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Endovascular treatment of cervical internal carotid artery (ICA) loop dissections in acute stroke interventions can be challenging. Flow diverters can effectively reconstruct vessel loops and treat the injured vessel and provide a safe conduit for intracranial catheterization.We retrospectively reviewed our neurointerventional database and identified all patients with ICA loop dissections treated with flow diverters in the acute setting between August 2016 and September 2020. Patient demographics, procedural data, imaging follow-up results, and clinical outcome information were collected.Seven patients with a mean age of 62 years (range: 43-85 years) who underwent reconstruction of an ICA (loop) dissection with flow diverters were included. Four ICA dissections were treated with the Surpass Streamline flow diverter and 3 with the Pipeline embolization device. All cases were technically successful. All stroke cases achieved intracranial flow ≥thrombolysis in cerebral infarction 2B. Observed intracranial hemorrhages were all asymptomatic. All cases showed patent flow diverter(s) with or without (carotid) stent(s) on follow-up imaging. Semielectively treated patients did not show a change from baseline modified Rankin scale related to the procedure. Patients with acute stroke had a modified Rankin scale ≤2 in 4 of 5 cases (80%) at 3 months. Two patients died due to medical issues unrelated to the procedures. No patient showed new or recurrent symptoms.Use of flow diverters, in some cases in conjunction with (carotid) stents, is an effective treatment option for cervical carotid artery (loop) dissections.

BackgroundPlatelets and von Willebrand factor (vWF) are key components of acute ischemic stroke (AIS) emboli. We aimed to investigate the CD42b (platelets)/vWF expression, its association with stroke etiology and the impact these components may have on the clinical/procedural parameters.MethodsCD42b/vWF immunostaining was performed on 288 emboli collected as part of the multicenter STRIP Registry. CD42b/VWF expression and distribution were evaluated. Student’s t-test and χ2test were performed as appropriate.ResultsThe mean CD42b and VWF content in clots was 44.3% and 21.9%, respectively. There was a positive correlation between platelets and vWF (r=0.64, pConclusionsThe vWF level and CD42b/vWF distribution pattern in emboli were correlated with AIS etiology and revascularization outcome. Platelet content was associated with response to thrombolysis.

Background: Tissue hypoxia plays a critical role in the events leading to cell death in ischemic stroke. Despite promising results in preclinical and small clinical pilot studies, inhaled oxygen supplementation has not translated to improved outcomes in large clinical trials. Moreover, clinical observations suggest that indiscriminate oxygen supplementation can adversely affect outcome, highlighting the need to develop novel approaches to selectively deliver oxygen to affected regions. This study tested the hypothesis that intravenous delivery of a novel oxygen carrier (Omniox-Ischemic Stroke [OMX-IS]), which selectively releases oxygen into severely ischemic tissue, could delay infarct progression in an established canine thromboembolic large vessel occlusion stroke model that replicates key dynamics of human infarct evolution. Methods: After endovascular placement of an autologous clot into the middle cerebral artery, animals received OMX-IS treatment or placebo 45 to 60 minutes after stroke onset. Perfusion-weighted magnetic resonance imaging was performed to define infarct progression dynamics to stratify animals into fast versus slow stroke evolvers. Serial diffusion-weighted magnetic resonance imaging was performed for up to 5 hours to quantify infarct evolution. Histology was performed postmortem to confirm final infarct size. Results: In fast evolvers, OMX-IS therapy substantially slowed infarct progression (by ≈1 hour, P P P =0.09). The final normalized infarct volume also did not show a significant difference (0.93 versus 0.95, OMX-IS drug versus control, P =0.34). Postmortem histologically determined infarct volumes showed excellent concordance with the magnetic resonance imaging defined ischemic lesion volume (bias: 1.33% [95% CI, −15% to 18%). Conclusions: Intravenous delivery of a novel oxygen carrier is a promising approach to delay infarct progression after ischemic stroke, especially in treating patients with large vessel occlusion stroke who cannot undergo definitive reperfusion therapy within a timely fashion.

BackgroundThe micro-architectonics of the subarachnoid space (SAS) remain partially understood and largely ignored, likely the result of the inability to image these structures in vivo. We explored transvascular imaging with high-frequency optical coherence tomography (HF-OCT) to interrogate the SAS.MethodsIn vivo HF-OCT was performed in 10 dogs in both the posterior and anterior cerebral circulations. The conduit vessels used were the basilar, anterior spinal, and middle and anterior cerebral arteries through which the perivascular SAS was imaged. The HF-OCT imaging probe was introduced via a microcatheter and images were acquired using a contrast injection (3.5 mL/s) for blood clearance. Segmentation and three-dimensional rendering of HF-OCT images were performed to study the different configurations and porosity of the subarachnoid trabeculae (SAT) as a function of location.ResultsOf 13 acquisitions, three were excluded due to suboptimal image quality. Analysis of 15 locations from seven animals was performed showing six distinct configurations of arachnoid structures in the posterior circulation and middle cerebral artery, ranging from minimal presence of SAT to dense networks and membranes. Different locations showed predilection for specific arachnoid morphologies. At the basilar bifurcation, a thick, fenestrated membrane had a unique morphology. SAT average thickness was 100 µm and did not vary significantly based on location. Similarly, the porosity of the SAT averaged 91% and showed low variability.ConclusionWe have demonstrated the feasibility to image the structures of the SAS with transvascular HF-OCT. Future studies are planned to further map the SAT to increase our understanding of their function and possible impact on neurovascular pathologies.

Background: Understanding clot composition may allow for better technical planning and improved outcomes in mechanical thrombectomy (MT). We sought to correlate clot composition with reperfusion outcomes in MT. Methods: Clinical, imaging, and clot data from patients enrolled in the STRIP Registry from September 2016 to September 2020 were analyzed. Samples were fixed in 10% phosphate-buffered formalin and stained with hematoxylin and eosin and Martius Scarlett Blue. Percent composition, richness, and gross appearance were evaluated. Outcome measures included the rate of First-Pass Effect (mTICI2c/3, FPE) and the number of device passes. Results: A total of 1430 patients (mean age, 68.4±13.5years; median [IQR] baseline NIHSS,17.2 [10.5-23]; IV-tPA use, 36%; Stent-Retrievers [SR], 27%; Contact Aspiration [CA], 27%; Combined SR + CA, 43%) were included. The median [IQR] number of passes was 1 [1-2]. FPE was achieved in 39.3% of the cases. There was no association between percent histological composition or clot richness and FPE in the overall population. However, the combined technique resulted in lower FPE rates for RBC-rich (P Conclusion: Despite the lack of correlation between clot histology and FPE in the overall population, our study adds to the growing body of evidence supporting the notion that clot composition influences reperfusion treatment strategy outcomes. Additional studies are needed.

BackgroundCompositional and structural features of retrieved clots by thrombectomy can provide insight into improving the endovascular treatment of ischemic stroke. Currently, histological analysis is limited to quantification of compositions and qualitative description of the clot structure. We hypothesized that heterogeneous clots would be prone to poorer recanalization rates and performed a quantitative analysis to test this hypothesis.MethodsWe collected and did histology on clots retrieved by mechanical thrombectomy from 157 stroke cases (107 achieved first-pass effect (FPE) and 50 did not). Using an in-house algorithm, the scanned images were divided into grids (with sizes of 0.2, 0.3, 0.4, 0.5, and 0.6 mm) and the extent of non-uniformity of RBC distribution was computed using the proposed spatial heterogeneity index (SHI). Finally, we validated the clinical significance of clot heterogeneity using the Mann–Whitney test and an artificial neural network (ANN) model.ResultsFor cases with FPE, SHI values were smaller (0.033 vs 0.039 for grid size of 0.4 mm, P=0.028) compared with those without. In comparison, the clot composition was not statistically different between those two groups. From the ANN model, clot heterogeneity was the most important factor, followed by fibrin content, thrombectomy techniques, red blood cell content, clot area, platelet content, etiology, and admission of intravenous tissue plasminogen activator (IV-tPA). No statistical difference of clot heterogeneity was found for different etiologies, thrombectomy techniques, and IV-tPA administration.ConclusionsClot heterogeneity can affect the clot response to thrombectomy devices and is associated with lower FPE. SHI can be a useful metric to quantify clot heterogeneity.

Transformative results of adeno-associated virus (AAV) gene therapy in patients with spinal muscular atrophy and Leber’s congenital amaurosis led to approval of the first two AAV products in the United States to treat these diseases. These extraordinary results led to a dramatic increase in the number and type of AAV gene-therapy programs. However, the field lacks non-invasive means to assess levels and duration of therapeutic protein function in patients. Here, we describe a new magnetic resonance imaging (MRI) technology for real-time reporting of gene-therapy products in the living animal in the form of an MRI probe that is activated in the presence of therapeutic protein expression. For the first time, we show reliable tracking of enzyme expression after a now in-human clinical trial AAV gene therapy (ClinicalTrials.gov: NTC03952637) encoding lysosomal acid beta-galactosidase (βgal) using a self-immolative βgal-responsive MRI probe. MRI enhancement in AAV-treated enzyme-deficient mice (GLB-1−/−) correlates with βgal activity in central nervous system and peripheral organs after intracranial or intravenous AAV gene therapy, respectively. With >1,800 gene therapies in phase I/II clinical trials (ClinicalTrials.gov), development of a non-invasive method to track gene expression over time in patients is crucial to the future of the gene-therapy field., Graphical abstract, We describe a bio-responsive contrast agent that informs on the biodistribution and durability of gene expression in the lysosomal storage disease, GM1 gangliosidosis. We illustrate the sensitivity of this contrast agent to detect β-galactosidase enzyme in the central nervous system and periphery of an AAV-GLB-1-treated mouse model of GM1.

BackgroundPreclinical testing of intracranial stents is currently performed in the peripheral circulation, and rarely in the basilar artery of the dog.ObjectiveTo 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.MethodsSix 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.ResultsWe 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.ConclusionWe describe a new preclinical model of intracranial stenting in the MCA. Such a model may prove useful for evaluating new surface modifications.

Optical coherence tomography (OCT) technology is a well-established diagnostic tool in multiple fields of medicine. Intravascular OCT has been used for more than a decade for the clinical imaging of coronary arteries, however, its use for the imaging of the human cerebrovasculature has been delayed by the challenges posed by the elevated vascular tortuosity. A novel high-frequency OCT (HF-OCT) probe designed for neurovascular use was evaluated in tortuous, ex vivo, human intracranial anatomy and, using an in vivo canine model, for the dynamic imaging of intracranial arteries and the subarachnoid trabecula (SAT). Using four cadavers, we investigated HF-OCT probe navigation and imaging performances in human anterior arterial circulation (from the M4 segment to internal carotid artery), in the posterior arterial circulation (from the P4 segment to vertebrobasilar junction) and in a broad range of venous sinuses. HF-OCT was able to gain distal access through elevated tortuosity and generate high-quality imaging data depicting vessel morphology, the vessel wall pathology (e.g., atherosclerotic disease and dissecting lesions), and the subarachnoid trabecula (SAT). Using an in vivo canine model, the HF-OCT probe was used to record stationary dynamic data in multiple intracranial vascular locations. Data showed the motion of the arteries and the SAT, including collisions between vessels, membranes, and the interaction between the SAT and the blood vessels. HF-OCT data allowed for the quantification of the dynamics of the vessels and the SAT, including vessel lateral motion with respect to the parenchyma, and collisions between large and small arteries. Results showed that the HF-OCT probe can overcome delivery obstacles in tortuous cerebrovascular anatomy and provide high-quality and high-resolution imaging at multiple distal locations, including M4 and P4 segments of the anterior and posterior circulations. HF-OCT has the potential to facilitate a better understanding of fine anatomical details of the cerebrovascular and perivascular environment, neurovascular disease, and collect real time information about the dynamics of the subarachnoid space and arteries and become a valuable diagnostic tool.

BackgroundHigh-frequency optical coherence tomography (HF-OCT) is an intravascular imaging method that allows for volumetric imaging of flow diverters in vivo.ObjectiveTo examine the hypothesis that a threshold for both volume and area of communicating malapposition can be predictive of early aneurysm occlusion.MethodsFifty-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.ResultsNo 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 (p3 or a normalized area less than 0.69 as quantified by HF-OCT was predictive of occlusion (pConclusionsHF-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.

BackgroundSeveral animal studies have demonstrated that mechanical thrombectomy (MT) for acute ischemic stroke (AIS) may cause vessel wall injury (VWI). However, the histological changes in human cerebral arteries following MT are difficult to determine.ObjectiveTo investigate the occurrence of VWI during MT by histological and immunohistochemical evaluation of AIS clots.MethodsAs part of the multicenter STRIP registry, 277 clots from 237 patients were analyzed using Martius Scarlett Blue stain and immunohistochemistry for CD34 (endothelial cells) and smooth muscle actin (smooth muscle cells).ResultsMT devices used were aspiration catheters (100 cases), stentriever (101 cases), and both (36 cases). VWI was found in 33/277 clots (12%). There was no significant correlation between VWI and MT device. The degree of damage varied from grade I (mild intimal damage, 24 clots), to grade II (relevant intimal and subintimal damage, 3 clots), and III (severe injury, 6 clots). VWI clots contained significantly more erythrocytes (p=0.006*) and less platelets/other (p=0.005*) than non-VWI clots suggesting soft thrombus material.Thrombolysis correlated with a lower rate of VWI (p=0.04*). VWI cases showed a significantly higher number of passes (2 [1–4] vs 1 [1–3], p=0.028*) and poorer recanalization outcome (p=0.01*) than cases without VWI.ConclusionsHistological markers of VWI were present in 12% of AIS thrombi, suggesting that VWI might be related to MT. VWI was associated with soft thrombus consistency, higher number of passes and poorer revascularization outcome. There was no significant correlation between VWI and MT device.

Background and aim Mechanical thrombectomy (MT) for large vessel occlusion often requires multiple passes to retrieve the entire thrombus load. In this multi-institutional study we sought to examine the composition of thrombus fragments retrieved with each pass during MT. Methods Patients who required multiple passes during thrombectomy were included. Histopathological evaluation of thrombus fragments retrieved from each pass was performed using Martius Scarlet Blue staining and the composition of each thrombus component including RBC, fibrin and platelet was determined using image analysis software. Results 154 patients underwent MT and 868 passes was performed which resulted in 263 thrombus fragments retrieval. The analysis of thrombus components per pass showed higher RBC, lower fibrin and platelet composition in the pass 1 and 2 when compared to pass 3 and passes 4 or more combined (P values 0.05). Similarly, when each composition of thrombus fragments retrieved in pass 3 and passes 4 or more combined were compared with each other, no significant difference was noted (P values >0.05). Conclusion Our findings confirm that thrombus fragments retrieved with each pass differed significantly in histological content. Fragments in the first passes were associated with lower fibrin and platelet composition compared to fragments retrieved in passes three and four or higher. Also, thrombus fragments retrieved after failed pass were associated with higher fibrin and platelet components.

BackgroundWe retrospectively evaluated the composition of retrieved clots from ischemic stroke patients to study the association between histological composition and stroke etiologyMethodsConsecutive patients enrolled in the Stroke Thromboembolism Registry of Imaging and Pathology (STRIP) were included in this study. All patients underwent mechanical thrombectomy and retrieved clots were sent to a central core lab for processing. Histological analysis was performed using martius scarlet blue (MSB) staining, and quantification for red blood cells (RBCs), white blood cells (WBCs), fibrin and platelets was performed using Orbit Image Software. A Wilcoxon test was used for continuous variables and χ2test for categorical variables.Results1350 patients were included in this study. The overall rate of Thrombolysis In Cerebral Infarction (TICI) 2c/3 was 68%. 501 patients received tissue plasminogen activator (tPA) (37%). 267 patients (20%) had a large artery atherosclerosis (LAA) source, 662 (49%) a cardioembolic (CE) source, 301 (22%) were cryptogenic, and the remainder had other identifiable sources including hypercoagulable state or dissection. LAA thrombi had a higher mean RBC density (46±23% vs 42±22%, p=0.01) and a lower platelet density (24±18% vs 27±18%, p=0.03) than CE thrombi. Clots from dissection patients had the highest mean RBC density (50±24%) while clots from patients with a hypercoagulable state had the lowest mean RBC density (26±21%).ConclusionsOur study found statistically significant but clinically insignificant differences between clots of CE and LAA etiologies. Future studies should emphasize molecular, proteomic and immunohistochemical characteristics to determine links between clot composition and etiology.

(1) Background: Intracranial pressure (ICP) monitoring plays a key role in the treatment of patients in intensive care units, as well as during long-term surgeries and interventions. The gold standard is invasive measurement and monitoring via ventricular drainage or a parenchymal probe. In recent decades, numerous methods for non-invasive measurement have been evaluated but none have become established in routine clinical practice. The aim of this study was to reflect on the current state of research and shed light on relevant techniques for future clinical application. (2) Methods: We performed a PubMed search for “non-invasive AND ICP AND (measurement OR monitoring)” and identified 306 results. On the basis of these search results, we conducted an in-depth source analysis to identify additional methods. Studies were analyzed for design, patient type (e.g., infants, adults, and shunt patients), statistical evaluation (correlation, accuracy, and reliability), number of included measurements, and statistical assessment of accuracy and reliability. (3) Results: MRI-ICP and two-depth Doppler showed the most potential (and were the most complex methods). Tympanic membrane temperature, diffuse correlation spectroscopy, natural resonance frequency, and retinal vein approaches were also promising. (4) Conclusions: To date, no convincing evidence supports the use of a particular method for non-invasive intracranial pressure measurement. However, many new approaches are under development.

Background Neurointerventionalists use in-vitro vascular models to train for worst-case scenarios and test new devices in a simulated use environment to predict clinical performance. According to the Food and Drug Administration (FDA), any neurovascular navigation device should be able to successfully navigate two 360-degree turns and two 180-degree turns at the distal portion of the anatomical model. Here, we present a device benchmarking vascular model that complies with FDA recommendations. Methods Our vascular model was assembled from quantitative characterization of 49 patients who underwent CT angiography either for acute ischemic stroke caused by large vessel occlusion or for aneurysm treatment. Following complete characterization of these data, the vascular segments were 3D reconstructed from CT angiograms of 6 selected patients that presented with challenging anatomy. The curvature and total rotational angle were calculated for each segment and the anatomical parts that complied with FDA recommendations were fused together into a single in-vitro model. Results The model was constructed containing two common carotid branches arising from a type two aortic arch and the dimensions of the overall model exceeded the recommendations of the FDA. Two experienced neurointerventionalists tested the model for navigation difficulty using several devices on an in-vitro perfusion system and concluded that the model provided a realistic, challenging scenario. Conclusions This model provides a first prototype designed according to FDA recommendations of cumulative angle while also integrating an aggregation of actual patient-specific anatomy. The availability of this clinically relevant benchmark model presents a potential standardized approach for neurovascular device testing.

BackgroundThe first-pass complete recanalization by mechanical thrombectomy (MT) for the treatment of stroke remains limited due to the poor integration of the clot within current devices. Aspiration can help retrieval of the main clot but fails to prevent secondary embolism in the distal arterial territory. The dense meshes of extracellular DNA, recently described in stroke-related clots, might serve as an anchoring platform for MT devices.ObjectiveEvaluate the potential of DNA reacting surface toaid the retention of the main clot as well as of its small fragments within the thrombectomy deviceand improve the potential of MT procedures.MethodsDevice-suitable alloy experimental samples were coated with 15 different compounds and contacted with extracellular DNA or with human peripheral whole blood, to compare their binding to DNA versus flowing blood elements,in vitro. Clinical-grade MT devices were coated with two selected compounds and evaluated in functional bench tests aiming to studying clot retrieval and distal emboli release, concomitant with contact aspiration, using an M1 occlusion model.ResultsBinding properties of samples coated with all compounds were increased for DNA (≈ 3-fold) and decreased (≈ 5-fold) for blood elements, essentially platelet, as compared to the bare alloy samples,in vitro. Functional testing showed that surface modification with DNA-binding compounds improved clot retrieval and significantly reduced secondary embolism during experimental recanalization of occluded artery 3D model by thrombectomy procedures.ConclusionOur results suggest that device coating with DNA-binding compounds can considerably improve the outcome of MT procedures in stroke patients.What is already known on this topic –New mechanical thrombectomy device are being improved on the conformation and shape to increase the interaction clot on the physical point of view. However, none interact specifically with the structure or composition of the clot.What this study adds –The design of a chemical surface modification of the device opens the way for a specific targeting tool to increase the interaction with the clot on the molecular level.How this study might affect research, practice or policy –This new surface modification, which can be applied to all commercially available mechanical thrombectomy devices, leads to a decrease in secondary embolization which cannot and is not monitored during the procedure and responsible for new territory damage.

BACKGROUND AND PURPOSE: Transradial access for neurointerventional procedures has been proved a safer and more comfortable alternative to femoral artery access. We present our experience with transradial (distal radial/anatomic snuffbox and radial artery) access for treatment of intracranial aneurysms using all 3 FDA-approved flow diverters. MATERIALS AND METHODS: This was a high-volume, dual-center, retrospective analysis of each institution’s data base between June 2018 and June 2020 and a collection of all patients treated with flow diversion via transradial access. Patient demographic information and procedural and radiographic data were obtained. RESULTS: Seventy-four patients were identified (64 female patients) with a mean age of 57.5 years with a total of 86 aneurysms. Most aneurysms were located in the anterior circulation (93%) and within the intracranial ICA (67.4%). The mean aneurysm size was 5.5 mm. Flow diverters placed included the Pipeline Embolization Device (Flex) (PED, n = 65), the Surpass Streamline Flow Diverter (n = 8), and the Flow-Redirection Endoluminal Device (FRED, n = 1). Transradial access was successful in all cases, but femoral crossover was required in 3 cases (4.1%) due to tortuous anatomy and inadequate support of the catheters in 2 cases and an inability to navigate to the target vessel in a patient with an aberrant right subclavian artery. All 71 other interventions were successfully performed via the transradial approach (95.9%). No access site complications were encountered. Asymptomatic radial artery occlusion was encountered in 1 case (3.7%). CONCLUSIONS: Flow diverters can be successfully placed via the transradial approach with high technical success, low access site complications, and a low femoral crossover rate.

The first-pass effect during mechanical thrombectomy improves clinical outcomes regardless of first-line treatment approach, but current success rates for complete clot capture with one attempt are still less than 40%. We hypothesize that the ThrombX retriever (ThrombX Medical Inc.) can better engage challenging clot models during retrieval throughout tortuous vasculature in comparison with a standard stent retriever without increasing distal emboli. Thrombectomy testing with the new retriever as compared to the Solitaire stent retriever was simulated in a vascular replica with hard and soft clot analogs to create a challenging occlusive burden. Parameters included analysis of distal emboli generated per clot type, along with the degree of recanalization (complete, partial or none) by retrieval device verified by angiography. The ThrombX device exhibited significantly higher rates of first-pass efficacy (90%) during hard clot retrieval in comparison with the control device (20%) (p 200 μm) across both device groups (p = 0.0147), and no significant differences in numbers of distal emboli were noted between the ThrombX and Solitaire techniques. Irrespective of clot composition, use of the ThrombX retriever demonstrated high rates of complete recanalization at first pass in comparison with a state-of-the-art stent retriever and proved to be superior in the hard clot model. Preliminary data suggest that risk of distal embolization associated with the ThrombX system is comparable to that of the control device.

Preliminary experience with distal radial artery (dRA) access for diagnostic cerebral angiography and some neurointerventional procedures has proved to be promising with good technical results and a reliable safety profile. Vascular access via the dRA may further improve minimally invasive treatment of intracranial aneurysms. Between July 2019 and June 2020 we identified 11 patients (9 females) with a mean age of 63.5 years who underwent WEB device placement for treatment of their intracranial aneurysm via the dRA approach. The mean aneurysm size (largest diameter) was 6.7 mm. One patient required conversion to femoral access due to severe brachial artery fibromuscular dysplasia. Placement of the WEB device was successful in all other cases via dRA approach. In all but one case, a low profile triaxial catheter system with the 6F Benchmark guide catheter (Penumbra) and 5F Sofia distal access catheter (Microvention) were used. No access related complications were observed. The combination of the intrasaccular WEB device and dRA access represents an ideal approach which offers operators a low risk vascular access and high procedural success by maintaining the ability to precisely place and manipulate the device using low-profile catheter systems. At the same time, this approach offers patients the most minimally invasive experience currently available for treatment of intracranial aneurysms with quick postprocedural recovery, minimal restrictions and low risk for access site complications.

BackgroundHigh-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.MethodsIn 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).ResultsAdequate 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; PConclusionHF-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.

Purpose To report use of distal radial artery (dRA) access for carotid artery stenting (CAS) and to discuss procedural setup and technical considerations for a successful intervention. Methods A retrospective review of our prospective neurointerventional database of CAS was conducted between May 2019 and March 2020. All CAS cases via dRA in the anatomical snuffbox were identified. Patient demographics, clinical information, procedural and radiographic data was collected. Results 22 CAS procedures in 20 patients via dRA were identified. Patients’ mean age was 69.4 years (range 53–87 years). 3 patients were female. Mean radial artery diameter was 2.1 mm (range 1.6–2.8 mm). dRA access was achieved in all cases. Conversion to femoral access was required in 2 cases (9.1%) due to persistent radial artery vasospasm resulting in patient discomfort despite multiple additional doses of intraarterial vasodilators and added intravenous sedation as well as tortuous vessel anatomy and limited support of the catheters in a type 3 aortic arch for left CAS. Conclusion Our preliminary experience with dRA access for CAS suggests this approach to be feasible and safe for patients. Technical considerations are important and preprocedural planning is necessary for a successful intervention. Catheter systems and devices specifically designed for radial access are needed to enable more interventionalists to safely perform neurointerventional procedures via wrist access.

Intravascular imaging has emerged as a valuable tool for the treatment of coronary and peripheral artery disease; however, no solution is available for safe and reliable use in the tortuous vascular anatomy of the brain. Endovascular treatment of stroke is delivered under image guidance with insufficient resolution to adequately assess underlying arterial pathology and therapeutic devices. High-resolution imaging, enabling surgeons to visualize cerebral arteries' microstructure and micron-level features of neurovascular devices, would have a profound impact in the research, diagnosis, and treatment of cerebrovascular diseases. Here, we present a neurovascular high-frequency optical coherence tomography (HF-OCT) system, including an imaging console and an endoscopic probe designed to rapidly acquire volumetric microscopy data at a resolution approaching 10 microns in tortuous cerebrovascular anatomies. Using a combination of in vitro, ex vivo, and in vivo models, the feasibility of HF-OCT for cerebrovascular imaging was demonstrated., High resolution intravascular imaging in the brain is limited by the high tortuosity of the vasculature. Here the authors present a fiber optic imaging technology using high-frequency optical coherence tomography (HF-OCT) to provide volumetric high resolution images in the highly tortuous cerebral vasculature.

Thalamic infusion of adeno-associated viral (AAV) vectors has been shown to have therapeutic effects in neuronopathic lysosomal storage diseases. Preclinical studies in sheep model of Tay-Sachs disease demonstrated that bilateral thalamic injections of AAV gene therapy are required for maximal benefit. Translation of thalamic injection to patients carries risks in that (1) it has never been done in humans, and (2) dosing scale-up based on brain weight from animals to humans requires injection of larger volumes. To increase the safety margin of this infusion, a flexible cannula was selected to enable simultaneous bilateral thalamic infusion in infants while monitoring by imaging and/or to enable awake infusions for injection of large volumes at low infusion rates. In this study, we tested various infusion volumes (200-800 μL) and rates (0.5-5 μL/min) to determine the maximum tolerated combination of injection parameters. Animals were followed for ∼1 month postinjection with magnetic resonance imaging (MRI) performed at 14 and 28 days. T1-weighted MRI was used to quantify thalamic damage followed by histopathological assessment of the brain. Trends in data show that infusion volumes of 800 μL (2 × the volume required in sheep based on thalamic size) resulted in larger lesions than lower volumes, where the long infusion times (between 13 and 26 h) could have contributed to the generation of larger lesions. The target volume (400 μL, projected to be sufficient to cover most of the sheep thalamus) created the smallest lesion size. Cannula placement alone did result in damage, but this is likely associated with an inherent limitation of its use in a small brain due to the length of the distal rigid portion and lack of stable fixation. An injection rate of 5 μL/min at a volume ∼1/3 of the thalamus (400-600 μL) appears to be well tolerated in sheep both clinically and histopathologically.

Background Tissue growth over covered branches is a leading cause of delayed thrombotic complications after flow-diverter stenting (FDS). Due to insufficient resolution, no imaging modality is clinically available to monitor this phenomenon. Objective To evaluate high-frequency optical coherence tomography (HF-OCT), a novel intravascular imaging modality designed for the cerebrovascular anatomy with a resolution approaching 10 microns, to monitor tissue growth over FDS in an arterial bifurcation model. Methods FDS were deployed in a rabbit model (n = 6), covering the aortic bifurcation. The animals were divided in different groups, receiving dual antiplatelet therapy (DAPT) (n = 4), aspirin only (n = 1), and no treatment (n = 1). HF-OCT data were obtained in vivo at 3 different time points in each animal. For each cross-sectional image, metal and tissue coverage of the jailed ostium was quantified. Scanning electron microscopy images of harvested arteries were subsequently obtained. Results Good quality HF-OCT data sets were successfully acquired at implant and follow-up. A median value of 41 (range 21-55) cross-sectional images were analyzed per ostium for each time point. Between 0 and 30 d after implant, HF-OCT analysis showed a significantly higher ostium coverage when DAPT was not given. After 30 d, similar growth rates were found in the DAPT and in the aspirin group. At 60 d, a coverage of 90% was reached in all groups. Conclusion HF-OCT enables an accurate visualization of tissue growth over time on FDS struts. The use of FDS in bifurcation locations may induce a drastic reduction of the jailed-branch ostium area.

The implantation of flow diverters requires administration of dual anti-platelet therapy, posing the potential for complications. The p48MW HPC (phenox, Bochum, Germany) hydrophilic-coated flow diverting stent is designed to be anti-thrombotic, thus opening the potential for single anti-platelet therapy. We deploy a novel intravascular high-resolution imaging technique, high-frequency optical coherence tomography (HF-OCT), to study in an animal model the acute thrombus formation on coated p48MW devices versus uncoated control devices. Three pigs were implanted with 4 flow diverters each, two test hydrophilic-coated devices, and two control uncoated devices (p48MW). Each pig was treated with a different anti-platelet regime: no anti-platelet therapy, aspirin only, aspirin and clopidogrel. Twenty minutes after the flow diverter was implanted, an HF-OCT data set was acquired. Acute clot formed on the flow diverter at each covered side branch was measured from the HF-OCT slices. Factors considered to be important were the device type (pHPC versus bare metal), aspirin, clopidogrel, and vessel location. A linear model was constructed from the significant factors. Both coating (p

Proximal flow control achieved with a balloon guide catheter (BGC) during endovascular treatment of acute ischemic stroke is reviewed in this article. In clinical practice, BGCs offer a multi-faceted approach for clot retrieval by creating proximal flow arrest, reducing embolic burden, and shortening procedure time. Evaluation of frontline thrombectomy procedures with BGCs revealed advantages of combined use over the conventional guide catheter (CGC), notably in the significant reduction of distal emboli to both the affected and previously unaffected territories. Recently, new measures of early and complete reperfusion at first thrombectomy pass have been identified as independent predictors of improved outcomes, which were consistently demonstrated with use of BGC as a safe and effective option to minimize number of passes during intervention. Prior randomized controlled trials reported the positive correlation between BGC-treated patients and a lower risk of mortality as well as shortened procedure time. While BGC use is more common in stent retriever-mediated mechanical thrombectomy, preliminary data has shown the potential benefit of device application during contact aspiration thrombectomy to achieve successful recanalization. However, the question of which major endovascular strategy reigns superior as a frontline remains to be answered. Along with clinical case assessments, BGC performance during in-vitro simulation was analyzed to further understand mechanisms for optimization of thrombectomy technique.

Translation of acute ischemic stroke research to the clinical setting remains limited over the last few decades with only one drug, recombinant tissue-type plasminogen activator, successfully completing the path from experimental study to clinical practice. To improve the selection of experimental treatments before testing in clinical studies, the use of large gyrencephalic animal models of acute ischemic stroke has been recommended. Currently, these models include, among others, dogs, swine, sheep, and nonhuman primates that closely emulate aspects of the human setting of brain ischemia and reperfusion. Species-specific characteristics, such as the cerebrovascular architecture or pathophysiology of thrombotic/ischemic processes, significantly influence the suitability of a model to address specific research questions. In this article, we review key characteristics of the main large animal models used in translational studies of acute ischemic stroke, regarding (1) anatomy and physiology of the cerebral vasculature, including brain morphology, coagulation characteristics, and immune function; (2) ischemic stroke modeling, including vessel occlusion approaches, reproducibility of infarct size, procedural complications, and functional outcome assessment; and (3) implementation aspects, including ethics, logistics, and costs. This review specifically aims to facilitate the selection of the appropriate large animal model for studies on acute ischemic stroke, based on specific research questions and large animal model characteristics.

Localized delivery of diagnostic/therapeutic agents to cerebral aneurysms, lesions in brain arteries, may offer a new treatment paradigm. Since aneurysm rupture leading to subarachnoid hemorrhage is a devastating medical emergency with high mortality, the ability to noninvasively diagnose high‐risk aneurysms is of paramount importance. Moreover, treatment of unruptured aneurysms with invasive surgery or minimally invasive neurointerventional surgery poses relatively high risk and there is presently no medical treatment of aneurysms. Here, leveraging the endogenous biophysical properties of brain aneurysms, we develop particulate carriers designed to localize in aneurysm low‐shear flows as well as to adhere to a diseased vessel wall, a known characteristic of high‐risk aneurysms. We first show, in an in vitro model, flow guided targeting to aneurysms using micron‐sized (2 μm) particles, that exhibited enhanced targeting (>7 folds) to the aneurysm cavity while smaller nanoparticles (200 nm) showed no preferable accumulation. We then functionalize the microparticles with glycoprotein VI (GPVI), the main platelet receptor for collagen under low‐medium shear, and study their targeting in an in vitro reconstructed patient‐specific aneurysm that contained a disrupted endothelium at the cavity. Results in this model showed that GPVI microparticles localize at the injured aneurysm an order of magnitude (>9 folds) more than control particles. Finally, effective targeting to aneurysm sites was also demonstrated in an in vivo rabbit aneurysm model with a disrupted endothelium. Altogether, the presented biophysical strategy for targeted delivery may offer new treatment opportunities for cerebral aneurysms.

The introduction of flow diverter technology to the field of neurointervention has revolutionized the treatment of intracranial aneurysms. The therapy approach has shifted from intrasaccular aneurysm treatment to exclusion of the aneurysm from the blood circulation with remodeling of the parent artery. Previously, "difficult"-to-treat aneurysms including fusiform and blister aneurysms, but also aneurysms arising from a diseased vessel segment, can now be safely and permanently treated with flow diverters. A little over a decade ago, after extensive bench testing and refinement of the flow diverter concept, the device was eventually available for clinical use and today it has become a standard treatment for intracranial aneurysms. Currently, United States Food and Drug Administration (FDA)-approved flow diverters are the Pipeline Embolization Device (Medtronic) and the Surpass Streamline Flow Diverter (Stryker). The devices can either be delivered or deployed via a standard femoral artery approach or a radial artery approach. Other considerations for catheter setup and device deployment strategies depending on aneurysm location or vessel anatomy are described.

Given recent evidence suggesting the clot composition may be associated with revascularization outcomes and stroke etiology, clot composition research has been a topic of growing interest. It is currently unclear what effect, if any, pre-thrombectomy thrombolysis has on clot composition. Understanding this association is important as it is a potential confounding variable in clot composition research. We retrospectively evaluated the composition of retrieved clots from ischemic stroke patients who did and did not receive pre-treatment tPA to study the effect of tPA on clot composition.Consecutive patients enrolled in the Stroke Thromboembolism Registry of Imaging and Pathology (STRIP) were included in this study. All patients underwent mechanical thrombectomy and retrieved clots were sent to a central core lab for processing. Histological analysis was performed using Martius Scarlett Blue (MSB) staining and area of the clot was also measured on the gross photos. Student's t test was used for continuous variables and chi-squared test for categorical variables.A total of 1430 patients were included in this study. Mean age was 68.4±13.5 years. Overall rate of TICI 2c/3 was 67%. A total of 517 patients received tPA (36%) and 913 patients did not (64%). Mean RBC density for the tPA group was 42.97±22.62% compared to 42.80±23.18% for the non-tPA group (P=0.89). Mean WBC density for the tPA group was 3.74±2.60% compared to 3.42±2.21% for the non-tPA group (P=0.012). Mean fibrin density for the tPA group was 26.52±15.81% compared to 26.53±15.34% for the non-tPA group (P=0.98). Mean platelet density for the tPA group was 26.22±18.60% compared to 26.55±19.47% for the non-tPA group (P=0.75). tPA group also had significantly smaller clot area compared to non-tPA group.Our study 1430 retrieved emboli and ischemic stroke patients shows no interaction between tPA administration and clot composition. These findings suggest that tPA does not result in any histological changes in clot composition.

Acute ischemic stroke (AIS) is caused by blockage of an arterial blood vessel in the brain by a thrombus, which interrupts oxygen supply to the brain parenchyma. The goal of endovascular stroke treatment (mechanical thrombectomy) is to restore blood flow as quickly and completely as possible. There are numerous factors that influence endovascular treatment success. They can be broadly grouped into a) factors related to blood vessels, b) factors related to the thrombus, c) factors related to endovascular treatment technique and tools and d) operator-related factors. While blood vessel and tgthro thrombus-related factors are mostly non-modifiable in the acute setting, operator and technique-related factors can be modified, and extensive research is currently being done to investigate the complex interplay of all these variables, and to optimize the modifiable factors to the maximum possible extent. In this review, we will describe these factors and how they interact with each other in detail, and outline some of their practical implications. We will conclude with a short summary and outlook on future directions for optimizing endovascular treatment success.

Purpose To evaluate the effectiveness and safety of image-guided percutaneous bleomycin sclerotherapy as a minimally invasive treatment approach for craniofacial (veno)lymphatic malformations in children and adolescents. Material and Methods We retrospectively reviewed our prospectively maintained Neuro IR database between January 2018 and June 2020 and identified all children and adolescents (1 to 19 years) who underwent percutaneous fluoroscopy guided bleomycin sclerotherapy for craniofacial (veno)lymphatic malformations. Patient clinical and imaging follow up data was collected. Results We identified 4 patients (2 female patients) between 20 months and 12 years old who presented with clinical and radiographic craniofacial (veno)lymphatic malformations. Two lesions were macrocystic, 1 microcystic and 1 mixed. No procedural complications ensued. On first follow up examination 2 patients report obvious decrease in size of the malformation which is confirmed with ultrasound and/or visual inspection. One patient subjectively reported minimal decrease in size with the ultrasound evaluation not showing any change from prior to the procedure. One patient who showed initial decrease in size of the lesion already underwent a second sclerotherapy session and is awaiting his next follow up appointment. The other 2 patients are scheduled to undergo their next sclerotherapy session as well. One patient did not reach the first follow up time point yet. Conclusion Sclerotherapy should be considered in selected patients with craniofacial (veno)lymphatic malformations as it represents a safe and successful treatment option, especially if surgical excision is considered challenging, with a high risk of complication and postoperative recurrence. Patients and parents have to be aware that sclerotherapy may require several sessions to achieve results. Generally, patients and parents are satisfied with sclerotherapy treatment outcomes, specifically the cosmetic results. Disclosures A. Kuhn: None. A. Puri: 1; C; NIH, Stryker Neurovascular, Medtronic, Cerenovus. 2; C; Microvention, QApel, Perfuze Medical, Arsenal Medical, Merit Medical, Stryker Neurovascular, Medtronic, Cerenovus. 4; C; InNeuroCo Inc, Galaxy therapeutics, Agile Medical, Perfuze medical and NTI. C. Zoppo: None. K. de Macedo Rodrigues: None. F. Massari: None. M. Gounis: 1; C; National Institutes of Health (NIH), the United States – Israel Binational Science Foundation, Anaconda, ApicBio, Axovant, Cerenovus, Cook Medical, Gentuity, Imperative Care, InNeuroCo, Magneto. 2; C; Cerenovus, Imperative Care, phenox, Medtronic Neurovascular, Route 92 Medical, Stryker Neurovascular. 4; C; Imperative Care, InNeuroCo and Neurogami. J. Singh: None.