relationship between the speed of blood flow and blood pressure, systolic blood pressure can be determined using the previously determined calibration parame-ters. In our investigations, we have examined the optimal position of the two ROIs and optimized the method for precise time measurement. The comparative measurements show that a robust determination of blood pressure is possible. In further investigations it will be clarified whether this procedure can also be transferred to other fields of application.


On estimating fractal dimensions of subviral particle motion Andreas Rausch, Technische Hochschule Mittelhessen (THM), FB Life Science Engineering (LSE), Institut für Biomedizinische Technik (IBMT), Wiesenstr. 14, 35390 Gießen, Germany, e-mail: [email protected] Thomas Schanze, Technische Hochschule Mittelhessen (THM), FB Life Science Engineering (LSE), Institut für Biomedizinische Technik (IBMT), Wiesenstr. 14, 35390 Gießen, Germany, e-mail: [email protected] In the last five years the Ebola virus caused a high death toll during several epidemics in Westafrica. Especially with the increasingly fast ongoing globalization a worldwide spread of the disease is a present danger. Thus, finding an effective medicine against hemorrhagic fever pathogens is a highly urgent task. An enoumous amount of pharmaceutical experi-ments with infected cells need to be evaluated to understand the influence of possible medicines on the subviral parti-cles. An automation of the analysation processes is needed. In previous work we presented algorithms to automatically detect and track subviral particles in fluorescence image sequences. Additionally, we showed that it is possible to char-acterise the subviral particle movement by fractal dimension estimation. In this publication we first test the fractal di-mension determination via box count on simulated fractal like trajectories of subviral particles. In contrast to theoretical fractals in a two-dimensional domain, which can have fractal dimensions between one and two, it is reasonable that real subviral particle tracks have a limited range of possible fractal dimensions. Thus, they are more likely describable as partial or constrained fractals. To get an idea about these limitations we investigate a high number of real subviral parti-cle tracks for their fractal dimensions. To avoid the influence of artifacts only particle tracks with a minimum presence of ten frames in the image sequences were analysed. The evaluation of simulated fractal sequences shows that our frac-tal dimension estimation results match the theoretical values fairly good, but there is a tendency to underestimate the true. Furthermore, the evaluation of the real subviral particle tracks show a mean fractal dimension of 𝐹𝐷 = 1.089 with a standard deviation 𝑠𝑡𝑑 = 0.142 (𝑁 = 993 𝑡𝑟𝑎𝑐𝑘𝑠). In future work other estimation algorithms should be tested and compared.


Vision-Based Depth Measurement for Laparoscopic Hyperspectral Imaging Michael Unger, Innovation Center Computer Assisted Surgery, Leipzig, Germany, [email protected] Hannes Köhler, Innovation Center Computer Assisted Surgery, Leipzig, Germany, [email protected] Nico Arnold, Innovation Center Computer Assisted Surgery, Leipzig, Germany, [email protected] Claire Chalopin, Innovation Center Computer Assisted Surgery, Leipzig, Germany, [email protected] Hyperspectral imaging (HSI) provides valuable information about tissue perfusion and pathologies. Current HSI camer-as are too large to be used in minimally invasive surgery. Future applications will include the integration of a miniatur-ized camera in the endoscope which leads to new demands for system calibration. Especially, the calibration requires a white balancing of the HSI system. This step is performed once if the distance between the examined tissue and the op-tic is fixed. Ensuring a fixed distance during laparoscopic surgery is unfeasible. Therefore, methods to measure this dis-tance are needed. In this paper, we present a vision-based approach for the estimation of depth. A digital laparoscopic camera provides videos with high resolution. Two visual markers were applied to a laparoscopic surgical instrument. The markers placed at known distances from the tip were extracted by transforming the RGB image to the HSV-space and performing threshold segmentation. By measuring the diameter of the markers and comparing them to a reference value of a known distance, the depth of the marker, and therefore the tip of the instrument can be measured. Therefore, the distance be-tween optic and object can be estimated by pointing the region of interest with the tip of the instrument. The image-based distance measurement was validated using an optical tracking system (NDI Polaris Vicra). The accuracy of the vision-based measurement was 3.32 mm ± 2.39 mm over a depth of 50 mm to 150 mm. We showed that a vision-based approach can be used to measure distances during laparoscopic interventions. The image processing techniques need to be further improved to reduce measurement errors. Currently, the surgical instrument was modified by adding visual markers. Because this approach is not suitable in a clinical environment, solutions to over-come this problem need to be investigated in the future.


Automatic image analysis system to measure wound area in vitro Adchiya Dhamodharan, Institute of Technical Medicine, Furtwangen University, Villingen-Schwenningen, Germany, [email protected] Jacquelyn Dawn Parente, Institute of Technical Medicine, Furtwangen University, Villingen-Schwenningen, Ger-many, [email protected] Sabine Hensler, Institute of Technical Medicine, Furtwangen University, Villingen-Schwenningen, Germany, [email protected] Claudia Kuhlbach, Institute of Technical Medicine, Furtwangen University, Villingen-Schwenningen, Ger-many, [email protected] Margareta M. Mueller, Institute of Technical Medicine, Furtwangen University, Villingen-Schwenningen, Ger-many, [email protected] Knut Möller, Institute of Technical Medicine, Furtwangen University, Villingen-Schwenningen, Germany, [email protected] In vitro wound area measurement tracks the rate of wound healing. This project develops and validates an automatic image analysis system to calculate wound area from digital images of an in-vitro 3D tissue model wounded with a biopsy punch. The algorithms were evaluated for repeatability, reliability, and reproducibility, and validated against a known area. Repeatability was checked through repeated measurements under repeated conditions. Reproducibility was evalu-ated using a Bland Altman plot and paired t-test. Reliability was tested using ANOVA. Reliability was validated using an image of known pixel area as control. Then, the validated image analysis system calculated wound area from digital camera and microscope images obtained from an in vitro photobiomodulation treatment experiment. A total of 48 wounded tissues were grouped into red and blue light treatment groups and untreated controls. All daily images were fed into the image analysis system to calculate wound area. The wound area (normalized by day 0) is plotted along the 2-week treatment experiment period to observe wound area in time. The absolute difference between the consequent meas-urements made under constant conditions is zero, showing that the system under study is repeatable. The reproducibility of the system is proved in terms of agreement and absence of bias between the methods of measurement using Bland Altman plot and paired t-test, respectively. Results obtained from reliability test show that the algorithms are 99% reliable. The validated image analysis system is repeatable, reliable, and reproducible. The normalised wound area plotted across treatment days show no change in wound area during the treatment period. Future work will adapt the imaging system for visualizing the reepithelization cell front marked by live dyes.


Neuronal current imaging using 3D ultra-low field MRI – preliminary results Nora Höfner1,*, Jan-Hendrik Storm1, Peter Hömmen1, Rainer Körber1 1Physikalisch-Technische Bundesanstalt, Abbestr. 2-12, 10587 Berlin, Germany *[email protected] Neuronal current imaging (NCI) aims at directly detecting the influence of weak neuronal magnetic fields on MRI signals. Utilizing the linear relationship between the Larmor frequency of 1H spins and their local surrounding magnetic field, NCI could provide an unambiguous localization and overcome the long-standing barrier of the ill-posed inverse problem in MEG source localization. Furthermore, we perform NCI in the ultra-low-field (ULF) regime (~µT) to avoid measurable susceptibility changes of haemoglobin, which places high demands on system noise and temporal stability of the meas-urement setup. The NCI setup consists of a coil system realizing the 3D Fourier gradient echo imaging sequence, which is located in a two layered magnetically shielded room. A key component of the setup is a DC-SQUID current sensor connected to a second-order gradiometer and operated in an ultra-low-noise dewar. Thus, a system noise level of ~380 aT/•Hz could be reached. In order to detect the weak neuronal magnetic fields, we record an influenced and a reference image to calculate the difference amplitude image. For testing the performance of the ULF MRI setup regarding NCI, we model a long-lasting neuronal activity with respect to its time evolution, field pattern and source depth using a current dipole within a head phantom. Keeping these variables constant, we varied the signal amplitude to determine the resolution limit of the measurement setup. At present, we achieved to detect a maximum current dipole strength of 150 nAm for an isotropic voxel size of 25³ mm³. This resolution limit is just a factor of 3 larger compared to a physiological realistic value of 50 nAm. By improving the signal-to-noise ratio by a factor of 3 the detection of neuronal currents by NCI based on ULF MRI could become possible.


Pose Estimation by using corresponding facial Landmarks in monocular Image Sequences Stefan Patzke, Research Center for BioMedical Technology, Universityof Applied Sciences and Arts, Dortmund, Ger-many, [email protected] Dominik Fromme, Research Center for BioMedical Technology, University of Applied Sciences and Arts, Dortmund, Germany, [email protected] Jörg Thiem, Research Center for BioMedical Technology, Univerity of Applied Sciences and Arts, Dortmund, Germany, [email protected] The detection and use of facial landmarks is part of a wide variety of applications, e.g. visual speech recognition, gesture recognition or pose estimation. In many cases, the use of 3D landmarks is necessary or could improve the results at least. Therefore, a 3D reconstruction may be performed if the application is restricted to a monocular camera setup. To obtain optimal results, a precise reconstruction is needed. In this paper, the 3D reconstruction will be performed by tracking facial landmarks over an image sequence. Those tracked landmarks are used as corresponding points to obtain depth information by calculating disparity between those points. Furthermore, to improve accuracy and robustness with respect to the heads orientation in particular, some additional constraints are taken into account. The accuracy of the estimated 3D poses is evaluated using a high-precision 6-axis robotic arm with a stereo camera attached to the end effector. This robot enables the simulation of varied realistic head movements with precise repititions. The stereo camera is used to generate ground truth data which is used to evaluate the algorithm. To be able to compare the ground truth data to the estimated depth, a precise landmark detection has to be assumed. Therefore, a model head with fixed facial landmarks is being used.


Feasibility test of 2D tracked Ultrasound for 3D Heart reconstruction Jens Ziegle, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany, [email protected] Axel Boese, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany, [email protected] Sandy Engelhardt, Faculty of Computer Science, Otto-von-Guericke University, Magdeburg, Germany, [email protected] Robert Kreher, Faculty of Computer Science, Otto-von-Guericke University, Magdeburg, Germany, [email protected] Thomas Groschek, University Clinic for Cardiology and Angiology, Otto-von-Guericke University, Magdeburg, Ger-many, [email protected] Rüdiger Braun-Dullaeus, University Clinic for Cardiology and Angiology, Otto-von-Guericke University, Magdeburg, Germany, [email protected] Michael Friebe, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany, [email protected] Cardiovascular procedures and diagnostic are often based on medical imaging. These datasets are usually acquired by X-Ray angiograpy, MRI, CT and US imaging that each offer different advantages in visualization of anatomy and func-tional information. US is a cost efficient imaging method with high availability, good imaging of soft tissue and real time imaging that allows acquisition of dynamic information like motion and deformation. 3D US data can be generated by special volume probes or by a combination of 2D ultrasound and tracking. But US volume imaging of the heart is challenging due to the strong motion. We propose a technology to provide 3D datasets of the moving heart by recon-struction of tracked 2D US images and a slice selection as postprocessing. For our tests we used a Piur Imaging tomo-graphic ultrasound system combined with a Siemens Acuson US device and sector probe. A proband heart was imaged in a laying position by an experienced cardiologist. Tracked swipes are acquired between the ribs to cover the heart in a longitudinal direction. These datasets were used for reconstruction with ImFusion software. A first reconstruction showed large motion artefacts due to heart movement. In a postprocessing step, image slices were sorted accordingly to the heart rhythm. This allows now reconstruction of several volumes within the heart cycle depicting the different mo-tion status. Since selection of images was done intuitively and not precisely triggered, still some artefacts are visible. The described method is promising and it will be further investigated.


Lung perfusion homogeneity during a PEEP titration from EIT measurement

Bo Gong, Institute of Technical Medicine, VS-Schwenningen, Germany, [email protected]

Sabine Krueger-Ziolek, Institute of Technical Medicine, VS-Schwenningen, Germany, Sabine.Krueger-Ziolek@hs-

furtwangen.de

Knut Moeller, Institute of Technical Medicine, VS-Schwenningen, Germany, [email protected]

Respiratory physiology consists of the interactions between lung ventilation and perfusion. Their combination essential-

ly influences the effectiveness of mechanical ventilation on the intensive care unit (ICU) patient. Electrical impedance

tomography (EIT) is a non-invasive imaging modality. EIT image represents the regional impedance changes in the

human body with a high time resolution. This allows us to monitor fast impedance changes of tissues such as those in-

duced by pulmonary perfusion.

We study the lung perfusion distribution changes on an acute respiratory distress syndrome (ARDS) patient during the

lung recruitment maneuver through a positive end-expiratory pressure (PEEP) titration. EIT measurement has been per-

formed during such a PEEP trial. A sequence of EIT images has been reconstructed. Their pixel value representing the

local impedance changes. The impedance changes on each pixel of this image sequence form a time-series. This time-

series is a superimpose of two wave formed impedance changes induced by lung ventilation and perfusion of the me-

chanically ventilated patient. These two waves formed signals are separated by a low-pass filter and a band-pass filter.

At each pixel, the amplitude of the lung perfusion wave has been determined. The collection of this amplitude value

forms an image representing the lung perfusion distribution.

In previous studies, the EIT based global inhomogeneity (GI) index has been used to quantify the tidal volume distribu-

tion. This parameter has been claimed to be highly correlated with lung recruitability. In this study, GI parameter has

been evaluated at each PEEP step for ventilation and perfusion. Initial results indicate that the homogeneity of lung per-

fusion might be increased associating with lung recruitment.






Human-sized Magnetic Particle Imaging as a Brain Perfusion Monitoring Unit Matthias Graeser, Section for Biomedical Engineering, University Medical Center Hamburg, Hamburg, Germany, ma.graeser@uke,de Florian Thieben, Section for Biomedical Engineering, University Medical Center Hamburg, Hamburg, Germany, Patryk Szwargulski, Section for Biomedical Engineering, University Medical Center Hamburg, Hamburg, Germany, Nadine Gdaniec, Section for Biomedical Engineering, University Medical Center Hamburg, Hamburg, Germany, Martin Möddel, Section for Biomedical Engineering, University Medical Center Hamburg, Hamburg, Germany, Franziska Werner, Section for Biomedical Engineering, University Medical Center Hamburg, Hamburg, Germany, Marija Boberg, Section for Biomedical Engineering, University Medical Center Hamburg, Hamburg, Germany, Peter Ludewig, Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Bernhard Gleich, Research Laboratories, Philips GmbH Innovative Technologies, Hamburg, Germany Oliver Woywode, Imaging Components, Philips Medical Systems DMC GmbH, Hamburg, Germany Dionys van de Ven, Sensing and Inspection Technologies GmbH, Huerth,Germany Oliver Weber, Philips GmbH Market DACH, Hamburg, Germany Tobias Knopp, Section for Biomedical Engineering, University Medical Center Hamburg, Hamburg, Germany, Ischaemic stroke is one of the most deadly diseases in the developed countries. In addition it is the first cause of disabil-ity. In clinical routine, brain perfusion imaging is performed as soon as possible, to distinguish the ischaemic stroke from cerebral heammorage. As both have to be treated in a very different manner, typically a native computer tomogra-phy (CT) image is taken to detect haemorrhage followed by a bolus measurement to determine the perfusion parameters like the mean-transit-time or the cerebral blood flow. After treatment, the patient has to be monitored in short time in-tervals as patients have a high risk of bleeding induced by the treatment or a restenosis of the supplying vessel. There-fore, if the patient’s status is deteriorating, the patient is transferred from the intensive care unit to the radiology to reperform imaging. Due to the critical state of the patient and the connected life supporting machines this leads to a high risk for the patient and high effort for the medical staff. In contrast to CT or magnet resonance tomography (MRT) magnetic particle imaging (MPI) can work in unshielded environments as recent developments show. In this work we present an MPI imager on a human scale, which can be mounted directly on the patient’s bed. The system is already able to cover a 72h surveillance time with one image per hour while the amount of tracer is still below the maximum tracer dose applicable for humans. In this work, we give an overview about the system and sketch a protocol how the scanner can be used as a monitoring device.


Automated alignment detection of an additively manufactured Z-frame marker to process instrument targeting signals in interventional MRI Odenbach, Robert, Department of Medical Engineering, Otto-von-Guericke University Magdeburg, Germany,

[email protected]

Parsanejad, Parisa, Department of Medical Engineering, Otto-von-Guericke University Magdeburg, Germany, [email protected]


Due to its high soft tissue contrast, Magnetic Resonance Imaging (MRI) is an advantageous imaging modality for guiding minimally invasive interventions. Usually, MRI-guided interventions (iMRI) are performed under a freehand instrument targeting approach to guide and feed the instrument (e.g. biopsy needle) along the desired trajectory. However, this tech-nique requires many iterative movements either from the interventionist or of the patient and MRI table being moved in and out of the MRI tunnel, which is cumbersome, time-consuming and expensive. To overcome these downsides, inter-ventional MRI procedures can be facilitated with potentially remotely controllable assistance systems for instrument alignment. These systems require an accurate registration and tracking of the position and orientation of the instrument. Passive fiducial marker frames (e.g. additively manufactured Z-frame marker) are capable of providing a full six-degree-of-freedom estimate of a device’s pose.

In this research, we present an automated alignment detection algorithm that is capable to track a Z-marker from screen-captured images. This approach by using screen capturing methods enables a universal application of our tracking system on each imaging system (MRI, CT). It computes the required alignment which is needed for a potentially mechanically or robotically operated assistance system to reach a pre-defined instrument trajectory.

We evaluated the algorithm´s precision by analysing the computation results of different marker alignments shown in the MR-images in comparison to our schematic gold standard images. This comparison allows the differentiation between the quality of the algorithm in relation to other error sources (e.g. MR-imaging quality, image capturing errors, setup alignment errors). Our combined setup, that consists of the additively manufactured Z-frame marker, a micropositionable alignment system and the related detection algorithm, offers a fast, simple, independent and accurate automated instru-ment targeting for iMRI. For future work, we plan to conduct phantom targeting tests in a clinical environment.


Remotely controllable phantom rotation system for ultra-high field MRI to improve Cross-Calibration

Thoma, Niklas, Department of Mechanical Engineering, Otto-von-Guericke University Magdeburg, Germany, [email protected]

Odenbach, Robert, Department of Medical Engineering, Otto-von-Guericke University Magdeburg, Germany, [email protected]

Mattern, Hendrik, Department of Biomedical Magnetic Resonance, Otto-von-Guericke University Magdeburg, Germany, [email protected]


Magnetic resonance imaging (MRI) is frequently used for non-invasive neuroimaging. At ultra-high field, the available signal-to-noise ratio enables MR images with up to 250 μm isotropic voxel size. At this high resolution even unintentional small head motions can degrade the image quality.

Optical tracking systems, such as the Moiré Phase Tracking (MPT) system, can be used to correct motion prospectively. Thereto one MRI-safe camera is mounted in the MRI bore to detect motion by tracking a marker which is rigidly attached on the subject’s head. To enable prospective updates within the imaging volume, and therefore to correct motion from the subject, the motion estimates need to be transformed into the scanner coordinate system. The process of finding the transformation between both coordinate systems is called cross-calibration and is essential for the overall motion correction performance. For the cross-calibration, a MR-visible phantom with an attached MPT-marker is imaged in multiple specific orientations. To reduce cross-calibration errors, it is essential to position the phantom precisely. Due to the long bore of ultra-high field systems (> 3 m), it cannot be moved by a technician who is leaning inside the scanner bore. Thus, to rotate the phantom after each image acquisition either a technician has to operate it from inside the bore, which is suboptimal due to safety concerns, or the table must be moved in and out of the scanner, which is suboptimal due to potential repositioning errors.

To improve the current cross-calibration procedure, we have developed an MR-safe phantom rotation system, which can be controlled remotely and precisely from outside the MRI-bore. Even for ultra-high field imaging, the rotation system is fully MRI-compatible. Initial tests were performed at a 7T whole-body MR system and have proven the benefit of our rotation system: the calibration procedure was 26.8% faster during an overall better calibration performance. For future work, the system will be evaluated in multiple MR-sites.


Probabilistic Estimation of Human Interaction Needs in Context of a Robotic As-sistance in Geriatrics

Patrick Philipp, Vision and Fusion Laboratory IES, Karlsruhe Institute of Technology KIT, Karlsruhe, Germany,

[email protected] Marie Bommersheim, Fraunhofer Institute Optronics, System Technologies and Image Exploitation IOSB, Karlsruhe,

Germany, [email protected] Sebastian Robert, Fraunhofer Institute Optronics, System Technologies and Image Exploitation IOSB, Karlsruhe, Ger-

many, [email protected] Jürgen Beyerer, Fraunhofer Institute Optronics, System Technologies and Image Exploitation IOSB, Karlsruhe, Germany,

[email protected], Jürgen Beyerer, Vision and Fusion Laboratory IES, Karlsruhe Institute of Technology KIT, Karlsruhe, Germany,

[email protected]

The key purpose of assistance robots is to help people coping with work-related or everyday tasks. To ensure an intuitive

and effective support by an assistance robot, its expectation conform behaviour is essential. In particular, when using

assistance robots in geriatrics to assist elderly patients, special attention to the human-robot interaction should be paid.

Assistance by the robot should only be offered to the patient when it is needed. Therefore, the continuous estimation of

the patient’s need for interaction is of particular importance. For enabling suitable models to estimate this need, we elab-

orate the use of Bayesian Networks.

Bayesian Networks are well suited for this specific use case, since the probability of the patient’s need for interaction can

be calculated by successively adding observation values derived from the robots environmental sensors through time.

Thereby, fragmentary values and, inter alia, uncertainty originating from pre-processing algorithms are taken into account.

Furthermore, expert knowledge of the underlying process can be incorporated directly, tackling the challenge of the lack

of training data and thus differing from models such as common artificial neural networks.

In our approach, the root node of the Bayesian Network represents the need for interaction. Child nodes represent obser-

vations, e.g. activities, such as whether the person is standing, walking or waving. Moreover, it is taken into account what

the person's attention is focused on, e.g., on the robot, on specific objects or on another person. To initialize the Bayesian

Network, we incorporate expert knowledge by estimating the probability of a person performing a certain activity while

having or not having the need for interaction. With the model parameterized in this way and using Bayesian inference,

we are then able to determine the probability of patients’ needs for interaction. The analysis of our results seems promis-

ing, yielding a robust and practical approach.












Development of an extraction method for microplastics from biological materials and fast prognosis of contamination based on autofluorescence. Adrian Monteleone, Lena Brandau, Andreas Fath, Folker Wenzel Medical and Life Sciences, Furtwangen University, Villingen-Schwenningen, Germany

Since the beginning of industrial production in 1950, plastic production has continued to grow strongly worldwide and is now at 335 million tonnes in the year 2016. From these very high production volumes ever larger quantities are found in the environment. There the plastics degradate to microplasticity and spread ubiquitously in the world. The present work deals with the possible uptake of microplastic particles in human organisms. For the detection of these plastic particles, an extraction method was developed and validated. Biological materials consist of human blood (healthy volunteers, n = 5) and different tissues of pigs and cattles. Various lysis solutions were tested for degradation efficiency of biological material and for effects on the plastics. The mass loss, surfaces and structure variations as well as the physiochemical spectrum of the material were observed after treatment by electron microscopy (EM), Fluorescent microscope and Fourier transform infrared spectrometry (FTIR). The different plastic types as polyamides (PA), polycarbonate (PC), polyethylene (PE), polypropylene (PP), polystyrene (PS), polyvinyl chloride (PVC) could be clearly differentiated and identified by FTIR. Regarding the surface control, especially PVC showed detectable alterations: After extraction an irregular surface structure caused by protuberances or bubbles could be observed. However, instead of these alterations an equivalent count

of plastic particles was found in correlation to the applied plastic amount (recovery rate overall was 99,35 0,43%).). Increasing the intensity of autofluorescence by means of temperature treatment makes the particles visible on the membranes, which can be counted automatically by the computer program ImageJ. The autofluorescence can be used for an initially and fast prognosis of microplastic contamination on the membranes. The applied method can be used for plastic extractions from human or animal tissues without remarkable effects on the plastics.


Universal LIMS based platform for the automated processing of cell-based as-says Florian Schmieder, Christoph Polk, Felix Gottlöber, Patick Schöps, Fraunhofer IWS Dresden, Dresden, Germany Ronny Deuse, Aline Jede, Thomas Petzold, Qualitype GmbH, Dresden, Germany Frank Sonntag, Fraunhofer IWS Dresden, Dresden, Germany Nowadays, cell-based assays are an elementary tool for diagnostics, animal-free substance testing and basic research. Depending on the application, the spectrum ranges from simple static cell cultures in microtiter plates to dynamic co-cultures in complex micro physiological systems (organ-on-a-chip). Depending on the complexity of the assay, numer-ous working steps have to be performed and the data from different analysis systems have to be processed, combined and documented. A universal platform has been developed for the automated handling of cell-based assays, which combines a laboratory information management system (LIMS) with a laboratory execution system (LES), a universal laboratory automation platform and established laboratory equipment. The LIMS handles the administration of all laboratory-relevant infor-mation, the planning, control and monitoring of laboratory processes, as well as the direct and qualified processing of raw data. Using a kidney-on-a-chip system as an example, the realization of complex cell-based assays for the animal-free charac-terization of the toxicity of different antibiotics will be demonstrated. In the kidney-on-a-chip system the artificial proximal tubular barrier was formed by seeding human immortalized prox-imal tubule cells (RPTEC) and human blood outgrowth endothelial cells (BOEC) on ThinCert™ membranes. Transepi-thelial electrical resistance (TEER) was measured daily to evaluate the barrier function of the cellular layers. Fluid handling and TEER measurements were performed using a laboratory automation platform that communicates directly with the LIMS. The LES supports laboratory assistants in executing the manual handling steps of the experi-ments.


Artifact Reducing Medical Stimulator Early Evoked Potentials Karin H. Somerlik-Fuchs, inomed Medizintechnik GmbH, Emmendingen, Germany, [email protected] Michael Tomilov, inomed Medizintechnik GmbH, Emmendingen, Germany, [email protected] Celine Wegner, inomed Medizintechnik GmbH, Emmendingen, Germany, [email protected] Thilo B. Krueger, inomed Medizintechnik GmbH, Emmendingen, Germany, [email protected] Electrical stimulation causes electrical artefacts in simultaneous recordings. If the recording site is quite close to the stimulation site, physiologic responses might be masked by these superimposed artefacts. A basic paradigm of electrical stimulation is to prevent disadvantagous electrochemical processes at the electrode surface due to stimulation pulses, so they need to be charged balanced. Typically this charge balance is executed immediately after the stimulation pulse, thus resulting in a sharp electric event, which causes large artefacts in the electric recording. We therefore implemented a delayed charge equalisation, performed after an adjustable time which has to be selected longer than the expected latency of the physiologic answer. Thereby the stimulation artefact, masking early signal re-sponses can strongly be reduced and a second artefact due to charge equalisation can be timed user-defined as not to influence the signal interpretation. We now integrated this charge-balance delay paradigm into our medical approved neuromonitoring device. This offers us the possibility to monitor so far non-recordable responses, like cortico-bulbar motor evoked potentials in high quality.


Identification of factors influencing insertion characteristics of cochlear implant electrode carriers Silke Hügl*, Department of Otolaryngology and Cluster of Excellence EXC 2177/1 “Hearing4all”, Hannover Medical School, Hanover, Germany, [email protected] Nina Aldag*, Department of Otolaryngology and Cluster of Excellence EXC 2177/1 “Hearing4all”, Hannover Medical School, Hanover, Germany; Institute for Multiphase Processes, Leibniz University Hannover, Hanover, Germany; [email protected] Alexander Becker, Institute for Multiphase Processes, Leibniz University Hannover, Hanover, Germany, [email protected] Thomas Lenarz, Department of Otolaryngology and Cluster of Excellence EXC 2177/1 “Hearing4all”, Hannover Med-ical School, Hanover, Germany, [email protected] Birgit Glasmacher, Institute for Multiphase Processes, Leibniz University Hannover, Hanover, Germany, glasmacher@imp. uni-hannover.de Thomas S. Rau, Department of Otolaryngology and Cluster of Excellence EXC 2177/1 “Hearing4all”, Hannover Med-ical School, Hanover, Germany, [email protected] * authors contributed equally Insertion studies in artificial cochlea models (aCM) are used for the analysis of insertion characteristics of different cochlear implant electrode carrier (EA) designs by measuring insertion forces. These forces are summed forces due to their measuring position which is directly underneath the aCM. The current hypothesis is that they include dynamic friction forces during the insertion process and the forces needed to bend an initially straight EA into the curved form of the aCM. For the purposes of the present study, straight EA substitutes with a constant diameter of 0.7 mm and 20.5 mm intra-cochlear length were fabricated out of silicone in two versions with different stiffness due to a variation of embedded wires. The EA substitutes were inserted into three different models made of polytetrafluorethylene (PTFE), each model showing only one constant radius. Three different insertion speeds were used (0.11 / 0.4 / 1.6 mm/s) with an automated insertion test bench. For each parameter combination (curvature, speed, stiffness) twelve insertions were conducted. Measurements included six full insertions and six paused insertions. Paused insertions include a ten second paused time interval without further insertion movement each five millimetres. Measurements showed that dynamic and static components of the measured summed forces can be identified. Dynamic force components increase with increased insertion speeds and also with increased stiffness of the EA substitutes. Both force components decrease with larger radius of the PTFE model. After the insertion, the EA substitutes showed a curved shape, which indicates a plastic deformation of the embedded wires through the insertion into the curved mod-els. The results can be used for further research on an analytical model to predict the insertions forces of a specific combina-tion of selected parameters as insertion speed and type of EA, combined with given factors as cochlear geometry.


Characterization of a measurement setup for thermomechanical investigation of curved shape memory alloy actuators Nuha Suzaly*, Department of Otolaryngology, Hannover Medical School, Hanover, Germany, [email protected] Marie Christina Keller*, Department of Otolaryngology, Hannover Medical School, Hanover, Germany; Institut für Werkstoffkunde (Materials Science), Leibniz Universität Hannover, Garbsen, Germany, [email protected] Silke Hügl, Department of Otolaryngology and Cluster of Excellence EXC 2177/1 “Hearing4all”, Hannover Medical School, Hanover, Germany, [email protected] Elvira Karsten, Institut für Werkstoffkunde (Materials Science), Leibniz Universität Hannover, Garbsen, Germany, [email protected] Thomas Lenarz, Department of Otolaryngology and Cluster of Excellence EXC 2177/1 “Hearing4all”, Hannover Medical School, Hanover, Germany, [email protected] Thomas S. Rau, Department of Otolaryngology and Cluster of Excellence EXC 2177/1 “Hearing4all”, Hannover Medical School, Hanover, Germany, [email protected] *authors contributed equally The bend and free recovery (BFR) test according to ASTM F2082 is a standard method to determine the transition temperatures of nitinol shape memory alloys (SMAs). Unfortunately, this standard method is limited to SMA wires with a trained shape that is straight and is thus not suitable for the thermomechanical characterization of curved nitinol SMA wires which should in future serve as actuators in cochlear implants. For curved SMA wires, the active austenite finish (Af) temperature determines the completion of the shape recovery upon heating. For the determination of their active Af temperature, a modified BFR measurement setup was developed. The focus of this study was to investigate the influence of the heating rate used on the observed active Af temperature and to verify the repeatability of the measurement setup. A parametric study of the measurement setup was carried out. A microscope camera was used to record the shape change of previously straightened wires by recording 20 images per Kelvin between 5°C and 45°C. Five different heating rates were employed: 0.25 K/min, 0.33 K/min, 0.5 K/min, 1 K/min as well as an unregulated maximum heating rate achievable of approximately 1.5 K/min. Furthermore, a test-retest reliability was performed with three wires by repeating the experiment ten times with each wire. The results of this study revealed no influence of the heating rate on the thermomechanical response of the wires. Through this study, a regulated heating rate of 1 K/min was decided to be used for future investigations which reduces the duration of the measurement from four hours to less than an hour. The values obtained from each wire through the test-retest reliability investigation showed a standard deviation of 1.81 K, 0.90 K and 0.51 K respectively. Therefore, the repeatability of the measurements using the developed method was able to be verified.


Protective role of vitamin E to reduce oxidative degradation of soft implantable polyurethanes: In vitro study Larysa Kutuzova, Reutlingen University, Reutlingen, Germany, [email protected] Olga Molentor, Reutlingen University, Reutlingen, Germany, [email protected] Feng Wu, Reutlingen University, Reutlingen, Germany Wenyao Song, Reutlingen University, Reutlingen, Germany Andreas Kandelbauer, Reutlingen University, Reutlingen, Germany, [email protected] Günter Lorenz, Reutlingen University, Reutlingen, Germany, [email protected] The Vitamin E (VE) additives are important in treating osteoarthritis inclusive cartilage regeneration due to their antiox-idant and anti-inflammatory properties [1]. The current research focuses on the ability of biological antioxidant VE (alpha-tocopherol isoform) to reduce or minimize oxidative degradation of soft implantable polyurethane (PU) elastomers after 5 months in vitro. Structural design of the tested bio-stable PU-based formulations (Fig.1) as well as their synthesis and processing tech-niques were the same as those described previously in [2-3]. The high molecular weight block-co-polymers with properly controlled molecular structure were produced using in situ real time analytical monitoring of every step during the polymerization process. The spectroscopic, calorimetric and rheological in line control provided the morphological (i.e. mechanical) reproducibility of the medical product on the preparative scale. Effect of the oxidation storage media on the morphology of the segmented PUs was evaluated by mechanical softening, crystallization and melting behavior of both soft and hard segments (SS, HS) using calorimetric and dynamic-mechanical analysis (DSC, DMA). Bulk mechanic properties of the potential implant materials during ageing were predicted from comprehensive mechanical testing of the biomaterials under tension and compression cyclic loads. Structural changes due to the rearrangement of the H-bonds and crosslinking of SS resulted in changes in crystallinity of both segmental phases. They were studied by spectroscopic methods. 5-months in vitro data suggest that the optimized siloxane-polycar-bonate-urethane formulations have sufficient resistance against degradation to be suitable materials for chondral long-term bio-stable implants. Most importantly, the positive effect of the incorporating VE (0.5-1.0% w/w) as bio-antioxidant and lubricant on the biostability was observed for all PU-types. VE-additives protected the surface layer from erosion and cracking during chemical oxidation in vitro as well as from thermal oxidation during extrusion reprocessing.


Preparation of electrospun nanofiber tubular scaffolds as carriers for rhBMP-2 and rhVEGF165 to enhance bone induction Andrea Sowislok1, Eva Dohle4, Goerg H. Michler2, Sven Henning3, Shahram Ghnaati4, C. James Kirkpatrick4, Herbert P. Jennissen1, 1Institut für Physiologische Chemie und Klink für Orthopädie & Unfallchirurgie, Universität Duisburg-Essen, D-45122 Essen, 2IPW e.V., D-06217 Merseburg, 3Fraunhofer IMWS, D-06120 Halle/S, 4Klinik für Mund-, Kiefer-und Plastische Gesichtschirurgie, Universitätsklinikum, D-60596 Frankfurt am Main (KGU) Due to the refractoriness of human bone tissues towards their own rhBMP‐2 and the therapy of patients with unphysiological dosages, resulting in serious side-effects, the development of multimodal biohybrid scaffolds by elec-trospinning for the sequential release of growth factors was addressed. Proteins can either be encapsulated as inclusates or adsorbed on the fiber surface as adsorbates. For electrospinning 320 mg poly(D,L-lactide) (PDLLA) was dissolved in 80% hexafluoro-2-isopropanol (HFIP) for preparing non-woven 2D nanofiber fleece- or 3D tubular-scaffolds with an inner diameter of 3 mm on a custom-made electrospinning instrument by depositing the fibers either on a fine patterned steel wire grid or on a rotating mandrel re-spectively. The fiber geometry was optimized by using a focused electrospinning method. Temperature, spinning volt-age and the rotational speed of the mandrel were adjusted to avoid bending instabilities. Scanning electron microscopy (SEM) was performed to image the fiber structure on the surfaces both in the outer layer and the inner layer of the tubes. The mean fiber diameter of the fleece scaffolds was 225-295 nm. In the tubes the fiber diameters showed a mon-omodal distribution and a mean fiber diameter of 700-1000 nm. Work is underway to reduce the fiber diameter to a mean of 300 nm. For optimizing the mechanical stability 3 mm tubes of varying wall thickness corresponding to 9-15 mg/cm tube were prepared. The PDLLA nanofiber fleeces carrying adsorbates of VEGF or BMP-2 were tested in co-culture of primary osteoblasts and endothelial cells and shown to be non-toxic. In addition, they led to the activation of microvessel formation as shown for in vitro bone healing models. In the next step biohybrid rings prepared from the tubular scaffolds will be test-ed in an osseous critical size defect model in vivo. (supported by DFG KI 601/9-3, JE 84/15-3, MI 358/37-3)


Enhancing the biocompatibility of silicone-polycarbonate urethane based im-plant materials Kiriaki Athanasopulu, Reutlingen University, Reutlingen, Germany, [email protected] Larysa Kutuzova, Reutlingen University, Reutlingen, Germany, [email protected] Joana Mirjam Thiel, Reutlingen University, Reutlingen, Germany Günter Lorenz, Reutlingen University, Reutlingen, Germany, [email protected] Ralf Kemkemer, Reutlingen University, Reutlingen, Germany & Max Planck Institute for Medical Research, Heidelberg, [email protected] Enhancing the biocompatibility and performance of implantable polymer materials is one of the key challenges in bio-materials engineering and regenerative medicine [1, 2]. For chondral implants, for example, the development of materials with improved adhesion of chondrocytes, facilitating their growth while keeping their phenotype, are crucial for various joint regeneration approaches[3]. Aims of this work are (i) to modify the surface of soft biostable polyurethan-based model implants (TPCU and SiTPCU) with high-molecular weight hyaluronic acid (HA) using an optimized multistep strategy of immobilization, and (ii) to evaluate the cytotoxicity of the materials, and (iii) to test bioactivity of TPCU modified biomaterials with bioactive surface in vitro. Synthesis, structural design and mechanical properties of the tested bio-stable TPCU-based formulations were described in previous study [4-5]. The processable thermoplastic polyurethane elastomers are block-copolymers with systematically varied soft and hard segments. The results of the cytotoxitity studies show no cytotoxic potential of the TPCUs. The HA-bioactive molecules (Mw = 700 kDa) were immobilized onto the polyurethane surface of the implantable mate-rials via polyethylenimine PEI spacers. The successful modification was confirmed by FTIR as well as by contact angle measurements. The surface density of the immobilized HA was quantified by using a modified Sandwich Elisa Assay. Highly functionalized TPU-HA materials were tested in vitro with porcine chondrocytes and demonstrated the notably superior bioactivity compared to other systems. In addition, the multistep strategy of surface modification by HA suggests that the surfaces may facilitate low bacterial and platelet adhesion as well as enzymatic degradation.






Characterization of Atrial Septal Defect Occluders by right and left atrial pull-out forces

Markus Brudsche1C, Bruno Ismer1 and Nikolaus A. Haas2 1Peter Osypka Institute for Pacing and Ablation at Offenburg University of Applied Sciences, Germany

2Department of Pediatric Cardiology and Intensive Care, Ludwig Maximilians University Munich, Germany CCorresponding author: [email protected]

In case of the therapeutical closure of Atrial Septal Defects (ASD), occluders made of the shape memory alloy Nitinol are commonly used. Until now, standard parameters are missing defining the mechanical properties of these implants. This hampers both, their comparability and the patient individually selection. Therefore, special measuring setup was developed to determine mechanical properties of ASD occluders. Pull-out forces were examined on the Occlutech Figulla Flex II 29ASD12 and the AGA Amplatzer 9-ASD-012 Septal Occluder. ASDs were simulated by 3D-printed, flexible septal models. Central pull-out forces were measured for the left and right atrial side at room temperature in air and in isotonic saline solution with a temperature of 37° C. Pull-out forces in saline solution were found to be significant (p < 0.01) lower than in air. This can be explained by decreased friction. Comparing the tug forces which are needed to pull out the implants at the left atrial side, it takes significant (p< 0.01) more force to extract the Occlutech occluders in both environments. Comparing the pull-out forces of the two implants on the right atrial side in air, the differences are not significant. But in isotonic saline solution it requires significant (p< 0.01) more force to extract the AGA occluder. We explain these differences with the slightly different shapes. The AGA occluder for example has a hub on both sides, the Occlutech occluder only on the right atrial side. Our findings demonstrate that different forces are needed to pull out ASD occluders from the left and right atrial side. Respecting the pressure differences in the atria, both left and right pull-out forces in various environments combined with the manufacturers tolerances could be standard parameters allowing comparison of different makes of occluders. Its differences should be individually considered in selecting and by implanting occluders.


Development of an in vitro test procedure for the characterization of left atrial appendage occluder devices. Finja Borowski, Institute for ImpantatTechnologie and Biomaterials e.V., Friedrich-Barnewitz-Str. 4, 18119 Rostock-Warnemünde, Germany, e-mail: [email protected] Sebastian Kaule, Institute for ImpantatTechnologie and Biomaterials e.V., Friedrich-Barnewitz-Str. 4, 18119 Rostock-Warnemünde, Germany Stefan Siewert, Institute for ImpantatTechnologie and Biomaterials e.V., Friedrich-Barnewitz-Str. 4, 18119 Rostock-Warnemünde, Germany Niels Grabow, Institute for Biomedical Engineering, Rostock University Medical Center, Friedrich-Barnewitz-Str. 4, 18119 Rostock-Warnemünde, Germany Klaus-Peter Schmitz, Institute for Biomedical Engineering, Rostock University Medical Center, Friedrich-Barnewitz-Str. 4, 18119 Rostock-Warnemünde, Germany Michael Stiehm, Institute for ImpantatTechnologie and Biomaterials e.V., Friedrich-Barnewitz-Str. 4, 18119 Rostock-Warnemünde, Germany The implantation of a left atrial appendage occluder (LAAO) is an emerging therapy for treating patients having a con-traindication to oral anticoagulation and suffer from atrial fibrillation. The LAAO provides a reduction of the potential risk of strokes by thromboembolism. Currently, only a few CE-approved devices are available on the market and the number of clinical trials is comparatively low. Furthermore, there is currently no standardized test method available for testing the functionality of the occluder, especially for testing safe anchorage. Therefore, the aim of this study is to es-tablish an in vitro test method to prove anchorage mechanism and protective affect of LAAO devices and prototypes against thromboembolism under physiological conditions. A standardized technical and fully parameterized silicone model of a left atrial appendage (LAA), based on studies of different morphologies and sizes, was invented. The devel-oped LAA model was mounted onto the left atrial chamber of the ViVitro pulse duplicator system (ViVitro Labs, Cana-da) to simulate physiological hemodynamic conditions. The test was performed using the Watchman device (Boston Scientific, USA; size: 31 mm). The inner implantation diameter of the LAA model was designed according to a target compression of 10% for the Watchman in the implanted configuration. Furthermore, thrombus-like particles (n=150, d=1,7±0,05 mm) were added to the LAA model to represent the flushing of thrombi out of the LAA after device im-plantation. Within several cycles it was confirmed that no particles were washed out of the LAA model with the im-plantet occluder leading to a full protective affect. It could also be shown that the occluder is firmly anchored in the LAA. Pressure measurements with probes in the left atrium and in the LAA distal to the occluder could also show that the occluder has no influence on the pressure conditions in the LAA.


Support function of self-expanding nitinol stents – are radial resistive force and

crush resistance comparable?

Christoph Brandt-Wunderlich, Institute for ImplantTechnology and Biomaterials e.V., Rostock-Warnemuende, Ger-

many, e-Mail: [email protected],

Wolfram Schmidt, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock-Warnemuende,

Germany, e-Mail: [email protected],

Stefan Siewert, Institute for ImplantTechnology and Biomaterials e.V., Rostock-Warnemuende, Germany,

e-Mail: [email protected]

Reimer Andresen, Institute of Diagnostic and Interventional Radiology / Neuroradiology, Westkuesten-Klinikum

Heide, Academic Teaching Hospital of the Universities of Kiel, Luebeck and Hamburg, Heide, Germany,

e-Mail: [email protected]

Niels Grabow, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock-Warnemuende,

Germany, e-Mail: [email protected]

Klaus-Peter Schmitz: Institute for ImplantTechnology and Biomaterials e.V. and Institute for Biomedical Engineering,

Rostock University Medical Center, Rostock-Warnemuende, Germany, e-Mail: [email protected]

The main task of any vascular stent is the mechanical support the re-opened vessel. This support function may be quan-

tified by the compressive properties of the stent in radial outer loading conditions. Different test methods are standard-

ized and are accepted to provide relevant data. The aim of this study was to evaluate two test methods for the investiga-

tion of the compressive properties of self-expanding stents.

Self-expanding nitinol stents with a nominal diameter and length of 6.0 x 80 mm (Cordis S.M.A.R.T Control, GORE

TIGRIS, Boston Scientific Innova, Abbott Absolute Pro, Medtronic Complete SE, BIOTRONIK Astron Pulsar) were

investigated. The crush resistance was measured by means of parallel plates and a universal testing machine (Zwick-

Roell, Ulm, Germany) equipped with a 100 N load cell. The test samples were compressed from the expanded state to a

minimum distance of 3 mm between the parallel plates. Radial force measurements were conducted using a segmented

head testing machine (Blockwise, Tempe, USA) from the expanded state to a minimum diameter of 3 mm. Both meas-

urements were conducted at 37 °C and a cross head speed of 5 mm/min. All measured forces were normalized to the

nominal stent length of 80 mm.

Stents with a high crush resistance (0.061 – 0.078 N/mm for Complete SE, TIGRIS, Innova and S.M.A.R.T. Control),

show also high radial resistive forces (0.885 – 0.915 N/mm), and the stent with low crush resistance (0.037 N/mm for

Astron Pulsar) revealed a low radial resistive force (0.300 N/mm). However, due to design differences the Absolute Pro

showed a comparable crush resistance (0.058 N/mm) to the TIGRIS, Innova and S.M.A.R.T. Control stents but revealed

only about 45% of their radial resistive force (0.407 N/mm).

The different behaviour is based on the different loading mechanisms. Since both loads may apply in vasculature, both

test methods should be considered to describe the compressive properties of self-expanding stents.


Non-destructive analysis of drug content in polymer coatings with Raman spec-troscopy Thomas Reske, Institute for ImplantTechnology and Biomaterials e.V., Rostock, Germany, [email protected] Katharina Wulf, Institute for Biomedical Engineering, University Medical Center Rostock, Rostock, Germany, [email protected] Thomas Eickner, Institute for Biomedical Engineering, University Medical Center Rostock, Rostock, Germany, [email protected] Niels Grabow Institute for Biomedical Engineering, University Medical Center Rostock, Rostock, Germany, [email protected] Klaus-Peter Schmitz, Institute for Biomedical Engineering, University Medical Center Rostock, Germany and Institute for ImplantTechnology and Biomaterials e.V., Rostock, Germany, [email protected] Stefan Siewert, Institute for ImplantTechnology and Biomaterials e.V., Rostock, Germany, [email protected] A growing number of implantable medical devices is being equipped with drugs in an attempt to improve implant/host interaction, such as drug-eluting stents or drug coated balloons in the field of cardiovascular intervention. The analysis of device drug content typically occurs by means of chromatographic methods such as high performance liquid chroma-tography (HPLC) or liquid chromatography–mass spectrometry (LCMS). These approved methods are particularly fast and cost-efficient, and they are ubiquitous in chemical-analytical laboratories. However, these quantitative methods ne-cessitate the drug being eluted, which is a destructive process. A novel alternative to these well-established methods is the Raman spectroscopy, which is fast and cost-efficient, as well. Additionally, it offers the advantage of non-destructive analysis and sample preparation is unnecessary. Within our investigation we were able to use the Raman spectroscopy for the qualitative and quantitative analysis of dexame-thasone (DMS), a glucocorticoid, incorporated in a silicone matrix. The investigation occurred in a rectangular area on the sample surface. The required number of measuring points (spectra) was determined. Calibration was performed with samples containing different amounts of DMS. The evaluation of Raman spectra is based on the analysis of the peak areas of the bands at 795 rel. cm-1 and 1663 rel. cm-1. Remarkably, next to a precise overview of DMS distribution, an exact and reproducible quantification of incorporated DMS could be obtained.


Influence of leaflet geometry on hydrodynamic performance of transcatheter aortic valve prostheses Sebastian Kaule, Institute for ImplantTechnology and Biomaterials e.V., Rostock-Warnemünde, Germany, [email protected]; Sylvia Pfensig, Institute for ImplantTechnology and Biomaterials e.V., Rostock-Warnemünde, Germany, [email protected]; Stefanie Kohse, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock-Warnemünde, Germany, [email protected]; Stefan Siewert, Institute for ImplantTechnology and Biomaterials e.V., Rostock-Warnemünde, Germany, [email protected]; Niels Grabow, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock-Warnemünde, Ger-many, [email protected]; Klaus-Peter Schmitz, Institute for ImplantTechnology and Biomaterials e.V. and Institute for Biomedical Engineering, Rostock University Medical Center, Rostock-Warnemünde, Germany, [email protected] Michael Stiehm, Institute for ImplantTechnology and Biomaterials e.V., Rostock-Warnemünde, Germany, [email protected] The implantation of transcatheter aortic valve prostheses (TAVP) for therapy of aortic stenosis shows more and more clinically non-inferiority results compared to surgical valve replacement in intermediate and low risk patients. Com-monly clinically used TAVP are manufactured from chemically fixed xenograft leaflet material, e.g. bovine or porcine pericardium. While the clinical use of TAVP currently extends, challenges concerning valve durability and leaflet calci-fication have to be addressed. In this regard, artificial leaflet materials represent a promising option for next generation of TAVP. As a first step for the development of TAVP from polymeric nonwoven, the aim of this study was to determine the in-fluence of leaflet geometry on hydrodynamic performance of TAVP prototypes. Based on a parametric model of the valve leaflets, we varied the curvature of the belly line forming the leaflet coaptation area from an initial, quite concave, leaflet geometry with a value of 0.5° to an almost straight geometry for the leaflets with a value 0.15°. Manufacturing of TAVP prototypes was conducted by means of electrospinning technique with a polycarbonate based silicone elastomer. Hydrodynamic characterization according to ISO 5840-3 standards was performed using a pulse duplicator system with a heart rate of 70 BPM, systolic duration of 35%, mean aortic pressure of 100 mmHg and a stroke volume of 96 ml. Cardiac Output as well as mean transaortic pressure gradient, closing volume, leakage volume and regurgitation were measured to compare the different leaflet geometries. To summarize, the curvature of the leaflets’ belly has a crucial impact on TAVP hydrodynamics under physiological test conditions. In particular, the opening and closing behaviour is strongly influenced by a steeper curvature leading to larger closing volumes and higher regurgitant fractions. Further studies are planned to identify an optimum with respect to leaflet material selection, leaflet geometry and hydrodynamic properties of TAVP.


Numerical simulation of the functionality of a stent structure for venous valve prostheses Julia Schubert, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock-Warnemünde, Germany, [email protected] Kerstin Schümann, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock-Warnemünde, Germany, [email protected] Michael Stiehm, Institute for ImplantTechnology and Biomaterials e.V., Rostock-Warnemünde, Germany, [email protected] Sylvia Pfensig, Institute for ImplantTechnology and Biomaterials e.V., Rostock-Warnemünde, Germany, [email protected] Sabine Kischkel, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock-Warnemünde, Germany, [email protected] Jonas Keiler, Department of Anatomy, Rostock University Medical Center, Rostock, Germany, [email protected] Andreas Wree, Department of Anatomy, Rostock University Medical Center, Rostock, Germany, [email protected] Wolfram Schmidt, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock-Warnemünde, Germany, [email protected] Klaus-Peter Schmitz, Institute for ImplantTechnology and Biomaterials e.V., Rostock-Warnemünde, Germany, [email protected] Niels Grabow, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock-Warnemünde, Germany, [email protected] Chronic venous insufficiency (CVI) is a common disease characterized by impaired venous drainage leading to conges-tion in the lower limbs. The therapy of CVI is often limited to symptomatic treatment. Currently, there are no artificial or biological venous valve prostheses commercially available. Previous minimally invasive design concepts failed to achieve sufficient long term results in animal or in vitro studies. Requirements of a prosthesis include durability, secure anchoring, valve opening and closing at minimal pressure difference, prevention of reflux at high pressure, as well as minimum flow stagnation areas. The aim was to implement structural numerical simulation of clinically relevant loading cases for minimally invasive implantable venous valve prostheses. A bicuspid valve design was choosen as it showed superior results compared to tricuspid valves in previous studies. The self-expanding support structure was developed by using diamond-shaped ele-ments in order to simplify first simulations. Using finite-element analysis (FEA), various loading cases including ex-pansion and crimping of the stent structure and the release into a venous vessel, were simulated. The diameter of the vein model was based on literature data. A superelastic material model of the shape memory alloy Nitinol was imple-mented to model the stent structure. A hyperelastic constitutive law for the vascular model was generated from uniaxial tensile test data of unfixated human vein walls. This study also compared numerical and experimental results regarding compliance and tensile tests to validate the vein material model. The calculated performance regarding expansion and crimping, as well as the release of the stent into a venous vessel, demonstrated the suitability of the stent design for minimally invasive application. Further research will focus on mo-delling of bicuspid valve structures within the developed stent design to simulate valve opening and closing under phy-siological conditions.


Actinomycin D for fibrosis management in ophthalmic implant surgery Andreas Brietzke, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, [email protected] Thomas Eickner, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, [email protected] Thomas Reske, Institute for Implant Technology and Biomaterials e. V., Rostock, [email protected] Claudia Matschegewski, Institute for Implant Technology and Biomaterials e. V., Rostock, [email protected] Rudolf Guthoff, Department of Ophthalmology, Rostock University Medical Center, Rostock, [email protected] Niels Grabow, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, [email protected] Thomas Stahnke, Department of Ophthalmology, Rostock University Medical Center, Rostock, [email protected] In ophthalmic implant surgery, fibrosis is still one of the main causes for postoperative complications. Implants that fea-ture a drug delivery system loaded with antifibrotically active drugs provide a promising approach to address this chal-lenge. Actinomycin D is a cytostatic agent that has a drug approval for use in cancer therapy. This transcription inhibi-tor intercalates between guanine-cytosin pairs of the DNA, which inhibits eventually the mRNA synthesis. This study is intended to clarify whether Actinomycin D has an impact specifically on components of the extracellular matrix (ECM) and its formation in human primary fibroblasts of the tenon (hTF). In addition, an active substance must have the ability to be incorporated into a drug delivery system and also to enable appropriate release kinetics. To address these two as-pects we examined the efficacy of the agent, as well as its suitability in drug delivery systems. For the characterisation of the antifibrotic potential of the agent, hTFs were treated with TGF to induce increased synthesis of ECM compo-nents. The impact of Actinomycin D on matrix deposition was analysed with RT-qPCR and Western Blot. Drug incor-poration and release studies were performed with poly(N-vinylpyrrolidone)-poly(methylmethacrylate)(PVP-co-PMMA) as a model drug delivery system. The detection of Actinomycin D was carried out with HPLC. RT-qPCR revealed a significant downregulation of ACTA2, COL1A1 and Fn1 genes in cells stimulated with TGF and additionally treated with Actinomycin D. However, these findings could only be confirmed on SMA protein level. Collagen I and fibron-ectin synthesis stayed unaffected. The diffusion based incorporation of Actinomycin D into the polymer model proved to be very effective. The release of the agent was retarded with a promising kinetic. By preventing the TGF-ß1 induced transformation of hTF into fibrotic active myofibroblasts Actinomycin D appears to be an promising antifibrotic agent in ophthalmic implant surgery.


Method for the improvement of mechanical properties of biodegradable poly-

meric scaffolds

Kerstin Schümann, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, Germany,

[email protected]


[email protected]

Niels Grabow, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock, Germany,

[email protected]

Klaus-Peter Schmitz, Institute for Biomedical Engineering, Rostock University Medical Center and Institute for Im-

plantTechnology and Biomaterials e.V., Rostock, Germany, [email protected]

Although current permanent metallic drug-eluting coronary stents show excellent clinical results, the drawbacks of a

permanent foreign body in the heart remain. Therefore, a focus in the field of stent technologies is the development of

biodegradable stents as the next step in stent evolution. Especially degradable thermoplastic polymers used for stent ap-

plication, e.g. poly(l-lactic acid) (PLLA), show inferior mechanical properties compared to permanent metals. To

achieve improved mechanical stent properties, especially reduced elastic recoil, increased radial stiffness and enhanced

expandability without strut ruptures, a method for thermo-mechanical treatment of polymeric stents was established.

The procedure for the thermo-mechanical treatment comprises two steps: 1. expansion of the stents at a temperature

above glass transition temperature (Tg) and 2. crimping of the stents at a temperature slighty below Tg.

Stent prototypes with different stent designs were fabricated by femtosecond laser cutting of dip-coated tubes made of

PLLA and a PLLA-based blend material. They were mounted on standard balloon catheters with an appropriate length

corresponding to the stent length and a nominal diameter of 3.0 mm. The stents were heated to 80 °C in a water bath

and expanded to their nominal diameter by balloon inflation. Heating above Tg enables molecular rearrangement, allow-

ing for a molecular chain orientation along the mechanical load direction. To set the stent profile for implantation, a

subsequent crimping process is required. The stents were crimped with an iris crimping tool at 50 °C, where a rear-

rangement of the molecules is inhibited, but the polymer features a certain flexibility.

In contrast to stents without thermo-mechanical treatment the treated stents show no strut ruptures for all tested stent

designs. The comparison of the mechanical stent properties shows a considerable reduction of the acute and long-term

elastic recoil, but no significant change in collapse pressure due to thermo-mechanical treatment.


Extrusion as a manufacturing process for polymer micro-tubes for various bio-medical applications

Olga Sahmel, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock-Warnemünde, Ger-

many, [email protected]

Stefan Siewert, Institute for ImplantTechnology and Biomaterials e.V., Rostock-Warnemünde, Germany, stef-

[email protected]

Daniela Arbeiter, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock-Warnemünde,

[email protected]

Christine Friederike Kreiner, KreCo Kreiner Consulting Gesellschaft für wissenschaftlich-technisches Projektmanage-

ment mbH, [email protected]

Rudolf Guthoff, Department of Ophthalmology, University Medical Center Rostock, [email protected]

rostock.de

Klaus-Peter Schmitz, Institute for ImplantTechnology and Biomaterials e.V. and Institute for Biomedical Engineering,

Rostock University Medical Center, Rostock-Warnemünde, Germany, [email protected]

Niels Grabow, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock-Warnemünde, Ger-


In various biomedical applications extrusion represents a common manufacturing process for polymeric semi-finished prod-

ucts. Extrusion allows the processing of a wide range of biomaterials, as well as different cross-sectional geometries. The cur-

rent work focuses on the development of an extrusion process for polymer micro-tubes used for the manufacturing of medical

devices, for example microstents for minimally invasive glaucoma therapy. Semi-finished products were manufactured based

on biodegradable poly-L-lactide (PLLA) and a non biodegradable polycarbonate based silicone elastomer (ChronoSil) by

means of extrusion and dip-coating. The target outside diameter of micro-tubes ranges from 300 to 400 µm. Manufactured

semi-finished products were analyzed morphologically by means of biaxial laser measurement and scanning electron micros-

copy (SEM). For the analysis of mechanical and thermo-mechanical properties of the specimens uniaxial tensile testing and

differential scanning calorimetry (DSC) were performed. The outside diameter d and the wall thickness t of ChronoSil semi-

finished range from do = 365 µm and t = 66 µm (extrusion) to do = 360 µm and t = 89 µm (dip-coating). While dip-coated mi-

cro-tubes show a smooth and homogeneous surface, SEM micrographs of extrudes micro-tubes show some longitudinal

grooves. The mechanic properties of extruded and dip-coated micro-tubes are comparable. Elastic modulus E, tensile strength

σm and elongation at break εB of extruded semi-finished products made of PLLA were E = 2218 N/mm², σm = 239 N/mm² and

εB = 344%. Dip-coated semi-finished products generally show a higher degree of crystallinity which is characterized by a sig-

nificant melting peak in DSC thermograms. The presented extrusion process is suitable for the manufacturing of polymer mi-

cro-tubes in a sub-millimeter scale. A future improvement of nozzle design will allow for a smooth surface of extruded semi-

finished products.


Pressure sensor emulator to improve long-term stability of heart valve

testing systems

Carsten Tautorat, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock-Warnemünde, Germany, [email protected] Sebastian Kaule, Institute for ImplantTechnology and Biomaterials e.V., Rostock-Warnemünde, Germany, [email protected] Jörg Kaminsky, Institute for ImplantTechnology and Biomaterials e.V., Rostock-Warnemünde, Germany, [email protected] Klaus-Peter Schmitz, Institute for ImplantTechnology and Biomaterials e.V., Rostock-Warnemünde, Germany, [email protected] Niels Grabow, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock-Warnemünde, Germany, [email protected] Wolfram Schmidt, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock-Warnemünde, Germany, [email protected]

In vitro fatigue test procedures of artificial heart valve prostheses can take several months with up to 400 million

cycles to assess valve performance and durability under simulated cardiac conditions. Reliable investigations and

a minimum of user interventions for recalibration are required. In these tests, pressure data are collected for

hydrodynamic heart valve characterization and for closed-loop control on pressure loading. In our study, the

improvement of commercial heart valve testing systems (Vivitro Pulse Duplicator, Vivitro Labs Inc. and VDT-

3600i, BDC Laboratories) is considered by substituting the built-in disposable pressure sensors by long-term

stable sensors.

The selected highly accurate sensors (86A, TE Connectivity Corp.) provide amplified, linearized, calibrated and

temperature compensated analog output signals. Their stainless steel construction allows for high media

compatibility with corrosive liquids. Due to different sensitivity characteristics, these sensors are not fully

compatible to the original circuitry. To overcome this limitation, application-specific interfaces were developed

to connect the new sensors to the data acquisition part of the validated valve testing systems. To stay consistent

with manufacturer’s device and software specification, we utilized fast analog signal conditioning including

scaling, offset calibration, out of range alarm and displays for precise sensor emulation. Compared to the original

pressure sensors, emulator parameters, such as pressure range, precision, resolution, accuracy, response time,

remained unchanged or even improved. For system verification the response characteristic, long-term stability

and dynamic properties were examined in comparative studies.

Two emulator solutions are presented for different valve testing systems. The interface of the VDT-3600i system

emulates the use of a simple passive, resistive-bridge sensor with extremely low sensor output signal voltages for

an operating range of 0 to 5 bar. The emulator for the Vivitro Pulse Duplicator operates similar to an amplified

sensor with integrated signal conditioning from 0 to 300 mmHg (0.4 bar), relevant for blood pressure

measurements. The developed sensor emulator circuits have shown to be precise and long-term stable, well

suitable for use in test equipment for high-risk medical implants. Calibration intervals can be extended.


Numerical investigation of stent designs for wireless access to integrated sensors Swen Grossmann, Institute for ImplantTechnology and Biomaterials e.V., Friedrich-Barnewitz-Str.4, 18119 Rostock, Germany, e-Mail: [email protected] Robert Ott, Institute for ImplantTechnology and Biomaterials e.V., Friedrich-Barnewitz-Str.4, 18119 Rostock, Germany, e-Mail: [email protected] Wolfram Schmidt, Institute for Biomedical Engineering, Rostock University Medical Center, 18119 Rostock, Germany, e-Mail: [email protected] Niels Grabow: Institute for Biomedical Engineering, Rostock University Medical Center, 18119 Rostock, Germany, e-Mail: [email protected] Klaus-Peter Schmitz, Institute for ImplantTechnology and Biomaterials e.V., Friedrich-Barnewitz-Str.4, 18119 Rostock, Germany, e-Mail: [email protected] Stefan Siewert, Institute for ImplantTechnology and Biomaterials e.V., Friedrich-Barnewitz-Str.4, 18119 Rostock, Germany, e-Mail: [email protected] In recent years, a progressive interest in the implementation of wireless access to cardiovascular implants has been es-tablished. This manifests in new devices, such as arterial pressure sensors, or additional functionalities added to estab-lished implants like stents. In such devices the stents have to satisfy the mechanical requirements, but also need to pro-vide wireless access and in consequence act as an electromagnetic resonator. Both, the mechanical as well as the elec-tromagnetic properties, are highly influenced by the stent design. However, common designs, possessing highly opti-mized mechanical properties, often consist of cylindrical arranged struts with connections in-between which can be considered as short-circuited inductive coils. As a consequence, the small inductance raises the resonance frequency, which may decrease the in vivo performance of the wireless connection between the stent and the external readout de-vice. Thus, new designs were developed to overcome this limitation, for example by avoiding the short-circuit due to a helical arrangement of the struts. Within this work we compare the performance of a common stent design and a helical design by means of numerical simulations. We are using two designs which only differ in the arrangement of the struts. The stents vary in length between 10 and 30 mm and possess a strut width of 90 µm. The electromagnetic and mechani-cal properties are investigated using a finite-difference time-domain algorithm and finite element method, respectively. We will show how the helical design is influencing the electromagnetic properties by tuning the resonance towards smaller frequencies as well as their dependency on the design parameters. Furthermore, we compare the mechanical performance of the two designs and reveal individual distinctions. Optimized wireless access especially to cardiovascu-lar implants can open up new possibilities in the therapy and early diagnosis of aneurysms, restenosis, and thrombosis.


Development of an experimental setup for the in vitro investigation of mitral

valve repair devices

Robert Ott: Institute for ImplantTechnology and Biomaterials e.V., Friedrich-Barnewitz-Str. 4, 18119 Rostock-

Warnemünde, Germany, E-mail: [email protected]

Sebastian Kaule: Institute for ImplantTechnology and Biomaterials e.V., Friedrich-Barnewitz-Str. 4, 18119 Rostock-


Swen Großmann: Institute for ImplantTechnology and Biomaterials e.V., Friedrich-Barnewitz-Str. 4, 18119 Rostock-


Sylvia Pfensig: Institute for ImplantTechnology and Biomaterials e.V., Friedrich-Barnewitz-Str. 4, 18119 Rostock-


Michael Stiehm: Institute for ImplantTechnology and Biomaterials e.V., Friedrich-Barnewitz-Str. 4, 18119 Rostock-


Niels Grabow: Institute for Biomedical Engineering, Friedrich-Barnewitz-Str. 4, 18119 Rostock-Warnemünde, Germa-

ny, E-Mail: [email protected]

Klaus-Peter Schmitz: Institute for ImplantTechnology and Biomaterials e.V., Friedrich-Barnewitz-Str. 4, 18119 Ros-

tock-Warnemünde, Germany, E-Mail: [email protected]

Stefan Siewert: Institute for ImplantTechnology and Biomaterials e.V., Friedrich-Barnewitz-Str. 4, 18119 Rostock-

Warnemünde, Germany, E-Mail: [email protected]

Mitral regurgitation (MR) occurs with a prevalence of approximately 10 percent in patients aged 75 and older and there-

fore is one of the most frequent indications for heart valve surgery. During the last decade surgical mitral valve repair

procedures emerged as the gold standard for the treatment of clinically relevant MR. However, for surgically inoperable

or high-risk patients transcatheter-based mitral valve repair devices present a valuable treatment option. Within the cur-

rent study, we developed an experimental setup to investigate the hydrodynamic performance of transcatheter-based mi-

tral valve repair devices in vitro. The bicuspid mitral valve model employed in the experimental setup features an oval-

shaped mitral valve annulus with d1 = 34 mm, d2 = 40 mm and chordae tendineae with a length of l = 25 mm attached to

two papillary muscles structures. Pressure gradient - velocity characteristics were investigated for backward flow at

steady-state flow conditions with transvalvular pressure gradients in the range of 0.75 mmHg ≤ ∆p ≤ 103.13 mmHg.

Distilled water at 37 °C with a dynamic viscosity of 1.002 mPa∙s and a density of 998 kg/m3 was used. A test-chamber

consisting of a press-fit mitral valve holder cassette and a cylindrical in- and outflow tract was developed. Different de-

signs for the exchangeable press-fit mitral valve holder were manufactured using additive manufacturing technologies

providing an optimal fitting for variable mitral valve sizes and pathologies. In- and outflow tracts featuring a diameter

of d = 50 mm and a height of h = 60 mm were made from transparent polymethylmethacrylate to allow for easy optical

access during measurements. The experimentally investigated pressure gradient - velocity characteristic yields a quad-

ratic correlation for the open mitral valve and a linear correlation for the closed mitral valve. The transvalvular closing

pressure for the mitral valve model is 4.9 ± 0.1 mmHg.


Evaluation of Adjustable Loop Suspensory Anterior Cruciate Ligament Fixation Devices Mira Dreier, Student, Institute of Health Care Engineering, TU Graz, Graz, Austria, [email protected] Samuel Bachmaier, Senior Research Engineer, Arthrex, Munich, Germany, [email protected] Christian Baumgartner, Univ. Professor, Institute of Health Care Engineering, TU Graz, Graz, Austria, [email protected] Jörg Schröttner, Assoc. Professor, Institute of Health Care Engineering, TU Graz, Graz, Austria, [email protected] Along with increasing enthusiasm for sports comes an increase of sport related injuries. One of the most common inju-ries in the human knee is the tear of the anterior cruciate ligament (ACL). The selection of a graft fixation device is an important factor that determines the outcome of an anterior cruciate ligament reconstruction. Before the healing process is completed, the graft is dependent on tibial and femoral fixation devices to maintain normal ACL graft tension. Among various devices, the use of an adjustable loop suspensory fixation device (ALD) in soft-tissue graft reconstruc-tion attracts current interest. An advantage of the ALD is the ability to draw the graft to the depth of the bone tunnel to achieve adequate graft tension while minimizing the empty space in the tunnel. In this study a comprehensive controlled laboratory investigation is performed to examine the biomechanical properties of commonly used cortical fixation de-vices, with the aim of implementing a standard testing procedure for adjustable loop devices. The procedure consists of three test series, a loop shortening test and two different stability test series (singe device and tendon device test). Those test series are used to compare the performance of a new ALD from Arthrex (Naples, USA) with five competitor devic-es already on the market. In order to obtain representative results eight samples of each device are tested. In comparison to the previously performed studies, a complete unloading is applied in the stability tests, which allows for a detailed examination of the ALDs locking mechanisms in dynamically loaded test situations. Furthermore, the performed loop shortening tests reveal important aspects, such as the shortening accuracy and settling effects of the loops, that are not found in previous studies. Therefore, the used test protocol can be recommended for further testing.


Low-turbulence displacement-flow for an operating environment – Specifica-tions, prototyping and first measurements of a low-cost solution

Julia Heinz, Institute of Medical Device Technology (IMT), University of Stuttgart, 70569 Stuttgart, Germany, e-mail:

[email protected]

Max B. Schäfer, Institute of Medical Device Technology (IMT), University of Stuttgart, 70569 Stuttgart, Germany, e-

mail: [email protected]

Kent W. Stewart, Institute of Medical Device Technology (IMT), University of Stuttgart, 70569 Stuttgart, Germany, e-

mail: [email protected]

Peter P. Pott, Institute of Medical Device Technology (IMT), University of Stuttgart, 70569 Stuttgart, Germany, e-mail:

[email protected]

In developing countries airborne micro-organisms are one of the most common causes of surgical wound infection. In

the operating room low-turbulence displacement-flow has been shown to reduce the influence of airborne bacteria.

However, due to complexity and cost, current systems are not accessible to all potential users. In this paper a low-cost

ventilation system is presented that provides low-turbulence displacement-flow over a surgical operating environment.

The system was developed in order to achieve the DIN 1946-4 standard, while being a low-cost, simple, and mobile in-

stallation with flexible expansion. Flow visualizations with evaporated fluid, and turbulence measurements with a ther-

moelectric air-flow sensor (Schiltknecht GmbH) were taken.

A stand-alone, simple to assemble, mobile airflow system was developed with an outlet height of 2.39 m and uses the

principle of speed compensation for laminar airflow. From visual inspection the airflow was seen to be undisturbed to a

height of 1.3 m above the ground. When using the full outlet area the air flow velocity was below 0.15 m/s, outside the

range of the sensor used, and thus no turbulence level could be determined. When the flow was diverted into a smaller

outlet area to increase air velocity, an air velocity of 0.25 m/s and a turbulence level of less than 10 % was measured at

a height of 2 m.

In summary, the system generates a continuous downwards displacement of air over the protected area around the situs

(5.6 m2). The entire system can be assembled quickly with minimal standard tools, making it very suitable for mobile

use, such as in disaster areas. However, future work is required to achieve the height of laminar flow field required by

the DIN standard. Overall, the low-cost and simple system could provide many potential users access to the technology

and thus improving hygiene conditions in their operating environment.


Alternative treatment of prostate cancer: new strategies using focused ultrasound

Shaonan Hu, Innovation Center Computer Assisted Surgery, Leipzig University, Leipizg, Germany, [email protected] Lisa Landgraf, Innovation Center Computer Assisted Surgery, Leipzig University, Leipzig, Germany, [email protected] Michael Unger, Innovation Center Computer Assisted Surgery, Leipzig University, Leipzig, Germany, [email protected] Andreas Melzer, Innovation Center Computer Assisted Surgery, Leipzig University, Leipzig, Germany, [email protected] Prostate cancer (PCa) is common in men and some subtypes exhibit high metastatic rate. Hormone therapy with testosterone (T) could reduce invasiveness of androgen dependent PCa. Focused ultrasound (FUS) is reported to enhance effects of other treatment modalities. The aim of this study is to characterize thermal and mechanical effects of FUS on PCa and hormone metabolism. Androgen independent (PC-3) and androgen dependent (LNCap) PCa cell lines (ATCC) were cultured in FUS penetrable 96 well plates (Greiner-Bio-One). We have used special sonicator for cell culture plates developed at IMSaT (University Dundee) and modified by us comprised by a programmable VXM motor controller and a NEMA 17 stepper motor (VELMEX Inc.) for treatment with a customized 1.14 MHz single focused transducer. To investigate mechanical effects, cavitation dose was evaluated with terephthalic acid method (Sigma) and via hydrophone (Precision Acoustic) which measure broadband noise. For analysis of T metabolism, cells were treated with T (Sigma) at concentrations of 1 – 32 ng/ml for 12 days. Cell viability (WST-1 assay, Roche) was evaluated for both treatments. The acoustic threshold where cavitation occured was determined at 106 W/cm2. Different cavitation doses lead to decreased cell viability of 87% (3 W, 40 s: 150 AU or 0.25 mV*s) and 74% (11.5 W, 40 s: 1500 AU or 2 mV*s) in PC-3 24h post treatment. Preliminary experiments of T metabolism lead to a concentration dependent loss in LNCap cell viability to 34%, 25% and 23% for 1, 8 and 32 ng/ml, respectively. In contrast, no effect of T treatment was observed in PC-3 cells. The first data suggest that cavitation can cause minor damage to PC-3 cells, mechanical effects will be further studied. In the future, cell sensitivity to T and metabolism combined with FUS treatment will be investigated.


Potential and Challenges of Inkjet-Printing for Wearable Medical Devices Liane Koker, Institute for Automation and Applied Informatics (IAI), Karlsruhe Institute of Technology (KIT), Karls-ruhe, Germany, [email protected] Maher Mansour, German-Jordanian University, Amman, Jordan, [email protected] Martin Ungerer, Institute for Automation and Applied Informatics (IAI), Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany, [email protected] Klaus-Martin Reichert, Institute for Automation and Applied Informatics (IAI), Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany, [email protected] Peter Stiller, Institute for Automation and Applied Informatics (IAI), Karlsruhe Institute of Technology (KIT), Karls-ruhe, Germany, [email protected] Ulrich Gengenbach, Institute for Automation and Applied Informatics (IAI), Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany, [email protected] With the use of printing technologies, a variety of materials can be structured onto the surface of potentially any sub-strate; thus opening up a great potential for versatile applications. Due to the additive manufacturing technique, the ma-terial consumption of printed systems is reduced in comparison to conventional manufacturing techniques. The advanc-es in the development of functional inks allow not only for printing of electrical wiring, but also passive and active elec-tronic devices. By using thin polymer substrates, surface-conformable and inexpensive electronic systems can be real-ised. With digital printing technologies like inkjet-printing, fabrication starting from lot-size one is possible. The potential of digitally printed systems was demonstrated by the setup of a functional inkjet-printed astable multivi-brator circuit presented in this paper. The circuit was printed on thin PET substrate and contains printed conductors, resistors, capacitors and cross-connects. But it was also shown, that the technical implementation is still very challeng-ing. The interaction of ink, substrate and print head has to be adjusted to the desired functionality of each printed ele-ment. Reproducibility of substrates, inks and processes and therefore of the printed circuits is a challenging issue; as well as process yield and ageing behaviour in operation. Complex components, e.g. a microcontroller, will not be print-able in foreseeable future. Therefore, a process chain for the manufacturing of hybrid systems is being setup, composed of inkjet printing and mounting of discrete components. Now, promising applications for printed systems are being explored. Medical devices are of special interest, since the digital inkjet-printing allows for patient-individual production. The surface-conformable circuits especially fit the re-quirements of medical devices applied to the skin, like wearables and smart plasters. Existing approaches and products were investigated and are introduced here. Since applications of inkjet-printing are still limited, also systems realised with other printing technologies like screen-printing are included. The evaluated applications of wearable printed sys-tems include, but are not limited to, vital signs monitoring, sweat analysis, saliva analysis, wound monitoring and appli-cations in diagnostic instruments like coils for MRI examinations.


Concept and development of a current measurement system for ultra-low power electronics in medical wearables Jakob Reck, FG Biosignalverarbeitung TU Ilmenau, Ilmenau, Germany, [email protected] Daniel Laqua, FG Biosignalverarbeitung TU Ilmenau, Ilmenau, Germany, [email protected] Peter Husar, FG Biosignalverarbeitung TU Ilmenau, Ilmenau, Germany, [email protected] The measurement of current consumption for ultra-low power applications is a challenge for most of the common labor-atory and handheld ammeters. The aim of this work is to design a current measurement system for several laboratory applications in the field of ultra-low power electromedical prototyping for medical wearables. The field of application is the current consumption measurement of low-power electronics in the range of 100 mA down to currents of less than 1 µA. An analog measuring system for direct current measurement as well as the measurement of alternating currents was developed. With the build system it is possible to plot and analyze the current curve. The developed high-side measuring system can be adjusted by using different shunt resistors for sensing range setup. Main element of the circuit is the instru-mentation amplifier INA326 from Texas Instruments for differential measurement of the voltage drop over the shunt resistor. The high input impedance of 10 G• and the low offset voltage of this IC is suitable for the measurement task in order not to burden the source during measurements. A low-pass filter with 1 kHz cutoff frequency was used to minimize auto-correction circuitry noise of the instrumentation amplifier. This output filter also serve as an anti-aliasing filter ahead of the Analog-to-Digital converter.. The developed circuit is able to sense currents in low ranges from 100mA down to approx. 1 µA with a measurement error of less than 2.5 %. An average error of less than 1 % is achieved. Even a current of 400 nA was recorded within the error limits. Thus, the developed current sensing system is suitable for characterizing ultra-low power electronics in medical wearables.


Contactless sensor system for capacitive ECG monitoring in medical wearables Daniel Laqua, Biosignal Processing Group, Technische Universität Ilmenau, Germany, [email protected] David Sambale, Biosignal Processing Group, Technische Universität Ilmenau, Germany, [email protected] Jakob Reck, Biosignal Processing Group, Technische Universität Ilmenau, Germany, [email protected] Peter Husar, Biosignal Processing Group, Technische Universität Ilmenau, Germany, [email protected] ECG measurement using galvanic coupled electrodes is an established method for monitoring cardiac activity in medicine. Under certain circumstances long-term measurements of 24 hours or even longer may be necessary to obtain a conclusive diagnose. Therefore, the most common procedure is to apply self-adhesive gel electrodes to the patient´s skin. In some cases, the use of gel electrodes leads to skin irritations. In addition, the electrodes have to be connected to the ECG recorder via cable. Wearing the electrodes and cables is inconvenient for the patient and they can lead-off unnoticed during motion. There is also a psychological effect related to the wearing of medical devices, which can influence the diagnostic assay. The motivation is to improve the long-term application on patients by using a non-galvanic capacitive ECG measurement system completely integrated in a smart shirt. The developed measurement system consists of two circular sensors with active and passive shielding. A 150 Hz Bessel low-pass filter is used as antialiasing filter for analog filtering. The analog to digital converter is controlled by an ultra-low power microcontroller. The data is transmitted to PC via UART to USB interface. Three FIR filters (0.5 Hz high pass, 50 Hz notch and 150 Hz low pass) are used for digital signal processing. A Pan-Tompkins algorithm for R-wave detection has also been implemented in MatLab. First motion tests of the measuring system with an ergometer were successful for medical wearables. It can be stated that the results of the capacitive ECG measurements are comparable with those of the galvanic measurement.


Development of a smart fabric force-sensing glove for physiotherapeutic Appli-cations Andreas Spilz, University of Applied Sciences, Institute of Medical Engineering and Mechatronics, Ulm, Germany, [email protected] Marius Karge, former University of Applied Sciences, Institute of Medical Engineering and Mechatronics, Ulm, Germany, [email protected] Michael Munz, University of Applied Sciences, Institute of Medical Engineering and Mechatronics, Ulm, Germany, [email protected] Thomas Engleder, University of Applied Sciences, Institute of Medical Engineering and Mechatronics, Ulm, Germany, [email protected] In this work, a smart fabric force-sensing glove is developed which is able to measure the total amount and direction of the force a person applies on a patient in a physiotherapeutic context. A device like this would be beneficial for the edu-cation of physiotherapists, to measure the progress of a patient and to evaluate the treatment. The glove has to be usable in a treatment context, therefore flexible sensors based on smart-fabric are being used in or-der to avoid irritation of the patient. This sensor is based on a piezoresistive fabric which changes its electrical re-sistance according to the applied stress. The characterization of this sensor revealed that the change in resistance of the sensor is dependent of the amount of force, the loaded area, the total time the sensor is loaded and hysteresis. To com-pensate these effects, an additional sensor based on the same smart fabric was developed which measures the loaded area of the first sensors. By combining these two sensors, it is possible to calculate the applied force. The anatomy of the human hand is composed of many small moveable segments that all play together in the process of applying force to an object. Two steps are necessary to determine the combined force of all segments. First, a force sen-sor needs to be installed on every segment and second, the orientation of the segmentation towards each other is needed. To determine the orientation of the segments, commercially available piezoresistive bending sensors were used. Addi-tionally, the orientation of the hand in space is determined using IMUs. The results show the feasibility to build a measurement system out of smart fabric material, that is able to measure the applied force. Furthermore the protoype shows promising results in determining the applied force in amount and direc-tion.


Current Monitoring and Compensation of Bioimpedance Measurements Alexandru-Gabriel Pielmus, Chair of Electronics and Medical Signal Processing, Technische Universität Berlin, Berlin, Germany, [email protected] Christoph Herold, Chair of Electronics and Medical Signal Processing, Technische Universität Berlin, Berlin, Germany, [email protected] Michael Klum, Chair of Electronics and Medical Signal Processing, Technische Universität Berlin, Berlin, Germany, [email protected] Timo Tigges, Chair of Electronics and Medical Signal Processing, Technische Universität Berlin, Berlin, Germany, [email protected] Reinhold Orglmeister, Chair of Electronics and Medical Signal Processing, Technische Universität Berlin, Berlin, Ger-many, [email protected]

Measurements of the complex electrical conductivity in biological tissue can be grouped under the term bioim-pedance. Due to its noninvasive and compliant acquisition, it has various applications in modern medicine, ranging from plethysmography to imaging. The typical, tetrapolar measurement setup, however, poses some technical challeng-es. The injected current needs to be a constant, known quantity, as is assumed in the calculation of the impedance from only voltage measurements across the load. This necessitates extremely linear and high-impedance output current driv-ing circuits over a broad frequency range. For large currents or frequencies, therefore, increasingly complex circuits are required. Alternatively, actively measuring the output current of the source can compensate the need for precise hard-ware, or further increase the accuracy thereof.

We measure a range of known fixed resistors and RC models, as well as peripheral locations of live human pro-bands with the aim of acquiring the plethysmographic arterial pulse wave. Our improved Howland current pump drives a 10 kHz, 100 µA sine current with 1 M• output. The load voltage and output current are synchronously sampled with 400 kHz each.

Voltage and current measurement are used to compute the compensated impedance, whilst the uncompensated one is derived solely from the voltage curve and mean current value. The computed difference between the impedance signals is up to 4.13%, with 1.28% on average. However, for the variable bioimpedance, considerable morphological discrepancies can be observed between the curves throughout all measurements.

In conclusion, even using very precise current injection, the morphology of the acquired impedance signals var-ies visibly between the two methods. These discrepancies cannot be detected or suppressed by other means, which makes the voltage-only signal unreliable. Active current monitoring can rectify this, and also reduce the strict current source performance requirements. Thereby it increases measurement accuracy whilst decreasing circuit complexity and cost.


Endoscopic Pan/Tilt Camera for Thorax Interventions – Design and first results

Alexander Mrokon, Institute of Medical Device Technology, University of Stuttgart, Pfaffenwaldring 9, 70569

Stuttgart, Germany, [email protected]

Volker Steger, Center for Thoracic Oncology, University Hospital of Tuebingen, Herrenberger Str. 23, 72070 Tübing-

en, Germany, [email protected]

Peter P. Pott, Institute of Medical Device Technology, University of Stuttgart, Pfaffenwaldring 9, 70569 Stuttgart, Ger-


Minimally invasive surgery in some cases suffers from a limited view because certain areas are obscured by others. In

this paper, a system is described, which can be used in minimally invasive procedures as an addition to a standard endo-

scope to improve the range of view. Through FEM simulation a magnetic circuit was designed to position the camera

head. Subsequently, a camera positioning system was set up that includes an extracorporeal and an intracorporeal unit.

The first controls the intracorporeal system. The latter has a camera inclination angle of up to 65° and an additional ver-

tically downward viewing angle when aligned in parallel (inclination angle 0°). The panning angle is 360°. The camera

system was evaluated in lab and cadaver trials. It has been found that the size of the intracorporeal system (16 × 10 ×

150 mm) represents a major problem. Future work will focus of the reduction of the system’s size, the improvement of

the camera image quality, and design changes considering mechanical stability.





Revolving biopsy gun for soft tissues single access multi sample collection Marwah AL-Maatoq, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany, [email protected] Asmita Doshi, Biomedical engineering department, Martin-Luther-University Halle-Wittenberg, Germany, [email protected] Marco Kalmar, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany, [email protected] Axel Boese, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany, [email protected] Michael Friebe, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany, [email protected] Core needle biopsy is an established method for diagnosis of cancerous tissue. To achieve high sensitivity of the diag-nosis multiple samples are collected from and around the suspected tumour zone. This is connected to multiple punc-tures and removal of the biopsy gun. Another possibility is the use of biopsy guns with large diameters. Both lead to high traumatization of the healthy tissue and the risk of tumour cell distribution. To provide multiple sampling from a single access channel, a concept for a new revolving biopsy gun is proposed in this work. The coaxial design uses a curved, hollow NITINOL core needle to collect the samples in a slight angle. After placing the needle in front of a lesion under image guidance, the bended core needle will be shot into the tissue to col-lect the first sample. During the pullback of the bended core, the biopsy sample is sucked into a magazine on the proxi-mal end by underpressure. Then, the core needle is rotated in a defined angle and advanced again to collect the next sample in a different angle. This can be repeated until the magazine is filled without a pullback of the whole coaxial needle. Thus up to four samples can be collected from one access channel. A prototype of the revolving biopsy gun was realized and combined with a vacuum suction pump. Sample collection was tested on tissue samples. To prove accuracy, X-ray contrast agent mixed with colour was injected into the meat to mimic a target structure. Multiple samples were collected and analysed under the microscope. Samples of 10mm length could be retrieved. The presented setup allows multiple biopsies at changed areas with only one tissue entry channel for tumour sizes of up to 10mm in diameter and depth. An adaption to larger tumour sizes is possible.


Arm extension and device holding concept for minimal invasive image guided in-terventions Marco Kalmar, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany,

[email protected]

Guido Buß, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany,

[email protected]

Holger Fritzsche, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany,

[email protected]

Axel Boese, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany,

[email protected]

Michael Friebe, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany,

[email protected]

Minimal invasive image guided procedures are based on small access points into the human body mostly provided by

needle punctures. As imaging modalities X-ray, computed tomography (CT) or Magnetic resonant imaging (MRI) are

widely used. They come with limited patient access, in X-ray and CT due to the radiation at the puncture zone, in MRI

due to the dimensions of the system itself. For this reason needle punctures are performed sequentially, needle infeed –

imaging - needle infeed-imaging…, or with high radiation exposure in case of CT guidance or in uncomfortable position

of the doctor in case of MRI.

To simplify needle punctures under MR guidance and to raise safety in CT interventions we propose a new needle holder

concept as an extension of the users arm. This concept is based on a double lever principle to offer a high level of accuracy,

freedom of movement, force support and ease of use. The stand of the needle holder can be placed under the mattress of

the patient table for simple fixation. The stand arm is self-holding but allows movement in three degrees of freedom. On

this stand, the horizontal arm extension is mounted. On the distal tip of this arm a forceps is mounted that can be operated

from the proximal end of the extension. The forceps includes two rotatable plates that hold the needle. Since needles of

different providers have different shapes and dimensions, the needle holder has to tolerate these variances.

The system was set up as a prototype. All materials used were MR compatible. Handle, forceps, stand plate and connectors

were realized by 3D printing, the stand arm and the extension by pipes.

The setup was tested in a simulated intervention under MRI guidance and X-ray guidance. Needle placement was eval-

uated in a gel phantom with target structure.


Guided surgical suturing with a parallel kinematic based single-port-robot

Johannes Bilz1, Christian Hatzfeld(†)1,Fatih M. Bostanci1, Andreas Kirschniak², Helmut F. Schlaak1 1 Technische Universität Darmstadt, Laboratory Microtechnology and Electromechanical Systems, Darmstadt, Germany,

[email protected]

² University Hospital Tübingen, University Clinic of General, Visceral and Transplant Surgery Workgroup Surgical Tech-

nology and Training, Tübingen, Germany

Sewing is one of the oldest methods of closing wounds. Working with needle and thread is still used today to accelerate

wound healing or as part of surgical incissions. Particularly in minimally invasive procedures, however, suturing requires

a high degree of coordination and is a demanding and stressful task for the surgeon.

Robot-assisted surgery can have a relieving effect by improving mobility of the grippers compared to laparoscopic sur-

gery. In addition, robots can be used to support the user in the execution of movements or to perform partial steps com-

pletely autonomously.

In this paper, surgical suturing is performed using the FLEXMIN surgical robot, developed at TU Darmstadt and UK

Tübingen. FLEXMIN is a single port surgical robot with two grippers based on parallel kinematic structures. The kine-

matics allow 3-DOF motion plus infinite rotation of the grippers. In addition, haptic feedback in the form of intracorporeal

interaction force measurement and output of these measured forces to the surgeon via a haptic user interface is possible

with the robot.

The special features and different strategies caused by the different working space and agility of the robot system com-

pared to laparoscopic surgery are discussed and compared with classical suture methods. Therefore different types of

sutures are presented and advantages and drawbacks of using FLEXMIN are discussed.

The ability to output force to the user is used to support the execution of movements required for suturing in a novel

approach. The surgeon feels a corrective force, but can overcome it at any time to respond to unforeseen events. This

approach supports and relieves the surgeon without reducing his decision-making power.

Surgical suturing is divided into sub-steps and analysed. For these, dynamic trajectories are planned in the control soft-

ware Matlab Simulink. A position controller for force output with adjustable maximum force is implemented for motion

execution.



Preclinical MR-guided Focused Ultrasound Hyperthermia in 7 Tesla MRI Upasana Roy, Innovation Center Computer Assisted Surgery, Leipzig, Germany, [email protected]. Marc Fournelle, Fraunhofer Institut für Biomedizinische Technik, St. Ingbert, Germany, [email protected]. Sebastian Greiser, Fraunhofer Institute for Cell Therapy and Immunology, Department of Cell Therapy, Leipzig, Ger-many, [email protected]. Robbert van Gorkum, Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland, [email protected]. Daniel Speicher, Fraunhofer Institut für Biomedizinische Technik, St. Ingbert, Germany, [email protected]. Thomas Grunwald, Fraunhofer Institute for Cell Therapy and Immunology, Department of Cell Therapy, Leipzig, Ger-many. [email protected]. Sebastian Kozerke, Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland, [email protected]. Steffen Tretbar, Fraunhofer Institut für Biomedizinische Technik, St. Ingbert, Germany, [email protected]. Lisa Landgraf, Innovation Center Computer Assisted Surgery, Leipzig, Germany, [email protected]. Andreas Melzer, Innovation Center Computer Assisted Surgery, Leipzig, Germany, [email protected]. Magnetic resonance-guided focused ultrasound (MRgFUS) allows precise and non-invasive hyperthermia treatment at 41-46°C (Reike et al. JMRI 2008) which may allow to radio-sensitize tumor cells for Radiation Therapy (RT). The pur-pose of this study was the validation of the implementation of a preclinical FUS system and MRI based thermometry for FUS hyperthermia in a preclinical MRI system. A novel MRI conditional preclinical FUS array transducer (11x11 elements, copper shielding, aperture size of 10x10 mm, frequency 960 kHz) was installed at the whole body rat bed in a 7 T MRI (PharmaScan 7T, Bruker). To determine heating effeicieny in vivo and implement MRI thermometry, first experiment was performed with a dead mouse using the muscle in the right hind leg as target. A small slice (0.6 mm thick) of agar pad was placed between the FUS transducer and target tissue with ultrasound gel for coupling. This way signal loss at the transducer site and ringing artefact at the surrounding tissue was avoided. The sonication was manually started at intensity of 4.8W/cm2 for 55 s followed by MR imaging with FLASH sequence [parameters: TE 4.5 ms, TR 275 ms, FOV 8x5 cm2, 15 slices with thickness 1.5 mm and matrix 256x256; acquisition time: 52 s]. Real-time temperature monitoring was performed with fiber optic probes (Luxtron) positioned inside the leg muscle. PRF thermometry was realized offline by reconstructing k-space MRI data in MATLAB. Artefact free MR Images from target tissue showed a 2.4 fold reduction of the signal-to-noise ratio (SNR) with presence of the transducer. The SNR with FLASH sequence parameters, was 32. The temperature at the target tissue was increased from 33°C to 40°C within 50 minutes. There has been only •0.8•°C temperature discrepancy between the temperature measured with fiber optic and PRF thermometry. This study showed that FUS heating and MRI based temperature control is feasible in a small animal 7T MRI and hyper-thermia temperature could be achieved. To realize in vivo combination experiments of MRgFUS hyperthermia and RT, higher sonication intensity need to be provided for faster heating within 5 minutes in tumor bearing mice.


Technical support of wound healing processes: Project status Jacquelyn Dawn Parente, Institute of Technical Medicine, Furtwangen University, Villingen-Schwenningen, Germany, [email protected] Sabine Hensler, Institute of Technical Medicine, Furtwangen University, Villingen-Schwenningen, Germany, [email protected] Claudia Kuhlbach, Institute of Technical Medicine, Furtwangen University, Villingen-Schwenningen, Germany, [email protected] Margareta M. Mueller, Institute of Technical Medicine, Villingen-Schwenningen, Germany, [email protected] Knut Möller, Institute of Technical Medicine, Furtwangen University, Villingen-Schwenningen, Germany, [email protected] The optimized wound healing (OWID) project provides technical support of wound healing processes. Advanced bio-physical treatment therapies using light (photobiomodulation), negative pressure wound therapy (NPWT), and electrical stimulation show biological effects. Specifically, a biphasic dose-response curve is observed where lower doses activate cells, while above a threshold, higher doses are inhibitory. However, no standard protocols and no multi-modal treat-ment studies determine specific therapy needs. The OWID project aims to develop a multi-modal treatment device and model-based therapy for individualized wound healing. This work presents the OWID project status. Currently, a pho-tobiomodulation prototype delivers red, green, and blue light ‘medicine’ at prescribed therapeutic ‘doses’. The calcula-tion of incident light necessarily considers transmission properties of the intervening cell culture plate. Negative pres-sure wound therapy (NPWT) and electrical impedance tomography (EIT) hardware are being adapted for use in vitro. Development of mathematical models of wound healing and therapy control are supported by treatment experiment out-come measures conducted in a wounded 3D tissue model. Parameter sensitivity analysis conducted on an existing math-ematical model of reepithelialization results in changing parameter values influencing cellular movement rates. Thus, the model is robust to fit model parameters to observed reepithelialization rates under treatment conditions impacting cellular activation, inhibition, and untreated controls. Developed image analysis techniques have not captured changes in wound area after photobiomodulation treatment experiments. Alternatively, EIT will be tested for wound area analy-sis. Additionally, live dyes will be introduced to non-invasively visualize the reepithelialization front on a smaller, cel-lular scale. Finally, an overall therapeutic feedback control model uses model reference adaptive control to incorporate the intrinsic biological reepithelialization mechanism, treatment loops, and treatment controller modulation at a wound state. Currently, the OWID project conducts photobiomodulation treatment experiements in vitro and has developed mathematical models. Future work includes the incorporation of multi-modal wound healing treatment experiments.


Experimental and numerical investigations of a small animal coil for ultra-high field magnetic resonance imaging (7T) Maíra M. Garcia, Laboratory for General and Theoretical Electrical Engineering (ATE), Faculty of Engineering, Univer-sity of Duisburg-Essen, Duisburg, and Faculty of Electrical Engineering and Applied Natural Sciences, Westphalian Uni-versity, Campus Gelsenkirchen, Germany, [email protected] Tiago R. Oliveira, Department of Biomedical Engineering, Federal University of ABC, São Bernardo do Campo, Brazil, [email protected] Daniel Papoti, Department of Biomedical Engineering, Federal University of ABC, São Bernardo do Campo, Brazil, [email protected] Khallil T. Chaim, Department and Institute of Radiology, University of São Paulo, São Paulo, Brazil, [email protected] Maria C. G. Otaduy, Department and Institute of Radiology, University of São Paulo, São Paulo, Brazil, [email protected] Daniel Erni, Laboratory for General and Theoretical Electrical Engineering (ATE), Faculty of Engineering, University of Duisburg-Essen and CENIDE – Center of Nanointegration Duisburg-Essen, Duisburg, Germany, [email protected] Waldemar Zylka, Faculty of Electrical Engineering and Applied Natural Sciences, Westphalian University, Campus Gel-senkirchen, Germany, [email protected] Magnetic resonance imaging (MRI) is a non-invasive and non-ionizing imaging technique, which uses energy in the radio frequency (RF) range. During MRI procedures the patient's body can absorb this energy, resulting in tissue heating, which can be significant for systems that use higher magnetic fields (�⃗� ). Usually, patient safety is assessed through the dosi-metric term called specific absorption rate (SAR). For ultra-high fields (B0≥7T), electrical (�⃗�) and magnetic (�⃗� ) compo-nents of RF fields, as well as the SAR profile in the object imaged, are highly complex and spatially non-uniform. There-fore, 3D numerical methods are used to design and analyse MRI RF coils and to assess �⃗� and SAR. In the present study, a birdcage coil for B0=7T was designed and constructed to investigate small animals. It has a cylindrical shape with 10cm diameter, 16.4cm height and is made of copper. Experiments using a spherical phantom (diameter: 7cm) filled with a solution of water, 1g/L 𝑁𝑎𝐶𝑙 and 2g/L 𝐶𝑢𝑆𝑂 were conducted at the 7T MRI scanner installed at PISA - imaging platform in the autopsy room, at the University of São Paulo, Brazil. �⃗� field distributions generated by the birdcage coil were measured and cross-checked with the numerical results in order to validate the methodology developed for �⃗� and �⃗� simulations. Using the electric field and postprocessing of the simulation results, local SAR values are predicated in various tissue samples. The simulated 𝐵 maps presents a very homogeneous internal distribution and both simulated and experimental results for water phantom are very similar. Predictions of SAR distribution were achieved for a 7cm diameter sphere filled with muscle-like tissue. The results indicate that the sample would not suffer any unsafe deposition of energy. Therefore, the workflow developed here seeks to ensure animal safety when using the designed coil in 7T MRI proce-dures.


Generation of a Simplified Brain Geometry for the Calculation of Local Cerebral Temperature using a 1D-Hemodynamics Model

Rosa Daschner, Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany, pub-

[email protected]

Lorena Krames, Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany

Yannick Lutz, Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany

Axel Loewe, Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany

Giorgio Cattaneo, Adceris GmbH & Co KG, Pforzheim, Germany

Olaf Dössel, Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany

In Western countries, stroke is the third-most widespread cause of death; 35–55% of the survivors experience permanent

disability. Therapeutic hypothermia (TH) showed neuroprotective effect in patients returning from cardiac arrest and is

therefore assumed to decrease stroke induced cerebral damage. Recently, an intracarotid cooling sheath was developed

to induce local TH in the penumbra using the cooling effect of cranial blood flow via collaterals. Unfortunately, so far

the control of cerebral temperature requires invasive measurements. Computational modeling provides unique opportu-

nities to predict the resulting cerebral temperature without invasive procedures. In this work, we generated a simplified

brain model to establish a cerebral temperature calculation using Pennes’ Bio-Heat-Equation and a 1D-hemodynamics

model of the cranial artery tree. In this context, we performed extensive literature research to assign the terminal segments

of the latter to the corresponding perfused brain tissue. Simulating intracarotid blood cooling, we analyzed the resulting

temporal and spatial cerebral temperature profiles for different degrees of an MCA stenosis. The simulation results

showed a significant influence of collateral flow on the penumbra cooling. The lower the degree of stenosis, the faster

and stronger cooling could be achieved. In the physiological contral case, as in case of minor stenoses, a temperature

decrease of 1.5 °C occurred within 10-15 minutes, whereas in case of a 100% stenosis, a decrease of 0.7 °C was observed

after one hour. In all cases, the systemic temperature decreased by less than 0.3 °C after 60 minutes of cooling. Further-

more, our model demonstrated the importance of considering the spatial distribution of gray and white matter. Summa-

rizing, our model can be used to study the induction of local TH in the penumbra of an acute stroke and the effect on

systemic temperature. In future, the influence of variations of the collaterals on cerebral cooling can be evaluated.


Modeling of the Human Cerebral Collateral Circulation: Evaluation of the Im-pact on the Cerebral Perfusion in Case of Ischemic Stroke

Lorena Krames, Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany, [email protected] Yannick Lutz, Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany Rosa Daschner, Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany Axel Loewe, Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany Giorgio Cattaneo, Adceris GmbH & Co KG, Pforzheim, Germany Olaf Dössel, Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany

Stroke is the third-most widespread cause of death in developed countries. 87% of all strokes are ischemic strokes. A new promising treatment method in case of an ischemic stroke is selective intracarotid blood cooling combined with mechanical artery recanalization. However, so far the control of the treatment requires invasive measurement of cere-bral temperature. An auspicious alternative is the use of computational modeling. In this work, we extended an existing 1D-hemodynamics model including the characteristics of the anterior, middle and posterior cerebral artery. Further-more, seven ipsilateral anastomoses were additionally integrated for each hemisphere. A stenosis was integrated into the M1 segment of the middle cerebral artery, due to the highest risk of occlusion there. The extended model was evaluated for various degrees of collateralization (“poor”, “partial” and “good”) and degrees of stenosis (0 %, 50 %, 75 % and 100 %). Moreover, cerebral autoregulation was considered in the model. The higher the degree of collateralization and the degree of stenosis, the higher was the blood flow through the collaterals. Hence, a patient with a good collateraliza-tion could compensate a higher degree of occlusion and potentially has a better outcome after an ischemic stroke. For a 100 % stenosis, a summed mean blood flow through the collaterals of 1.48 ml/s was predicted in case of good collat-eralization. Consequently, the blood supply via the terminal branches of the middle cerebral artery could be compen-sated by 57.08% of the physiological blood supply. In combination with a temperature model, our model of the cerebral collateral circulation can be used for a tailored therapy of hypothermal patients who suffered from an ischemic stroke.


Adaption of Avolio’s 1D Hemodynamics Model for Use in Cerebral Tempera-ture Calculation Yannick Lutz, Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany, [email protected] Axel Loewe, Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany Giorgio Cattaneo, Adceris GmbH & Co KG, Pforzheim, Germany Olaf Dössel, Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany Target temperature management in the form of therapeutic hypothermia (TH) is known to be neuroprotective for cardi-ac arrest patients and is assumed to decrease cerebral harm in case of ischemic stroke. Selective intra-carotid blood cooling is promising as it is considerably more effective and has fewer side effects than the systemic cooling used to-day. A novel approach is a closed-loop ballon cooling catheter placed in the common carotid artery, which is compati-ble with catheters for mechanical recanalization. However, it is not possible to measure and control the spatial cerebral temperature distribution without a considerable interference with the intervention or even injury of the patient during therapy. A computational model considering cerebral blood flow could predict spatial temperature profiles instead. In this work, we adapted a detailed hemodynamics model, to enable a realtime coupling of cerebral blood flow and tem-perature calculation. Therefore, we reduced Avolio's model of the entire human arterial tree, which so far served as the model base, by replacing the torso and both arms with respective 4-element windkessels. For the optimal choice of the parametersets of each of these windkessels, we analyzed the frequency behavior of the original model and performed an optimization considering a spectrally weighted root mean square error. Compared to the original Avolio model, the computing time was reduced by approximately 35 %, while the mean flow rates and flow profiles changed only slightly. The mean flow in the torso increased by 0.2 % and in the arms by 0.7 %. The summed flow in the terminal segments of the middle cerebral artery reduced by 1.2 %. Summarizing, our new model delivers cerebral blood flow at reduced computational cost without changing the original flow conditions. Therefore, it can be used as a new hemodynamics base for the calculation of cerebral temperature profiles.


Manufacturing process for hydrogel vessel phantoms

Marco Kalmar, INKA & Research Campus STIMULATE, Institute for Medical Engineering, Otto-von-Guericke Univer-

sity, Magdeburg, Germany, [email protected]

Thomas Hoffmann, Research Campus STIMULATE, Institute for Medical Engineering, Otto-von-Guericke University,

Magdeburg, Germany, [email protected]

Jörg Sauerhering, LTT, Institute of Fluid Mechanics and Thermodynamics, Otto-von-Guericke University, Magdeburg,


Fabian Klink, LKT, Institute of Machine Construction, Otto-von-Guericke University, Magdeburg, Germany,

[email protected]

Phantoms mimicking special physiological processes of the human body are essential for evaluating prototypes of medical

devices. For thermometric MRI measurements especially, the temperature spread in brain needs to be simulated. Since

this parameter is depended on the tissue perfusion a new hydrogel by MAGDASSIS et al. was evaluated in this work for

building models with hollow artery structures. This hydrogel can be polymerized through UV-light due to the nanoparti-

cles contained in it. Additionally, thermal parameters were measured and compared to human brain tissue. The indirect

manufacture of hydrogel phantoms showed good qualitative results for vessels with a diameter > 3 mm. In this process a

3D printed wax core was inserted in the hydrogel and after molding UV cured. After curing the core was dissolved in an

isopropanol bath. The thermal properties, obtained by the transient plane-source-methode, showed similar values com-

pared to the literature values of human brain tissue. Further limitations in the manufacturing process needs to be overcome

to use the indirect manufacture approach for smaller vessels of the brain


Numerical simulation and in vitro examination of the flow behaviour within coronary stents Helena-Sophie Melzer, Karlsruher Institute of Technology (KIT), Institute of Microstructure Technology (IMT), Eg-genstein-Leopoldshafen, Germany, [email protected] Ralf Ahrens, Karlsruher Institute of Technology (KIT), Institute of Microstructure Technology (IMT), Eggenstein-Leopoldshafen, Germany, [email protected] Jakob Dohse, MeKo Laserstrahl-Materialbearbeitungen e.K., Sarstedt, Germany, [email protected] Andreas E. Guber, Karlsruher Institute of Technology (KIT), Institute of Microstructure Technology (IMT), Eggen-stein-Leopoldshafen, Germany, [email protected] Despite the continuous development of coronary stents, there are still clinical complications such as thrombosis or in-stent restenosis. The cause is considered to be the occurrence of recirculation areas in front of or behind the stent struts during the flow-through of the stent result-ing in low velocities and low wall shear stresses ( w<0.5 Pa). These changed hemodynamic flow conditions can be traced back to the design of the stent. In order to be able to make prognosis for the optimization of future stent designs, mathematical flow simulations were performed. The design parameters of the stent, such as the strut height and width, edge fillets and chamfers of the struts, were varied in order to investigate their effects on the size of the recirculation areas. It could be shown that a reduced strut height and a chamfering of the struts reduce the recirculation zones. In order to verify these numerical results, experimental investigations were performed. Therefor the micro-particle image ve-locimetry (micro-PIV) method was used. This is a non-contact measurement method in which particles are added to the flow. The flow area is illuminated with two successive light pulses. The backscattered light is captured by a microscope camera and by means of a software the local flow velocity can be calculated by cross correlation. Since the PIV method is an optical method, it was necessary to transfer the existing metallic stents into transparent channel systems made of PDMS. A dilated stent in a tube with a similar diameter than a coronary vessel was used as a mould. The resulting negative of the stent structure was then used to cast the transparent channel systems. The PIV measurements correspond well with the numerical simulations. In further examinations, the strut-connectors will be investigated, as they also influence the hemodynamic flow conditions of the stent.


Towards enzyme-free tissue dissociation by predictive modelling

Stefan Scheuermann, Fraunhofer IPA, Theodor-Kutzer-Ufer 1-3, Mannheim, Germany,


Armin Schäfer, Neslihan Islak, Jens Langejürgen and Christian Reis, Fraunhofer IPA, Theodor-Kutzer-Ufer 1-3, Mann-

heim, Germany

The future of personalised diagnostics commences on the single cell level. Even high-end technologies like Next Gener-

ation Sequencing can be improved if applied on pure single cell populations (e.g., tumor cells without contaminating

stromal cells) or on a single cell level (DNA/RNA sequencing). The vast majority of these technologies need individual

and preferably unadulterated cells for the analytical process. Thus, decisive prerequisite for high-end analytics is the fast

and reproducible generation of pure and individual single cells from tissue samples.

The ability to extract individual cells from tissues is currently a bottleneck for cell-based diagnostic technologies and

remains crucial in the areas of tissue engineering, regenerative medicine and personalised medicine approaches. Tissue is

typically disintegrated by proteolytic digestion and various mechanical treatments. However, success has been limited by

long processing times, low yield and high manual workload leading to a significant increase in the overall analysis time.

To overcome these limitations, we developed a mechanical tissue dissociation process based on counter-rotating rows of

grinding teeth. In addition to this, we now present a method for a precise control of tissue dissociation enabling fast and

enzyme-free treatment. This method is based on an integrated torque sensor that provides continous information about

the struture integrity of the tissue sample during the dissociation process. We combine this sensor data with measured

single cell yields and quality in a predictive modelling approach. This is paving the way for automised individual pro-

cessing of tissue samples resulting in optimal process parameters and a minimised processing time.

The combination of predictive modelling with mechanical dissociation and tissue specific protocol development provides

single cell suspensions with high cell viability and preserved surface markers suitable for immunofluorescent staining,

flow sorting and subsequent molecular analyses. The proposed method can thus lead to condsiderable improved work-

flows regarding personalised diagnostic approaches.


Model of SpO2 signal of the neonate Veronika Huttova1,2, [email protected] Jakub Rafl1,2, [email protected] Knut Möller2, [email protected] Thomas E. Bachman1, [email protected] Petr Kudrna1, [email protected] Martin Rozanek1, [email protected] Karel Roubik1, [email protected] 1Department of Biomedical Technology, Faculty of Biomedical Engineering, Czech Technical University in Prague, Kladno, Czech Republic 2Institute of Technical Medicine, Furtwangen University, Villingen-Schwenningen, Germany The advantages of automatic control of the fraction of inspired oxygen in neonates have been documented in recently published clinical trials. Many control algorithms are available, but their comparison is missing in the literature. A math-ematical model of neonatal oxygen transport could be a useful tool for comparison of both automatic control algorithms and manual control of fraction of inspired oxygen. As both the automatic and manual control of oxygenation is primarily based on pulse oximetry, a module linking arterial (SaO2) and peripheral (SpO2) oxygen saturation must be included in the model. Many studies show that SpO2 measurement systematically overestimates SaO2 in neonates. Also, low perfusion or high noise can cause a low signal-to-noise ratio leading to inaccurate pulse oximeter readings. The aim of this study was to describe both the bias between SaO2 and SpO2 and the noise, characteristic for continuous SpO2 time record, for use in a computer model of oxygenation of a premature infant. The model of the output signal of the pulse oximeter consists of two principal components: The SpO2–SaO2 bias and the SpO2 measurement noise. The SpO2–SaO2 bias de-scribes a typical deviation of the SpO2 measurement as a function of the true SaO2 value. The bias function was based on clinical data published previously by Ross et al. In the interval 70–96% SaO2, the bias was best characterized using a third order polynomial function. At SaO2 below 70%, the bias was held constant. At SaO2 higher than 96%, the bias was estimated as zero. The SpO2 measurement noise was considered as a random process that affects biased SpO2 values at each time point. The statistical properties of the random noise were estimated from 24-hour SpO2 continuous records (2s sampling, 4s averaging) of three stable newborns. The results of the study will help to refine a computer model of neonatal oxygenation to the real situations observed in the clinical practice.


A new approach to quickly edit geometries and estimate stresses and discplacements of implants in real-time

Christopher Fleischmann, Institute for Biomedical Engineering, Weiden, Germany, [email protected] Reinhold Hartwich, Institute for Biomedical Engineering, Weiden, Germany, [email protected] Marc Hainke, Institute for Biomedical Engineering, Weiden, Germany, [email protected] Stefan Sesselmann, Institute for Biomedical Engineering, Weiden, Germany, [email protected] Finite Element Analysis (FEA) has a wide range of applications in the field of biomechanics. Besides calculating stresses and deformations of anatomical structures like bones and joints also new implant designs are routinely assessed by using FEA. Biomechanical data derived from motion capturing and forceplate measurements as a basis for multibody simulation and FEA, allow in silico simulations of implant stress limits under defined loadcases and how changes in the geometry can reduce critical stress levels. Thus, FEA reduces prototyping expenses and accelerates development processes. ANSYS Discovery Live (ANSYS, Inc., Canonsburg, Pennsylvania, US) is an innovative real-time FE-solution to assess stresses, displacements or other mechanical parameters under conditions of varying geometries and boundaries without the need of meshing tools. Object geometry can be edited easily by just shifting edges of the 3D-model by mouse dragging. New results are generated without time-consuming remeshing and adaption of boundary conditions. In this work, a volar-mounted titanium plate for osteosynthesis of fractures of the distal radius and corresponding screws were reverse engineered using a CT-scanner. Boundary conditions, like compression and bending forces, were applied as stated in standard literature. Aim of this study was a comparing validation of ANSYS Discovery Live with three well-established FE solutions: ANSYS Workbench (ANSYS, Inc., Canonsburg, Pennsylvania, US), Abaqus FEA (Dassault Systèmes SE, Vélizy-Villacoublay, France) and OptiStruct (Altair Engineering Inc., Troy, Michigan, US). The maximum von Mises stress, the stress contour and the maximum deformation were calculated for comparison with all four software solutions. This work did not focus on the development of a valid FE-model of osteosynthesis-plates. The results show a good agreement for all parameters computed by ANSYS Discovery Live compared to all of the other tested FE software solutions.Nevertheless, ANSYS Discovery Live also revealed some limitations. First of all, there is no possibility to assign multiple material properties. Furthermore, the mesh cannot be evaluated leading to a possible misinterpretation of critical stress levels.


Development of a Novel Low-cost Lung Function Simulator Florian Bautsch, Institute for Electrical Engineering in Medicine, Universität zu Lübeck, Lübeck, Germany, [email protected] Georg Männel, Institute for Electrical Engineering in Medicine, Universität zu Lübeck, Lübeck, Germany, [email protected] Philipp Rostalski, Institute for Electrical Engineering in Medicine, Universität zu Lübeck, Lübeck, Germany, [email protected] In order to test medical devices, industry increasingly uses simulators closely reassembling the behaviour of physiologi-cal systems. In the context of respiratory therapy, most available simulators are designed similarly to the human lung, requiring a ventilated volume. This highly adjustable volume allowing for fast dynamical changes is considered to lead to very cost-intensive devices, when incorporating spontaneous breathing. Therefore, we introduce a novel concept for a low-cost lung simulator, capable of mimicking the ventilation behaviour of the human lung at the Y-piece of a mechan-ical ventilator. The proposed design does not require an enclosed space to hold inhaled air nor expensive precise linear actuators adjusting its volume. Instead, the setup is designed similarly to a mechanical ventilator, connecting the system with one port to the ventilator and then dividing the hose into two independent branches. Each branch has an integrated radial fan and a proportional valve, controlling the inspiratory and expiratory flow, respectively. The mass flow and pressure are measured at the systems inlet port, representing the condition at patient airway. These measurements are used to close a control loop and emulate the behaviour of a patient by controlling the radial fans. In contrast to existing setups, the proposed design is not limited by the physical properties of a volume such as fixed maximum size, allowing the simulation of various types of patients. Numerical simulations to evaluate this system design showed the ability to generate a realistic spontaneous breathing pattern. With a first experimental setup it was possible to prove the feasibility of this approach, by generating common pressure and flow curves at the Y-piece of a ventilator during spontaneous breathing. Building on this design, the approach could eventually lead to a more accessible method for testing mechani-cal ventilators and accessories and therefore ultimately contribute to patient safety.


Plug-in circuit board for the Raspberry-Pi microcomputer to reproduce multi-channel original electrocardiograms

Tobias Haber1C, Pascal Striebel1, Juraj Melichercik2 and Bruno Ismer1 1Peter Osypka Institute for Pacing and Ablation at Offenburg University of Applied Sciences, Offenburg, Germany 2MediClin Heart Center, Lahr/Baden, Germany CCorresponding author: [email protected] Evaluation of electrocardiograms (ECG) is of great significance in diagnosis and treatment of cardiac arrhythmias. These are recorded as surface ECG using adhesive electrodes on the skin and, during cardiac electrophysiological (EP) studies, by endo- and epicardial electrode catheters. In cases of cardiac rhythm disorders, ECG recordings from differ-ent positions provide informations about the origin and propagation of the excitation. Precise knowledge of these ena-bles targeted treatments with either implantable pacemakers, defibrillators or catheter ablation. ECG simulators are commercially available for research and training purposes. Unfortunately, all of them only provide synthetic ECGs of normal and diseased heart rhythms as simplified waveforms with small variations and number of channels, thus being insufficient to explain and study sophisticated electrophysiological problems. Therefore, we aimed to reproduce original intracardiac and surface ECGs of rhythm episodes, recorded during EP stud-ies in order to make them usable as true-to-life analogue signals for research and teaching purposes. To reproduce episodes of interest recorded and digitally stored on either magneto-optical disks or CDs during invasive procedures with an EP-Lab System, we developed a plug-in circuit board fitted for the Raspberry-Pi microcomputer format. Therefore, to reproduce simultaneously recorded ECG sequences they have to be selected from the Lab Sys-tem’s data sets and exported as data files to a SD card to be processed by the Raspberry-Pi and reconverted into ana-logue output ECG signals that can be repeated as an endless loop. For the intended applications, the number of ECG channels was initially set to 12. Combination of the channels can be chosen via user menu program. Simulation of multi-channel simultaneous true-to-life ECGs is helpful, for example in development, optimization and testing of new algorithms for automatic detection and discrimination of life-threatening arrhythmias and their adequate electrical treatment with implantable defibrillators. Furthermore, this simulator will be applied in teaching and training of young cardiologists, clinical electrophysiologists and their assistance staff as well as specialists of medical engineering companies.


MRI flow measurements with a flexible stenosis phantom Alina Ibbeken, Institute of medical imaging, Universität zu Lübeck, Lübeck, Germany, [email protected] Pragathi Gurumurthy, Institute of medical imaging, Universität zu Lübeck, Lübeck, Germany, [email protected] Fenja Zell, Institute of medical imaging, Universität zu Lübeck, Lübeck, Germany, [email protected] Christina Hagen, Institute of medical imaging, Universität zu Lübeck, Lübeck, Germany, [email protected] Martin Koch, Institute of medical imaging, Universität zu Lübeck, Lübeck, Germany, [email protected] Thorsten M. Buzug, Institute of medical imaging, Universität zu Lübeck, Lübeck, Germany, [email protected] Obstructive sleep apnea (OSA) is a common sleep disorder caused by the collapse of the upper airway during sleep due to a shift of soft tissues. To further optimize the treatment, one needs a better understanding of the patient-specific caus-es of OSA. As groundwork, a simplification of the pharynx geometry, a flexible phantom of a stenosis was built accord-ing to Geoghegan (2012). The phantom has been used to carry out MRI flow sensitive measurements, to investigate the occurring flow conditions that lead to the collapse. This contribution is concerned with the comparison and analysis of the flow and phantom deformation using varying boundary conditions, such as the Reynold’s number and transmural pressure.


3D MRI velocity measurements in coronary stent designs for the validation of numerical analyses Kristine John, Institute of Fluid Mechanics, University of Rostock, Albert-Einstein-Str. 2, 18059 Rostock, Germany, e-mail: [email protected] Martin Bruschewski, Institute of Fluid Mechanics, University of Rostock, Albert-Einstein-Str. 2, 18059 Rostock, Ger-many, e-mail: [email protected] Lukas Quirin, Institute of Fluid Mechanics, University of Rostock, Albert-Einstein-Str. 2, 18059 Rostock, Germany, e-mail: [email protected] Jan Oldenburg, Institute for Biomedical Engineering, Rostock University Medical Center, Friedrich-Barnewitz-Str. 4, 18119 Rostock-Warnemünde, Germany, e-mail: [email protected] Finja Borowski, Institute for ImplantTechnology and Biomaterials e.V., Friedrich-Barnewitz-Str. 4, 18119 Rostock-Warnemünde, Germany, e-mail: [email protected] Klaus-Peter Schmitz, Institute for ImplantTechnology and Biomaterials e.V., Friedrich-Barnewitz-Str. 4, 18119 Ros-tock-Warnemünde, Germany, e-mail: [email protected] Michael Stiehm, Institute for ImplantTechnology and Biomaterials e.V., Friedrich-Barnewitz-Str. 4, 18119 Rostock-Warnemünde, Germany, e-mail: [email protected] Sven Grundmann, Institute of Fluid Mechanics, University of Rostock, Albert-Einstein-Str. 2, 18059 Rostock, Germa-ny, e-mail: [email protected] Due to the pathologically altered blood flow, restenosis and thrombosis forming are typical post-operational complica-tions of implanting coronary stents. Therefore, stent designs must consider the influence of the implant on the flow to-pology. Computational Fluid Dynamics (CFD) is an important method to analyze these internal flows. However, only experimental data proves the reliability of numerical models and therefore improves the accuracy of the numerical de-signs. A promising tool for such experiments is Magnetic Resonance Imaging (MRI) which can provide three-dimensional velocity data of these internal flows within minutes. This study examines the applicability of MRI in the optimization process of future stent designs. As a proof of concept, this study investigates the MRI velocity data of three simplified stent designs (mirror-, row- and helical-pattern). To achieve a sufficient signal intensity and resolution, the stent models were 15 times the size of an original stent. According to fluid dynamics similarity laws, internal flows of the original and scaled model have similar properties if the Reynolds number is the same. A flow circuit connected the models inside the magnetic resonance scanner with a 100-liter tank and a pump. The flow medium was a mixture of water and glycerin with a kinematic viscosity of 6.04*10-5 m^2/s and a flow rate of Q=47 l/min, resulting in a Reynolds number of 460. The accuracy of the velocity measurements was verified with analytical solutions and flow rate meas-urements. A companion abstract is dedicated to the comparison of the MRI data with CFD data. It is shown that the numerical approach could be thoroughly validated with the help of MRI. In conclusion, the experimental flow analysis with MRI is a reliable method to support the numerical optimization of future stent designs.


Development of a constitutive law for numerical simulation of artificial leaflet-structures for transcatheter heart valve prostheses Sylvia Pfensig, Institute for ImplantTechnology and Biomaterials e.V., Rostock-Warnemünde, Germany, [email protected] Daniela Arbeiter, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock-Warnemünde, Germany, [email protected] Stefanie Kohse, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock-Warnemünde, Germany, [email protected] Sebastian Kaule, Institute for ImplantTechnology and Biomaterials e.V., Rostock-Warnemünde, Germany, [email protected] Michael Stiehm, Institute for ImplantTechnology and Biomaterials e.V., Rostock-Warnemünde, Germany, [email protected] Niels Grabow, Institute for Biomedical Engineering, Rostock University Medical Center, Rostock-Warnemünde, Ger-many, [email protected] Klaus-Peter Schmitz, Institute for ImplantTechnology and Biomaterials e.V. and Institute for Biomedical Engineering, Rostock University Medical Center, Rostock-Warnemünde, Germany, [email protected] Stefan Siewert, Institute for ImplantTechnology and Biomaterials e.V., Rostock-Warnemünde, Germany, [email protected] While the current generation of devices for minimally invasive treatment of severe symptomatic aortic valve stenosis is based on xenogenic leaflet material, artificial polymeric leaflet-structures represent a promising approach for future im-provement of heart valve performance. For enhanced long-term success of polymeric leaflet-structures, limitations re-garding calcification and durability have to be adressed. The objective of the presented study was the development of a constitutive law representing the material properties of artificial polymeric leaflet-structures of transcatheter heart valve prostheses in numerical simulation to assess the in sili-co leaflet performance. Mechanical characterization of casted films and nonwoven specimens of a polycarbonate based silicone elastomer were conducted by means of uniaxial tension and planar shear testing, respectively. For validation purposes, experimental data were compared with the results of finite-element analysis (FEA) using different hyperelas-tic models. Strain energy function for third-order ogden hyperelastic model achieved the best fit of the non-linear stress-strain behaviour of the isotropic polymeric material with the experimental data. It was choosen for further FEA of valve leaflet performance under physiological pressurization to analyze the suitability of various manufacturing processes for polymeric leaflet-structures. Therefore a specific leaflet design with wall thickness of 400 µm was used. As a result of FEA, time dependent leaflet deformation, leaflet coaptation surface area (CSA) and leaflet opening area (LOA) of cast-ed and nonwoven leaflet structures were calculated. While LOA was comparable for casted and nonwoven leaflet struc-tures, obtained leaflet dynamics in a cardiac cycle under physiological pressurization demonstrated crucial influence of the manufacturing process. For nonwoven leaflet structures, an enhanced CSA could be demonstrated in comparison to casted structures. FEA using a validated hyperelastic constitutive law represents a useful tool for in silico performance evaluation of pol-ymeric leaflet-structures under physiological loading and proves the suitability of the polymeric artificial leaflet-material for percutaneous heart valve prostheses.


A setup for magnetic nanoparticle targeting to the eye Diana Zahn, Institute for Biomedical Engineering and Informatics, TU Ilmenau, Ilmenau, Germany, [email protected] Katja Klein, Institute for Biomedical Engineering and Informatics, TU Ilmenau, Ilmenau, Germany, [email protected]

Dmitry Berkov, General Numerics Research Lab, Jena, Germany, [email protected]

Michael Eichhorn, Institut für Anatomie, LSII, Universität Erlangen-Nürnberg, Erlangen, Germany, [email protected]

Sergej Erokhin, General Numerics Research Lab, Jena, Germany, [email protected] Edgar Nagel, Ophthalmic Private Practice, Rudolstadt, Germany, [email protected]

Olena Semenova, General Numerics Research Lab, Jena, Germany, [email protected]

Ioan Stanca, Magnetworld AG, Jena, Germany, [email protected]

Minzhi Wu, Magnetworld AG, Jena, Germany, [email protected]

Silvio Dutz, Institute for Biomedical Engineering and Informatics, TU Ilmenau, Ilmenau, Germany, [email protected] A lot of diseases of the eye are treated by intravitreal injection of a pharmaceutical agent, where the vitreous serves as a drug depot. Since this injection is associated with substantial risks, the aim of our study is to replace the syringe injection by a “magnetic injection” where the drugs are coupled to magnetic nanoparticles and will be targeted into the eye magnetically. First, it has to be investigated, whether magnetic nanoparticles can be transported through different tissue types of the eye magnetically. A setup had to be designed and built up to perform these experiments. Main part of this setup is the magnetic field applicator, which generates the magnetic field gradient to move the magnetic nanoparticles. For this purpose, different helmet setups basing on arrays of permanent magnets as well as of superconducting magnets were designed. The resulting magnetic field gradient at the front of the eye was calculated by means of numerical simulations. In the first targeting experiments (using distinct tissues of the eye, e.g. sclera, cornea), the resulting field gradients of these helmet systems (5T/m for permanent magnets and 20 T/m for superconducting magnets) were emulated by simple permanent magnet arrays. Next, the magnetic nanoparticle had to be optimized for the targeting. For this purpose, magnetic iron oxide cores were prepared in multicore structures and coated by a variety of organic materials (e.g. different dextranes, starch, PEG). The stability of the particles within different biological fluids (e.g. artificial tears) was investigated by means of turbidimetry. It turned out that starch is the most promising coating for this purpose. In the contribution we present the basic setup for further tissue studies as well as first targeting results for larger multicore particles. Ongoing work is focused on the assembly of enhanced magnet arrays resulting in stronger mag-netic field gradients.


Biocompatibility of magnetic iron oxide nanoparticles for biomedical applica-tions Claudia Matschegewski, Institute for ImplantTechnology and Biomaterials e.V., Rostock, Germany, [email protected] Anja Kowalski, micromod Partikeltechnologie GmbH, Rostock, Germany, [email protected] Knut Müller, micromod Partikeltechnologie GmbH, Rostock, Germany, [email protected] Henrik Teller, micromod Partikeltechnologie GmbH, Rostock, Germany, [email protected] Swen Großmann, Institute for ImplantTechnology and Biomaterials e.V., Rostock, Germany, [email protected] Niels Grabow, Institute for Biomedical Engineering, University of Rostock, Germany, [email protected] Klaus-Peter Schmitz, Institute for ImplantTechnology and Biomaterials e.V., Rostock, Germany, [email protected] Stefan Siewert, Institute for ImplantTechnology and Biomaterials e.V., Rostock, Germany, [email protected] Magnetic nanoparticles are of exceeding interest in various biomedical applications including magnetic particle imaging (MPI), magnetic resonance tomography (MRT), cancer hyperthermia therapy or as drug carriers. Due to their different synthesis procedures and application-driven surface properties, biological characterization of magnetic nanoparticles is essential to assess their suitability for intended biomedical applications. The present study aims at assessing in vitro biocompatibility of two commercially available magnetic nanoparticle for-mulations: dextran-based magnetic nanoparticle synomag-D and bionized nanoferrite BNF-starch. Synomag-D possess-es a maghemite core with a dextran shell and a particle diameter of 50 nm, BNF-starch is composed of a magnetite core and a hydroxyethyl starch shell while reaching a particle diameter of 100 nm. Biocompatibility was assessed according to ISO 10993 by analyzing cell viability of human endothelial EA.hy926 cells with CellQuantiBlue Assay (BioAssay Systems, USA) after 24 h incubation with the nanoparticles at iron oxide concentrations ranging from 10 to 100 µg Fe/ml. For synomag-D, cell viability ranged between 94.0 – 109.3% showing no significant difference compared to the unloaded control. Exposure to BNF-starch at 10-50 µg Fe/ml demonstrated no significant alteration in cell viability compared to the unloaded control, while at 100 µg Fe/ml, cell viability of EA.hy926 was significantly decreased to 58.1 %. Confocal laser scanning microscopy showed no cellular uptake of synomag-D nanoparticles in EA.hy926 cells while uptake of BNF-starch nanoparticles similarly increased with Fe-concentration. In summary, both nanoparticle formulations were found to exhibit excellent biocompatibility according to ISO 10993, however, for BNF-starch cell viability was significantly decreased at 100 µg Fe/ml. Intracellular uptake was altered, probably due to distinct particle properties like surface functionalization or hydrodynamic diameter. Further research will provide deeper insights in cell-nanoparticle interactions towards the assessment of the biological performance of iron oxide nanoparticles and their suitability as theranostics.


Optical endovascular imaging by combination of endoscopy and OCT Axel Boese, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany, [email protected] Akhil Karthasseril Sivankutty, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany, [email protected] Michael Friebe, INKA, Institute of Medical Technology, Otto-von-Guericke University, Magdeburg, Germany, [email protected] For imaging of the vascular structure, angiography is state of the art. This can be done by contrast enhanced X-Ray, CT or MR imaging. But these modalities typically only show the blood flow and not a depiction of the vasculature itself. To provide information about the vessel walls and plaques narrowing the blood flow, catheter based intra vascular ultra-sound or vascular optical coherence tomography can be used. Optical endoscopic imaging is rarely used in vascular di-agnosis. But endoscopic imaging can depict superficial inflammations or defects of the intima vessel layer and the real anatomical shape of the inner vasculature e.g. at bifurcations or aneurysms. Since OCT and endoscopic imaging both need a flushing to remove the blood for a short time, a combination of both modalities seems obvious. For combining the two modalities, various background studies were performed including the selection of a feasible fibre endoscope, light source and camera system. A new pull-back and flushing device was designed and created for realizing the synchronous image acquisition using the two modalities. For calibration of the system and definition of the pullback and imaging parameters, first tests on artificial phantoms were performed. Then vascular and tissue models were imaged in a combined pullback mode after using the flush for complete blood removal. Endoscopic images were acquired in a video mode. The analysis of the images was done subjectively. As expected the OCT provided structural information of the wall. The endoscopic images in combination with pullback appear blurry in video mode. The flushing liquid hinders the au-tomatic focusing of the camera. Thus, smaller details could not be identified but bifurcations were visible. Even though the results were not good as expected, the study showed the potential of such a bimodal system and addressed the issues faced in the initial implementation.


Establishment and initial characterization of a simple 3D wound healing

model

Sabine Hensler, Institute of Technical Medicine, Furtwangen University, Villingen-Schwenningen,

Germany, [email protected] Claudia Kuhlbach, Institute of Technical Medicine, Furtwangen University, Villingen-Schwenningen,

Germany, [email protected] Jacquelyn Dawn Parente, Institute of Technical Medicine, Furtwangen University, Villingen-Schwenningen,

Germany, [email protected] Margareta M. Mueller, Institute of Technical Medicine, Villingen-Schwenningen, Germany, muem@hs-

furtwangen.de Knut Möller, Institute of Technical Medicine, Furtwangen University, Villingen-Schwenningen, Germany,

[email protected] Poor wound healing as consequence of malfunctions in the regulation of the healthy tissue repair response affects millions of people worldwide. The number of therapies available to successfully treat chronic wound is still very limited and their development is costly and time consuming. Therefore simple to use 3D systems, reflecting the in vivo tissue complexity, are urgently needed. We introduce a 3D organotypic model (OTC) containing the major cell components active during wound healing i.e. keratinocytes, fibroblasts and inflammatory cells that was established to analyze novel therapy options for chronic wounds. The model system allows to determine the effect of different therapeutic approaches on wound closure, cell differentiation and cytokine secretion. Besides treatment with hydrogels containing growth factor, there are first reports on irradiation with visible light of different wave length (Low Level Light Therapy) as a means to enhance wound closure. However the mechanisms underlying therapy as well as optimized wavelength and does regimens are not clear and were therefor analyzed using our 3D organotypic model. With this standardized model we could show epithelial closure under control conditions as well as differential effects of red and blue light irradiation with respect to stability of the newly formed epithelium and the time until epithelial closure. First results on cytokine expression show differential cytokine profiles upon different wavelength irradiation e.g. high expression of TGF beta and IL1 beta in red light irradiated cultures and increased GM-CSF expression with blue light irradiated and control cultures.


Investigation of the Inertial Cavitation Activity of Sonosensitive and Biocompatible Nanoparticles for Drug Delivery Applications Employing High Intensity Focused Ultrasound

Benedikt George, Department of Sensor Technology, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany, [email protected] Michael Fink, Department of Sensor Technology, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Ger-many, [email protected] Stefan J. Rupitsch, Department of Sensor Technology, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany, [email protected] Helmut Ermert, Department of Sensor Technology, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany, [email protected] Pia T. Hiltl, Department of Pharmaceutics, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany, [email protected] Geoffrey Lee, Department of Pharmaceutics, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany, [email protected] An approach to improve chemotherapy, while minimizing side effects, is a local drug release close to the tumorous tissue. For this purpose, the active drug component is often bound to nanoparticles employed as drug carriers. The suspension consisting of nanoparticles, carrier liquid as well as an active drug component is intravenously injected near by the tumor. As opposed to healthy tissue, malignant tissue has a defective vascular system because of rapid growth and is therefore finely fenestrated, making it permeable to particles in the nanometer range. This effect is widely known as the Enhanced Permeability and Retention Effect (EPR). Local drug release is activated due to the sonosensitive behavior of the nanoparticles by the inertial cavitation effect, which is generated by a High Intensity Focused Ultrasound (HIFU) field irradiating the tumorous area from outside the body. The aim of this method is to keep the treatment time as short as possible and at the same time to achieve a complete release of the active drug component. Presumably, the duration of the drug release depends on the cavitation activity, which is controlled by the emitted ultrasound signal. For this reason, it is crucial to develop a suitable ultrasound signal defined by its signal amplitude, signal frequency and signal duration to induce inertial cavitation. Within the scope of this work, solely the signal frequency (500 kHz to 1 MHz range) was varied using a broadband ultrasound transducer whereas other signal parameters were left constant. Investigations using a setup for passive cavitation detection (PCD) have shown, that lower frequencies lead to a higher cavitation activity than higher frequencies. Further investigations will include other signal parameters (e.g. bandwidth, wave form) to design an optimal ultrasound signal for a high cavitation activity rate to enable an efficient localized drug release.


Guiding and Accumulation of Magnetic Nanoparticles Employing High Intensity Focused Ultrasound for Drug Targeting Applications

Benedikt George, Department of Sensor Technology, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany, [email protected] Michael Fink, Department of Sensor Technology, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Ger-many, [email protected] Stefan J. Rupitsch, Department of Sensor Technology, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany, [email protected] Stefan Lyer, Section of Experimental Oncology and Nanomedicine, University Hospital Erlangen, Erlangen, Germany, [email protected] Christoph Alexiou, Section of Experimental Oncology and Nanomedicine, University Hospital Erlangen, Erlangen, Ger-many, [email protected] Helmut Ermert, Department of Sensor Technology, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany, [email protected] Magnetic Drug Targeting (MDT) is a cancer treatment technique that enables a local chemotherapy. In MDT, chemotherapeutic drugs are bound to magnetic nanoparticles and are accumulated in the tumor area by means of an external magnetic field. Unfortunately, a single magnet can only generate a pulling magnetic force. However, in some applications a pushing force on the nanoparticles could be advantageous. One possibility to do so is to exploit the acoustic radiation force generated by a high intensity focused ultrasonic transducer. In order to investigate whether the acoustic radiation force can be utilized to guide drug carrying nanoparticles through the vascular system, a test bench was built that emulates the anatomy of the vascular system. It contains a peristaltic pump, representing the human heart, a damping element acting as the aorta and a pipeline that branches into two sub-pipes acting as a vessel bifurcation. The focus of the ultrasonic transducer (835 kHz, 0.63 MPa, mechanical index MI=0.69 below the FDA limit for diagnostic ultrasound) is adjusted to the branching point of the pipeline system so that the pushing force on the nanoparticles should increase the particle concentration in a certain branch of the pipeline system. To verify the change of particle concentration, the content of iron in both branches is determined using microwave plasma atomic emission spectrometry (AES). After the measurements, the particle concentration in each of the branches was determined. Without acoustic irradiation of the branching point, the nanoparticles spread evenly over the two branches with equal particle densities. With acoustic irradiation the nanoparticle flow could be controlled in that way that the content of iron increased significantly in one of the branches as opposed to the other one. This proved that the acoustic radiation force could be employed for particle guiding and accumulation in drug targeting applications.


Design and first results of a phantom study on the suitability of iterative

reconstruction for lung-cancer screening with low-dose computer tomography

Britta König, Faculty of Medicine, University of Duisburg-Essen, and Faculty of Electrical Engineering and Applied

Natural Science, Westphalian University, Campus Gelsenkirchen, Germany, [email protected]

Nika Guberina, Institute for Diagnostic and Interventional Radiology and Neuroradiology, Faculty of Medicine,

University of Duisburg-Essen, Germany, [email protected]

Hilmar Kühl, Clinic for Radiology, St. Bernhard-Hospital Kamp-Lintfort GmbH, and Faculty of Medicine, University

of Duisburg-Essen, Germany, [email protected]

Waldemar Zylka, Faculty of Electrical Engineering and Applied Natural Science, Westphalian University, Campus

Gelsenkirchen, Germany, [email protected]

We report on computer tomography (CT) iterative reconstruction (IR) algorithms, specifically the impact of their

statistical and model-based strength on image quality in low-dose lung screening CT protocols in comparison to filtered

back projection (FBP). In a phantom study, we probed whether statistical, model-based IR in conjunction with low-dose,

and ultra-low-dose protocols are suitable for lung-cancer screening. This relates to previous studies, e.g. Lung-Cancer-

Screening-Trial (NLST), 2011, conducted in USA.

In a first setup, artificial lung nodules shaped as spheres with diameter d=8/10/12mm and made from material with

calibrated Hounsfield Units, HU=-690/-50/+100HU, were attached on marked positions in the lung structure of the

anthropomorphic LUNGMAN chest phantom PH-1 R16511. Additionally, two spherical targets with d=3/5mm, +100HU,

were inserted. Nodule positions were selected by distinguished radiologists. In a second setup, spheres were exchanged

by artificial spicules with diameters d=16/20/24mm, identical CT numbers and were placed at the same positions. Every

setup was scanned on Somatom Force CT Scanner (Siemens Healthineers, Erlangen, Germany) using following protocols:

(i) standard high contrast (SHC; 120kV/dose modulation), (ii) low-dose (LD; 120kV/40mAs) and (iii) ultra-low-dose

(ULD; 120kV/20mAs). For reconstruction FBP and the IR algorithm ADMIRE at three different strength levels were

used. Volume CT dose index CTDIvol and dose-length product DLP were recorded and the effective dose calculated.

Currently, radiologists extensively review all image series in terms of lung nodules. They assess subjective image quality

using a 6-point Likert scale, HU value, diameter of the largest and the smallest target, and signal- and contrast-to-noise

ratios.

For spherical targets CTDIvol was 2,99mGy (-70,1%) for SHC, 2,65mGy for LD (-73,5%) and 1,31mGy for ULD (-

86,9%). Considering spicules, CTDIvol was 3,01mGy (-69,9%) for SHC, 2,65mGy for LD (-73,5%) and 1,31mGy for

ULD (-86,9%). The drop of CTDIvol compared to the diagnostic reference value for chest CT (10mGy) issued by the

Federal Office for Radiation Protection, Germany, is given in parentheses. The associated probability calculated for all

protocols using Student's t-Test (paired, one sided) was p<0,00001.

Preliminary evaluation of objective and subjective quality parameters indicates that LD and ULD protocols in conjunction

with IR assert high quality lung-nodule detection. Concerning dose reduction and subjective image quality, preliminary

results reveal that IR algorithm with moderate to high strength is an indispensable alternative to FBP, thus, potentially

suitable for lung-tumour screening.


Influence of 12-bit and 16-bit CT values of metals on dose calculation in radiotherapy using PRIMO, a Monte Carlo code for clinical linear accelerators

Zehra Ese, Department of General and Theoretical Electrical Engineering, University of Duisburg-Essen and CENIDE –

Center of Nanointegration Duisburg-Essen, Campus Duisburg, Germany and Department of Electrical Engineering and

Applied Natural Science, Westphalian University, Campus Gelsenkirchen, Germany, [email protected]

Waldemar Zylka, Department of Electrical Engineering and Applied Natural Science, Westphalian University, Campus

Gelsenkirchen, Germany [email protected]

Patients with metallic implants are challenging the accuracy of radiotherapy treatment planning due to computed tomog-

raphy (CT) limitations on materials with high atomic number. On CT images metals above a certain electron density

(ED~3.4 relative to water) saturate at the maximum Hounsfield Unit (HU) value in the conventional 12-bit HU scale

(CHU) [-1024HU ;+3071HU]. This might lead to errors in dose calculations. An extended HU scale (EHU) allows the

proper representation of metals. We quantify the effect of CT values of metals in 12-bit and 16-bit on dose calculations

in radiotherapy treatment planning systems.

Dose simulations for metals in water environment were performed with the software PRIMO (version 0.3.1.1681).

PRIMO enables the simulation of clinical linear accelerators to estimate dose distributions and is based on PENELOPE,

a Monte Carlo code for the calculation of photon and electron transport. Artificial CT scans of a water phantom (350mm

x 350mm x 350mm) including a metal disk (diameter =21mm, thickness =5mm) placed in the upper part of the phantom

was generated. Monte Carlo calculations for titanium, chromium, copper and an artificial material with HU=CHUmax

(representing the saturation value of these metals at CHU) were performed. The HU values of these metals were quanti-

fied with Varian Eclipse™ (version 13.5) software. CT scans used for HU quantification were acquired with a GE Light-

Speed RT CT (General Electric, Boston, U.S.A) in 16-bit scale [-31743HU ;+31743HU]. For each simulation a static

field with a size of 100mm x 100mm were simulated in 6MV photon beam mode. The metal sample was aligned to the

center of the primary radiation field. A total dose of 62 Gy was applied in one single fraction. The depth dose profiles

were analyzed and the relative dose differences between the metals determined with EHU value and CHUmax value, re-

spectively, were calculated.

We quantified the following EHU values: for titanium EHUTI =3433HU, for chromium EHUCr=6156HU and for copper

EHUCu=7876HU. The dose differences ΔD increase with increasing electron density of a material.

In order to increase the accuracy of dose calculation on patients with implants, CT imaging in the extended HU scale is

required. This also ensures better dose monitoring on implants which can even reduce the risk of malfunction of active

implants to increase patient safety.






Robust motion tracking of deformable targets in the liver using binary feature libraries in 4D ultrasound Daniel Wulff, Universität zu Lübeck, Lübeck, Germany, [email protected] Ivo Kuhlemann, Institut für Robotik und Kognitive Systeme, Lübeck, Germany, [email protected] Floris Ernst, Institut für Robotik und Kognitive Systeme, Lübeck, Germany, [email protected] Achim Schweikard, Institut für Robotik und Kognitive Systeme, Lübeck, Germany, [email protected] Svenja Ipsen, Institut für Robotik und Kognitive Systeme, Lübeck, Germany, [email protected] In radiation therapy of abdominal targets, optimal dose delivery to the tumour can be challenging due to intrafractional motion. Current target localization methods mainly rely on X-ray imaging and implanted markers, leading to indirect, surrogate-based tracking and additional radiation exposure. In contrast, 4D ultrasound (4DUS) imaging can provide volumetric images of soft tissue tumours in real-time without ionizing radiation, thus facilitating non-invasive, direct tracking of the target structure. In this study, the target was defined by strong features located in its local neighbourhood. Features were extracted using the FAST detector and BRISK descriptor extended to volumetric images. To account for anatomical variability caused by soft tissue motion, a feature library covering 20 breathing cycles at 4Hz imaging frequency was generated. For li-brary creation, the target shape was manually annotated in each phase and corresponding, robust features and their rela-tive locations were automatically detected and stored. During tracking, features were extracted from the current 4DUS volume and compared to the feature library. The most similar features, measured by the hamming distance, were then used to estimate the current target position and shape. The developed method was evaluated in 4DUS sequences of the liver of 3 healthy subjects. For each dataset, a charac-teristic vessel bifurcation was defined as target and manually contoured in two discrete 90s segments (training and test phase). Training was used for library creation, the test phase for target tracking using the pre-generated library. Com-pared to the ground truth annotations, a mean 3D position error of 2.05mm and dice coefficient of 78.9% was measured in the test data over all subjects. These promising results show that binary feature libraries can be used for robust target localization in 4DUS data in vivo and could potentially enable a tracking method less sensitive to target deformation caused by soft tissue motion.


Comparison of approval procedures for medical devices in Europe and the USA Marcel Vila Wagner, Technische Hochschule Mittelhessen (THM), FB Life Science Engineering (LSE), Institut für Biomedizinische Technik (IBMT), Wiesenstr. 14, 35390 Gießen, Germany, e-mail: [email protected] Thomas Schanze, Technische Hochschule Mittelhessen (THM), FB Life Science Engineering (LSE), Institut für Biomedizinische Technik (IBMT), Wiesenstr. 14, 35390 Gießen, Germany, e-mail: [email protected] Amazing achievements such as the discovery of penicillin increased life expectancy in the 19th century. At the beginning of the 20th century, the influence of technical equipment and biomedical research led to a further leap in life expectancy. The use of technical equipment for disease detection and therapeutic applications led to an increase in life expectancy of over 80 years. In comparison, life expectancy has doubled in the last hundred years. Medical devices are nowdays present everywhere. The use of computer devices with sophisticated software, also improved the quality of life. This is linked to the fact that all these achievements have now led to the emergence of one of the largest import and export markets in the USA, alongside Europe. In Germany, sales in the medical technology sector alone amount to 28 billion euros. In order to guarantee a uniform quality of this abundance of different products and therapies, there are worldwide corresponding regulations, to which all manufacturers must adhere. The entry into force of these regulations, with the associated approval and testing obligations for each individual medical device, ensures that a consistently high quality of products is used on patients. Of course, high quality as well as high functionality and safety levels of medical products are a must. However, the implementation of these regulations is realized differently in the various markets, as there is no global harmonization. This work focuses on approval procedures for medical devices in Europe and the USA and compares significant differ-ences in the approval procedures. An example is an approval of medical devices by an US government agency (FDA). In Europe there is a manufacturer's declaration of conformity for the approval. In addition, the difficulties for manufacturers in obtaining approvals in the USA and Europe will also be discussed.


Analysis of regulatory requirements of medical devices and in-vitro diagnostics worldwide for the development of an efficient procedure of registration for man-ufacturers of medical products Magdalena Kedwani, Institute of Health Care Engineering, TU Graz, Graz, Austria, [email protected] Due to globalization and the quick development of technology, each government aims to ensure the safety and performance of products brought to their markets to protect its population. The peoples’ health state is of great significance and influenced easily by the quality of medical products. Therefore governments enact laws, directives and regulations to assure that quality. Nevertheless, these regulations can impede innovation and create trade barriers which result in an adverse effect on national economies. Where in some states no regulatory system is installed, others have highly sophisticated registration requirements that must be met. These diversities result in a challenge especially for small and medium sized companies, whose resources are often limited. Manufacturers must control this diverse regulatory requirements by analyzing each market. Therefore an efficient procedure of registration should be defined that streamlines different registration requirements and ensures regulatory compliance. Next to regulatory authorities describing these requirements also harmonization groups play an important role in the design of the global regulatory landscape. Therefore also the most important harmonization groups and their current activities were investigated. The analysis showed that the impact of harmonization groups can be identified easily since new defined or updated regulatory requirements are oriented on their guideline. Still the harmonization of regulatory requirements in the medical device sector is not sufficiently enhanced. Thus the confrontation with each national regulatory system is inevitable.


Mobile compressed gas supply for active orthoses and exo-skeletons

Laura Schwenkel, Institut für Medizingerätetechnik, Universität Stuttgart, Stuttgart, Deutschland, [email protected] Swantje Janzen, Institut für Medizingerätetechnik, Universität Stuttgart, Stuttgart, Deutschland, [email protected] Pia Mühlbauer, Institut für Medizingerätetechnik, Universität Stuttgart, Stuttgart, Deutschland, [email protected] Peter P. Pott, Institut für Medizingerätetechnik, Universität Stuttgart, Stuttgart, Deutschland, [email protected] In this study a basic principle for the gas supply of a pneumatic actuation for a mobile active knee joint orthosis is de-scribed. Instead of using a compressor or a bulky pressure reservoir, the system is supplied with pressurized gas directly from a thermodynamic process to reduce size and weight of the device. To achieve this goal a literature search was per-formed identifying chemical processes. These options were then analysed and evaluated considering the aspects energy density, safety, eco-friendliness, and technical feasibility of the construction. The expansion of liquified carbon dioxide with phase change achieves the best result due to its high level of safety and the simple technical feasibility of the sys-tem. However, CO2 cools down considerably during the expansion, so heating up again to room temperature is neces-sary. Therefore, the technical construction includes a passive and an active heat exchanger.


Validation of a test system for microclimatic properties of body-attached medi-cal aids (KliMed-HM) Simon Gallinger, Medical Engineering, Technische Universität Berlin, Berlin, Germany, [email protected] Christina Mittag, Medical Engineering, Technische Universität Berlin, Berlin, Germany, [email protected] In the BMBF-funded research project KliMed-HM microclimate test systems and methods in the field of medical tech-nology were developed. These are suitable for evaluating body-attached medical aids under standardized conditions with respect to their microclimatic properties. While previously the microclimatic properties of skin contact materials were tested by wearing the aids on human test subjects, the new test system is a laboratory test system without subject involve-ment and thus without individual, non-reproducible subject influence. Based on a comprehensive analysis of human sweat behavior in contact with various surfaces, techniques have been developed that allow a technical modeling of the typical behavior of the skin beneath the surface of the device. By adapting the temperature and humidity parameters, a physiological microclimate is generated and measured. The test system can simulate different load and occlusion situations. This paper describes the method and results of the validation of the prototype laboratory test system against human skin tests. Collaborating partners were the skin physiology of the Department of Dermatology, Venereology and Allergology at the Charité Universitätsmedizin Berlin for studies of human transpiration behavior and secondary diseases; the Rehabtech Research Lab GmbH for the development of the requirements for skin contact surfaces of a neighboring device and for the development of new auxiliary surfaces; the Berlin Certification, Testing and Certification Body for Medical Devices GmbH for the development of the specific requirements for microclimate testing in a certified testing laboratory; as well as the engineering office Reinhard Schulte for the development of the device electronics.


Individual Avatar Feedback Creation for Assisted Motion Control Lars Lehmann, Professur Digital- und Schaltungstechnik, Technische Universität Chemnitz, Chemnitz, Germany, [email protected] Gangolf Hirtz, Professur Digital- und Schaltungstechnik Technische Universität Chemnitz, Chemnitz, Germany, [email protected] In medical training therapy (MTT), the precise execution of the training exercises developed by a therapist is of decisive importance for the success of the therapy. Currently, a therapist must treat up to 15 patients simultaneously on an outpa-tient basis. The consequences of demographic change and increasing cost pressure in the health sector will further exac-erbate this problem. At the TU Chemnitz an assistance system was developed, which can evaluate both quantity and quality of the accomplished movement on the basis a purposeful model and can give by means of feedback directly to the patient recommendations for action. An avatar in traffic light colours signals in which body region an error has oc-curred. The individualization of the underlying three-dimensional avatar increases the willingness of the patients to par-ticipate in the exercises and to carry them out even without the supervision of the specialist staff. Thus, the increase of immersion contributes to successful motor rehabilitation. Here the skeleton, which is necessary for the movement anal-ysis and which is created with a 3D sensor, is connected with a triangle mesh and the attractive weights on the surface of the model are calculated for each individual bone. These weights indicate how strongly the skeletal motion moves the model. The actual animation calculation is done in a shader program on the GPU. Due to the hardware-oriented imple-mentation, movement and evaluation is possible in real time. Basically any wireframe model can be selected and con-nected to the system. Thus, the patient's preferences and change requests can be addressed at any time. The implementa-tion was done with Qt(C++), QML, OpenGL and GLSL. It is to be examined whether a further lifelike 3D scan of the person and the subsequent porting into the motion analysis system additionally supports the test persons in rehabilitat-ing learning.


Finite-Element-Analysis of 3-axial femural stress during the implanta-tion of hip endoprosthesis itle of contribution Subke Joerg, Life Science Engineering, Technische Hochschule Mittelhessen, Gießen, Germany, [email protected] Schubert Philipp, Life Science Engineering, Technische Hochschule Mittelhessen, Gießen, Germany, [email protected] Kerber Bastian, Life Science Engineering, Technische Hochschule Mittelhessen, Gießen, Germany, [email protected] Pitzer Martin, Maschinenbau & Energietechnik, Technische Hochschule Mittelhessen, Gießen, Germany, [email protected] Three- axial stress is an inherent problem in implantations of endoprosthesis. The endoprosthesis is driven into the me-dullary cavity in order to achieve a press-fit tight enough to endure the mechanical loads caused by everyday use. But too much tensile stress will result in fissures or even cracks in the bone that will in the end loosen the prosthesis and augment the risk of a second operation. The implantation is a complex process depending among others on factors like individual bone properties, the prosthe-sis’ geometry and surgical techniques. A FE-Model of the implantation could contribute to the estimation of the effects of different levels of tensil stress in the femur during and after the implantation. To this end an endoprosthesis (Zimmer, USA) was digitized by an optical 3D scanner, transferred into a CAD Model and then transformed into an HYPERMESH Finite-Element –Model (material properties: titan). A CAD Model of the femur was obtained with the help of a replica of a human femur enhanced by radiological data. (Bone properties of Reilly and Burstein (1975)). The FE-model was tried on different implantation techniques, the preparation of the medullary cavity varied as well as the cavity’s diameter and the axial, radial and tangential E-Moduli of the bone. The results of the simulation showed a correlation of tensil stress and the implantation conditions e.g. the implantation into a natural medullary cavity produced a stress level similar to a 3-point bending experiment while the adaptation of the femoral cavity tended to optimize pressure. In addition eroded FEM-elements gave valuable clues to the destruction of the bone structure.


New technology for determination of personal anaerobic threshold used a mass-

market heart rate sensors.

Oleg Anosov, University of Applied Sciences Gelsenkirchen, Gelsenkirchen, Germany, [email protected]

Iliya Tyuvaev, Tsiolkovsky Kaluga State University, Russia, [email protected]

Thomas Hilbel, University of Applied Sciences Gelsenkirchen, Gelsenkirchen, Germany, [email protected]

One of the recent trends in competitive sports is usage of smart individual training programs and fitness protocols de-

veloped to achieve a specific target. Anaerobic threshold is an excellent and broadly accepted guide for optimization of

training conditions and tracking the efficiency of training protocols.

Until now, determination of individual anaerobic threshold is an expensive and uncomfortable procedure. The two main

methods used to estimate individual anaeroboc threshold currently available on the market are respiratory gas analysis

and biochemical analysis of blood lactate during exercise. Both methods need laboratory environment and require spe-

cial skills and complicated equipment. Due to high cost of each measurement, physiologically effective training pro-

grams based on the individual anaerobic threshold available predominantly to professional athletes.

We proposes new technology for determination of individual anaerobic threshold noninvasively based on the intelligent

analysis of heart rate variability and used a mass-markt heart rate sensors.

Proposed technology implemented from algorithm developed and published by the author (Anosov et al. 2000) can now

be used with cheap sports wearables and is 10 to 20 times cheaper than current methods, making individual anaerobic

threshold measurements potentially available for general fitness and a wide range of medical applications.


In-Vitro comparison of pressure and velocity in vein with

oscillating infusion for different catheter sizes

Muhammad Faishal Rayhan, Fachhochschule Münster, Münster, Germany, [email protected]

Leonard Pawelzik, Fachhochschule Münster, Münster, Germany, [email protected]

Niels Hinricher, Fachhochschule Münster, Münster, Germany, [email protected]

Claus Backhaus, Fachhochschule Münster, Münster, Germany, [email protected]

Extravasation is a common complication in the infusion therapy of premature babies. In extravasation,

the infusion fluid is not pumped into the punctured vein but into the surrounding tissue. To detect

extravasations at an early stage, a sensor prototype was developed which determines the sensor position

by using impulse oscillometry. With this technique, a hydraulic impulse is applied to the patient's vein

and the resulting pressure and flow curves are analysed. The aim of this work is to investigate whether

the hydraulic impulses represent a risk for the patient.

For this purpose, infusion is simulated with the help of tissue models made of gelatine and artificial

veins. The artificial veins have an inner diameter of 2mm and 4mm and are punctured with 24G, 17G

and 14G catheters. The catheters are connected via an infusion tube to a syringe filled with a water-flour

solution. An actuator is used to compress the infusion tube and to generate the hydraulic impulse.

Sensors measure the maximum pressure in the vein after each impulse. The flow velocity is measured

directly at the distal end of the catheter using ultrasound. Each catheter was measured 10 times for both

veins.

A peak pressure of 21 mmHg was measured with the 14G catheter. If a 24G catheter is used, the pressure

pulse measured in the vein is reduced to 4 mmHg. A pressure of 19 mmHg was measured with the 17G

catheter. The measured flow velocities are approx. 50% lower with the 14G catheter compared to the

17G and 24G catheters. The 24G catheter offers the lowest possible risk as it produces a pressure below

the average peripheral venous pressure. For the larger catheters, it must be investigated to what extent

the hydraulic impulse can be reduced to lower the risk for the patient.


Quantifying the uncertainty of deep learning-based computer ...

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