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Background Intrasaccular flow-disrupting devices are a safe and effective treatment strategy for intracranial aneurysms. We utilized high-frequency optical coherence tomography (HF-OCT) and digital subtraction angiography (DSA) to evaluate SEAL Arc, a new intrasaccular device, and compare the findings with the well-established Woven EndoBridge (WEB) device in an animal model of saccular aneurysms. Methods In a rabbit model, elastase-induced aneurysms were treated with SEAL Arc (n=11) devices. HF-OCT and DSA were performed after implant and repeated after 12 weeks. Device protrusion and malapposition were assessed at implant time and scored on a binary system. Aneurysm occlusion was assessed at 12 weeks with the WEB Occlusion Scale and dichotomized to complete (A and B) or incomplete (C and D) occlusion. The percentage of neointimal coverage after 12 weeks was quantified using HF-OCT. We compared these data to previously published historical controls treated with the gold-standard WEB device (n=24) in the same model. Results Aneurysm size and device placement were not significantly different between the two groups. Complete occlusion was demonstrated in 80% of the SEAL Arc devices, which compared favorably to the 21% of the aneurysms treated with WEB devices (P=0.002). Neointimal coverage across SEAL Arc devices was 86±15% compared with 49±27% for WEB (P=0.001). Protruding devices had significantly less neointimal coverage (P<0.001) as did incompletely occluded aneurysms (P<0.001). Histologically, all aneurysms treated with SEAL Arc devices were completely healed. Conclusion Complete early aneurysm occlusion was frequently observed in the SEAL Arc treated aneurysms, with significant neointimal coverage after 12 weeks. [ABSTRACT FROM AUTHOR]

Background Flow diverters carry the risk of thromboembolic complications (TEC). We tested a coating with covalently bound heparin that activates antithrombin to address TEC by locally downregulating the coagulation cascade. We hypothesized that the neuroimaging evidence of TEC would be reduced by the coating. Methods 16 dogs were implanted with overlapping flow diverters in the basilar artery, separated into two groups: heparin-coated (n=9) and uncoated (n=7). Following implantation, high-frequency optical coherence tomography (HF-OCT) was acquired to quantify acute thrombus (AT) formation on the flow diverters. MRI was performed postoperatively and repeated at 1, 2, 3, 4, and 8 weeks, consisting of T1-weighted imaging, time-0f-flight (ToF), diffusion weighted imaging (DWI), susceptibility weighted imaging (SWI), and fluid attenuated inversion recovery (FLAIR) sequences. Neurological examinations were performed throughout the 8-week duration of the study. Results The mean AT volume on coated devices was lower than uncoated (0.014 vs 0.018 mm³); however, this was not significant (P=0.3). The mean number of foci of magnetic susceptibility artifacts (MSAs) on SWI was significantly different between the uncoated and coated groups at the 1-week follow-up (P<0.02), and remained statistically different throughout the duration of the study. The AT volume showed a direct linear correlation with the MSA count and 80% of the variance in the MSA could be explained by the AT volume (P<0.001). Pathological analysis showed evidence of ischemic injury at locations of MSA. Conclusions Heparin-coated flow diverters significantly reduced the number of new MSAs after 1 week follow-up, showing the potential to reduce TEC. [ABSTRACT FROM AUTHOR]

Background Flow diversion has become a standard treatment for cerebral aneurysms. However, major drawbacks include the need for dual antiplatelet therapy after implant and delayed complete occlusion of the aneurysm, which occurs when new tissue growth excludes the aneurysm from the parent artery. Biomimetic surface modifications such as the phosphorylcholine polymer (Shield surface modification) represent major advances in reducing thrombogenicity of these devices. However, in vitro studies have raised concerns that this modification may also delay endothelialization of flow diverters. Methods Bare metal Pipeline, Pipeline Shield, and Vantage with Shield devices were implanted in the common carotid arteries (CCAs) of 10 rabbits (two in the left CCA, one in the right CCA). Following implant and at 5, 10, 15, and 30 days, the devices were imaged with high-frequency optical coherence tomography and conventional angiography to evaluate tissue growth. At 30 days the devices were explanted and their endothelial growth was assessed with scanning electron microscopy (SEM) at five locations along their length using a semiquantitative score. Results The average tissue growth thickness (ATGT) was not different between the three devices. Neointima was apparent at 5 days and all devices demonstrated similar ATGT at each time point. On SEM, no difference was found in the endothelium scores between the device types. Conclusion In vivo, neither the Shield surface modification nor the device design (Vantage) altered the longitudinal healing of the flow diverter. [ABSTRACT FROM AUTHOR]

Background Preclinical testing of intracranial stents is currently performed in the peripheral circulation, and rarely in the basilar artery of the dog. Objective To test the feasibility of intracranial stenting in the middle cerebral artery (MCA) of the dog and explore the use of MRI to detect thromboembolic complications. Methods Six purpose-bred cross-hound dogs were used for proof-of-concept stenting of both MCAs in each animal. Immediately following the procedure, the animals were imaged with MRI. MRI was repeated weekly for 1 month. After the final angiography at 30 days, the animals were euthanized for pathological assessment of the stents and the brain. Results We successfully deployed 12 stents in the MCAs of all animals. We deployed three techniques for microcatheterization of the MCA--namely, directly through the internal carotid artery (ICA), using anastomotic arteries from the external carotid artery, or via the contralateral ICA through the anterior communicating artery. Two iatrogenic perforations of the ICA with formation of an arteriovenous fistula occurred, without clinical sequelae, which spontaneously resolved on follow-up. All animals tolerated the procedure and completed the follow-up surveillance. MRI revealed procedural thromboembolic induced areas of restricted diffusion, and only one instance of a delayed thromboembolic lesion during surveillance. At follow-up angiography, the devices were all patent. Conclusion We describe a new preclinical model of intracranial stenting in the MCA. Such a model may prove useful for evaluating new surface modifications. [ABSTRACT FROM AUTHOR]

Background High-frequency optical coherence tomography (HF-OCT) is an intravascular imaging method that allows for volumetric imaging of flow diverters in vivo. Objective To examine the hypothesis that a threshold for both volume and area of communicating malapposition can be predictive of early aneurysm occlusion. Methods Fifty-two rabbits underwent elastase aneurysm formation, followed by treatment with a flow diverter. At the time of implant, HF-OCT was acquired to study the rate and degree of communicating malapposition. Treated aneurysms were allowed to heal for either 90 or 180 days and euthanized following catheter angiography. Healing was dichotomized into aneurysm remnant or neck remnant/complete occlusion. Communicating malapposition was measured by HF-OCT using a semi-automatic algorithm able to detect any points where the flow diverter was more than 50 µm from the vessel wall. This was then summed across image slices to either a volume or area. Finally, a subsampled population was used to train a statistical classifier for the larger dataset. Results No difference in occlusion rate was found between device type or follow-up time (p=0.28 and p=0.67, respectively). Both volume and area of malapposition were significantly lower in aneurysms with a good outcome (p<0.001, both). From the statistical model, a volume of less than 0.56 mm3 or a normalized area less than 0.69 as quantified by HF-OCT was predictive of occlusion (p<0.001, each). Conclusions HF-OCT allows for measurements of both volume and area of malapposition and, from these measurements, an accurate prediction for early aneurysm occlusion can be made. [ABSTRACT FROM AUTHOR]

Background Direct aspiration thrombectomy techniques use large bore aspiration catheters for mechanical thrombectomy. Several aspiration catheters are now available. We report a bench top exploration of a novel beveled tip catheter and our experience in treating large vessel occlusions (LVOs) using next-generation aspiration catheters. Methods A retrospective analysis from a prospectively maintained database comparing the bevel shaped tip aspiration catheter versus non-beveled tip catheters was performed. Patient demographics, periprocedural metrics, and discharge and 90-day modified Rankin Scale (mRS) scores were collected. Patients were divided into two groups based on which aspiration catheter was used. Results Our data showed no significant difference in age, gender, IV tissue plasminogen activator administration, admission NIH Stroke Scale score, baseline mRS, or LVO location between the beveled tip and flat tip groups. With the beveled tip, Thrombolysis in Cerebral Infarction (TICI) 2C or better recanalization was more frequent overall (93.2% vs 74.2%, p=0.017), stent retriever usage was lower (9.1% vs 29%, p=0.024), and patients had lower mRS on discharge (median 3 vs 4, p<0.001) and at 90 days (median 2 vs 4, p=0.008). Conclusion Patients who underwent mechanical thrombectomy with the beveled tip catheter had a higher proportion of TICI 2C or better and had a significantly lower mRS score on discharge and at 90 days. [ABSTRACT FROM AUTHOR]

Background High-frequency optical coherence tomography (HF-OCT) is an intra-vascular imaging technique capable of assessing device-vessel interactions at spatial resolution approaching 10 µm. We tested the hypothesis that adequately deployed Woven EndoBridge (WEB) devices as visualized by HF-OCT lead to higher aneurysm occlusion rates. Methods In a leporine model, elastase-induced aneurysms (n=24) were treated with the WEB device. HF-OCT and digital subtraction angiography (DSA) were performed following WEB deployment and repeated at 4, 8, and 12 weeks. Protrusion (0-present, 1-absent) and malapposition (0-malapposed, 1-neck apposition >50%) were binary coded. A device was considered 'adequately deployed' by HF-OCT and DSA if apposed and non-protruding. Aneurysm healing on DSA was reported using the 4-point WEB occlusion score: A or B grades were considered positive outcome. Neointimal coverage was quantified on HF-OCT images at 12 weeks and compared with scanning electron microscopy (SEM). Results Adequate deployment on HF-OCT correlated with positive outcome (P=0.007), but no statistically significant relationship was found between good outcome and adequate deployment on DSA (P=0.289). Absence of protrusion on HF-OCT correlated with a positive outcome (P=0.006); however, malapposition alone had no significant relationship (P=0.19). HF-OCT showed a strong correlation with SEM for the assessment of areas of neointimal tissue (R²=0.96; P<0.001). More neointimal coverage of 78%±32% was found on 'adequate deployment' cases versus 31%±24% for the 'inadequate deployment' cases (P=0.001). Conclusion HF-OCT visualizes features that can determine adequate device deployment to prognosticate early aneurysm occlusion following WEB implantation and can be used to longitudinally monitor aneurysm healing progression. [ABSTRACT FROM AUTHOR]

Objective To investigate in situ decellularization of a large animal model of saccular aneurysm as a strategy for achieving aneurysmal growth and lasting inflammation. Methods 18 New Zealand White rabbits were randomized 2:1 to receive endoluminal sodium dodecyl sulfate infusion (SDS, 1% solution, 45 min) following elastase or elastase-only treatment (control). All aneurysms were measured by digital subtraction angiography every 2 weeks. Every 2 weeks, three of the rabbits (two elastase + SDS, one control) underwent MRI, followed by contrast injection with myeloperoxidase (MPO)-sensing contrast agent. MRI was repeated 3 hours after contrast injection and the enhancement ratio (ER) was calculated. Following MRI, aneurysms were explanted and subjected to immunohistopathology. Results During follow-up MRI, the average ER for SDS-treated animals was 1.63±0.20, compared with 1.01±0.06 for controls (p<0.001). The width of SDS-treated aneurysms increased significantly in comparison with the elastase aneurysms (47% vs 20%, p<0.001). Image analysis of thin sections showed infiltration of MPO-positive cells in decellularized aneurysms and surroundings through the 12-week observation period while control tissue had 5-6 times fewer cells present 2 weeks after aneurysm creation. Immunohistochemistry demonstrated the presence of MPO-positive cells surrounding decellularized lesions at early time points. MPO-positive cells were found in the adventitia and in the thrombi adherent to the aneurysm wall at later time points. Conclusions In situ decellularization of a large animal model of saccular aneurysms reproduces features of unstable aneurysms, such as chronic inflammation (up to 12 weeks) and active aneurysm wall remodeling, leading to continued growth over 8 weeks. [ABSTRACT FROM AUTHOR]

Introduction The neuroprotective benefit of therapeutic hypothermia (TH) has been demonstrated, but systemic side effects and time required to achieve effective TH in acute ischemic stroke (AIS) care limits clinical use. We investigate rapid and localized cooling using a novel insulated catheter in an ischemia-reperfusion model. Methods In phase I (n=4), cold saline was delivered to the canine internal carotid artery via an insulated catheter. Temperature was measured using intracerebral thermocouples. The coolant flow rate was varied to meet a target temperature of 31-32°C in the hemisphere infused. In phase II (n=8), a temporary middle cerebral artery occlusion was created. Five dogs underwent localized TH at the optimal flow rate from phase I, and the remaining animals were untreated controls. Cooling was initiated 5 min before recanalization and continued for an additional 20 min following 45 min of occlusion duration. The outcome was infarct volume and neurological function. results Ipsilateral tissue cooling rates were 2.2±2.5°C/min at a flow rate of 20-40 mL/min with an observed minimum of 23.8°C. Tissue cooling was localized to the ipsilateral side of the infusion with little impact on temperatures of the core or contralateral hemisphere of the brain. In phase II, animals tolerated TH with minimal systemic impact. Infarct volume in treated animals was 0.2±0.2 cm³, which was smaller than in sham animals (3.8±1.0 cm³) as well as six untreated historical control animals (4.0±2.8 cm³) (p=0.013). Conclusions Proof-of-concept data show that localised brain TH can be quickly and safely achieved through a novel insulated catheter. The small infarct volumes suggest potential benefit for this approach. [ABSTRACT FROM AUTHOR]

Background neo-intimal hyperplasia (NIH) is frequently observed after flow-diverter stent (FDS) implantation. Although mostly asymptomatic, this vascular response can sometimes lead to delayed ischemic strokes. This study intended to evaluate the factors potentially influencing the rates of NIH following FDs treatment. Material and Methods all aneurysm treatments performed with a Pipeline embolization device (PED) or a silK stent from May 2011 to May 2015 were collected in a prospectively maintained database. Patient demographics, clinical, and angiographic outcomes including both digital subtraction angiography and X-arm cone-beam CT were registered. Two blind reviewers rated the presence of nih on a binary scale (present/absent). Results From 148 patients, 63 datasets were available for analysis. Inter-reader agreement was excellent (Kappa=0.88). NIH was positively correlated with smoking, dyslipidemia, and high blood pressure, but not with aneurysm characteristics. At early follow-up (<12 months), NIH was more frequently associated with the use of the SILK stent (68%) rather than the PED (38%): P<0.02. At long-term follow-up, the NIH rate in the total population dropped from 55% to 26% with no more significant difference between the two stents. The complete occlusion rate as seen in early follow-up was higher in the SILK group with 76% vs 65% but without statistical significance (P=0.4). Conclusion nih is a dual-vessel reaction after FDs implant. When planning a treatment in locations at risk of ischemic complications if severe nih would occur, then the stent design should be considered. However, minimal nih might also be needed as it is involved in aneurysm healing. Before treatment patients should be recommended best medical management of their cardiovascular risks factors to prevent an excessive nih reaction. [ABSTRACT FROM AUTHOR]

Background Despite high recanalization rates achieved with endovascular treatment of acute ischemic strokes, around 50% of eligible patients will not achieve a good outcome. Parameters that may determine patient outcomes include: time from puncture to recanalization, the collateral status, the anesthesia regimen, blood pressure management, and distal emboli. Characterization of distal emboli generated during mechanical thrombectomy has been performed in previous studies. Objective To further investigate the risk of distal embolization associated with microcatheter navigation across the clot. Methods a contrast-enhanced clot analog was used in an in vitro model that mimicked a middle cerebral artery occlusion within a complete circle of Willis vascular replica. The clot was crossed with one of the following microcatheters: Pro18, XT-27 or 3MAX. The emboli generated during the procedure were collected and measured. Results The use of Pro18 and XT-27 resulted in a significant reduction of visible particles (size ≥500 µm) as compared with the 3MAX catheter (P<0.003). For the size range between 8 and 200 µm, there was a trend for Pro18 to generate fewer particles (-18%) than XT-27 but without statistical significance (P>0.05). in comparison with previously published data, acquired under the same conditions, it was found that the clot crossing maneuver accounts approximately for 12% of the total number of small emboli (<200 µm) induced during a stent retriever-mediated mechanical thrombectomy procedure via a balloon guide catheter. Conclusions The clot crossing maneuver has a significant effect on the total number of small particles induced during mechanical thrombectomy. smaller microcatheter sizes should be favored when possible. [ABSTRACT FROM AUTHOR]

Background Optical coherence tomography (OCT) is a high resolution intravascular imaging method that allows visualization of flow diverter struts and the vessel wall. In this study, malapposition of the flow diverter that continues into the neck of the aneurysm, named communicating malapposition (CM), was investigated as a potential factor for delayed aneurysm healing. Methods 40 New Zealand White rabbits underwent elastase induced aneurysm creation, and were subsequently assigned to one of four treatment groups based on flow diverter type and administration of antiplatelet therapy. All animals underwent post device deployment balloon angioplasty and subsequent OCT to assess device/vessel apposition. The incidence of CM seen on OCT was assessed with a binary scoring system: 0-CM present; 1-CM absent. At 30 days, DSA was acquired to assess aneurysm healing. Aneurysm healing on terminal DSA was measured using a previously developed 5 point scale, with a score of 3 or 4 considered a positive outcome. Results All animals were grouped into a single cohort for analysis as no difference in the rate of CM or healing was seen in the four treatment groups. Significant interaction between the absence of CM and a positive outcome was confirmed by Fisher exact test (P=0.0034). Angioplasty was shown to treat 33% of the cases of CM seen at implant, and these treated cases overwhelmingly had a positive outcome (P<0.001). Conclusion The use of OCT to assess CM of flow diverters has been shown to be predictive of the 30 day healing rate of an animal model of aneurysms. [ABSTRACT FROM AUTHOR]

Purpose Thromboembolic complications remain a limitation of flow diverting stents. We hypothesize that phosphorilcholine surface modified flow diverters (Pipeline Flex with shield Technology, sPED) would have less acute thrombus formation on the device surface compared with the classic Pipeline Embolization device (cPED). Methods Elastase-induced aneurysms were created in 40 rabbits and randomly assigned to receive cPED or sPED devices with and without dual antiplatelet therapy (DAPT) (four groups, n=10/group). Angioplasty was performed to enhance apposition and create intimal injury for a pro-thrombotic environment. Both before and after angioplasty, the flow diverter was imaged with intravascular optical coherence tomography. The outcome measure was the number of predefined segments along the implant relative to the location of the aneurysm with a minimum of 0 (no clot formation) and maximum of 3 (all segments with thrombus). Clot formation over the device at ostia of branch arteries was assessed as either present or absent. Results Following angioplasty, the number of flow diverter segments with clots was significantly associated with the flow diverter (p<0.0001), but not with DAPT (p=0.3872) or aneurysm neck size (p=0.8555). The incidence rate for clots with cPED was 1.72 times more than with sPED. The clots on the flow diverter at the location corresponding to side branch ostia was significantly lower with sPED than with cPED (OR 0.180; 95% CI 0. 044 to 0.734; p=0.0168), but was not associated with DAPT (p=0.3198). Conclusion In the rabbit model, phosphorilcholine surface modified flow diverters are associated with less thrombus formation on the surface of the device. [ABSTRACT FROM AUTHOR]

Background and purpose Currently, there is neither a standard protocol for vessel wall MR imaging of intracranial atherosclerotic disease (ICAD) nor a gold standard phantom to compare MR sequences. In this study, a plaque phantom is developed and characterized that provides a platform for establishing a uniform imaging approach for ICAD. Materials and methods A patient specific injection mold was 3D printed to construct a geometrically accurate ICAD phantom. Polyvinyl alcohol hydrogel was infused into the core shell mold to form the stenotic artery. The ICAD phantom incorporated materials mimicking a stenotic vessel and plaque components, including fibrous cap and lipid core. Two phantoms were scanned using high resolution cone beam CT and compared with four different 3 T MRI systems across eight different sites over a period of 18 months. Interphantom variability was assessed by lumen dimensions and contrast to noise ratio (CNR). Results Quantitative evaluation of the minimum lumen radius in the stenosis showed that the radius was on average 0.80 mm (95% CI 0.77 to 0.82 mm) in model 1 and 0.77 mm (95% CI 0.74 to 0.81 mm) in model 2. The highest CNRs were observed for comparisons between lipid and vessel wall. To evaluate manufacturing reproducibility, the CNR variability between the two models had an average absolute difference of 4.31 (95% CI 3.82 to 5.78). Variation in CNR between the images from the same scanner separated by 7 months was 2.5-6.2, showing reproducible phantom durability. Conclusions A plaque phantom composed of a stenotic vessel wall and plaque components was successfully constructed for multicenter high resolution MRI standardization. [ABSTRACT FROM AUTHOR]

Background Poor vessel wall apposition of flow diverter (FD) stents poses risks for stroke-related complications when treating intracranial aneurysms, necessitating long-term surveillance imaging. To facilitate quantitative evaluation of deployed devices, a novel algorithm is presented that generates intuitive twodimensional representations of wall apposition from either high-resolution contrast-enhanced cone-beam CT (VasoCT) or intravascular optical coherence tomography (OCT) images. Methods VasoCT and OCT images were obtained after FD implant (n=8 aneurysms) in an experimental sidewall aneurysm model in canines. Surface models of the vessel wall and FD device were extracted, and the distance between them was presented on a two-dimensional flattened map. Maps and cross-sections at potential locations of malapposition detected on VasoCT-based maps were compared. The performance of OCT-based apposition detection was evaluated on manually labeled cross-sections using logistic regression against a thresholded (≥0.25 mm) apposition measure. Results VasoCT and OCT acquisitions yielded similar Grading of Regional Apposition after Flow-Diverter Treatment (GRAFT) apposition maps. GRAFT maps from VasoCT highlighted 16 potential locations of malapposition, of which two were found to represent malapposed device struts. Logistic regression showed that OCT could detect malapposition with a sensitivity of 98% and a specificity of 81%. Conclusions GRAFT delivered quantitative and visually convenient representations of potential FD malapposition and occasional acute thrombus formation. A powerful combination for future neuroendovascular applications is foreseen with the superior resolution delivered by intravascular OCT. [ABSTRACT FROM AUTHOR]