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Our goal was to establish a contrast injection technique that uses the unique vascular anatomy of the rabbit ear to spare the valuable femoral artery access sites. The central artery of the left ear was cannulated. Contrast injected in a retrograde fashion opacified the right brachiocephalic artery and its branches. The technique can be used in rabbits with the usual bovine-type left common carotid artery origin.

The discovery of X-rays over a century ago enabled noninvasive examination of the human body. Contrast agents that enhanced X-ray images were soon developed that advanced angiology by allowing exploration of the vascular tree. Starting as a diagnostic tool, angiography underwent technological transformations over the last century and became a basis for interventional therapy as well. Initially a static two-dimensional record of the vasculature on screen films, angiography has evolved to real-time two-dimensional display of the vasculature on television monitors, three-dimensional reconstruction from computerized tomographic (CT) scans, and, more recently, three-dimensional cone-beam reconstruction. Cinematographic angiography is referred to as dynamic angiography in current terminology, but it essentially provides no more than images of vascular structures and changes therein. Although dynamic angiography has facilitated advances in image-guided interventions, the evaluation of blood flow rate, or perfusion, and blood flow velocity using angiography remains elusive. Many lines of research have been pursued toward enabling such evaluations, but none have found their way into clinical practice. This article reviews angiographic flow assessment methods attempted over the past several decades and explores some new avenues that may facilitate the transfer of such methods into the clinical practice of diagnostic and interventional angiography and, eventually, contribute to better patient care.

Therapeutic angiogenesis involves the introduction of exogenous growth factor proteins and genes into ischemic tissues to augment endogenous factors and promote new vessel growth. Positive results from studies in animal models of peripheral arterial disease (PAD) and coronary artery disease over the past decade have supported the implementation of clinical trials testing vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) proteins and genes. Although several clinical trials reported positive results, others have been disappointing and results of a recent Phase II trial of VEGF delivered by adenovirus (the RAVE trial) were negative. It has been suggested that the duration of gene expression following delivery by adenovirus may be insufficient to produce stable vessels. Here we present direct evidence in support of this using the rabbit ischemic hindlimb model injected with adenovirus encoding VEGF165. Immunohistology indicated an activation of endothelial cell cycling and proliferation 2-3 days after VEGF delivery that coincided closely with transient VEGF expression. Ki-67-positive endothelial nuclei were evident at high levels in capillaries and large vessels in muscles from treated animals. Angiography indicated increased density of both large and small vessels in Ad-VEGF-treated muscle at 1 week, but no significant differences thereafter. The early burst of endothelial proliferation was accompanied by increased nuclear fragmentation and condensation in VEGF-treated muscles, suggesting coincident apoptosis. No further endothelial cell proliferation took place after 1 week although there was still evidence of apoptosis. The results suggest that angiogenesis is confined to the short period of VEGF expression produced by adenovirus and early gains in collateralization rapidly regress to control levels when VEGF production ceases.

Introduction Carotid or vertebral artery dissections account for approximately 20% of strokes in young adults 1 . Optimal anticoagulation treatment is currently the standard therapy. Endovascular management of such lesions becomes necessary in the presence of concomitant intracranial occlusions, flow limiting haemodynamic changes, contraindications to anticoagulation or persistent thromboembolic episodes despite optimal medical management. Materials and Methods All patients who presented with either a carotid or vertebral artery dissection at our institution between January 2011 and October 2012 were identified. We then selected the patients who were treated with multiple overlapping stents (≥3 stents) for a long segment dissection. In addition, we analysed patients’ vascular risk factors, presenting symptoms, NIHSS and mRS on admission, follow-up imaging results and patient clinical outcome at discharge, 90 days and 6 months. Results We included 7 patients (4 males and 3 females) in our study who were treated with ≥3 stents for a long segment dissection of either the carotid or vertebral artery. Mean age of the patients was 53.6 years. Mean NIHSS and median mRS on admission was 9.3 and 3, respectively. Patients’ vascular risk factors included hypertension (57.1%), dyslipidaemia (42.9%), fibromuscular dysplasia (28.6%) and coronary artery disease (14.3%). Five patients (71.4%) presented with ischaemic lesions on imaging exams prior to endovascular treatment. Mean NIHSS at discharge was 4.4 and median mRS 2. Median mRS at 90 days and 6 months (n=5) was 1 and 0, respectively. 71.4% and 85.7% of patients presented with an mRS ≤2 at discharge and at 90-day follow-up evaluation. Mild in-stent intimal hyperplasia ( Conclusion The use of multiple stents for the treatment of long segment dissections allows for adequate vessel reconstruction and restoration of cerebral perfusion with favourable angiographic and clinical short-term results. In addition, stenting prevents further extension of the dissection and decreases the risk of intracranial thromboembolism. Disclosures A. Puri: None. A. Kuhn: None. S. Hou: None. M. Khan: None. J. Chueh: None. I. van der Bom: None. M. Gounis: None. A. Wakhloo: 1; C; Philips Healthcare. 2; C; Stryker Neurovascular, Boston Biomedical Assoc. 3; C; Harvard Postgraduate Course. 4; C; Boston Scientific. 6; C; NIH. Reference Bogousslavsky J, Pierre P. Ischemic stroke in patients under age 45. Neurol Clin .1992;10:113–124.

Objectives Validated through in vitro and in vivo experimental studies a new generation of flow diverters (Surpass™ FD) was evaluated for treatment of intracranial aneurysms (IA). We present our multicentre preliminary clinical and angiographic experience. Methods To achieve the calculated flow disruption between the parent artery and aneurysm, needed for a saccular thrombosis, single FDs, tailored to local haemodynamics, were placed endovascularly in parent arteries and bridging the aneurysm. Implants measured 2.5-5.3mm in diameter with a length of10–80mm. Enrolled were patients harbouring a wide range of non-acutely ruptured large and giant wide-neck, fusiform and multiple small aneurysms, blister-type aneurysms and aneurysms associated with segmental artery disease. All patients were pretreated with dual antiplatelet for at least 72 hours before surgery and continued on both agents for at least 3 months after treatment. Clinical and angiographic follow-up were typically performed at 1–3, 6, and 12 months. Results A total of 186 consecutive IA in 161 patients (mean age 57.1 years, range 28–82 years; 71% female) were treated at 23 centres. Fifty-three aneurysms were smaller than 5 mm, 64 were 5–9.9mm in diameter, 47 were10–20mm in diameter, and 22 were larger than 20mm (aneurysm diameter 10.4 ± 0.7mm, neck size 6.0 ± 0.5mm [mean ± SEM]). The aneurysms originated in 63.4% of the cases from the internal carotid artery; in 22% and 14.5% of the cases they were located in the anterior circulation distal to Circle of Willis and posterior circulation respectively. Technical success was achieved in 182 aneurysms (98%); incorrect FD placement with partial aneurysm coverage was observed in 5 aneurysms (2.7%). FDs were placed over 4 previously placed stents for coil embolisation; average number of devices used per aneurysm was 1.05. Permanent morbidity and mortality during the follow-up period of 8.7 months (range 1–24 months) including periprocedural complications were encountered in 5/134 (3.7%) and 2/134 (1.5%) of patients, respectively, within aneurysms of the anterior circulation; and 1/27 (3.7%) and 4/27 (14.8%) of patients, respectively, with posterior circulation aneurysm (one patient died from cancer, two patients died of pneumonia). Ninety-seven patients (60%) with 112 aneurysms were available for clinical and angiographic follow-up. Progressive thrombosis with complete occlusion was seen in 71% of aneurysms of the anterior circulation and 64% of aneurysms located distal to Circle of Willis and in 72% of aneurysms of the posterior circulation and included cases with improper device placement or FD covering previous stents. Occlusion in the range of range 95–100% was seen in 79%, 68% and 89% of aneurysms of the anterior circulation, aneurysms located distal to Circle of Willis and posterior circulation respectively. Conclusion Preliminary data demonstrate high safety and effectiveness profile of a new generation of FD for a wide range of IA of the anterior and posterior circulation without the need for coiling. Durability and high rate of progressive occlusion observed requires long-term follow-up studies. Disclosures A. Wakhloo: 2; C; Surpass Medical/Stryker. 4; C; Surpass Medical. 5; C; Surpass Medical. P. Lylyk: None. J. De Vries: 1; C; Surpass/Stryker. A. Biondi: 2; C; Surpass Medical/Stryker. C. Taschner: 2; C; Surpass Medical/Stryker. M. Hartmann: None. I. Szikora: None. L. Pierot: None. N. Sakai: None. N. Sourour: 2; C; Surpass Medical/Stryker. I. Rennie: None. M. Skalej: None. F. Mery: None. F. Turjman: None. P. Brouwer: None. E. Boccardi: None. M. Gounis: 2; C; Surpass Medical. T. Surpass User Group: None.

Hemodynamic mechanisms for the initiation and progression of carotid bifurcation atherosclerotic occlusive disease have been extensively researched during the past few decades. Attention has focused on the carotid bulb, or sinus, where most atherosclerotic plaques are found. Herein, the authors review the seminal works that have led to an understanding of not only complex local hemodynamics but also the elicited specific biologic response. In addition, new analysis of the age-dependent morphologic maturation of the human carotid bifurcation is unveiled. Understanding the role of hemodynamics in atherogenesis may lead to the improvement of minimally invasive endovascular therapy and noninvasive strategies.

Thirty New Zealand White rabbits were used in the study. The diameter of the origin of the CCA measured immediately after elastase incubation correlated positively to the aneurysm neck at three week follow up. Moreover, the aneurysm neck both after creation and three week follow-up had a positive correlation with the final dome height. Finally, the dome height was found to be related to the angle between the innominate artery and the aneurysm centerline for dome diameter/neck ratio of

Ever since x-ray cine-angiography was employed to visualize blood vessels, the observed flow of contrast through the vasculature enticed researches to attempt evaluation of blood flow or its velocity through the observed contrast dispersion. However, despite considerable efforts that were expended both in vitro on phantoms and in vivo, the determination of blood flow from the observed contrast remains elusive. What conspired to frustrate these efforts are the complex physical phenomena that govern the dispersion of a bolus of contrast in the pulsatile flowing blood solvent. Further, what compounded the difficulties is the deteriorating visibility of the contrast as it dispersed in the blood. In this experiment we investigate the dispersion of iodine based contrast material as is settles in slender glass vials filled with various fluids that are commonly used to either dilute the contrast material for in vivo application or as fluid media into which the contrast is injected both in vivo and in vitro.Copyright © 2004 by ASME

Therapeutic angiogenesis is the attempt to increase vascular density by means of an exogenously administered proangiogenic agent and offers a potential treatment for diseases associated with tissue ischemia. Vascular endothelial growth factor (VEGF) expressed by gene therapy has been shown to be a potent stimulator of angiogenesis and to improve the function of ischemic tissues in patients [Isner, 1998]. Unregulated gene therapy is disconcerting since there is no assurance that the treatment will target the ischemic territory. A new regulated adeno-associated viral vector expressing VEGF165 that is conditionally silenced has been developed by one of the authors (KAW). The transgene expression is regulated by silencing the genes in the absence of the disease and at the same time having strong and local activation in the presence of the disease. The purpose of this work is to establish protocols and techniques to quantify the efficacy of therapeutic angiogenesis. The initial phase of this research involves assessment of angiogenesis using an unregulated, adenoviral vector that is encoded to express VEGF165 . Using the rabbit hind limb ischemia model, angiography was performed on animals that were given the proangiogenic treatment and on a sham group, in which phosphate buffered saline (PBS) was injected. Angiographic contrast intensity curves were obtained, modeled, and the optimized model parameters provided insight into flow characteristics within the targeted vascular bed. In the second phase of the project the conditionally silent vector will be employed using the developed protocols and methods of the first phase to afford comparisons with the previous groups.Copyright © 2003 by ASME

Endovascular occlusion of cerebral aneurysms with bare platinum detachable coils is now recognized as preferable to surgical clipping (ISUIA Group, 2003, ISAT Group, 2002, Bavinzski et al, 1995, Thornton et al, 2002). Dependent on coil packing density (the ratio of the coil volume deposited in an aneurysm to that of the aneurysm volume), aneurysm location, size and neck width, coil compaction with recanalization of the aneurysm remains in the long-term a major concern. The aneurysm neck size is reported to be the main predictor for aneurysm recanalization (Fernandez-Zubillaga et al, 1994). The forces exerted on the coil mass at the aneurysm neck due to blood pulsatility are larger for wide neck aneurysms as compared to small neck aneurysms (Bavinzski et al, 1995). However, impingement forces have not been evaluated. We evaluated the force impinging on the aneurysm neck in a simplified aneurysm (basilar top) geometry utilizing the impulse-momentum equation and Womersley’s flow. Maximum impingement force as a function of aneurysm neck to parent lumen diameter ratio varies as a sigmoid curve. Analysis of the hemodynamic forces affecting coil compaction in cerebral aneurysms shows that the coil mass at the aneurysm neck may be subjected to cyclic impulse impingement due to redirection of blood momentum. Orientation of the aneurysm neck and the main axis of the aneurysm in relation to the oncoming parent vessel flow may help clinicians predict the risk of coil compaction and the location of subsequent aneurysm recanalization.Copyright © 2003 by ASME

Purpose Radiation therapy has shown to be an effective treatment of brain arteriovenous malformations (bAVMs).1 2 Target delineation is commonly performed on volumetric image data, such as MRI or CT data. However, the nidi of micro-AVMs may not be visualized adequately by these modalities due to their limited image resolution. In this report, we show a novel usage of high-resolution contrast-enhanced cone-beam computed tomography (CBCT) imaging and multi-modal image registration3 for radiation target delineation of a micro-AVM, a technique previously suggested for larger AVMs.4 Case A 42-year-old male presented with intraparenchymal hemorrhage in the mesencephalic tectum and left posterior thalamus. Conventional angiography revealed a left superior collicular AVM with a nidus of 3 mm. The AVM was successfully embolized but follow-up angiography examinations at 36 months demonstrated a small re-growth of the AVM (Abstract P-017 figure 1A). The patient was thus referred to radiosurgery. Thin slice contrast and non-contrast MRI acquired for target delineation did not show the AVM nidus. Therefore, the patient was transferred to the angiography suite for high resolution contrast-enhanced CBCT. Data was acquired using the angiography c-arm system with a reduced detector size of 22 cm. Contrast was injected with 2 ml/s for a total of 64 ml and a 2 sec delay) using a coupled power injector into the left vertebral artery with a 5Fr catheter. Volumetric CBCT data (FOV: 703 mm3, matrix: 0.143 mm3) was generated using a non-binned reconstruction algorithm. Lesion and nidus were visualized with CBCT. MRI, CT-simulator and CBCT data was then transferred to the radiation planning software and mutually co-registered. The nidus was delineated on CBCT data by an experienced neurointerventional radiologist for radiation therapy and dose/treatment plan was completed. Due to image registration, the target area could be directly transferred to MRI and CT data (Abstract P-0017 figure 1B). The patient received a total of 4 radiation sessions. Discussion and Conclusion Radiation target delineation of micro AVMs can be challenging with conventional 3D imaging techniques as their spatial resolution is relatively low for the application of visualization of the nidus. We were able to demonstrate the complementary value of high resolution contrast enhanced CBCT in radiation target delineation of a micro brain AVM. Multi-modal image registration of CBCT with MRI and CT-simulator has shown to be an effective method for radiation target delineation. Competing interests I van der Bom: None. A Wakhloo: Philips Healthcare. A Kuhn: None. L Ding: None. D Goff: None. M Gounis: None. References 1. AJNR 1995;16:299. 2. J Neurosurg 2002;97:779–84. 3. vanderBom IMJ,et al. J NeuroIntervent Surg 2011. In press. 4. Radvany MG,et al. J NeuroIntervent Surg 2011. In press.

BACKGROUND AND PURPOSE: Endovascular stent placement is an emerging technique in treating cerebral aneurysms. Thus far, no quantitative method is available to determine the effectiveness of stent deployment in reducing intraaneurysmal flow circulation, and thereby, in excluding the aneurysm from the cerebral vasculature. Our purpose was to develop a mathematical model congruent with flow transport phenomena observed in cerebral aneurysms and based on the washout of angiographic contrast medium from these aneurysms to provide quantitative indices for predicting the likelihood of stable thrombus formation after stent placement. METHODS: Angiographic data from an in vitro experiment involving an elastomer side-wall aneurysm model and data from five patients with cerebral aneurysms were collected and analyzed. A region of interest (ROI) delineating the aneurysm was selected in each case, and the temporal variation in average gray-scale intensity within this ROI was assessed. The mathematical model was fit to the gray-scale intensity curves by using least-squares minimization. Variations in model parameters before and after stent placement were studied. RESULTS: A marked variation in the model parameters was observed in both in vitro cases and when data suitable for mathematical modeling were available from the clinical setting. This variation supported the hypothesis of the model. CONCLUSION: On the basis of our results, we conclude that the model developed herein can be used to quantitatively depict and characterize alterations in aneurysmal blood-flow transport before and after endovascular stent placement. By inference, future versions of the model will be useful in predicting the long-term effectiveness of endovascular stent placement for cerebral aneurysms immediately after the procedure is performed.

BACKGROUND AND PURPOSE: Precise control of the polymerization dynamics of cyanoacrylate mixtures used in the embolization of cerebral arteriovenous malformations is required to achieve a safe and permanent obliteration of the lesion. In this study, in vivo embolization using mixtures of Histoacryl, Lipiodol Ultra-Fluid, and glacial acetic acid (GAA) was investigated. The present study investigated whether increased ethiodized oil concentration or the addition of GAA increased rate of embolization. METHODS: Using embolic mixtures containing Histoacryl (n-butyl 2-cyanoacrylate [NBCA]), the embolization process in the femoral and subclavian arteries of the rabbit was examined. Various embolic agents composed of ethiodized oil and N-BCA mixtures, either with or without the addition of minute quantities of GAA, were injected. Blood flow through the aforementioned arteries was measured during embolization. The transient decay of blood flow to zero was modeled, and an optimized model parameter, termed the time elapsed to flow arrest (TEFA) factor, was compared with the experimental data related to the embolization process. RESULTS: The TEFA factor was independent of the variation of the ethiodized oil concentration in the mixture (P > .05). In contradistinction, the addition of GAA significantly increased the TEFA factor (P < .05). Moreover, a linear relation between the TEFA factor and the quantity of GAA in the mixture was discerned. CONCLUSION: Predictable control of the embolization process with N-BCA in vivo is attained by varying the amount of GAA in the embolic mixture.

Introduction Preclinical testing of endovascular devices in an in-vivo environment provides a more realistic simulation of critical vessel viscoelastic and physiologic responses. In comparison, in-vitro and cadaveric models, though indispensible, can only assess structural and mechanical responses. Replicating the tortuosity of the carotid siphon in an in vivo model is a challenging endeavor. Models created by complex surgical maneuvers have previously been described1, often requiring the expertise of a skilled surgical team and considerable expense. We describe a novel porcine model of arterial tortuosity with a quantitative comparison of its geometric features with a population representative carotid siphon acquired from a patient dataset. Materials and Methods Three Yorkshire swine (sex: male, mean weight 46.6 kg) were used for the purposes of the study. The animals were anesthetized and femoral artery access was obtained through a 6F sheath. The microcatheter was successfully navigated to the brachial branch of the axillary artery and a selective digital subtraction angiogram was acquired in both extended and flexed right and left forelimb positions. Three dimensional rotational angiograms (3DRA) were also acquired. The vessel segmentation and centerline was generated using Mimics (Materialise, Leuven, Belgium) and a quantitative measurement of the geometric parameters was obtained as previously described. This was compared with a realistic population representative human carotid siphon model.2 Results The mean average curvature (AC), length and diameter calculated for the arterial segments (average±SE of the mean) in the extended (0.28±0.06 mm −1 , 13.99±1.66 mm and 2.60±0.19 mm) and the flexed (0.29±0.02 mm −1 , 17.59±0.77 mm and 2.59±0.12 mm) position are similar. In comparison, the values calculated for the population representative carotid siphon are 0.34±0.02 mm −1 , 22.60±0.79 mm and 4.15±0.09 mm, respectively. However, positioning the forelimb in the flexed position (Abstract O-023 figure 1A, arrows) increased the number of tortuous bends in comparison to the extended position (Abstract O-023 figure 1B, arrow). Conclusion We have described a reproducible in vivo model of arterial tortuosity in the brachial artery in the flexed forelimb position in the swine. This model offers a challenging target for the assessment of guidewires, microcatheters and endovascular implants since it closely mimics the curvature experienced at the carotid siphon.

Introduction Although coil embolization of brain aneurysms is safe and effective, aneurysm recurrence remains a limitation requiring surveillance imaging. Recently, MR angiography (MRA) has become a viable option for non-invasive follow-up. Often, a baseline MRA within one week of coiling is acquired for comparison. The coil mass produces magnetic susceptibility artifact that may obscure the evaluation of the host vasculature and the aneurysm. Although previous research into MR artifact has been done in vitro, the dynamic characteristics of a functional vascular system cannot be simulated. Our aim in this study was to evaluate the MR susceptibility artifact from coil masses over time using different MRA techniques. Materials and Methods Four mongrel canines were used: two venous side-wall aneurysms were created on each common carotid artery for a total of four aneurysms in each animal. Aneurysms were embolized receiving only one type of coils, GDC or a new coil prototype. After coiling, the animals were transferred to the 3T MRI. MRI protocol included axial 3D TOF MRA (TE of 3.5, 5 and 6.9), phase contrast MRA, and coronal contrast-enhanced MRA. Serial MRI studies were repeated at 1, 4, 6, 8, 14, and 28 weeks. The volume of the coil mass was measured using 3D radiography. MRA sequences were analyzed using Mimics 13.1 for 3D reconstruction and volume measurements. An overestimation factor (OEF) was calculated: OEF=V SA /V CM ; where the numerator represents the volume of the MR susceptibility artifact and the denominator is the true volume of the coil mass measured by 3D radiography. Results OEFs are largest immediately after embolization, and show a gradual decay until approximately 4 weeks (Abstract O-030 figure 1), when there is stabilization of the size of the artifact. By 6 weeks we found that there was mild coil compaction (average coil mass volume decrease by 9.4%). However, the susceptibility artifact reduced substantially during the same time period; with the OEFs decreasing by 30% after 6 weeks. The decrease of the artifact is currently under evaluation. Histopathological analysis of explanted aneurysms did not show corrosion of the metal detachment zone. The effect of compaction has also been excluded as a possible hypothesis in phantom experiments. Conclusion MR susceptibility artifact changes over time, being maximal in the post embolization setting and decaying until 4 weeks. The clinical implications of this study indicate that baseline MRA for comparison with future imaging should be acquired after 4 weeks post procedure.

Purpose Recanalization using intra-arterial fibrinolytic therapy in combination with mechanical clot disruption may be a more effective strategy for early reestablishment of cerebral blood flow in acute ischemic stroke. To validate our hypothesis, we evaluated a prototype balloon infusion wire (NeuroInterventions, Pittsburgh Pa) for delivering rtPA directly within the clot and compared its performance with the HyperGlide compliant balloon (eV3 Neurovascular, Irvine, CA) and microcatheter directed rtPA infusion in a rabbit common carotid artery (CCA) thromboembolic occlusion model. Materials and Methods New Zealand white rabbits (n=7) were selected for this work due to their similar response to rtPA as in humans. They were anesthetized and >50% luminal stenosis of the CCA was created bilaterally with 3-0 silk suture. Allogenic clot was injected through a 6F guide catheter and lodged consistently in the CCA proximal to the stenosis (arrows, A). The stenosis was released one hour post clot injection allowing sufficient time for clot-vessel lumen interaction. DSA was performed bilaterally to confirm the occlusion and assess the Thrombolysis in Cerebral Infarction (TICI) score. Each vessel was assigned to receive the device, balloon angioplasty, or microcatheter directed rtPA. The negative control group received no therapy. The primary endpoint was flow restoration. The secondary endpoint was time to recanalization and vascular safety, which was assessed by histological response on luminal scanning electron microscopy (SEM) and H&E staining. An assessment of the vascular safety from controlled operation of the infusion device and balloon occlusion in unembolized rabbit CCA was also made. Results We successfully created consistent thromboembolic occlusions with TICI 0 flow at the predetermined location within the CCA. The balloon infusion wire achieved an earlier recanalization with a TICI 2B score (B, 2D perfusion post MTT) in 14 min requiring 2.8 mg rtPA. In comparison, microcatheter directed rtPA achieved TICI 2B score in 29 min requiring 4 mg rtPA. Balloon angioplasty, when used alone, achieved an inferior TICI 2A final recanalization score in 20 min post treatment and often failed to recanalize the CCA. Histomorphometry and luminal SEM evaluation revealed that the operation of the infusion device is comparable to balloon angioplasty with endothelial cell denudation and an exposure of the internal elastic lamina, an acceptable level of disruption for mechanical revascularization devices. Conclusion Combined pharmaco-mechanical disruption achieves a high recanalization grade with a lower thombolytic dose more rapidly in comparison to either therapy (balloon angioplasty and thrombolysis) used alone.

Introduction/purpose A new option in the treatment of large and complex intracranial aneurysms centerd along the cavernous/intradural segment of the ICA, proximal to the PCom artery, includes the utilization of flow-diverter devices. Intracranial stent/ flow diverter deployment in the treatment of aneurysm usually requires the administration of dual antiplatelet therapy for 3–12 months. Our usual protocol is to switch to mono-therapy with Aspirin after 6 months. We analyzed the results after continuing dual anti-platelet therapy based on the intimal hyperplasia (IH) noted on the 6 month follow-up cerebral angiography. The purpose of this study is to assess at 1-year follow-up the efficacy of mono or dual antiplatelet therapy in the management of in-PED IH observed at the 6-month cerebral angiogram. Materials and methods From October 2011 to February 2014, a total of 93 intracranial aneurysms in 83 patients (16 men and 67 women; age range, 19–85 years; mean age, 56.6 years) were treated with pipeline embolization device (PED) at our institution. A cone-beam CT (Philips, Allura Biplane FD20/20, Philips Medical, Best, Netherlands) was obtained using the angiography C-arm to assess for IH at FU angiographies. At 6-month follow-up (39 patients with 46 aneurysms) 8 cases of in-PED no-flow limiting minimal IH ( Results In the 8 patients having IH at the 6 months angiogram, 4 patients have till now underwent a 1 year follow-up. Complete resolution of the intimal hyperplasia was seen in 3 patients, whereas a stable IH was noted in one patient. One year follow up angiography was available for an additional 11 patients, who did not have IH at the 6 month FU. The 1 year FU angiography in these patients demonstrated no interval development of IH after stopping Clopidogrel at the 6 month time period. Conclusion In our experience the adjustment of antiplatelet drug therapy post endovascular PED treatment of intracranial aneurysm depending on 6 month follow up findings is strongly associated with complete Pipeline Embolization Device patency at 1-year follow-up. Furthermore in our experience cone-beam CT is an accurate and precise tool in the assessment of in-PED intimal hyperplasia development during follow-up. Disclosures F. Massari: None. A. Puri: None. S. Hou: None. M. Perras: None. C. Brooks: None. C. Stout: None. M. Gounis: None. A. Wakhloo: None.

Introduction Improved recanalization rate and immediate flow restoration have been achieved by the latest clot retrieval (thrombectomy) systems in the acute ischemic stroke treatment. However, clot debris generated during mechanical thrombectomy can result in distal embolization. We hypothesise that the catheterization strategies (type and position of the suction catheter) affect the risk of distal embolization Materials and methods Hard fragment-prone clots (HFC) and soft elastic clots (SEC) were used to create MCA occlusions in the vascular phantom which included collateral circulation via PComA and ACA. Three different treatment strategies using stentrievers (Solitaire FR) included 1) Proximal flow control with an 8Fr balloon guide catheter (BGC) at the cervical ICA, 2) Thromboaspiration via a 5Fr intracranial guide catheter (IGC) in the origin of the MCA, and 3) Thrombectomy through a 6Fr guide catheter (GC) with the tip placed at the carotid-ophthalmic bifurcation (n = 8 per group). Characterization of the emboli smaller than 1000 µm was conducted by using the Coulter Principle. The primary endpoint was the number and size of the clot fragments generated during the procedure and the secondary endpoint was the flow recanalization rate Results The figure (top) shows the MCA occlusion model with the flow direction (blue arrows). A 5Fr IGC was used in this representative case. Approximately 45% to 60% of the clot debris was presented in the previously unaffected area (ACA), depending on the clot size range (figure, bottom). Similar findings were observed in the BGC and GC with different particle distribution. The results indicated that distribution of clot fragments was not dependent on the treatment strategy. IGC versus BGC technique efficacy appeared to depend on clot mechanics. IGC was the most efficient method for reducing HFC fragments (p Conclusion Efficient clot retrieval observed in the IGC group implied that aspiration location was related to suction efficacy. Successful clot removal with BGC revealed that temporary flow arrest during clot removal and use of large bore catheter minimised the chance of distal embolization. Disclosures J. Chueh: None. A. Puri: None. A. Wakhloo: 1; C; NIH, Philips Healthcare. 2; C; Stryker Neurovascular. M. Gounis: 1; C; eV3/Covidien, Philips Healthcare, NIH, Silk Road, Stryker Neurovascular. 2; C; fee-per-hour: Stryker Neurovascular, fee-per-hour: Codman Neurovascular.

Introduction Durability of coiling procedures varies widely, and a better understanding of coil dynamics may help improve the treatment strategy. The goal of this study is to evaluate how packing density (PD) and coil uniformity impact aneurysm occlusion efficiency, which is conceptually associated with coil mass permeability. Materials and methods Experimental A1 aneurysm models were coiled using Guglielmi detachable coils (GDC) or Target coils. Coiled aneurysms were connected to a flow system filled with 1 µm fluorescent microsphere solution. The coil permeability was defined as the ratio of the microspheres that passed through the coil mass to the microspheres that circulated in the parent vessel. One neck section and 2 dome sections were obtained from each aneurysm for image analysis, including surface area fraction (SAF) and uniformity measurements. SAF was defined as the ratio of coil mass cross-sectional area to aneurysm cross-sectional area, and uniformity was determined from fractal-based heterogeneity measure, lacunarity. Lacunarity values closer to 0 indicate a homogeneously distributed coil mass. A statistical model was used to predict coil mass permeability as the outcome, with packing and uniformity measures as predictor variables. If the packing and uniformity measures exhibited statistically significant correlation, then principal component regression analysis was used for statistical modeling. Results All aneurysm PDs fell within the range of 27.1% to 45.5%, with a mean PD of 34.3 ± 4.4%. Permeability varied as a function of spatial coil uniformity for a given packing density (36%, Figure 1). With a higher uniformity (lacunarity: 0.06 vs. 0.09), the Target coiled aneurysm allowed less microspheres through the coil mass, as compared to the GDC coiled aneurysm. The lacunarity measures showed that in general, the coil distribution at the cross section of the neck was less uniform than in the dome. Coil mass permeability was statistically correlated with PD, SAF of dome and lacunarity of dome. Principal component regression analysis identified a primary factor with similar weights for PD, SAF of dome, and lacunarity of dome (range: 0.55–0.61). Coil mass permeability was modeled better with principal component regression incorporating the above measures (r 2 = 0.7) than linear regression with PD alone (r 2 = 0.46). The analysis indicates the importance of including a uniformity measure for coil distribution in the dome along with packing measures. Conclusion In addition to packing density, coil mass distribution has an important impact on excluding the aneurysm from the circulation. Disclosures J. Chueh: None. S. Vedantham: None. A. Puri: None. A. Wakhloo: 1; C; NIH, Philips Healthcare. 2; C; Stryker Neurovascular. M. Gounis: 1; C; eV3/Covidien, Philips Healthcare, NIH, Silk Road, Stryker Neurovascular. 2; C; fee-per-hour: Stryker Neurovascular, fee-per-hour: Codman Neurovascular.

Introduction Intracranial placement of flow-diverter (FD) stents provides a safe and effective treatment for aneurysms.1 However, long-term angiographic follow-up is indicated, since in-stent stenosis and late thrombosis as a consequence of poor vessel wall apposition increase the risks of stroke-related complications.1,2 In addition to conventional angiography, high-resolution contrast-enhanced cone-beam CT (VasoCT) may provide improved three-dimensional visualization of stent deployment and apposition.2,3 Here we explored the use of VasoCT for the assessment of FD vessel wall apposition in comparison to concurrent optical coherence tomography (OCT) endoscopy. Catheter-based OCT delivers near-infrared images at a spatial resolution in the order of 10–50 μm, which enables superior intravascular tissue and device visualization.4 This work was performed in an experimental sidewall aneurysm model in canines. Materials and methods Two sidewall aneurysms were created on each common carotid artery (CCA) in female canines by anastomosis of sections of the detached right external jugular vein, as described before.5 Under fluoroscopic guidance (Allura Xper FD20, Philips, Best, The Netherlands), FD stents (Pipeline Embolization Device, EV3-MTI, Irvine, CA; Surpass, Stryker, Fremont, CA) were placed and apposition was assessed bilaterally using VasoCT, and in the right CCA using OCT (C7 System/Dragonfly Catheter, St Jude Medical, Westford, MA). Results [Figure 1][1] shows an example of poor apposition, approximately 7.5 mm proximal to the aneurysm on the right CCA. With OCT (right), the distance between the FD and vessel wall measured 0.39 mm. The vessel diameter in this plane was 3.24–3.53 mm, and the area between the stent and the vessel wall was 15% of the lumen area. A similar distance 0.35 mm could be observed in a 67 μm VasoCT reconstruction (left), although lumen and stent struts are rendered more smoothly as compared to OCT. ![Abstract P-001 Figure 1][2] Abstract P-001 Figure 1 Conclusion Due to its superior in-plane resolution, OCT clearly visualised the distinction between the vessel wall and the FD stent struts. Nevertheless, our example showed that VasoCT enables identification of apposition distances in the order of 0.5mm. Although OCT is clinically used in interventional cardiology, its neurovascular application is currently limited to the experimental setting. Here we showed that OCT can provide a gold-standard for the validation of VasoCT assessments of FD apposition. References 1. Pierot L, Wakhloo AK. Stroke 2013;44:2046–2054 2. Kizilkilic O, et al . J Neurosurg 2012; 117 :45–49 3. Flood TF, et al . J NeuroIntervent Surg 2014;doi:10.1136/neurintsurg-2013-010950 4. Bezerra HG, et al . J Am Coll Cardiol Intv 2009; 2 :1035–1046 5. Wakhloo AK, et al . Am J Neuroradiol 1994; 15 :493–502 Disclosures K. van der Marel: None. M. Gounis: 1; C; eV3/Covidien, Philips Healthcare, NIH, Silk Road, Stryker Neurovascular. 2; C; Stryker Neurovascular, Codman Neurovascular. R. King: None. A. Wakhloo: 1; C; NIH, Philips Healthcare. 2; C; Stryker Neurovascular. A. Puri: None. [1]: #F1 [2]: pending:yes

Introduction/purpose Fusiform aneurysms (FUANs) of vertebral artery are difficult to treat by using current surgical techniques. Endovascular techniques like parent vessel occlusion, trapping, coiling, stent assisted coiling or stent mono-therapy is currently used to treat these aneurysms. The purpose of this study is to assess the efficacy and safety of flow diverters (Pipeline Embolization Device) in the treatment of vertebral artery FUANs compared to currently used therapeutic modalities. Materials and methods From July 2012 to October 2013, a total of 5 vertebral artery fusiform dissecting aneurysms in 5 patients (2 men and 3 women; age range, 39–59 years; mean age, 50.8 years) were treated with pipeline embolization device (PED) at our institution. In 2 patients the aneurysms were an incidental finding whereas in the other 3 cases were associated to neurologic symptoms, such as visual changes, ataxia, facial numbness or vertigo. Location of the aneurysms was as follows: 4 aneurysms on the right and 1 on the left side. 4 aneurysms were centerd at the V4 segment of the vertebral artery (intradural); only one was located at the vertebral V3-V4 segments junction (intra/extradural). Only one patient had family history indicative for intracranial aneurysm. Aneurysms ranged from 5 to 13 mm in maximal diameter. The technical feasibility of the procedure, procedure-related complications, angiographic results, and clinical outcome were evaluated. Results In every case, endovascular treatment was achieved. Immediate angiography demonstrated intra-aneurysmal contrast stagnation, with parent artery preservation in all cases. Major procedure-related complications were not observed. A brief temporary episode of dysarthria was noted in one of the patient. None of the treated aneurysms experienced bleeding or thrombo-embolic complication during the follow-up time. At 6 month follow-up (4 patients) was noted a complete/near complete aneurysm obliteration in 3 patients and partial obliteration in 1 patient. At 1 year follow-up (2 patients) was noted a progression to complete aneurysm obliteration in 1 patient and stable partial embolization in 1 patient. No intimal hyperplasia was noted at 6–12 months follow-up in the cohort of patients analyzed. Conclusion In our preliminary experience vertebral artery fusiform dissecting aneurysms treatment with PED is a safe and efficacious option in treating dissecting or fusiform intracranial aneurysms. Long term studies and larger cohort is recommended for further evaluation of this treatment strategy. Disclosures A. Puri: None. F. Massari: None. S. Hou: None. M. Perras: None. C. Brooks: None. C. Stout: None. M. Gounis: None. A. Wakhloo: None.

Introduction/purpose Pipeline Embolization Device (PED) is currently indicated for treatment of large and complex intracranial aneurysms centerd along the cavernous/intradural segment of the internal carotid artery (ICA) proximal to the Posterior Communicating (PCom) artery. The purpose of this study is to assess the efficacy and safety of flow diversion treatment in unruptured complex aneurysms centerd along small vessel branches of the anterior and middle cerebral arteries. Materials and methods From August 2013 to December 2013, a total of 3 intracranial aneurysms located along small vessel branches of the anterior circulation in 3 patients (1 man and 2 women; age range, 60–71 years; mean age, 64.6 years) were treated with pipeline embolization device (PED) at our institution. In 2 patients the aneurysms were incidentally found during cerebral angiogram exam performed for additional unruptured intracranial aneurysm treatment planning; in the other case the aneurysm was prior source of a subarachnoid haemorrhage (SAH). The parent vessel size ranged from 1.8 to 2.2 mm, mean 2 mm. Location of the aneurysms was as follows: 2 aneurysms centerd along the pericallosal artery (1 left, 1 right), branch of the anterior cerebral artery (ACA), and 1 aneurysm located on the right angular artery, branch of the middle cerebral artery (MCA). In the patient group no family history for intracranial aneurysm is reported. Aneurysms ranged from 2.5 to 3.7 mm in maximal diameter. The technical feasibility of the procedure, procedure-related complications, angiographic results, and clinical outcome were evaluated. At 6 month follow-up (1 patient) was noted a complete right angular artery aneurysm obliteration, with mild in-PED intimal hyperplasia. Results In every case, endovascular treatment was achieved. Immediate angiography demonstrated a intra-aneurysmal contrast stagnation, with parent artery preservation. No major or minor procedure-related complications were noticed. None of the treated aneurysms experienced bleeding or thrombo-embolic complication intra-, post procedurally or on follow-up. Conclusion Although the experience is limited by the small volume of cases treated with PED for unruptured complex aneurysms centerd along less than 2.5 mm vessel branches of the anterior circulation, the procedure was noted to be a feasible, safe and effective method to obtain aneurysm occlusion without parent vessel occlusion. Disclosures A. Puri: None. F. Massari: None. S. Hou: None. M. Perras: None. C. Brooks: None. C. Stout: None. M. Gounis: None. A. Wakhloo: None.

A cerebral arteriovenous malformation (AVM) is a congenital vascular lesion of the brain composed of a complex tangle of arteries and veins, which are linked by one or more fistulae [1]. Arterial blood is shunted through the AVM directly to the venous system, precluding arterial blood from perfusing adjacent brain structures. The most common presentation of this disease is cerebral hemorrhage secondary to AVM rupture, with an associated mortality of 15% and a morbidity of 50% [1]. One modality to treat this pathology is endovascular embolization. Generally, endovascular embolization serves as an adjunct treatment to either surgery or radiosurgery, but is a curative treatment in approximately 15% of AVM cases [2]. The most common embolic agent used to occlude AVMs is a mixture of n-butyl 2-cyanoacrylate (NBCA) and Lipiodol®. NBCA is a rapidly polymerizing liquid adhesive that polymerizes with contact to blood. Lipiodol® is an ethiodized oil, which imparts radiopacity to the embolic mixture. Moreover, Lipiodol® has been reported to delay the polymerization of NBCA [3]. To further increase the polymerization time of NBCA, minute quantities of glacial acetic acid (GAA) may be added to the embolic mixture.

Purpose To develop, optimize and assess the clinical performance of a method for visualizing intracranial stents and their relationships to the host vasculature. Materials and methods Cone beam CT (CBCT) was performed using a flat panel detector angiography system. Datasets were reconstructed from 620 projection images acquired over a 200° arc (rotation time 20.7 s) at 80 kVp and a total of 260 mAs. To maximize spatial resolution, projection images were obtained using a small detector format (22 cm) and reconstructions were performed without pixel binning. A contrast injection protocol was optimized in a porcine model for balance between stent visualization host vessel opacification. Three different intracranial stents were deployed in the internal maxillary arteries of two Yorkshire swine. Selective CBCT angiography was performed at contrast concentrations between 10 and 30% (Iopamidol 51%, by volume in normal saline) and flow rates between 0.5 and 3.5 ml/s. The CBCT datasets were reviewed and the optimal combination of parameters was used for clinical testing. The clinical study was approved by our institutional review board. 57 CBCT examinations of implanted neurovascular stents were performed in 55 patients undergoing cerebral angiography. Two patients each received stents in two locations during treatments of separate aneurysms. Five cases were excluded from the study: four due to the use of balloon mounted stents that are visible with standard angiography and one due to failed contrast injection. The majority of included cases (46/52) were stents placed for treatment of intracranial aneurysms. Stents were placed in six cases to treat dissecting vertebral artery aneurysm, vertebrobasilar insufficiency, acute ischemic stroke and severe middle cerebral artery stenosis. For clinical evaluation, the CBCT dataset was reconstructed with a 5123 matrix covering a cubic FOV of 34.4 mm in each dimension (67 μm isotropic voxels). Images were assessed through blinded review by three interventional neuroradiologists using a structured questionnaire. Stent and host vessel visibility were rated on scales of 1–3, and the ability to assess stent apposition was rated ‘yes’ or ‘no’. Results The optimal injection protocol for carotid artery injections was 20% contrast at a flow rate of 3.0 ml/s. The flow rate was reduced to 2.0 ml/s for clinical vertebral artery injections. In 96.1% of cases (50/52), all reviewers rated visualization as sufficient to delineate the configuration and position of each stent (score≥2). In 100% of these cases, all reviewers agreed that the studies were sufficient to evaluate stent apposition to the vessel wall. Statistical agreement on the scoring of stent visualization in all cases was strong (ICC=0.67). In 15 cases, CBCT identified important findings that could not be well delineated on conventional angiography or multidetector CT. These included: the relationship between a stent, a coil mass and important vessels originating in close proximity to an aneurysm, stent thrombosis, neointimal hyperplasia, stent malapposition and calcified atheroma underlying a stent. Conclusion CBCT is a reliable technique that provides good quality visualization of intracranial stents and their host vessels, enabling neuroradiologists to identify important findings that are not seen using standard methods.

Embolization is an endovascular procedure used to treat cerebral arteriovenous malformations (AVMs). AVMs are pathological shunts between arteries and veins, which bypass normal brain structures. An embolic agent commonly used to occlude AVMs is n-butyl 2-cyanoacrylate (NBCA). Although NBCA has shown to be efficacious for this application, precise knowledge of its polymerization process in vivo is needed. Inadvertent occlusion of arterial feeders proximal to the AVM nidus will occur when polymerization of NBCA is too rapid. This may lead to revascularization of the AVM. Conversely, long polymerization times may result in the occlusion of draining veins, with subsequent brain hemorrhage and pulmonary emboli. It is therefore critical to understand the kinetics of the polymerization process to obtain a complete glue cast of the arteriovenous transition (nidus) thus, yielding safe obliteration of the AVM. In order to elucidate the polymerization kinetics of NBCA, we examined the embolization process in the femoral and subclavian arteries of the rabbit. Various embolic agents composed of NBCA/lipiodol mixtures with and without the addition of glacial acetic acid (GAA) were injected. Blood flow through the femoral and subclavian arteries was measured prior to and during embolization. All studies were recorded with high-speed digital subtraction angiography (DSA). Preliminary analysis of the data suggests that flow decay during embolization exhibits a behavior that can be modeled via a lagged-normal density curve. Optimized model parameters vis a vis the experimental data are related to the polymerization kinetics. These parameters can be used to form a quantitative basis of comparison for the various liquid embolic mixtures.

Purpose: Recanalization of the aneurysm sac is a major drawback of endovascular embolization that often necessitates retreatment. Recent evidence suggests that increased packing density of coils within the aneurysm sac may lower recanalization rates. The DeltaPaq microcoil system (Micrus Endovascular, San Jose, California, USA), designed to increase aneurysm packing density, features an initial wind design with a triangular profile and microscopic rotating rings which provides the coil with a low moment of inertia and the ability to easily change the coil's angular motion. Here, we performed safety and packing density analysis of DeltaPaq coils in the treatment of ruptured …

Introduction Intracranial stenting is an effective therapy for specific cerebrovascular disorders including treatment-resistant atherosclerosis, cerebral aneurysms, and arterial dissections. However, in-stent tissue growth (neointimal hyperplasia (NIH) and/or in-stent restenosis (ISR)), is a significant long-term complication that necessitates routine surveillance. Catheter-based digital subtraction angiography, (DSA), is the current imaging standard for NIH/ISR detection; however, DSA is invasive and relies on 2D vascular representations that may over- or underestimate asymmetric tissue growth and consequentially, confuse clinical management decisions. A less invasive 3D capable, cross-sectional imaging technique with resolution to detect NIH/ISR, could circumvent these limitations, better inform clinicians, and improve patient care. Herein, contrast-enhanced C-arm Cone-Beam Computed Tomography, (CE-CBCT), recently optimised for high resolution 3D stent imaging by reducing the field-of-view during acquisition and performing full-scale reconstruction1, was quantitatively compared to vessel histology in a porcine model of in-stent NIH to validate the CE-CBCT approach. Materials and Methods All experiments were approved by our IACUC. The following was performed to model in-stent NIH: - 3 days, adult pig started on daily aspirin; day 0, pig anaesthetised, arterial access obtained, 4 arterial areas identified, damaged via a cutting balloon, and stented (Neuroform), pig recovered alive and returned to the animal facility; day 42, daily aspirin stopped; day 49, pig anaesthetised, CE-CBCT data acquired, animal sacrificed and perfused, stented vessels explanted, embedded in resin, sectioned and stained for analysis. Image J was used to quantify stent and luminal area from CE-CBCT and histological cross-sections that were spatially matched to best approximation; the measurements were compared with statistical software (Prism). Results Stent struts, lumen, and in-stent growth were clearly visualised and easily demarcated for quantitative analysis in both CE-CBCT and histological cross-sections (fig. 1a). CE-CBCT stent, lumen, and in-stent tissue growth calculated areas closely correlated with corresponding histological measurements (r2 = 0.96, 0.84, 0.87, respectively; fig. 1b). However, CE-CBCT was found to consistently overestimate lumen area relative to histology, which resulted in a lower Pearson’s r2 value and a non-zero intercept in the latter two measurements. Conclusion CE-CBCT quantification of in-stent tissue growth correlates well with histology in a porcine model and may be an important new clinical tool for post-stent vascular surveillance. Further evaluation of intravenous CE-CBCT as a non-invasive alternative to DSA in post-stent cerebrovascular patients is ongoing. Disclosures T. Flood: None. I. van der Bom: None. L. Strittmatter: None. G. Hendricks: None. A. Puri: None. A. Wakhloo: 1; C; Philips Healthcare. M. Gounis: 1; C; Philips Healthcare. References 1. Patel et al. AJNR 2011;32 (1):137–144. 2. Psychogios et al. Investigative Radiology;2013:48 (2);98–103. 3. Psychogios et al. AJNR 2010;31 (10):1886–91.

Purpose Non-contrast-enhanced magnetic resonance angiography (MRA) is a widely accepted diagnostic imaging method. However, neurovascular diseases that present with slow or complex flow (eg, aneurysms) may not be fully appreciated due to flow artifacts 1 . In this report, the feasibility of using Chemical Exchange Transfer Saturation (CEST) 2 for angiography is investigated (angioCEST). Since contrast in CEST imaging is generated by the exchangeable protons in solute and not by blood flow, it is hypothesised that angioCEST will be less sensitive to slow/complex flow. Materials and Methods To evaluate generated CEST contrast from blood, experiments were performed using cylindrical tubes filled with porcine blood in acid citrate dextrose (ACD) that were emerged in saline. Imaging was performed on a 3.0T whole-body scanner using a custom-made solenoid T/R coil. CEST data was acquired using a single slice parallel to the short axis of the cylindrical tube and was corrected for B0-inhomogeneities using a WASSR 3 method. To provide proof-of-principle, angioCEST was performed on the intracranial vasculature of a healthy volunteer. Single axial WASSR and CEST slices were acquired of the brain superior to the ICA siphon using an 8-channel SENSE head coil. Regions of interest (ROIs) were manually drawn in WASSR data and automatically copied to corresponding CEST data (figure 1). Normalised Z-spectra were generated using the mean values per ROI and were filtered for noise and corrected for B0 inhomogeneities using WASSR. To quantify the generated CEST contrast, MTRasym was used 2 . Results MTRasym analysis of the porcine blood samples showed a CEST effect of approximately 12% relative to surrounding saline at 2.5 ppm offset frequency. CEST experiments were performed on ACD confirmed that the observed CEST effect was due to blood and not generated by the anticoagulant. MTRasym plots (figure 1) of arterial blood (solid line) and white matter (dashed line) are shown in the bottom panel. Corresponding ROIs were drawn in WASSR data (top left) and copied to CEST data (top right) for analysis. Arterial blood shows a clear CEST effect of approximately 8% with respect to surrounding brain tissue. Conclusion In-vitro and in-vivo experiments have shown feasibility to obtain CEST contrast from blood, which may enable development of a novel method for MR angiography that is less sensitive to flow artifacts than currently available non-invasive techniques. Disclosures I. van der Bom: None. S. Zheng: None. M. Gounis: None. References Bernstein et al. Magn Reson Med 2001;46:955–962. van Zijl et al. Magn Reson Med . 2011;65:927–948. Kim et al. Magn Reson Med . 2009;61:1441–1450.

Introduction Small sized aneurysms with Material and Methods All patients who underwent SACE or stent placement for small aneurysms at our institution between 2009 and 2012 were identified and included in our retrospective analysis. In addition, we collected information on patient vascular risk factors, mRS on admission, aneurysm characteristics, Hunt and Hess and Fisher grade, angiography follow-up and patient clinical outcome at discharge, 90 days, 6 and 12 months. Results We included a total of 14 patients (9 females and 5 males) in our study. Mean age of the patients was 57.9 years. Median mRS on admission was 0. Patients’ vascular risk factors included smoking (85.7%) and hypertension (64.3%). The majority of the aneurysms were located in the anterior circulation (78.6%). Mean maximum diameter of the aneurysms was 2.0 mm (range 1.0 to 2.8 mm). Median Hunt and Hess and Fisher grade was 0.5. Twelve patients were treated with SACE and 2 with stent placement only. Periprocedural development of vasospasm was seen in 2 ruptured aneurysm cases (14.3%). One of these patients died eventually from complications of vasospasm. Aneurysm perforation during coil placement occurred in the third ruptured aneurysm case but was managed with SACE. Two patients had thrombus formation during the procedure which was successfully treated with Abciximab. Near complete and complete aneurysm occlusion after treatment was seen in 12 patients. No patient required retreatment. Median mRS at discharge was 1.5 with 13 patients (92.6%) having an mRS ≤2 at the time of discharge. Six-month angiography follow-up was available for the remaining 13 patients (100%). One patient showed stable mild residual filling of the aneurysm and another patient presented with mild focal in-stent stenosis (Y-stenting case). No significant recanalisation could be detected at this time point. No aneurysm re-growth was seen. Median mRS at 90 days, 6 and 12 months was 1. Further angiography follow-up examinations were available for 2 patients (15.4%) at 12 and 36 months, respectively. Control angiography revealed stable aneurysm occlusion in both cases. Conclusion SACE and stent placement is a safe and efficient treatment option for patients with wide necked small sized aneurysms with stable long-term angiography results and good clinical outcome. Disclosures A. Puri: None. A. Kuhn: None. S. Hou: None. M. Khan: None. M. Gounis: None. A. Wakhloo: 1; C; Philips Healthcare. 2; C; Stryker Neurovascular, Boston Biomedical Assoc. 3; C; Harvard Postgraduate Course. 4; C; Boston Scientific. 6; C; NIH.

Introduction An imaging approach identifying patients who benefit from treatment of unruptured intracranial aneurysms (UIA) is desired. We investigate a potential biomarker of UIA instability, myeloperoxidase (MPO), in human aneurysm tissue and in parallel develop a MPO molecular imaging approach in experimental models. Materials and Methods We harvested 20 aneurysms from 17 patients during surgical clipping. Angiograms were evaluated for: 1. maximum diameter, 2. blebs, 3. surface architecture (berry/irregular), and 4. single-lobe or multilobular. The tissue samples were stained against human MPO. MRI sequence insensitive to complex intra-aneurysmal flow was optimised in vitro. A silicone vascular replica of a rabbit elastase aneurysm was built 1 and embedded in coconut oil. Flow was generated by a pulsatile pump simulating the rabbit aortic waveform1 using a blood analogue matching T1- and viscosity of blood. At 3T, we acquired motion-sensitised driven-equilibrium (MSDE) (TE=10ms, variable TR and FA) and optimised the flow velocity encoded gradient echo imaging parameter (VENC, 1–8cm/s), while using spectral pre-saturation inversion recovery (SPIR) fat suppression. Saccular aneurysm model in white New Zealand rabbits (n=8) was created 2 . The animals were imaged using the MRI protocol optimised in-vitro. Naive aneurysms were imaged before and 3 hours after injecting MPO-specific contrast agent. Animals returned to the surgical suite 1-week later for lipopolysaccharide (LPS)-induced inflammation of the aneurysm wall 3 . Two-days after the LPS administration, the MRI study was repeated before and after MPO-specific contrast agent infusion. The animals were euthanised and the aneurysms explanted for histology. Results Ten human aneurysms were positive for MPO. All ruptured aneurysms (n=3) were positive for MPO. UIAs described as irregular/complex had a positive trend for MPO infiltration (p=0.087). Aneurysms were more likely to be positive for MPO in patients who had a family history of subarachnoid haemorrhage (p In the phantom experiment we confirmed that the MSDE sequence with VENC of 1 cm/s and SPIR eliminated the signal from blood flow and adjacent fat, respectively, yet provided sufficient contrast to image a representative amount of the MPO-contrast. The optimised MSDE sequence was used in the rabbit aneurysm model. Significant motion artifact required respiratory-triggering. Consequently, T1-weighting was lost. An inversion pulse was added to the sequence as to gain T1-sensitivity by inversion recovery (IR, IR delay optimised to 800ms). As compared to the naive aneurysm, there was a 40-fold increase in the SNR change from pre to post-contrast MSDE imaging in the inflamed aneurysm model (p Conclusion Human aneurysms with associated risk factors for rupture or that have ruptured contain MPO within the aneurysm wall; suggesting that MPO could be a valuable biomarker for assessment of aneurysm propensity for rupture. A diagnostic MR imaging protocol has been optimised in vitro and applied for detection of an MPO-specific contrast agent in an animal model of aneurysms. Disclosures M. Gounis: 1; C; NIH. I. van der Bom: None. A. Wakhloo: None. S. Zheng: None. J. Weaver: None. A. Puri: None. A. Kuhn: None. A. Bogdanov: 1; C; NIH. References Seong, et al. Biorheology 2005;42:345–361 Cloft, et al. Radiology 1999;213:223–228 DeLeo, et al. Radiology 2009;252:696–703

Purpose The hypothesis is that proximal flow control with a balloon guide catheter (BGC) in the cervical internal carotid artery (ICA) during mechanical thrombectomy will reduce the amount of distal emboli. Materials and Methods The model system included a true-to-scale vascular replica of the ICA/middle cerebral artery (MCA), an embolus analog (EA), and physiologically relevant flow loop. The flow loop provided a reproducible physiologic hemodynamics, and the replica was constructed based on human anatomy with moderate tortuosity to allow for realistic device tracking. The EA was injected into the system and reproducibly created an MCA occlusion. We had four experimental groups with two independent variables: 1. EA type—two EAs were used (“hard” vs “soft”) 1 and 2. Use of BGC. The endpoints included the recanalization rate, the amount of flow restored and the risk of the embolic shower as indicated by the size distribution of the distal EA fragments. Characterization of the shed EA fragments produced during mechanical thrombectomy was conducted by Coulter principle, and grouped into three categories: fragments with a diameter 1. >1 mm, 2. Between 200 μm and 1 mm, and 3. Results All the procedures that were performed to clear the hard EA through a BGC with the use of Merci v2 soft Retriever achieved complete flow restoration (average number of passes: 1.1), giving a recanalization rate of 100%. With the absence of proximal flow control, the Merci retriever was not able to retain the hard EA within the helix loop during retrieval in 6 out of 10 experiments (40% recanalization rate, average number of passes: 2.3) regardless of the device selected (v2 soft, v2.5 soft or v2.5 firm). Dislodgement of the hard EA was frequently seen when the device was passing the ICA siphon. In our model system, the Merci V2 soft retriever achieved 100% recanalization after a single pass in all experiments with the soft EA, with or without using the BGC. Large distal emboli (>1 mm) were found in the following groups: hard EA without BGC (23 emboli), soft EA without BGC (7 emboli) and soft EA with BGC (2 emboli). Temporary proximal flow arrest significantly reduced the production of small distal emboli ( Conclusion Proximal flow control reduced the number of thrombectomy attempts and increased the recanalization rate in the hard EA occlusions. As compared to the soft EA, the increased stiffness and lack of elasticity of the hard EA may account for the lower recanalization rate. The risk of distal embolization was reduced with the use of BGC. Competing interests J Chueh: None. A Kuhn: None. S Wilson: Concentric Medical. C Estrada: Concentric Medical. M Gounis: Concentric Medical, Stryker Neurovascular. Reference 1. Chueh et al. AJNR 2011; 32 :1237.

Purpose: Current approaches for ensuring adequate visualization of neuroendovascular devices that are implanted under fluoroscopic guidance, such as stents and flow diverters, are based on ad hoc methods and measures. Lack of specific standards makes it difficult to determine the adequacy of device contrast under clinical conditions. Inadequate device contrast due to low attenuation may result in increased radiation dose to the patient either due to prolonged fluoroscopy or due to the use of high dose‐ rate imagingsequence. Alternatively, this may lead to inaccurate positioning of these devices within cerebrovascular structures with potential impact on clinical outcome. We developed a protocol and applied it for evaluating such devices. Methods: The protocol comprises three parts: quantitative measurement of equivalent attenuation (in mm of Al) under conditions used for characterizing imaging system performance (RQA5 of IEC standards), visual assessment of device contrast in homogenous background (water phantom) of anatomically relevant thickness, and visual assessment of the device contrast with anatomic background. Ten devices (2 Ni‐Ti stents, 7 Co‐Cr and 1 Ni‐Ti flow diverters) were assessed using this protocol. Results: Quantitative assessment of the stents showed substantial equivalent attenuation of the device end/tip marker (Pt) bands but poor attenuation characteristics of the device body. The flow diverters demonstrated improved attenuation along the device body than the stents. The newer generation of flow diverters with Pt wires interwoven with the Co‐Cr wires demonstrated improved attenuation characteristics compared to previous generation which did not include Pt wires. Visual assessment under homogenous (16 cm water phantom) and anatomic background (skull phantom immersed in 16 cm water) provided qualitative confirmation. Conclusions: The proposed protocol with further refinements can serve as the basis for evaluating the adequacy of x‐ray contrast of neuroendovascular devices that are implanted under fluoroscopic guidance. Devices provided by Surpass Medical LTD. (Tel Aviv, Israel). Research supported in part by NIH/NCI R01CA128906 and NIH/NIBIB R21EB007767. The contents are sole responsibility of the authors and do not reflect the official views of the NIH, NCI or NIBIB. MG: Has been a consultant per hour for Micrus Endovascular and Codman Neurovascular; receives research support from Stryker Neurovascular, Micrus Endovascular, Codman Neurovascular, Neurointerventional Technologies, Neuravi, Thrombolysis Scientific Inc, and Concentric Medical. AW: Has been a consultant per hour for Codman Neurovascular, Stryker Neurovascular, Boston Medical Associates, Surpass Medical Ltd; holds ownership interest in Surpass Medical Ltd; receives research support from Philips Healthcare.

Purpose Stent assisted coiling techniques have improved the endovascular treatment of wide necked (neck >4 mm or dome to neck ratio Materials and methods Between June 2007 and February 2010, 102 wide necked and fusiform/dissecting intracranial aneurysms in 92 patients were treated endovascularly using the Enterprise stent. Seventeen (17%) aneurysms were located in the posterior circulation. Ten (11%) were treated acutely following subarachnoid hemorrhage. The aneurysms were defined as wide neck (79, 77%), dissecting or fusiform (16, 16%) or blister (seven, 7%) aneurysms. Some aneurysms included in this group were treated due to recanalization following primary coiling (24, 24%) or clipping (two, 2%). The mean aneurysm diameter and neck size was 6.0 mm (SD 4.0 mm, range 2–25 mm) and 4.8 mm (SD 2.6 mm, range 2–15 mm), respectively. The mean dome to neck ratio was 1.3. All patients were pretreated with aspirin and clopidogrel and maintained on both of these medications for 6 months. Follow-up catheter angiography was available for 48 patients (52%) at a mean of 9.7 months (range 6–18 months). Immediate postprocedure control and follow-up angiograms were evaluated using the Raymond scale by investigators not involved in the coiling procedure. Clinical evaluations were performed using a modified Rankin scale. Results Immediate control angiography demonstrated total aneurysm occlusion in 38 aneurysms (37%), neck filling was seen in 32 aneurysms (32%) and dome filling was seen in 31 aneurysms (31%). The mean packing density was 44% (SD 27%). There were 13 (13%) intraoperative thromboembolic complications that were successfully treated with intra-arterial thrombolytics (tissue plasminogen activator and abciximab). There was one case of acute stent migration during the treatment of a basilar tip aneurysm and another case of intraoperative aneurysm perforation. There was no periprocedural morbidity. One patient that presented with a ruptured aneurysm died from subarachnoid hemorrhage shortly after treatment (mortality 1%), and aneurysm rebleeding could not be excluded. Angiography at follow-up demonstrated total occlusion in 39 aneurysms (82%), six neck remnants (12%) and three residual aneurysms (6%). Four cases showed recanalization secondary to coil compaction of which three aneurysms have been retreated. In the follow-up period, there have been no cases of stent migration, two cases of mild, asymtomatic in-stent stenosis, six cases of delayed thromboembolic complications and one case of symptomatic parenchymal hemorrhage following shunt placement for hydrocephalous treatment 30 days post-coiling. Median modified Rankin scale at follow-up is 0. Conclusion This large series adds to the growing evidence demonstrating the safety, effectiveness and maneuverability of the Enterprise stent in the treatment of intracranial aneurysms. Although initial complete occlusion rates determined from the Raymond scale were not favorable, most aneurysms (82%) imaged at a mean of 9.7 months after stent assisted coil embolization are completely occluded. Data on long term occlusion and in-stent stenosis rates are pending.

Purpose Patient selection for endovascular revascularization based on penumbral imaging may help to improve outcomes for victims of acute ischemic stroke. Although MR perfusion–diffusion mismatch is well validated, its clinical application has been hampered by lack of availability of MR imaging in the ER setting. Increasingly, CT based perfusion–cerebral blood volume mismatch is employed to triage patients. The goal of this work is to compare CT cerebral blood volume (CBV), MR diffusion weighted imaging (DWI) and histopathology in an experimental model of acute ischemic stroke. Materials and methods Seven purpose bred adult beagle dogs (mean weight 10 kg) were anesthetized as per the procedures approved by our IACUC. Autologous blood clot was prepared by mixing whole blood with thrombin and barium, and allowed to age for 24 h. Following baseline MR imaging, a 5 F catheter was placed into the selected internal carotid artery and the clot fragment (mean length 1 cm) was delivered into the middle cerebral artery. MRI was performed on a 3.0 T system using an eight channel receive only SENSE knee coil and serial diffusion (prestroke and 0.5, 1, 2.5 and 4 h post stroke) and perfusion (1.5 and 4 h post stroke) sequences were acquired. Immediately following the last diffusion scan, the animals were transferred to the adjacent angiographic suite where non-contrast and contrast enhanced flat panel cone beam CT sequences were acquired. Animals were then killed and the coronal brain sections were stained with 2% 2,3,5-triphenyltetrazolium chloride (TTC). Apparent diffusion coefficient (ADC) maps were generated and imported into Matlab for image processing. ADC values below 0.53×10−3 mm2/s were identified and segmented. Using a calibration curve, the CBCT data were converted into Hounsfield units (HU). CBV was determined by ΔHUBrain/ΔHUBlood×VVoxel×N, where the change was between the contrast and non-contrast studies, VVoxel was the volume of the voxel and N was the number of voxels in 100 g of brain. At this time, CBV maps were generated and the threshold for abnormal CBV was set at 1.0 ml/100 g of brain (based on the canine data). Volumes were derived by taking the product of the segmented area and the slice thickness. Time to peak perfusion images were analyzed using commercial software. Results TIMI grade 0 flow was successfully induced with an embolus lodged in the middle cerebral artery in all animals. The perfusion imaging revealed hypoperfused brain with heterogeneous severity due to the variability of collateral circulation. The final infarct size, as determined by the ADC decrease, was 4385±1930 mm3 (mean±SE), approached the mean MR perfusion lesion (6483±1515 mm3) and was found comparable with lesion volume measured histologically using TTC (4408±1805 mm3). The mean CBV lesion from CT slightly overestimated (5199±741 mm3) the infarct size. Compared with the very close agreement between DWI and TTC (R2=0.92), the correlation between the CBV lesion volume and TTC was not as strong (R2=0.78). Conclusion Our preliminary results indicate that while there is a close agreement between infarct lesion volumes measured on MR DWI and histopathology, estimates of lesion volume from CT CBV requires further study.

Introduction Efficacy and safety of devices for the endovascular recanalization of acute ischemic stroke (AIS) are mostly validated in experimental vascular models and in vivo animal models. Efforts have been made to develop mechanically stable clot models to explore the interactions between the clots and devices; however, little is known about the mechanical similarities between these clot models and the human sources of embolic thrombi. The aim of this study is to explore the structure and mechanical properties of the possible sources of the cerebral emboli extracted from patients and model clots produced in vitro using human, porcine and bovine donors. Materials and methods Six thrombi were collected during carotid endarterectomies (CEA) and two thrombi were obtained from the internal carotid artery (ICA) of AIS patients. In vitro clots were prepared by simultaneously injecting whole blood/ACD mixture and CaCl 2 /thrombin solution into silicone tubing. Three variables of in vitro clotting included species, thrombin concentration and addition of the radio-opaque component, barium sulfate. Dynamic mechanical analyzer was used to acquire the stress–strain behaviors of the clots in the controlled force mode which gave an indication of clot hardness. Clot elasticity was studied in stress–relaxation mode by recording the strain recovery. Scanning electron microscopy (SEM) and Martius Scarlet Blue stained sections were used to investigate the structure and composition of the specimens. Results Two secant moduli, designated E1 and E2, are calculated from the toe region (initial to 75% strain) and high strain (75–95%) of the stress–strain curve, respectively. The calcified thrombi from CEA (n=2) had lower elongation and higher moduli (E1=737.8±296.9 Pa, E2=12313±165.7 Pa) whereas red cell rich thrombi (n=4 from CEA and n=2 from ICA) showed higher elongation and lower moduli (E1=585.7±98.37 Pa, E2=6651±675 Pa). Interspecies differences in the mechanical properties of clot models were observed. Overall, bovine clots had the highest hardness followed by porcine and human clots. Addition of thrombin significantly increased E1 and E2 of the human and porcine clot models (p Conclusion In this research we move beyond studying composition of thromboemboli by additionally investigating the mechanical properties of these sources of AIS. As newer generations of endovascular recanalization devices become available, it will be important to create a variety of characterized clot models to study the safety and efficacy of the devices preclinically. More human cerebral thrombi will be analyzed to provide a library of mechanical properties to construct a framework for further development of clot models.

Purpose To describe our early experience with the balloon expandable Pharos Vitesse stent for symptomatic, high grade intracranial stenosis. Materials and methods Our center has enrolled five patients to date in the VISSIT (Vitesse Intracranial Stent Study for Ischemic Therapy) Trial.1 This prospective, multicenter, randomized trial is designed to compare best medical therapy alone to best medical therapy plus stenting for symptomatic, high grade intracranial stenosis. In conformance with the study design, patients were treated for 70–80% stenosis (inclusion criterion 70–99%) of the intracranial internal carotid, middle cerebral or intradural vertebral arteries. The patients ranged from 49 to 76 years of age (mean 63). There were four men and one woman. All target lesions and vessels were of appropriate size for treatment using the Pharos Vitesse stent. All patients underwent neurological assessment, including evaluation of the modified Rankin Scale (mRS) and CT studies prior to diagnostic digital subtraction angiography (DSA). Four patients also underwent CT perfusion (CTP). After diagnostic DSA, three patients were randomized to the stenting arm of the trial. One patient who was randomized to the medical therapy arm failed medical therapy and underwent stenting after recurrent ischemic stroke in the territory of the stenotic vessel. After stenting, mRS and CTP were performed in all patients prior to discharge. Results Stenting was technically successful in all cases. In three cases, there was no residual stenosis. In one case, heavily calcified, concentric atherosclerotic plaque resulted in residual stenosis of 30%. There were no procedural complications. One patient recovered from anesthesia with neurologic deficits localizable to the treated territory. These resolved completely and spontaneously within 24 h. No other periprocedural neurological adverse events were encountered. Two of three patients undergoing stenting had abnormal CTP findings in the territory distal to the stenotic lesion. In one, MTT was prolonged (>1.5× the contralateral side) in a large portion of the right middle cerebral artery (MCA) territory (90.8 cm3 tissue volume). In another, MTT was prolonged in the right MCA/posterior communicating artery watershed territory (5.3 cm3 tissue volume). All patients had normal CTP examinations at discharge. The 30 day mRS (median 1, range 0–6) were either stable or improved, compared with the mRS at presentation, in 3/4 patients. The fourth patient died >30 days after randomization due to complications of a previously unknown metastatic prostate cancer. The patient that was randomized to medical therapy awaits 30 day assessment. One patient returned 5 months after stenting with symptoms of transient ischemic attack in the treated territory. Although no residual stenosis was present initially, a flow restricting restenosis was identified on DSA. This was treated successfully using balloon angioplasty. Conclusion In our early experience, treatment of symptomatic, high grade intracranial stenosis with the Pharos Vitesse stent is a safe procedure that has resulted in no permanent procedure related complications. Following stenting, CTP showed completely restored blood flow to the pre-existing hypoperfused territories. The 30 day mRS score was stable or improved after stenting in 3/4 patients.

Purpose: To quantitatively characterize the noise performance of a neurointerventional c‐arm based flat‐panel cone‐beam computed tomography (FP‐CBCT) system with an aim of exploring the feasibility of performing cerebral blood volume (CBV) calculations. Method and Materials: Five CBCT scans of ∼11 cm diameter water phantom positioned at the isocenter were acquired at 120kVp and reconstructed to 5123 matrix with 0.33mm voxels. Central Regions of Interest (ROIs) of 1933 matrix corresponding to ∼(63mm)3 were extracted from each scan. Spatial uniformity was determined using the standard deviation (SD) in Hounsfield Units (HU) and repeatability was measured using the root‐mean‐squared deviation (RMSD) of mean signal and using the coefficient of variation (COV) of SD metrics. 3‐D noise power spectra (NPS) were computed with and without subtraction of the average ROI volume from each ROI, which allowed determination of structural noise.Results: Mean signal and SD determined from (193)3 matrix and averaged over the 5 scans were 9.3HU (range: 8.4–10.3; RMSD=0.5) and 19.1HU (range: 19.05–19.15; COV

Purpose: The Cerecyte Coil System (Micrus Endovascular, San Jose, California, USA) is a polyglycolic acid loaded coil that can deliver a stable aneurysm framing while delivering a bioactive copolymer. Here we report our mid-term results on the use of this coil system for the treatment of intracranial aneurysms. Materials and Methods: From July 2005 to August 2008, 62 patients with 67 aneurysms were treated using Cerecyte coils exclusively or in combination with bare platinum coils. We compared this cohort with 65 patients with …

Purpose: Stent assisted coiling techniques have improved the endovascular treatment of wide necked (neck >4 mm or dome-to-neck ratio

Author summary After an ischaemic stroke—one where a clot blocks a major artery in the brain—patients can undergo a procedure where the clot is removed mechanically via a catheter—a thrombectomy. This reopens the blocked vessel, yet some patients don’t achieve blood flow returning to their tissue downstream. One hypothesis for this phenomenon is that the clot fragments into smaller clots (called micro-emboli) which block smaller vessels downstream. However, this can’t be measured in patients due to the inability of clinical imaging resolving the micro-scale. We therefore develop a computational model here, based on experimental thrombectomy data, to quantify the impact of micro-emboli on blood flow in the brain after the removal of a clot. With this model, we found that micro-emboli are a likely contributor to the no-reflow phenomenon after a thrombectomy. Individual blood vessel geometries, clot composition, and thrombectomy technique all impacted the effect of micro-emboli on blood flow and should be taken into consideration to minimise the impact of micro-emboli in the brain. Furthermore, the computational model developed here allows us to now build large-scale models of blood flow in the brain, and hence simulate stroke and the impact of micro-emboli on the entire brain., Many ischaemic stroke patients who have a mechanical removal of their clot (thrombectomy) do not get reperfusion of tissue despite the thrombus being removed. One hypothesis for this ‘no-reperfusion’ phenomenon is micro-emboli fragmenting off the large clot during thrombectomy and occluding smaller blood vessels downstream of the clot location. This is impossible to observe in-vivo and so we here develop an in-silico model based on in-vitro experiments to model the effect of micro-emboli on brain tissue. Through in-vitro experiments we obtain, under a variety of clot consistencies and thrombectomy techniques, micro-emboli distributions post-thrombectomy. Blood flow through the microcirculation is modelled for statistically accurate voxels of brain microvasculature including penetrating arterioles and capillary beds. A novel micro-emboli algorithm, informed by the experimental data, is used to simulate the impact of micro-emboli successively entering the penetrating arterioles and the capillary bed. Scaled-up blood flow parameters–permeability and coupling coefficients–are calculated under various conditions. We find that capillary beds are more susceptible to occlusions than the penetrating arterioles with a 4x greater drop in permeability per volume of vessel occluded. Individual microvascular geometries determine robustness to micro-emboli. Hard clot fragmentation leads to larger micro-emboli and larger drops in blood flow for a given number of micro-emboli. Thrombectomy technique has a large impact on clot fragmentation and hence occlusions in the microvasculature. As such, in-silico modelling of mechanical thrombectomy predicts that clot specific factors, interventional technique, and microvascular geometry strongly influence reperfusion of the brain. Micro-emboli are likely contributory to the phenomenon of no-reperfusion following successful removal of a major clot.