REVIEW

Technology developments in endovascular treatmentof intracranial aneurysmsRobert M Starke,1 Aquilla Turk,2 Dale Ding,1 Richard W Crowley,1,4 Kenneth C Liu,1,4

Nohra Chalouhi,3 David M Hasan,5 Aaron S Dumont,6 Pascal Jabbour,3

Christopher R Durst,4 Raymond D Turner7

▸ Additional material ispublished online only. To viewplease visit the journal online(http://dx.doi.org/10.1136/neurintsurg-2014-011475).1Department of NeurologicalSurgery, University of Virginia,Charlottesville, Virginia, USA2Department of Radiology,Medical University of SouthCarolina, Columbia, SouthCarolina, USA3Department of Neurosurgery,Thomas Jefferson University,Philadelphia, Pennsylvania,USA4Department of Radiology andMedical Imaging, University ofVirginia, Charlottesville,Virginia, USA5Department of NeurologicalSurgery, University of Iowa,Iowa City, Iowa, USA6Department of NeurologicalSurgery, Tulane University, NewOrleans, Louisiana, USA7Department of Neurosurgery,Medical University of SouthCarolina, Columbia, SouthCarolina, USA

Correspondence toDr RM Starke,Department of Neurosurgery,University of Virginia,PO Box 800212,Charlottesville, VA 22918,USA;bobby.starke@gmail.com

Received 22 September 2014Revised 24 October 2014Accepted 4 November 2014

To cite: Starke RM, Turk A,Ding D, et al. JNeuroIntervent SurgPublished Online First:[please include Day MonthYear] doi:10.1136/neurintsurg-2014-011475

ABSTRACTAdvances in the management and endovasculartreatment of intracranial aneurysms are progressing at atremendous rate. Developments in novel imagingtechnology may improve diagnosis, risk stratification,treatment planning, intraprocedural assessment, andfollow-up evaluation. Evolution of devices, includingmicrowires, microcatheters, balloons, stents, and novelscaffolding devices, has greatly expanded the potentialto treat difficult aneurysms. Although developments intechnology have greatly improved the efficiency andefficacy of treatment of neurovascular disorders, noveldevices do not always improve outcomes and may beassociated with unique complications. As such, it isparamount to have an in-depth understanding of newdevices and the implications of their introduction intoclinical practice. This review provides an update ondevelopments in endovascular treatment of intracranialaneurysms.

INTRODUCTIONEndovascular treatment of intracranial aneurysmshas significantly increased, and is the primary treat-ment modality at many centers. Additionally,advances in the management and endovasculartreatment of intracranial aneurysms are progressingat a tremendous rate. This includes imaging technol-ogy as well as devices used in treatment.Developments in novel imaging technology mayimprove patient evaluation and treatment.Evolution of devices may also significantly helpimprove the efficiency and efficacy of treatment.Although developments in technology have greatlyimproved, novel devices do not always improve out-comes and may be associated with unique complica-tions. As such, it is important to have an in-depthunderstanding of new devices and the implicationsof their introduction into clinical practice. Thisreview provides an update on developments inendovascular treatment of intracranial aneurysms.

DEVELOPMENTS IN IMAGING TECHNOLOGYImprovements in imaging technology are greatlyexpanding our ability to assess and understand themorphology of intracranial aneurysms. Althoughdigital subtraction angiography (DSA) is the goldstandard, non-invasive modalities, computerenhanced alterations, and intraprocedural adjunctscan improve evaluation. Future developments inimaging may improve diagnosis, risk stratification,

treatment planning, intraprocedural assessment,and follow-up evaluation.

Three-dimensional evaluationDuring cerebral angiography, multiple images can beobtained during rotation of a single C arm to createa three-dimensional image. Three-dimensional rota-tional angiography may decrease fluoroscopy timeand contrast load while helping with diagnosticevaluation, treatment planning, and catheter naviga-tion (figure 1A). Three-dimensional imaging canprovide detailed assessment of intracranial aneurysmanatomy as well as associated parent vessels and per-forator arteries. Studies have found that this mayallow detection of small aneurysms which areunable to be visualized in two-dimensional angiog-raphy.1 Three-dimensional imaging also allowsselection of optimal working projections for aneur-ysm treatment. After developing a treatment plan,an interactive three-dimensional roadmap can becreated that allows three-dimensional imaging to beoverlaid on live fluoroscopy in any working projec-tion to guide catheterization through complex vas-cular anatomy or aneurysms.2

Flat panel detectionFlat panel detector angiographic CT imaging canalso be carried out during cerebral DSA with asingle C arm to create a three-dimensional imagewithin the associated bony anatomy with less beamhardening from coils, stents, or intra-aneurysmalflow diverters (figure 1B).3 4 Flat panel detectorsoftware can greatly improve visualization of stentposition, configuration, and apposition to theparent vessel wall. This provides detailed anatomicdata that can help define in-stent stenosis, throm-bosis, endoleaks, fractures, incomplete deployment,and twisting.5 6 Additionally, flat panel CT can beused to evaluate for intraprocedural complications,such as subarachnoid or intraparenchymal hemor-rhage, without the necessity for patient transfer toa CT scanner.7

Four-dimensional assessmentTime resolved three-dimensional phase contrast vel-ocity mapping can be performed with CT or MRIto provide a fourth dimension of volumetric bloodflow. Most recently, this has been used during con-ventional three-dimensional cerebral angiographyto generate time resolved sequences with improvedspatial and temporal output.8

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These three-dimensional reconstructions of cerebral bloodflow can provide multidirectional velocity data and assessmentof flow patterns, including laminar, helical, or turbulent bloodflow within complex vascular lesions.9 Post-processing softwareallows quantification of pre- and post-procedure blood volume,calculation of three-dimensional pressure differences, and deriv-ation of hemodynamic indices, such as wall shear stress andpulse wave velocity, based on vascular compliance.9 This hemo-dynamic evaluation may provide improved risk assessment forthe likelihood of aneurysm rupture and prediction of periproce-dural complications or aneurysm obliteration.

Microangiography fluoroscopyContinual imaging improvements in DSA allow clearer visualiza-tion of vascular anatomy. Specifically, microangiography usesextreme fluoroscopic resolution within a small field to provideexquisite detail. For complex anatomy, this may help definemicrowire or microcatheter position. Additionally, this may beparticularly beneficial during the treatment of very small orlarge, partially thrombosed aneurysms in defining areas ofincomplete coiling or residual aneurysm filling.10

Intravascular ultrasoundIntraprocedural cerebral angiography is greatly limited in itsevaluation of the wall thickness of cerebral blood vessel walls.

Unlike MRI, CT, and DSA, ultrasound provides a limited three-dimensional assessment of vessel wall layers (figure 1C). In theexample of a dissection, visualization is achieved by determiningthe alterations in contour and caliber of the intima and identify-ing potential contrast extravasation/stasis within the vesselwall.11 Intravascular ultrasound has seen little use in cerebrovas-cular pathology, but development of smaller delivery cathetersmay allow expansion of its use into the intracranial realm. Thistechnique has the benefit of being able to provide a real timeevaluation of both intravascular and vascular wall pathology,and it has been used extensively in coronary angiography in thedelineation of a wide range of pathology, including plaque,thrombus, and dissections.11 12 Additionally, large trials havedemonstrated that intravascular ultrasound may improve stentplacement, apposition, and overall technical outcomes.13 Incerebral pathology, ultrasound may help further define intralum-inal and extraluminal aneurysm morphology not fully definedby angiography.14

Optical coherence tomographyIntravascular ultrasound is limited by artifact and overall tissuepenetration. Optical coherence tomography (OCT) is an opticalsignal acquisition and processing method that can capturemicroscopic resolution of tissue from a light source mountedwithin a microcatheter. Similar to confocal microscopy, an

Figure 1 Three-dimensional (3D) reconstruction of a basilar tip aneurysm (A). Flat panel 3D CT angiography following placement of a Surpass flowdiverter stent for a giant internal carotid artery aneurysm (B). Intravascular ultrasound demonstrates the navigation of a vessel with a diameter of4 mm (C). Optical coherence tomography following stent placement demonstrates incomplete apposition of the stent (arrow) to the blood vessellumen with associated artifact from the stent (broken arrow; D).

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optical based technique, OCT penetrates more deeply into sur-rounding tissue. Unlike confocal microscopy, OCT can provideimaging at a microscopic, but not subcellular, resolution.Frequency domain OCT provides advantages in signal to noiseratio, thereby permitting faster signal acquisition. This can allowreal time imaging of a 5 cm length of blood vessel segmentwhile the light source and camera move within a stationaryrapid exchange 0.014 inch microcatheter positioned over amicrowire. This generates a cross sectional and longitudinalimage that can be re-created into a three-dimensional image orvideo. Microscopic imaging allows visualization of vessel wallcomponents, including the intima, media, and adventitia, andcan clearly identify small perforating arteries.11 15 16 This hasbeen adapted in the coronary vasculature to improve visualiza-tion of vessel pathology and can be used to differentiate amongfibrous, calcified, and lipid plaques, and between acute, redcolored clot, and chronic white colored thrombus oremboli.11 15 16

Intraprocedurally, this imaging can be rapidly acquired follow-ing stent deployment to obtain additional microscopic evaluationof stent struts, apposition to the parent vessel, endoleaks, patencyof perforating arteries, in-stent stenosis or thrombosis, and tissueprolapse through the stent.11 15 16 On follow-up angiography,OCT may demonstrate neointimal growth, restenosis, and stentfracture, foreshortening, or prolapse (figure 1D).11 15 16 Sincethis modality relies on a light source, there is no additional radi-ation. Therefore, OCT may be a safer modality than both DSAand flat panel technology for imaging of stents and coils afterdeployment.

DEVELOPMENTS IN ANEURYSM TREATMENT TECHNOLOGYDetachable coilsFor endovascular treatment of intracranial aneurysms, there is awide selection of detachable coils. Recent advances with softercoils have expanded the endovascular repertoire. Prior trialscomparing surgical and endovascular treatment of aneurysmsdid not include aneurysms of very small size,17 in part due tothe potentially increased risk of intraoperative rupture withendovascular therapy for small aneurysms (<3 mm).18 With theadvent of smaller (1 mm in diameter) and softer coils, it is nowpossible to treat these small aneurysms. A study comparingmicrosurgical to endovascular treatment of small aneurysmsdemonstrated higher complication rates with microsurgical clip-ping and higher retreatment rates with endovascular therapy,but similar overall functional outcomes between modalities.19

Further prospective studies are indicated; the Effectiveness andSafety of Small Aneurysm Coiling Trial (NANO trial) aims toprospectively assess the long term outcomes of small aneurysmstreated with microcoils.

For larger aneurysms, coils with an increased secondary diam-eter are now available that may decrease the number of coilsnecessary to achieve an adequate packing density. The P400coils (Penumbra Inc, Alameda, California, USA) have increasedtheir primary shape diameter to 0.0020 inches while utilizing asmaller nitinol coil for support. Preliminary results from a smallsingle center experience demonstrated acceptable results20 butwe await the final outcomes of the Aneurysm Coiling EfficiencyStudy of the Penumbra Coil 400 System (ACE trial). A numberof coils have also recently been developed to achieve greaterpacking density with fewer coils by increasing the outer diam-eter of the primary coil from 0.010 to 0.014 inches while allow-ing selection from coils of varying stiffness.

A number of bioactive coils have been developed. These coilshave a coating that is meant to expand after contact with blood.

These novel coils have the potential to increase packing densityand decrease retreatment rates. Despite these theoretical advan-tages, multiple randomized clinical trials, including the recentlyreleased long term results of the Matrix and Platinum Science(MAPS) trial did not shown the superiority of bioactive coilsover bare platinum coils.21–23

Liquid embolicsUnlike coils, liquid embolization may allow for complete occlusionof the aneurysm as a liquid agent may be better able to assume theconformation of the aneurysm. The most widely tested agent is anethylene vinyl alcohol copolymer, Onyx HD500 (ev3 Inc, Irvine,California, USA). Liquid embolics are typically delivered through amicrocatheter jailed within the aneurysm by a balloon. Althoughthis has only been reported in the treatment of arteriovenuousmalformations, newer dual chamber balloons may allow simultan-eous flow cessation and Onyx delivery.24 Despite these potentialadvantages, liquid embolic agents have been associated with highcomplication rates, and parent vessel stenosis and occlusion atfollow-up.25–27 As such, liquid embolic agents are often reservedfor retreatment of complex aneurysms not amenable to alternativetreatment strategies.27

DEVELOPMENTS IN STENT TECHNOLOGYThe area of greatest advancement over the past several years hasbeen in the field of primary and adjunct endoluminal devicesfor the treatment of complex aneurysms. This includes the useof stents for coiling assistance, intra- and extra-aneurysmal flowdiversion technology, and aneurysmal neck reconstruction andcoil support devices. While offering additional treatmentoptions, these devices are not without a number of unique risks.The use of an endoluminal device often necessitates that thepatient be placed on dual antiplatelet therapy, which can predis-pose the patient to gastrointestinal bleeding, bruising, or bleed-ing, and exacerbation of intraoperative complications.

As delivery catheters must be navigated distal to the aneurysmneck prior to device deployment, there is the potential for distalvessel injury in addition to local parent vessel or aneurysm per-foration.28 This may also increase the risk of thromboembolicevents. In ruptured aneurysms, the use of dual antiplatelettherapy may be associated with an increased incidence of com-plications, especially in post-subarachnoid hemorrhage patientswho require permanent CSF diversion.29 In the long term, theendoluminal devices may be associated with in-stent stenosis,thrombosis, and thromboembolic complications.28

Low surface area coverage stentsCurrently, there are two stents approved by the Food and DrugAdministration (FDA) through a humanitarian device exemptionfor the treatment of intracranial aneurysms which provideapproximately 5% parent vessel coverage. The partially opencell (hybrid architecture) Neuroform stent (StrykerNeurovascular, Fremont, California, USA) (see online supple-mentary figure IA) and closed cell Enterprise stent (CordisCorporation, Miami Lakes, Florida USA) (see online supplemen-tary figure IB) are both self-expanding stents produced fromthin film nitinol hypotubes. Stent assisted coiling has been asso-ciated with relatively higher rates of aneurysm obliteration andlower rates of aneurysm recurrence compared with coil embol-ization alone, but the associated incidence of complications maybe increased.30–32 Although there have been no prospective ran-domized studies to compare the Enterprise and Neuroformstents, a number of studies have compared institutional out-comes. Two earlier studies found greater difficulties with the

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delivery of the Neuroform stent,33 34 two studies found greateraneurysm recanalization rates with the Neuroform stent,33 35

and one study found increased complications associated withthe Enterprise stent.33 Disparities in outcomes between stenttechnologies may be partly attributable to older designs.33 34

Next generation Neuroform stents have greatly improved thedelivery mechanism. The next generation of Enterprise stents,which are not currently available in the USA, have an improvedplatform that will likely improve stent apposition to the parentvessel around tight bends and improve angiographic visualiza-tion (see online supplementary figure IC).

The Liberty stent (Penumbra) is a self-expanding stent cur-rently under review in an ongoing clinical trial.36 Comparedwith the Enterprise (0.042 mm) and Neuroform (0.066 mm)stents, the Liberty stent is produced from an ultrathin 0.005 mmnitinol hypotube that may improve delivery, decrease thrombo-embolic complications, and decrease the incidence of associatedvessel injury and perforation.37 38

Although originally designed for use in stent assisted coilingof cerebral aneurysms, the Solitaire stent (Covidian, Mansfield,Massachusetts, USA) has predominantly been used in mechan-ical thrombectomy for the treatment of acute ischemic stroke.This stent may also be detached, and recently more centers inEurope have been using it in stent assisted coiling of aneur-ysms.39 As the Solitaire may be retrieved and has limited metalcoverage, this stent may be associated with fewer thrombo-embolic complications which make it a potentially more attract-ive alternative in the treatment of ruptured wide neckedaneurysms.40 41 Further studies are necessary to determine thebenefits and optimal indications for low coverage nitinol stents.

Intermediate coverage stentsWoven or braided stents are cut from nitinol fiber with anapproximate diameter of 0.05 mm to create an intermediate

degree of parent vessel coverage (∼15%) which is greater thanconventional nitinol hypotube stents (∼5–10%) but less thanflow diverting stents (∼30%). Stents with greater parent vesselcoverage have the potential advantage of increased parent vesselsupport and protection, but this may be offset by greater diffi-culties accessing the aneurysm through the tines of the stent orremoving jailed microcatheters, poorer trackability, and a greaterrisk of thromboembolic complications. Currently, there are noFDA approved woven or braided stents, but three stents are cur-rently in use in other countries and the subject of current clin-ical trials. The closed cell Leo stent used in Europe (BaltExtrusion, Montmorency, France) has a number of advantagesover the Neuroform and Enterprise stents, including radiopaquemarkers which increase visibility, and the ability to be retrievedafter 90% unsheathing. In seven retrospective series of 9–28patients, the Leo stent resulted in complete aneurysm occlusionin 65% of patients, complications in 8.9%, and recurrence in7.7%.42–48 Further assessment with long term follow-up isindicated.

The newest woven or braided stent is the low profile visua-lized intraluminal support (LVIS; MicroVention, Tustin,California, USA) device, which is currently only available in theUSA as part of a clinical trial (figure 2A). Similar to the Leostent, it is cut from nitinol wire (0.056 mm), has improved radi-opaque markers compared with the Enterprise and Neuroformstents, and is retrievable after up to 80% deployment.49 Asmaller version (LVIS Jr) is available which can be placedthrough a microcatheter with an inner diameter of 0.0165inches (figure 2B). This may facilitate stenting of aneurysmswith smaller parent vessel diameters or creation of Y configur-ation stent constructs with easier navigation through the tines ofa larger stent. Preliminary in vivo and clinical outcomes withthe LVIS stents are encouraging, but current clinical trials havenot yet been completed.49 50

Figure 2 The low profile visualized intraluminal support (LVIS) stent (A). Middle cerebral aneurysm status after placement of the LVIS Jr (B, C).Final treatment image status after stent assisted coiling of the middle cerebral artery aneurysm with the LVIS Jr (D).

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Flow diverting stentsObservation of the altered flow dynamics in an aneurysm afterstenting prompted the development of specialized devices thatcould be used for endoluminal reconstruction of the artery andflow diversion away from the aneurysm. These devices, whichprovide higher coverage of the parent vessel (30–50%) thanconventional intracranial stents, can decrease blood flow intothe aneurysm, resulting in stasis of the intrasaccular blood pro-ducts and eventual aneurysmal thrombosis.51 This may also leadto potential aneurysm regression, thereby reducing aneurysmrelated mass effect. Flow diverters theoretically provide an alter-native therapy for wide necked, giant, or fusiform aneurysmsthat are associated with significant morbidity and mortality fol-lowing treatment with either microsurgical or traditional endo-vascular treatments.52 Studies have also found these devices tobe an acceptable alternative therapy for small aneurysms,53

blister aneurysms,54 and pseudoaneurysms55 that may be diffi-cult to treat with conventional endovascular approaches. Adrawback of flow diverters is delayed obliteration, which is par-ticularly risky with these fragile aneurysms which may be asso-ciated with high re-rupture rates.

Currently, there are four flow diverters available for the treat-ment of cerebral aneurysms but only two are available outsideof research studies: the pipeline embolization device (PED; ev3)(figure 3) and the silk flow diverter (SFD; Balt Extrusion),which is only available outside of the USA. The PED is manu-factured from 48 microfilaments with a consistency of 25% plat-inum–tungsten and 75% cobalt–chromium–nickel, providing30–35% parent vessel metal coverage.51 Since the original pro-spective studies of PED treatment for large (>10 mm) anteriorcirculation aneurysms, there have been numerous additionalreports in a wide variety of aneurysms. A recent meta-analysisof 29 studies of 1451 patients with 1654 aneurysms treatedwith the PED found an occlusion rate of 76% at 6 months

(95% CI 70% to 81%) and an associated morbidity and mortal-ity of 5% (95% CI 4% to 7%) and 4% (95% CI 3% to 6%),respectively.51

As with many procedures, increasing experience leads todecreased complications,56 but novel devices may be associatedwith previously unseen complications or a higher frequency ofcommonly observed complications. With the PED, there is par-ticular concern regarding the risk of perforator artery infarction,which was noted to occur in 3% of cases (95% CI 1% to 5%),with a significantly lower rate of perforator infarction in patientswith anterior circulation aneurysms compared with those withposterior circulation aneurysms (OR 0.01; 95% CI 0.00 to0.08; p<0.0001).51 Additionally, ischemic strokes occurred in6% of patients (95% CI 4% to 9%), also at a significantly lowerrate in patients with anterior circulation aneurysms (OR 0.15;95% CI 0.08 to 0.27; p<0.0001). In particular instances, per-forators may remain open following PED treatment, which mayrepresent a significant demand phenomena that continues topull blood through the perforator artery.54

The rates of postoperative subarachnoid and intraparenchymalhemorrhage after flow diverter treatment are each 3% (95% CI2% to 4%).51 Most alarming are distal intraparenchymal hemor-rhages that have been reported weeks to months after flow diver-sion. One recent histopathological review of three cases ofdelayed fatal ipsilateral intraparenchymal hemorrhage followingPED treatment demonstrated the presence of foreign materialoccluding small distal vessels within the hemorrhagic area in allpatients.57 Fourier transform infrared spectroscopy demonstratedthe presence of polyvinylpyrrolidone in the specimens, a sub-stance that is commonly used for the coating of interventionaldevices.

Finally, complications have occurred due to the inability toappropriately deploy PEDs, direct parent vessel occlusion, andpersistently enlarging giant thrombotic aneurysms despite parent

Figure 3 Pipeline embolization flow diverting stent (A). Intraoperative removal of the pipeline embolization device during microsurgical clipping ofa giant expanding aneurysm despite flow diversion (B). The Surpass flow diverter stent (C). Stagnation of contrast within a giant internal carotidartery aneurysm following placement of the Surpass (D).

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vessel reconstruction.58 59 For these instances and other failedtreatments with flow diverters, alternative endovascular ormicrosurgical treatments may be particularly difficult.58 59 Thenext generation pipeline flex embolization device, which is stillunder FDA review, includes improvements in delivery andpotential for post-deployment resheathing.

The SFD was approved for use in Europe in 2008 and is com-posed of four platinum and 48 nitinol microfilaments.60

Adjunctive intrasaccular coiling is recommended with the SFD,and the device is resheathable up to 90% deployment. Thus far285 patients with 317 aneurysms treated with the SFD havebeen reported in the literature, with an associated delayed occlu-sion rate of 82% at 12 months and morbidity, mortality, andintracerebral hemorrhage (ICH) rates of 12.5% 4.9%, and1.4%, respectively.61

Two other flow diverting stents, the Surpass flow diverter(Stryker Neurovascular) (figure 3) and the flow redirectionendoluminal device (FRED; MicroVention) (see online supple-mentary figure II), are currently only available as part of clinicaltrials in the USA. The Surpass provides surface coverage ofapproximately 30% but with a consistent porosity of approxi-mately 70% across all sizes that may reduce the usage of mul-tiple overlapping stents.61 The only published Surpass series,comprising 37 patients with 49 aneurysms, reported an obliter-ation rate of 83% at 6 months, with mortality, morbidity, andICH rates of 0%, 14.3%, and 2.0%, respectively.62 The FREDhas a unique overlapping stent design with a high porosity outerstent and a low porosity inner stent comprised of 48 nitinolstrands. There have been three reported series with the FRED,including treatment of 51 patients with 59 aneurysms, with100% occlusion rates in those with more than 6 months offollow-up, and morbidity and mortality rates of 3.8% and 0%,respectively, without any cases of delayed ICH.63–65 Furtherstudies are necessary to better define the optimal aneurysms forspecific flow diverting devices, long term obliteration rates, asso-ciated complications, and alternative therapies for aneurysmsthat have failed flow diversion.

Intra-aneurysmal flow diversionIntra-aneurysmal flow diverting three-dimensional constructshave been developed that are composed of braided nitinol wirethat are deployed within the aneurysm sac to disrupt blood flowinto the aneurysm and promote thrombosis.66 67 These devicesare optimal for bifurcation aneurysms that are not easily treatedwith current flow diverting stents or conventional coil emboliza-tion. As these devices are intra-aneurysmal, they may notrequire dual antiplatelet therapy and are not associated withparent vessel stenosis, as can be found with stents. Both theLuna (Covidien Vascular Therapies, Irvine, California, USA)(figure 4A) and the Woven Endo-Bridge (SequentMedical, AlisoViejo, California, USA) (figure 4B) have demonstrated promisingearly clinical results.66 67

Aneurysmal neck reconstruction and coil support devicesWide necked cerebral aneurysms that are located at bifurcationsare particularly challenging for endovascular treatment.Endovascular approaches for wide necked bifurcation aneurysmsmay require Y configuration stenting which involves placementof a secondary stent within a primary stent,68 a ‘double-barrel’construct of two side by side stents,69 or intrasaccular placementof one end of a stent to create a ‘waffle cone’ appearance.70

Several case series have reported these techniques, but endovas-cular treatment of wide necked aneurysms is nonetheless asso-ciated with relatively higher rates of periprocedural morbidityand mortality.28 68

A number of new devices have been created to alleviate thedifficulties associated with the treatment of wide necked bifurca-tion aneurysms. The Barrel stent (Reverse Medical, Irvine,California, USA) (figure 5) is a self-expanding stent that canundergo significant expansion in the central portion of the stentto increase aneurysmal neck coverage and provide a strongerscaffold for stent assisted coiling. The Pulsar vascular aneurysmneck reconstruction device (ANRD; Pulsar Vascular, San Jose,California, USA) and Pulse Rider (Pulsar Vascular) are novelscaffolding devices for the treatment of wide necked bifurcation

Figure 4 The Luna (A) and placement within an aneurysm in vitro (B). Woven Endo-Bridge (WEB) (C) and cerebral angiography before and aftertreatment of a middle cerebral artery aneurysm with the WEB, demonstrating aneurysm obliteration. Arrow demonstrates right middle cerebral arteryaneurysm prior to treatment.

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aneurysms (figure 6).71 The ANRD is a T shaped implant com-posed of 0.002 inch nitinol, is deployed through a microcath-eter, and can support coils placed within the aneurysm.Compared with stents, there is significantly decreased metalsurface area. The eClips device (Evasc Medical Systems,Vancouver, British Columbia, Canada) is similar to the ANRDand Pulse Rider in that it is anchored across a wide neckedbifurcation aneurysm and, when deployed, creates a highdensity ‘leaf-like’ structure that can support intrasaccular coilswithout affecting branch artery patency (see online supplemen-tary figure III). Initial in vivo and human studies are promisingbut limited. Similarly, the PpCONus (Phenox, Bochum,Germany) is a stent-like structure that was recently approved forthe treatment of wide necked aneurysms in Europe. It isdeployed with the tip within the aneurysm and may allow foran easier waffle cone stent assisted coiling technique.30

Nevertheless, these novel neck reconstruction devices mayimprove our ability to treat morphologically complexaneurysms.

FUTURE ADVANCES AND OUTCOMESDevelopments in the management of intracranial aneurysms andin neuroendovascular technology are progressing rapidly.Although advances in interventional therapies have increasedthe complexity of aneurysms amenable to endovascular treat-ment, the overall rates of aneurysmal obliteration have beenincreasing, and rates of recurrence and retreatment have beendecreasing over time.21–23 72 73 Similarly, there have beenimprovements in overall patient functional outcome over time.In a systematic review of 97 studies of 7172 patients with cere-bral aneurysms treated with endovascular therapies, patientstreated after 2004 had better functional outcomes (unfavorable

outcome 3.1%) than patients treated during 2001–2003(unfavorable outcome 4.7%) or in 2000 and before (unfavorableoutcome 5.6%).32 A review of 60 studies of 9845 patients with10 845 aneurysms treated with endovascular therapies from1990 to 2011 also demonstrated a significant decrease in mor-bidity over time.73 Better outcomes may be attributable to awide variety of reasons, including improved imaging, endovas-cular and surgical treatment, and neurocritical care. Furthermatched and randomized clinical studies are required to deter-mine the overall benefits and changes over time as overall assess-ment may be limited by overall quality, heterogeneous patientpopulations, and publication bias.

Despite these advances, increased morbidity has been associatedwith novel developments, including the use of liquid embolicagents in the endovascular treatment of aneurysms.25–27 32

Additionally, complication rates and unfavorable outcomes areincreased following treatment of aneurysms with balloon remodel-ing, stent assistance, and flow diverting devices.32 This may be par-tially explained by the increased morbidity and mortalityassociated with the treatment of giant and complex aneurysms.Future studies, including the LARGE randomized clinical trial,which will compare endovascular coiling, stent assisted coiling,and flow diversion for large and giant aneurysms,74 are necessaryand may help define the optimal treatment strategies for thesepatients.

CONCLUSIONImprovements in cerebrovascular imaging may lead to refinedpatient evaluation before, during, and after endovascular inter-vention. Evolution of endovascular devices has greatly increasedthe potential to treat difficult aneurysms but can also be asso-ciated with unique complications. It is imperative to have a

Figure 5 Incomplete stent coverage across the neck of a basilar artery aneurysm, ‘Y’ stenting of a basilar artery aneurysm with two stents, andtreatment of a basilar artery aneurysm with the Barrel stent (A). The Barrel stent after stent placement for a basilar tip aneurysm, and angiographyafter Barrel stent assisted coiling (B).

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comprehensive understanding of these novel devices and tofollow preliminary treatment reports in order to assess the longterm outcomes and complications. Further studies are necessaryto identify the optimal devices for endovascular treatment ofintracranial aneurysms.

Contributors All authors: substantial contributions to the conception and designof the work; interpretation of the data for the work; drafting the work and revisingit critically for important intellectual content; final approval of the version to bepublished; and agreement to be accountable for all aspects of the work in ensuringthat questions related to the accuracy or integrity of any part of the work areappropriately investigated and resolved.

Competing interests AT: consultant for Covidien, MicroVention, Penumbra,Stryker, Siemens, and Codman. ASD: consultant for ev3 and Stryker. PJ: consultantfor ev3, Codman, and Mizuho. RDT: consultant for Covidien, Microvention, CodmanNeurovascular, Stryker, Penumbra, and Blockade Medical.

Provenance and peer review Not commissioned; externally peer reviewed.

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Figure 6 The Pulse Rider (A). A basilar artery aneurysm before treatment (B) and after stent assisted coiling with the Pulse Rider (C, D).

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10 Starke RM, et al. J NeuroIntervent Surg 2014;0:1–10. doi:10.1136/neurintsurg-2014-011475

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treatment of intracranial aneurysmsTechnology developments in endovascular

Christopher R Durst and Raymond D TurnerLiu, Nohra Chalouhi, David M Hasan, Aaron S Dumont, Pascal Jabbour, Robert M Starke, Aquilla Turk, Dale Ding, Richard W Crowley, Kenneth C

published online November 20, 2014J NeuroIntervent Surg 

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