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Rev Esp Med Nucl Imagen Mol. 2013;32(3):167–176

pecial collaboration

ositron emission tomography/magnetic resonance: Present and future�

.A. Kohana, J.L. Vercher Conejeroa,∗, M.C. Gaetaa, L. Pelegrí Martinezb, P.R. Rosa

Departamento de Radiología, University Hospitals Case Medical Center/Case Western Reserve University, Cleveland, OH, United StatesDepartamento de Radiología, Hospital de Sant Joan Despí Moisès Broggi, Barcelona, Spain

a r t i c l e i n f o

eywords:ositron emission tomographyagnetic resonance

ttenuation

a b s t r a c t

PET/MRI has recently been introduced onto the market after several years of research and development.The simple notion of combining the molecular capabilities of the PET and its different available radiotrac-ers with the excellent tissue resolution of the MRI and wide range of multiparametric imaging techniqueshas generated great expectations upon the possible uses of this technology. Many challenges must beworked out. However, the most urgent one is the derivation of the MRI-based attenuation correctionmap. This is especially true because the PET/CT has already demonstrated a huge clinical impact withinoncology, neurology and cardiology during its short existence. Despite these difficulties, research is beingcarried out at a rapid pace in the clinical setting in order to find areas in which the PET/MRI is superior toother existing imaging modalities. In the few initial publications found up to date that have analyzed itsclinical role, areas have been identified where PET/CT can migrate to PET/MRI, even if only to suppress theCT scan’s ionizing radiation. Nonetheless, there are many theoretical applications in which the PET/MRIcan further improve the field of diagnostic imaging. In this article, we will review those applications, theevidence existing regarding the MRI and PET that support those premises as well as that which we havelearned in the short period of one year with our experience using the PET/MRI.

© 2012 Elsevier España, S.L. and SEMNIM. All rights reserved.

Tomografía por emisión de positrones/resonancia magnética: presente y futuro

alabras clave:omografía por emisión de positronesesonancia magnéticatenuación

r e s u m e n

La PET/RM fue introducida al mercado recientemente tras muchos anos de investigación y desarrollo. Lasimple idea de combinar la capacidad molecular de la PET y sus diversos radiotrazadores con la excelenteresolución tisular de la RM y la amplia gama de técnicas multiparamétricas que esta posee generan muchaexpectación sobre los posibles usos de esta tecnología. Existen muchos desafíos que hay que resolver, peroel más urgente es la derivación del mapa de atenuación de las secuencias de RM; especialmente porquela PET/TC ya ha demostrado en su corta existencia un gran impacto clínico en oncología, neurología ycardiología. A pesar de estas dificultades, la experimentación clínica se está desarrollando de maneraacelerada con el afán de encontrar aquellas áreas donde la PET/RM demuestre superioridad sobre los

métodos de imagen existentes. En las pocas publicaciones iniciales hasta la fecha que analizan su papelclínico se describen áreas en donde la migración de la PET/TC hacia la PET/RM se realiza aunque sea solopara eliminar la radiación de la TC. Sin embargo, son muchas las aplicaciones teóricas que la PET/RMpodría aportar al campo del diagnóstico por imágenes. En esta revisión haremos un repaso de ellas, laevidencia existente en RM y PET que avalan esas premisas y lo que nuestra experiencia con un equipo dePET/RM nos ha ensenado en el corto periodo de un ano.

ntroduction

he current situation of positron emission tomography/computedomography

Positron emission tomography (PET) is one of the imaging tech-

iques of greatest interest in the past years because of its diagnosticapacity not only in oncology, in which this technique is well estab-ished, but also in cardiology and neuropsychiatry.

� Please cite this article as: Kohan AA, et al. Tomografía por emisión deositrones/resonancia magnética: presente y futuro. Rev Esp Med Nucl Imagen Mol.013;32:167–76.∗ Corresponding author.

E-mail address: jlvercher@hotmail.com (J.L. Vercher Conejero).

253-8089/$ – see front matter © 2012 Elsevier España, S.L. and SEMNIM. All rights reser

© 2012 Elsevier España, S.L. y SEMNIM. Todos los derechos reservados.

In 1998, Townsend introduced the first equipment combin-ing the two imaging techniques, PET and computed tomography(PET/CT) in the University of Pittsburgh. The principal idea of thedesign of this PET/CT equipment was the possibility to obtain emis-sion (PET) and transmission (CT) images in the same study. The useof the CT images for the correction of attenuation and the correctionof the radiation dispersed was secondary.1

One of the main limitations of PET is the scarce informationrelated to the anatomy and spatial resolution. This has significantlyimproved with the new PET equipment, achieving resolutions ofless than 5 mm. In turn, the combination with CT has represented agreat advance, considerably improving the anatomical resolution,2

with this hybrid equipment replacing PET equipment within a fewyears.

The ability of PET/CT to anatomically localize abnormal fociof metabolic activity has led to a revolution in the detection and

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68 A.A. Kohan et al. / Rev Esp Med N

taging of many tumors. Likewise, the evolution of this technologyogether with the development and introduction of new radiotrac-rs has broadened the potential indications of this equipment notnly in oncology but also in cardiology, neurology, inflammatoryathologies, etc.

agnetic resonance at present

Magnetic resonance (MR) has undergone an important evolu-ion and diffusion in the past years. This evolution has been fulfilledith progressive technical improvements of the equipment which

nfluence the reduction of image acquisition time, improvementn spatial resolution and the time of reconstruction. The use of MRas therefore revolutionized medical imaging, since it allows betterifferentiation of the different anatomical structures on multiplelanes than any other diagnostic imaging test, with a non invasivepproach and without ionizing radiation.

Some of the technical advances are directed at the improve-ent in the efficiency of the MR equipment, favoring an increase

n its productivity or facilitating its management. Other advancesave allowed the development of new advanced applicationsf MR, which provide more than anatomical information, beingsed for qualitative and quantitative measurement of biologi-al metabolism. This includes perfusion and weighted diffusionincluding diffusion tensor) images, extraction of the tumoral

etabolic profile by hydrogen 1H proton spectroscopy, the studyf tumoral hypoxia by BOLD sequencing or the measurement ofegional pH by phosphorus 31P spectroscopy.3,4

Indeed, MR is demonstrating an unsuspected potentiality and,t present, is probably in the beginnings of a history which willontinue to revolutionize medical imaging.

istory of positron emission tomography/magnetic resonance

In the past years, PET/CT has shown great advances in oncology,ainly in tumoral staging. However, its scarce tissular differentia-

ion does not allow this multimodular technique to replace MR inome indications such as T staging of sarcomas of soft tissue, theectum and cervix, primary liver tumors and metastatic staging (M)f mainly the brain and liver.5 This is why the idea of combining thenformation of PET and MR is old,6 and for a long time PET and MRtudies were fusioned in suboptimum conditions for their analysis.

Similar to the significant evolution of MR in the last decade, thereas been a revolution in the technology of PET imaging, especially

n the development of new detectors able to improve the resolu-ion or to be functional under an intense magnetic field such as

R. All these advances have represented a challenge for the tech-ical investigation teams. The detectors based on the technologyf avalanche of photodiodes (APD), considered as the equivalentemiconductor of the photomultipliers or, more recently, the sili-on photomultipliers, have demonstrated promising results underxperimental conditions, with an excellent immunity to environ-ents with an elevated magnetic field.7,8 Thus, the use of these new

etectors has allowed the integration of MR and PET in the samequipment (PET/MR) or examination room.

echnology

There are currently 3 types of equipment allowing PET/MR studyn the market, each of which presents a different approach: simul-aneous and direct or indirect sequencing (Table 1).

imultaneous method

This method integrates the ring of the PET with MR ands currently commercialized by Siemens® (Biograph mMR®,

agen Mol. 2013;32(3):167–176

Siemens Healthcare, Erlangen, Germany).9 This method uses APDdetectors10 which are an essential element to work within a highmagnetic field. These detectors have not been popularized for use incommercial PET/CT due to their high production costs. The advan-tages of this equipment lie in the better anatomical (MR) andmolecular (PET) superposition available in the market and in thefuture development of applications which will benefit from simul-taneous acquisition of PET and MR images. On the other hand, thedisadvantages are: the high cost of the APD technology and theimpossibility to use time of flight (TOF) technology. It is impor-tant to know that it has been reported that total integration of theBiograph mMR® does not necessarily reduce the study times incomparison with other equipment,9,11 and that, at present, thereare no approved clinical applications that can only be performedwith simultaneous acquisition. Nor is there evidence that simulta-neous acquisition is better than sequential acquisition in dynamicstudies.

Direct sequencing method

This method is based on the installation of MR and PET equip-ments in the same room separating the two sufficiently so that,with the appropriate magnetic isolation of the detectors, the mag-netic field does not alter the acquisition of the PET. Between thetwo equipments there is a single revolving examination bed whichallows the study to be carried out without moving the patient.This equipment is currently commercialized by Philips® (IngenuityTF PET/MR®, Philips Healthcare, Cleveland, OH, USA).11 The mainadvantage of this equipment is that it has the best technologiesof the 2 modalities available in the market.12 The PET unit hasPMT-LYSO detectors and TOF technology and the MR unit is of 3T, without generating dependence between the two. This allowsseparate updating of the parts while evolving (for example, moresensitive crystals, better resonance coils, etc.). Another advantageis its lower cost of production, and thus, lower market cost incomparison with the simultaneous model. Among the disadvan-tages, the most important is the inability to perform simultaneousacquisition, even in the absence of applications, which requirethis characteristic. It is also important to note that the alignmentbetween the PET and MR images may not be perfect, similar to whatsometimes occurs with PET/CT.

Indirect sequencing method

This method is based on the installation of PET/CT and MRequipment in continuous rooms with a study bed which is movedfrom one room to another without moving the patient. The fusionof the images is performed at a work station connected to thetwo apparatus. This method of PET/CT+RM is commercialized byGE® (Discovery PET/CT 690® + Discovery MR750®, GE Healthcare,Waukesha, WI, USA).13 The main advantage of this method is thatit uses the best method of attenuation to date; a low radiationCT, in addition to being the most economical way of performingPET/MR and having and working individually with the best equip-ment available. The main disadvantage is that it continues exposingpatients to the radiation of CT, apart from the impossibility ofsimultaneous acquisition. Theoretically this model is more proneto presenting bad alignment between PET and MR.

Methods of attenuation

The greatest challenge of PET/MR for implementation is toobtain the map of attenuation with which to correct the acquisi-tion of PET. The main problem in using the MR images to generatean attenuation map lies in that both air and bone are visualized

A.A. Kohan et al. / Rev Esp Med Nucl Imagen Mol. 2013;32(3):167–176 169

Table 1Equipment available in the market vs. PET/CT.

Biograph mMR® Ingenuity TF PET/MR Discovery PET/CT690® + Discovery MR750® PET/CT

Study time 20–30 min 20–30 min 20 min 20 minCost of equipment $$$$ $$$ $$ $PET detectors APD-LSO PMT-LYSO PMT-LYSO14 PMT-LYSO or PMT-LSOSimultaneous evaluation Yes No No NoCT radiation No No Yes YesPET and MR alignment +++ ++ + ++FOV of the PET 60 cm 70 cm 70 cm 70 cm

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PD: avalanche photodiodes; FOV: field of view; LSO: lutetium oxyorthosilicate; LYipliers; MR: magnetic resonance; CT: computed tomography.he time of the study is estimated without having considered the time of sequences

s black tissue, despite having very different coefficients of atten-ation. The reason is that while air has few water protons, boneas an extremely short T2 relaxation time and thus, the protonsecover equilibrium before the equipment makes a reading. Bothhenomena are translated as an absence of signal in the image pro-uced. In turn, there is no direct relationship between the intensityf signal of a tissue in MR and the density of electrons, making theirect transformation of this information into an attenuation mapuch as in CT impossible.14

There are currently multiple techniques for the generation ofttenuation maps in PET/MR; those based on atlas15,16 and the seg-entation of images are the most studied. The latter is what weill explain in greater detail since it is what is used at present by

he equipment available in the market.11,15,17,18 It is important toemember that each method has strengths and weaknesses whichark their performance in the following areas: precision of the

egmentation algorithms (present in all the commercial methods),anagement of the truncation artifact, segmentation of the bone

issue and correct classification of the tissues. It is also importanto remember that the attenuation map is not the only factor influ-ncing the SUV values measured,19 and thus, in PET/MR the coilsnd table should be taken into account for correct attenuation.11

The atlas or template-based methods use models or preexistentmages with their respective attenuation maps which are com-ared with the images acquired in the study. After determininghe most similar preexistent image, complex computer programs

odify this image so that it completely coincides with the imagecquired and, once this is achieved, the same changes are appliedo the corresponding attenuation map.15,16 This method is useful inhe areas of the body with little morphological variation and withymmetry such as the head and the brain. In other regions such ashe abdomen and the thorax it loses effectiveness and may involveifficulties such as the absence of an organ or extremity.15,20 Thisechnique was already used before the appearance of the PET/MRn the search to reduce the times for the correction of attenuationased on transmission.

The methods based on image segmentation can, at present, dif-erentiate 3 or 4 tissues.

egmentation into 3 tissues (soft tissue, lung and air)

The PET/MR equipment commercialized by Philips®11 uses ahole body 3D T1 sequence which segments the lungs, assigning

heir respective attenuation coefficient and the soft tissue in theemainder of the body is thereafter given an attenuation coefficient.verything which is not classified as body or lung, whether insideair in the intestine, etc.) or outside the body, is given the attenua-ion coefficient of the air. The main disadvantage of this method

s the absence of segmentation of the bone and, on prioritizing

rapid acquisition time (between 2 and 3 min from supraorbitalegion to thighs), the resolution is not excellent thereby, at times,aking anatomical localization of the lesions difficult. However,

tetium yttrium orthosilicate; PET: positron emission tomography; PMT: photomul-

ted to organs, which would extend the PET/MR times by approximately 30–45 min.

this method is shown to be consistent and the differences betweenthe attenuation obtained with this method and CT are small, beingmore relevant in bone lesions.17

Segmentation into 4 tissues (soft tissue, fat, lung and air)

The PET/MR equipment commercialized by Siemens®9,16 uses asimilar technique to that of segmentation of 3 tissues, although onusing the DIXON sequence, which may obtain up to 4 sequencesin a single reading, the adipose tissue may be differentiated fromthe soft tissue. In this way the attenuation map obtained by thismethod differentiates 4 types of tissues instead of 3. The disad-vantages of this method are similar to those of segmentation into3 tissues, although on generating 4 sequences, better anatomicallocalization may be achieved, similar to the localization obtainedby low radiation CT.18 Many authors consider the differentiationof fat and soft tissue as one of the strengths of this technique, butothers play down the importance of this14 considering the similar-ity between the two attenuation coefficients (� = 0.086 cm−1 for fatand � = 0.096 cm−1 for soft tissue). As occurs with the 3-tissue seg-mentation method, this method does not segment the bone, withthe subsequent underestimation of the SUV values which, accord-ing to the different studies, vary from 11.2 ± 5.4% for bone lesionsand 3.2 ± 1.7% for lesions near the bone.21

Regardless of the segmentation technique used, these meth-ods have demonstrated consistency, precision and relative speed intheir performance and calculation of the attenuation map. Despitethe underestimation of bone lesions, this problem in recognizedand understood and should, therefore, not cause any problem.

To solve the incapacity of these methods to identify and segmentbone, UTE sequences (ultrashort echos) began to be used whichallow visualization of the bone tissue on acquisition of the imagebefore the bone loses the signal. From this first image or first echoin which the bone is seen but not the air, a second image or secondecho is extracted and generated immediately afterwards. In thisimage the bone and the air are no longer observed, thereby suc-cessfully removing anything that is not bone from the image.14 Thisinformation may then be used for the generation of an attenuationmap by analysis of voxels, segmentation or even templates.

This concept was taken even further with the aggregation of athird echo20 which is able to not only obtain the localization ofthe bone but also generate a DIXON sequence thereby allowing thediscrimination of 5 tissues (bone, fat, soft tissue, lungs and air). Themain problem of the sequences using UTE is that prolonged acqui-sition times are required22 reducing their utility until this problemis solved.

The literature does not clearly establish a definitive method.

While many authors see the absence of a single method for cor-rection of attenuation as a weakness of PET/MR, others believe thatthe large number of options is a strength since where one methodmay fail other methods may provide a valid alternative.

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70 A.A. Kohan et al. / Rev Esp Med N

linical role of positron emission tomography/magneticesonance

ossible clinical indications

The new combination of these 2 techniques has been longwaited particularly to improve the precision of T staging of tumorsn which MR is essential while maintaining N and M staging in

hich PET is shown to be superior.5 Moreover, the excellent tis-ular resolution provided by MR and the absence of the emission ofonizing radiation converts this equipment into a strong candidateor use in pediatric population.

Nonetheless, despite the evident potential benefits of the mul-imodality PET/MR equipment, there continue to be limitations,uch as the detection of micrometastasis.23–25 Another very rel-vant limitation which, as mentioned before, remains unsolved, ishe correction of attenuation based on MR.

Reports on the combined use of PET/MR published to date doot allow conclusions to be made or to establish indications. This isue to the few centers with PET/MR equipment, to the even fewerenters using this equipment on a daily clinical basis and to the facthat most of the literature is made up of reduced groups of patients.onetheless, the first studies emphasize the potential value of this

echnique in the field of oncology as well as its probable applicationn cardiology and neurology.

Different groups have described their experience with this newechnology and have made preliminary conclusions.26–30 The pos-ible oncologic indications are summarized in Table 2.

ead and neck

In neurology PET/MR would be useful not only in oncologicaliseases but also in neurodegenerative and epileptic disorders.

MR is the method of choice in the study of seizures andementias31 because of its great capacity to reproduce the cerebralnatomy, detect alterations in the gray-white matter relationshipnd detect foci of microbleeding, among other functionalities. Withegard to oncologic disease, the capacity to spectroscopically eval-ate infiltration,32 even in the absence of morphologic changes,o evaluate the routes of the axons in the white matter and theirnvolvement or not by the tumor and to precisely determine theype of histologic grade of the tumor are very valuable tools foreurosurgeons and oncologists.

The combination of these characteristics with the capacity of PETo demonstrate cerebral metabolic activity was done prior to theppearance of the PET/MR equipment.33 However, the capacity too this in the same study allows, among other things, better fusionf the images, facilitates the work flow, provides greater patientomfort and allows a fully integrated evaluation of the disease. Inddition, the new PET radiotracers in oncology and neurodegener-tive diseases can be evaluated together with MR, allowing moreetailed and precise analysis of the real utility of the same. For thiseason, the paradigm of performing MR and PET/CT separately inneurological patient will slowly migrate to the performance of

ET/MR.It is of note that this may be the field which will obtain the

reatest advantage from the simultaneous acquisition of images,or example, for the correction of patient movement.31 How-ver, theoretical benefits, such as the superiority of the dynamicnd simultaneous study of the distribution of the radiotracer andadolinium over sequencing studies remain to be demonstratedn practice by serious, unbiased studies. In turn, in neurodegen-

rative diseases it should be analyzed whether the performancef resonance sequences while dynamically studying the distribu-ion of FDG does not generate a false accumulation in the temporalobes due to equipment noise. In our experience with sequencing

agen Mol. 2013;32(3):167–176

equipment we have not found significant limitations in the studyof oncologic or neurologic patients.

In oncologic head and neck pathology MR is known to be thebest method to determine tumoral extension,34 while PET/CT hasdemonstrated great precision in the determination of lymph nodeinvolvement and the evaluation of distant metastasis.34 Thus, thecombination of the two methods into PET/MR (Fig. 1) not onlyimproves patient comfort but also allows better fusion. In our expe-rience, in the cohort in which PET/CT was studied, the head andneck was the body region which most frequently changed positionbetween the two studies, thereby making the fusion of PET withMR difficult if done with different equipment. In turn, multiparam-etric sequences such as diffusion-weighted whole body imaging(DWIBS) in MR may complement the information of PET by the gen-eration of an image into a scale of grays similar to that of PET. In thissequence only the structures presenting restriction to the diffusionare observed, which, in this case, would correspond to lymph nodeswith metastatic involvement.35 This sequence, together with thedynamic studies with contrast could, in the future, further improvethe characterization of the lymph nodes.

Thorax

PET/CT will probably not be completely replaced by PET/MR inoncologic thoracic disease because of the presence of the lungs. OThe presence of the lungs in oncologic thoracic disease will prob-ably not allow PET/CT to be fully replaced by PET/MR. However,MR has shown a greater capacity than CT in evaluating tumoralextension in lesions near the mediastinum and the thoracic wall.36

This, in addition to the excellent results published on the use ofdiffusion37 and STIR sequences38 in the staging of the mediastinum,and the fact that MR is obligatory to rule out distant metastasis inthe brain, indicates that PET/MR may have a role to fulfill in cer-tain situations. In our experience, even in the absence of the use ofspecific sequences such as those previously mentioned, the perfor-mance of PET/MR is similar to that of PET/CT. The latter coincideswith the work published by another center in which no differenceswere observed between PET/MR and PET/CT in the staging of 10patients.36

Since the breast is an area in which both PET/CT and MR havevery specific indications, it is believed that PET/MR will improvethe evaluation of tumoral extension in advanced oncological pro-cesses and in the assessment of response to treatment. Both MRwith perfusion techniques with or without the use of intravenouscontrast39 and PET with the different radiotracers currently avail-able (18F FDG and 18F Na) and 18F FES in the future40,41 will allowcomplete, exhaustive initial and adjuvant post-treatment evalua-tion, eliminating the ionizing radiation of CT. However, MR studyrequires the patient to be in a prone position with the breasts sus-pended. Although this position may, in theory, improve the spatialresolution of PET in the breast,42 it restricts the type of patient inwhom the procedure may be done due to the size of the MR ring.Nonetheless, despite the size of obese patients not allowing a posi-tion such as this, PET/MR may play an interesting role, especially inyoung patients since it eliminates the ionizing radiation of CT in ahighly sensitive tissue such as the mammary gland.

In this group of patients simultaneous acquisition could improvethe correction of patient movement. This mode of acquisition couldthus be beneficial, particularly because the prone position is moreuncomfortable than the supine position. In turn, dynamic studiesin breast disease may be of great utility and thus, studies should becarried out to determine possible differences between equipment

using simultaneous versus sequential acquisition.

In the field of cardiology, PET/MR will probably have a predomi-nant role. MR is considered the most reproducible imaging methodto evaluate the global anatomy and cardiac volumes.43 In turn, the

A.A. Kohan et al. / Rev Esp Med Nucl Imagen Mol. 2013;32(3):167–176 171

Table 2Possible clinical indications in oncology.

Characterization Tumoral extension Lymph node involvement Metastasis Restaging or suspicion of recurrence Response to treatment

Brain +++ +++ − − +++ +++Head and neck + +++ +++ +++ +++ +++Lung − +++ ++ +++ ++ −Breast − +++ ++ ++ +++ +++

Abdomen and pelvisLiver +++ +++ ++ − +++ +++Pancreas +++ ++ ++ +++ +++ +++Kidney +++ ++ ++ +++ +++ +++Bowel + − ++ +++ +++ −Rectum ++ +++ +++ +++ +++ +++Ovary +++ ++ ++ +++ +++ +++Uterus +++ +++ +++ +++ +++ +++Cervix +++ +++ +++ +++ +++ +++Prostate +++ +++ ++ +++ +++ +++

Bone +++ +++ − +++ +++ +++

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Soft tissue +++ +++ +++Melanoma − − ++Lymphoma − − +++

se of radiotracers such as 82Rb, 13N and 18FDG in nuclear medicines considered the imaging test with the best diagnostic perfor-

ance in ischemic disease.44 The fusion of these two qualities willrobably not only allow shorter study protocols in both meth-ds but will also provide better characterization of the diseases.onetheless, the experience published up to now is limited.45 It is

mportant to take into account that the presence of several anatom-cal regions with air–soft tissue interfaces makes the thorax onef the greatest challenges for the different methods of attenuationvailable. In turn, on again considering the disjunction between these of sequential or simultaneous equipment, the greatest evidenttrength of the simultaneous method is the correction of respira-ory movement. With regard to the use of dynamic studies, it shoulde taken into account that in MR these studies are done performing

ultiple apneas while PET is done with free breathing. This is why

he advantage of simultaneous versus sequential acquisition is notompletely clear and requires more in depth study.

ig. 1. Staging of a patient with tumoral lesion of unknown etiology in the subthyroid rusion of the two (C and F) showing a solid (arrow heads), slightly heterogeneous lesionhe plane of separation between this lesion and the structures of the neck are clearly visu

+++ +++ ++++++ +++ +++− +++ +++

Abdomen and pelvis

The abdominal-pelvic region is probably where the indicationsof PET/CT and PET/MR overlap the most. The reason for this is thatwhile MR allows better evaluation of certain organs (liver, prostate,rectum and internal gynecological organs) and better characteri-zation of certain tumors (pancreas, adrenal gland, and renal), CTallows better more detailed evaluation of vascular anatomy, whichis, in many cases, essential in the staging and selection of treatment.However, in this last section, the better resolution of the high mag-netic field resonance equipment and the development of perfusiontechniques and angiographies without contrast (BOLD, SAL, VIM)46

will progressively replace CT to a limited number of indications orsituations in which the access to MR is limited.

In the liver MR has demonstrated to be more sensitive than allthe other non-invasive diagnostic methods in lesions of less than10 mm.47 The use of hepatobiliary contrasts (i.e. Primovist®) is, in

egion. Axial (A–C) and coronal slices (D–F) of MR (A and D), PET (B and E) and thewith a similar intensity to that of the soft tissue and with intense avidity for FDG.alized in the MR T1 sequence (white arrows).

172 A.A. Kohan et al. / Rev Esp Med Nucl Imagen Mol. 2013;32(3):167–176

Fig. 2. Patient undergoing presurgical assessment for a moderately differentiated ductal adenocarcinoma in the pancreas. In the axial T2 (A), coronal T2 (B) and axial T2 fats pancri ualizec

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uppression (C) slices a macrocystic lesion is observed compromising the tail of thes shown in the fusion images (G–I). Small foci of 18F-FDG uptake (arrow points) visorresponds to a small solid portion of the previously described lesion.

art, responsible for this48 and may, in the future, reduce the lengthf the study on diminishing the number of sequences necessaryo characterize an hepatic lesion. Likewise, DWIBS sequencing iseing evaluated in the detection of peritoneal implants,49 althoughET has demonstrated to be better in the detection of extrahepaticisease.50

In the pancreas (Fig. 2), the use of sequences allowing visual-zation of the biliary tract without the need for contrasts is a verymportant tool for characterizing a tumoral lesion. The combinationf this capacity with future angiographic MR techniques and thebility of PET to detect distant lesions and lymph node involvementill allow patients to be staged in a single study.

Dynamic CT studies of the adrenal glands have shown a greatapacity to characterize tumoral lesions.51 However, study of theseesions by MR not only has the capacity of carrying out a dynamictudy similar to that performed in CT,51 but the use of in-phase andpposed-phase sequences which detect the presence of intracellu-ar fat may, on occasions, obviate the use of contrast.51 In this wayhe presence of adrenal lesions in oncologic patients could be easilylassified in a PET/MR study, even in studies without intravenousontrast and in the absence of FDG uptake.

In renal tumors MR is being used to characterize lesions fromtissular point of view52 and to evaluate the grade of perfusion

f the lesions without the use of contrasts.46 This benefits patientsith renal insufficiency and those in whom treatment involves the

blation of one of the two kidneys because it avoids any type ofenal damage. In this clinical situation, PET/MR would provide allhe information of the patient necessary for decision making inetermined situations on taking advantage of the capacity of PET

o evaluate distant disease.

In the pelvis MR is currently considered a reliable imaging tech-ique for local assessment of neoplastic diseases of the rectum53

Fig. 3), ovary,54 uterus,55 cervix55 and prostate.56 Although this

eas (white arrow). The cystic part of the lesion does not present 18F-FDG uptake asd in the axial (D and F) and coronial (E) PET slices. The fusion images show that this

superiority is based on the great tissular resolution of MR, italso has the capacity of performing multiparametric sequences(spectroscopy, diffusion, perfusion, etc.) which help to better char-acterize the lesions and determine the therapeutic options. In turn,since the extension of these diseases may involve bone, the liver,lymph nodes or peritoneum, the possibility of performing PET/MRallows better and more complete evaluation of the patient with nodelay in decision making.

This anatomical region is the least affected by the currentresonance-based attenuation methods, although the proximity ofsome pelvic structures to the bone may generate underestimationof the SUV.21 Similar to what was previously mentioned in thethorax, the benefits of a simultaneous over a sequential methodin the pelvis are not very clear and need to be evaluated by ade-quate systematic comparison to determine whether one methodis truly superior to the other. In our experience, similar to othercenters in Europe,57 we have been able to optimize the work flowwith the sequential method, taking advantage of the period of theincorporation of the radiotracer with no problems of alignment ordistribution of the radiotracer.

Musculoskeletal system

Both CT and MR fulfill well defined roles in musculoskeletaltumoral diseases. While CT allows characterization of the com-position of bone tumors and the changes associated with theirpresence,58 MR is what best evaluates the tumoral extension ofany sarcoma27 at both a local and distant level, being of greatutility particularly in certain tumors which do not have great

avidity for FDG such as the chondrosarcoma.58 In this context,although PET with FDG is not always useful, other markers couldcompensate for this weakness. In turn, some studies have indi-cated that in tumors with avidity for FDG, adjuvant pre- and

A.A. Kohan et al. / Rev Esp Med Nucl Imagen Mol. 2013;32(3):167–176 173

Fig. 3. Patient with cancer of the rectum undergoing a study for presurgical staging. Axial (A), coronal (D) and sagittal (G) slices of TSE T2 sequences at the level of the pelvis.T I). Paw for F

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he same slice in the PET reconstruction (B, E and H) and the PET/RM fusion (C, F andith no evidence of perirectal adenomegalias. This thickening presents high avidity

ost-treatment PET may be used to determine the tumor gradend prognosis58 as well as aid on suspicion of recurrence.27

he use of multiparametric sequences in MR also seems tolay a significant role in the prognosis and grade of tumoralesponse.27 It can therefore be expected that the combinationf the two methods, with adequate selection of the radiotracer,hould work synergically in the evaluation of patients with sar-oma.

In the case of melanoma the greatest advantage of this hybridechnology is the absence of the ionizing radiation of CT andhe great ability of MR to characterize hepatic and cerebralesions.59 The greatest disadvantage is the duration of the stud-es, which is usually prolonged since the whole body must betudied. In this context the simultaneous method may be bene-cial since both the PET and MR of the whole body are acquiredt the same time. Nonetheless, in our experience, the reduc-ion in time achieved with the use of TOF technology in the PET

ay be taken advantage of in the MR, obtaining not very dif-erent, albeit always greater, performances than those reportedith the use of simultaneous equipment.60 Since dual studies are

urrently still performed in these patients for the validation ofhis new technology (PET/CT and PET/MR), the patients becomeery tired and artifacts of nonalignment have been observedt the level of the lower extremities. This would probably notccur or at least to a lesser degree with simultaneous equip-ent.Studies of the musculoskeletal system as well as those of head

nd neck oncologic pathology have shown the greatest limitationsue to the lack of bone segmentation with the attenuation methods

urrently on the market. However, since this error is systematicnd is always of around 10–20%, depending on the method used,21

t should not significantly affect the clinical management of theatient.

rietal thickening of the rectum is observed between 8 and 12 o’clock (white arrows)DG with no pathological uptake beyond the rectum.

Pediatric population

In the future the pediatric population will probably most benefitfrom the introduction of PET/MR into the market. The possibility ofeliminating the ionizing radiation in this population is very impor-tant considering their remaining years of life which make themmore susceptible to having stochastic effects.61 The same benefitsmentioned for adults in the different anatomical regions may beapplied to pediatric patients. The only inconvenience is the possi-ble need for sedation or anesthesia, requiring adequate equipmentcompatible with MR as well as a determined training of the anesthe-siologists and other professionals. Moreover, compared to PET/CT,the duration of the study is longer, which would prolong the timesof anesthesia or sedation.

A clear example of the potential benefits of PET/MR in the pedi-atric population is the role this technique may play in lymphoma,which is a frequent disease in young patients. In this disease, MRhas a limited role in that, despite performing sequences such asDWIBS which allow whole body assessment of the lymph nodes,62

there is no evidence supporting its use. However, the fact that MRallows correct anatomical localization of the lesions,18 associatedwith the fact that patients with lymphoma must undergo multiplePET/CT studies after diagnosis, may be reason enough to indicatePET/MR in this population. Some centers have even described theirexperience in the migration of PET/CT to PET/MR in patients withlymphoma with excellent in pre- and post-treatment results.63

Challenges

The use of PET/MR faces several challenges before inclusion inroutine clinical practice, but in this section we will focus on thechallenges, which have an impact on the interpretation and orga-nization of the studies: the artifacts and work flow.

174 A.A. Kohan et al. / Rev Esp Med Nucl Imagen Mol. 2013;32(3):167–176

Fig. 4. Multiple MR images (A–C), 3-segment attenuation maps (D–F) and corrected PET reconstructions (G–I) showing artifacts. In the first column (A, D and G) a MRt is doe ®

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runcation artifact is observed and the corresponding attenuation map (arrows); thquipment. The column in the middle (B, E and H) shows a metallic artifact of a storrected PET (arrow points). The right column (C, F and I) shows an artifact seconone (asterisk) as lung or air without the presence of metallic prostheses to favor th

The artifacts involved are those of the new methodology itselfr those which require new techniques for their prevention. Thequipment marketed by GE® does not present these artifactsecause of the continued use of a CT-based attenuation map.

rtifacts by magnetic resonance

Among the different artifacts produced by MR and from whichhe attenuation map is obtained, one of the most frequent artifactss that of truncation. Truncation artifacts are due to the differencen the size of the field of transversal view (FOV) of PET and/or MR

hich is of 59 cm and 50 cm with the Biograph mMR®64 and of8 cm and 53 cm with the Ingenuity TF PET/MR®, respectively,11

nd the width of the subject.This artifact is produced in large patients or on scanning with

he arms in a downward position which is the most often used inET/MR because of the lengthy study times and to not have thertifact problem of beam hardening as in CT. When the patientxceeds the FOV of the MR, whatever is located outside the FOVskin, arms, etc.) is truncated (Fig. 4). The absence of information ofhe presence of this tissue or member is propagated to the attenua-ion correction map derived from these images, thereby obtainingtruncated map. This artifact, thus, generates an erroneous correc-

ion of attenuation since the tissue located outside the FOV of theR is interpreted as air, generating an underestimation of the SUV.

n addition, the truncation may produce an anteroposterior gradi-nt in the uptake of the radiotracer in the liver, thereby altering itsuantification.60

The PET/CT techniques currently used to recover the informa-

ion of the truncated zone and to avoid these artifacts are notpplicable in PET/MR since, in contrast with CT, the information ofhe tissue outside the FOV does not exist in the scanner database.o compensate the truncation, Philips® uses the non corrected PET

s not propagate to the corrected PET by the algorithm which Philips has in theirmy wire which propagates to the attenuation map and, to a lesser degree, to the

o the segmentation algorithm. The same interpreted a sector of the soft tissue andifact. The propagation of this artifact to the corrected PET is very evident.

images filling in the outline of the patient which could not be visu-alized in the MR. Unfortunately the procedure is suboptimal in theconcave regions of the body.11

Other artifacts propagated in MR to the corrected PET imageare those generated by metallic implants (Fig. 4). These implantsalter the magnetic field and, in certain sequences, are translatedas a loss of local signal which ends up affecting the algorithm ofsegmentation which erroneously classified this sector as air, gen-erating an underestimation of the distribution of the radiotracer inthis area. To the contrary, in PET/CT the presence of metal leads toan overestimation of the uptake of the radiotracer. Unfortunately,at present, there is no consistent method of correction for this typeof artifact.60,64

Artifacts by the attenuation map

The main artifact associated with the attenuation maps, if,indeed, it can be considered as an artifact, is the underestimationof lesions located in regions which do not adequately segment.However, when working with the same PET/MR equipment thesame error should be repeatable and should therefore not affectthe interpretation of the study.

On the other hand, errors in the segmentation of the lungshave been described in that occasionally, one or both lungs arenot correctly identified and an air cavity without tissue or bloodis interpreted in their place, generating an incorrect correction ofthe PET data. Other authors have described attenuation maps inwhich several small erroneously identified cavities are observed

as air instead of pulmonary tissue.17 In addition, when the delim-itation of the lung in the MR sequence is not good, the algorithmmay exceed these limits and classify adjacent soft tissue parts aspulmonary or air cavities (Fig. 4).

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A.A. Kohan et al. / Rev Esp Med N

Whatever the new artifacts introduced by this new technologyay be, the introduction of CT also brought with it other artifactshich only required their comprehension to avoid interferenceith the interpretation of the studies. The PET/MR technology isnder continuous development and thus, in the future, some ofhese artifacts will not exist or will have methods of correction tovoid them.

onclusions

Although PET/MR has been under development for less than0 years, this technology has recently achieved the potential andapacity to be used in the clinical setting. It is not only a recentechnology in itself, with all that this implies with respect tonvestigating its strengths and weaknesses, but it is made up of

components which still have a great deal of development tondergo. These conditions require commitment from the medicalommunity to investigate and develop this technology together tohereby determine its real utility in the shortest time possible. Inurn, manufacturers should work together in relation to the meth-ds of attenuation since the presence of equipment which producesifferent results will make it difficult for physicians to adequatelyarry out the follow up of the patients.

It has been possible to evaluate the consistency of the methodrom the little literature available, allowing, with due precaution,he migration of PET/CT to PET/MR to begin in particular cases suchs in lymphoma.34 This method is of interest if only to eliminate theadiation of CT since there are still no conclusive studies demon-trating the superiority or inferiority of one method over the other.

What is sure is that the future development of equipment andhe integration of new and old radiotracers and multiparametricmages will allow a new view of the diseases which will have anmpact on the clinical management of the patients.

cknowledgment

The authors thank Christian Rubbert, Sasan Partovi and Oliverteinbach for their support in this study.

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