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Current approaches for localized intravascular treatments rely on using solid implants, such as metallic coils for embolizing aneurysms, or on direct injection of a therapeutic agent that can disperse from the required site of action. Here, we present a fluid-based strategy for localizing intravascular therapeutics that leverages surface tension and immiscible fluid interactions, to allow confined and focal treatment at brain aneurysm sites. We first show, computationally and experimentally, that an immiscible phase can be robustly positioned at the neck of human aneurysm models to seal and isolate the aneurysm's cavity for further treatment, including in wide-neck aneurysms. We then demonstrate localized delivery and confined treatment, by selective staining of cell nuclei within the aneurysm cavity as well as by hydrogel-based embolization in patient-specific aneurysm models. Altogether, our interfacial flow-driven strategy offers a potential approach for intravascular localized treatment of cardiovascular and other diseases.

Neurological disorders pose a challenge for targeted therapy due to restricted access of therapeutic agents to the central nervous system (CNS). Current methods are limited by procedure-related risks, invasiveness, and insufficient CNS biodistribution. A novel percutaneous transvenous technology, currently in clinical trials for communicating hydrocephalus, offers a minimally invasive approach by providing endovascular access to the cerebrospinal fluid-filled cerebellopontine angle (CPA) cistern. We hypothesized that drug delivery to the CPA cistern could yield widespread CNS distribution. Using an ovine model, we compared the biodistribution of scAAV9-CB-GFP following CPA cistern infusion with previously reported cisterna magna (CM) administration. Targeting both the CPA cistern and CM in sheep, we employed a lumbar spine-inserted microcatheter under fluoroscopy. CPA delivery of AAV9 demonstrated biodistribution and transduction in the cerebral cortices, striatum, thalamus, midbrain, cerebellum, and spinal cord, with minor liver distribution comparable to CM. The favorable safety profile in humans with hydrocephalus suggests that percutaneous endovascular injection into the CPA could offer a clinically safer and minimally invasive delivery system for CNS gene and cell-based therapies., Competing Interests: Declaration of interests C.B.H. is a shareholder, consultant, investor, and co-founder of CereVasc, Inc. B.M.B. is a shareholder and employee of CereVasc, Inc. M.J.G. is a consultant on a fee-per-hour basis for Alembic LLC, Astrocyte Pharmaceuticals, BendIt Technologies, Cerenovus, Imperative Care, Jacob’s Institute, Medtronic Neurovascular, Mivi Neurosciences, phenox GMbH, Q’Apel, Route 92 Medical, Scientia, Simcerre, Stryker Neurovascular, Stryker Sustainability Solutions, Wallaby Medical; holds stock in Imperative Care, InNeuroCo, Galaxy Therapeutics, Kapto, Neurogami and Synchron and receives research support from the NIH, the United States-Israel Binational Science Foundation, Anaconda, ApicBio, Arsenal Medical, Axovant, Balt, Cerenovus, Ceretrieve, CereVasc LLC, Cook Medical, Galaxy Therapeutics, Gentuity, Gilbert Foundation, Imperative Care, InNeuroCo, Insera, Jacob’s Institute, Magneto, MicroBot, Microvention, Medtronic Neurovascular, MIVI Neurosciences, Naglreiter MDDO, Neurogami, Q’Apel, Philips Healthcare, Progressive Medical, Pulse Medical, Rapid Medical, Route 92 Medical, Scientia, Stryker Neurovascular, Syntheon, ThrombX Medical, Wallaby Medical, the Wyss Institute, and Xtract Medical. A.M.M. is a shareholder, consultant, investor, and co-founder of CereVasc, Inc., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Intrasaccular flow-disrupting devices are a safe and effective treatment strategy for intracranial aneurysms. We utilized high-frequency optical coherence tomography (HF-OCT) and digital subtraction angiography (DSA) to evaluate SEAL Arc, a new intrasaccular device, and compare the findings with the well-established Woven EndoBridge (WEB) device in an animal model of saccular aneurysms., Methods: In a rabbit model, elastase-induced aneurysms were treated with SEAL Arc (n=11) devices. HF-OCT and DSA were performed after implant and repeated after 12 weeks. Device protrusion and malapposition were assessed at implant time and scored on a binary system. Aneurysm occlusion was assessed at 12 weeks with the WEB Occlusion Scale and dichotomized to complete (A and B) or incomplete (C and D) occlusion. The percentage of neointimal coverage after 12 weeks was quantified using HF-OCT. We compared these data to previously published historical controls treated with the gold-standard WEB device (n=24) in the same model., Results: Aneurysm size and device placement were not significantly different between the two groups. Complete occlusion was demonstrated in 80% of the SEAL Arc devices, which compared favorably to the 21% of the aneurysms treated with WEB devices (P=0.002). Neointimal coverage across SEAL Arc devices was 86±15% compared with 49±27% for WEB (P=0.001). Protruding devices had significantly less neointimal coverage (P<0.001) as did incompletely occluded aneurysms (P<0.001). Histologically, all aneurysms treated with SEAL Arc devices were completely healed., Conclusion: Complete early aneurysm occlusion was frequently observed in the SEAL Arc treated aneurysms, with significant neointimal coverage after 12 weeks., Competing Interests: Competing interests: CTZ, JK, RMK, ME, and VA declare no competing interest. TW, AB, EP, and OZ: co-founders of Galaxy Therapeutics. ASR: employee of Galaxy Therapeutics. BP: Consultant for Medtronic, Microvention, Cerenovus and MIVI NeurosciencesGJU: Employee of Gentuity LLC. MJG: 1. Consultant on a fee-per-hour basis for Alembic LLC, Astrocyte Pharmaceuticals, BendIt Technologies, Cerenovus, Imperative Care, Jacob’s Institute, Medtronic Neurovascular, Mivi Neurosciences, phenox GMbH, Q’Apel, Route 92 Medical, Scientia, Simcerre, Stryker Neurovascular, Stryker Sustainability Solutions, Wallaby Medical; holds stock in Imperative Care, InNeuroCo, Galaxy Therapeutics, Kapto, Neurogami and Synchron; 2. Research support from the NIH, the United States–Israel Binational Science Foundation, Anaconda, ApicBio, Arsenal Medical, Axovant, Balt, Cerenovus, Ceretrieve, CereVasc LLC, Cook Medical, Galaxy Therapeutics, Gentuity, Gilbert Foundation, Imperative Care, InNeuroCo, Insera, Jacob’s Institute, Magneto, MicroBot, Microvention, Medtronic Neurovascular, MIVI Neurosciences, Naglreiter MDDO, Neurogami, Q’Apel, Philips Healthcare, Progressive Medical, Pulse Medical, Rapid Medical, Route 92 Medical, Scientia, Stryker Neurovascular, Syntheon, ThrombX Medical, Wallaby Medical, the Wyss Institute and Xtract Medical; 3. Associate Editor of Basic Science on the JNIS Editorial Board. OOZ: Consultant for: Stryker, Cerenovous, Penumbra, Medtronic; Research Grant: Stryker, Cerenovous, Penumbra, Medtronic, Genentech, MicroVention; PI: Investigator Initiated trials: TESLA Trial, PI: PICASSO Trial, NIH StrokeNet: Endovascular Committee, StrokeNet Steering Committee; PI: Sterling Aneurysm Registry; Steering Committee: ASSIST Registry, EXCELLENT Registry; Investor: Neuro Technology Investors (NTI)Co-Founder: Galaxy Therapeutics., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Therapeutic hypothermia has shown potential in cardiac intervention for years; however, its adoption into the neurovascular space has been limited. Studies have pointed to slow cooling and limited depth of hypothermia yielding negative outcomes. Here we present an insulated catheter that allows for consistent infusion of chilled saline directly to the brain. Direct delivery of cold saline allows a faster depth of hypothermia, which could have a benefit to the growth of ischemic lesions., Methods: Ten canines were randomized to either receive selective brain cooling or no additional therapy. Eight animals were successfully enrolled (n = 4 per group). Each animal underwent a temporary middle cerebral artery occlusion (MCAO) for a total of 45 min. Five minutes prior to flow restoration, chilled saline was injected through the ipsilateral internal carotid artery using an insulated catheter to ensure delivery temperature. The treatment continued for 20 min, after which the animal was transferred to an MRI scanner for imaging., Results: Of the 8 animals that were successfully enrolled in the study, 3 were able to survive to the 30-day endpoint with no differences between the cooled and control animals. There was no difference in the initial mean infarct size between the groups; however, animals that did not receive cooling had infarcts continuing to progress more rapidly after the MCAO was removed (13.8% vs 161.3%, p = 0.016, cooled vs control)., Conclusions: Selective hypothermia was able to reduce the post-MCAO infarct progression in a canine model of temporary MCAO., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: RMK, ME, NH, and CR declare no competing interest. VA: Consultant on a fee-per-hour basis for Stryker Neurovascular. MSS: 1. Consultant on a fee-per-hour basis for Sanofi; 2. Research support from the Breast Cancer Research Foundation. TLM, SH, and JM: employees of FocalCool. ASP: consultant for Medtronic Neurovascular, Stryker Neurovascular, Balt, Q’Apel Medical, Cerenovus, Microvention, Imperative Care, Agile, Merit, CereVasc, and Arsenal Medical; research grants from NIH, Microvention, Cerenovus, Medtronic Neurovascular, and Stryker Neurovascular; holds stocks in InNeuroCo, Agile, Perfuze, Galaxy and NTI. MJG: 1. Consultant on a fee-per-hour basis for Alembic LLC, Astrocyte Pharmaceuticals, BendIt Technologies, Cerenovus, Imperative Care, Jacob's Institute, Medtronic Neurovascular, Mivi Neurosciences, phenox GMbH, Q’Apel, Route 92 Medical, Scientia, Simcerre, Stryker Neurovascular, Stryker Sustainability Solutions, Wallaby Medical; holds stock in Imperative Care, InNeuroCo, Galaxy Therapeutics, Neurogami and Synchron; 2. Research support from the NIH, the United States – Israel Binational Science Foundation, Anaconda, ApicBio, Arsenal Medical, Axovant, Balt, Cerenovus, Ceretrieve, CereVasc LLC, Cook Medical, Galaxy Therapeutics, Gentuity, Gilbert Foundation, Imperative Care, InNeuroCo, Insera, Jacob's Institute, Magneto, MicroBot, Microvention, Medtronic Neurovascular, MIVI Neurosciences, Naglreiter MDDO, Neurogami, Q’Apel, Philips Healthcare, Progressive Medical, Pulse Medical, Rapid Medical, Route 92 Medical, Scientia, Stryker Neurovascular, Syntheon, ThrombX Medical, Wallaby Medical, the Wyss Institute and Xtract Medical; 3.

Dynamic perviousness is a novel imaging biomarker, with clot density measurements at multiple timepoints to allow longer contrast to thrombus interaction. We investigated the correlations between dynamic perviousness and clot composition in the setting of acute ischemic stroke. Thirty-nine patients with large vessel occlusion (LVO) undergoing mechanical thrombectomy (MT) were analyzed. Patients received a three-phase CT imaging pre-thrombectomy and histopathological analysis of retrieved clots. Clot densities for every phase and change in densities between phases were calculated, leading to four patterns of dynamic perviousness: no contrast uptake, early contrast uptake with and without washout and late uptake. Clots were categorized into three groups based on dominant histologic composition: red blood cell (RBC)-rich, fibrin/platelet-rich and mixed. Clot composition was correlated with dynamic perviousness using the Kruskal-Wallis test and Pearson's correlation analysis. The dynamic perviousness categories showed a significant difference between fibrin-rich clots when compared to RBC-rich plus mixed groups. The uptake without washout category had significantly fewer fibrin clots compared to the uptake with washout ( p = 0.036), and nearly significantly fewer fibrin clots when compared to the no uptake category ( p = 0.057). Contrast uptake with different patterns of contrast washout showed significant differences of the likelihood for fibrin-rich clots.

Background: Flow diverters carry the risk of thromboembolic complications (TEC). We tested a coating with covalently bound heparin that activates antithrombin to address TEC by locally downregulating the coagulation cascade. We hypothesized that the neuroimaging evidence of TEC would be reduced by the coating., Methods: 16 dogs were implanted with overlapping flow diverters in the basilar artery, separated into two groups: heparin-coated (n=9) and uncoated (n=7). Following implantation, high-frequency optical coherence tomography (HF-OCT) was acquired to quantify acute thrombus (AT) formation on the flow diverters. MRI was performed postoperatively and repeated at 1, 2, 3, 4, and 8 weeks, consisting of T1-weighted imaging, time-0f-flight (ToF), diffusion weighted imaging (DWI), susceptibility weighted imaging (SWI), and fluid attenuated inversion recovery (FLAIR) sequences. Neurological examinations were performed throughout the 8-week duration of the study., Results: The mean AT volume on coated devices was lower than uncoated (0.014 vs 0.018 mm 3 ); however, this was not significant (P=0.3). The mean number of foci of magnetic susceptibility artifacts (MSAs) on SWI was significantly different between the uncoated and coated groups at the 1-week follow-up (P<0.02), and remained statistically different throughout the duration of the study. The AT volume showed a direct linear correlation with the MSA count and 80% of the variance in the MSA could be explained by the AT volume (P<0.001). Pathological analysis showed evidence of ischemic injury at locations of MSA., Conclusions: Heparin-coated flow diverters significantly reduced the number of new MSAs after 1 week follow-up, showing the potential to reduce TEC., Competing Interests: Competing interests: AP: consultant for Medtronic Neurovascular, Stryker Neurovascular, Balt, Q’Apel Medical, Cerenovus, Microvention, Imperative Care, Agile, Merit, CereVasc, and Arsenal Medical; research grants from NIH, Microvention, Cerenovus, Medtronic Neurovascular, and Stryker Neurovascular; holds stocks in InNeuroCo, Agile, Perfuze, Galaxy and NTI. JMA and ABB are employees of Stryker Neurovascular. ASA: Consultant for Arsenal, Balt, Johnson and Johnson, Medtronic, Microvention, Penumbra, Scientia, Siemens, Stryker. Research support from Balt, Medtronic, Microvention, Penumbra and Siemens. Shareholder Azimuth, Bendit, Cerebrotech, Endostream, Magneto, Mentice, Neurogami, Neuros, Revbio, Scientia, Serenity, Synchron, Tulavi, Vastrax, VizAI. DF: Consultant: Medtronic, Cerenovous, Microvention, Stryker, Balt USA, MENTICE-Vascular Simulations, Neurogami, Marblehead, RAPID.AI, RAPID Medical, Qapel Medical, Arsenal Medical, Phenox Medical, Scientia Medical, Perfuze; Research Support: Microvention, Stryker, Balt USA, Siemens; Scientific Advisory Boards: Scientia Medical, NVMed, Perfuze; Holds Stock in: MENTICE-Vascular Simulations, Neurogami, Marblehead, Scientia Medical, NVMed, Perfuze. MJG: Has been a consultant on a fee-per-hour basis for Alembic LLC, Astrocyte Pharmaceuticals, BendIt Technologies, Cerenovus, Imperative Care, Jacob’s Institute, Medtronic Neurovascular, Mivi Neurosciences, phenox GMbH, Q’Apel, Route 92 Medical, Stryker Neurovascular, Stryker Sustainability Solutions, Wallaby Medical; holds stock in Imperative Care, InNeuroCo, Galaxy Therapeutics and Neurogami; and has received research support from the National Institutes of Health (NIH), the United States – Israel Binational Science Foundation, Anaconda, ApicBio, Arsenal Medical, Axovant, Balt, Cerenovus, Ceretrieve, CereVasc LLC, Cook Medical, Galaxy Therapeutics, Gentuity, Gilbert Foundation, Imperative Care, InNeuroCo, Insera, Jacob’s Institute, Magneto, MicroBot, Microvention, Medtronic Neurovascular, MIVI Neurosciences, Naglreiter MDDO, Neurogami, Philips Healthcare, Progressive Medical, Pulse Medical, Rapid Medical, Route 92 Medical, Scientia, Stryker Neurovascular, Syntheon, ThrombX Medical, Wallaby Medical, the Wyss Institute and Xtract Medical. MJG is Associate Editor of Basic Science on the JNIS Editorial Board., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Multiple studies and meta-analyses have described the technical and clinical outcomes in large cohorts of aneurysm patients treated with flow diverters (FDs). Variations in evaluation methodology complicate making comparisons among studies, hinder understanding of the device behavior, and pose an obstacle in the assessment of further advances in FD therapy., Methods: A multidisciplinary panel of neurointerventionalists, imaging experts, and neuroradiologists convened with the goal of establishing consensus recommendations for the standardization of image analyses in FD studies., Results: A standardized methodology is proposed for evaluating and reporting radiological outcomes of FD treatment of intracranial aneurysms. The recommendations include general imaging considerations for clinical studies and evaluations of longitudinal changes, such as neointimal lining and stenosis. They cover standards for classification of aneurysm location, morphology, measurements, as well as the assessment of aneurysm occlusion, wall apposition, and neck coverage. These reporting standards further define four specific braid deformation patterns: foreshortening, fish-mouthing, braid bump deformation, and braid collapse, collectively termed 'F2B2'., Conclusions: When widely applied, standardization of methods of measuring and reporting outcomes will help to harmonize the assessment of treatment outcomes in clinical studies, help facilitate communication of results among specialists, and help enable research and development to focus on specific aspects of FD techniques and technology., Competing Interests: Competing interests: JF: Research support: German Ministry of Science & Education (BMBF) and of Economy and Innovation (BMWi), German Research Foundation (DFG), European Union (EU), Hamburgische Investitions- und Förderbank (IFB), Medtronic, Microvention, Route92, Stryker. Consultant for: Acandis, Cerenovus, Medtronic, Microvention, Penumbra, Phenox, Roche, Stryker, TG Med, Tonbridge. Stockholder: Tegus Medical, Vastrax, Eppdata. DF: Medtronic – Consulting, Proctoring, Cerenovous – Consulting, Microvention – Consulting, Proctoring, Research Support, Penumbra – Consulting, Research Support, Stryker – Consulting, Research Support, Balt USA – Consulting, Research Support, Siemens – Research Support, MENTICE-Vascular Simulations – Consultant, Neurogami – Stockholder, Consultant, RAPID. AI – Consultant, RAPID Medical – Consultant, Qapel Medical –Consultant, Arsenal Medical – Consultant, Phenox Medical – Consultant, Scientia Medical – SAB, Consultant, Stockholder, NVMed – SAB, Stockholder, Perfuze – SAB, Consultant, Stockholder, Vesalio - ConsultantIS: Consulting and proctoring agreement with Medtronic & Microvention. SH: Consulting and proctoring agreement with Medtronic & Microvention. Stocks: Neuravention Inc., Vesalio Inc., Synchron Inc., Bend It Technologies, Sim & Size Inc., Borvo Medical Inc., Prometheus Inc., Piraeus Inc., Neuros Medical Inc. MJG: (1) Consultant on a fee-per-hour basis for Alembic, Astrocyte Pharmaceuticals, BendIt Technologies, Cerenovus, Imperative Care, Jacob’s Institute, Medtronic Neurovascular, Mivi Neurosciences, Phenox GMbH, Q’Apel, Route 92 Medical, Scientia, Simcerre, Stryker Neurovascular, Stryker Sustainability Solutions, Wallaby Medical; holds stock in Imperative Care, InNeuroCo, Galaxy Therapeutics, Kapto, Neurogami and Synchron; (2) Research support from the National Institutes of Health (NIH), the United States–Israel Binational Science Foundation, Anaconda, ApicBio, Arsenal Medical, Axovant, Balt, Cerenovus, Ceretrieve, CereVasc, Cook Medical, Galaxy Therapeutics, Gentuity, Gilbert Foundation, Imperative Care, InNeuroCo, Insera, Jacob’s Institute, Magneto, MicroBot, Microvention, Medtronic Neurovascular, MIVI Neurosciences, Naglreiter MDDO, Neurogami, Q’Apel, Philips Healthcare, Progressive Medical, Pulse Medical, Rapid Medical, Route 92 Medical, Scientia, Stryker Neurovascular, Syntheon, ThrombX Medical, Wallaby Medical, the Wyss Institute, Xtract Medical; and (3) Associate Editor of Basic Science on the JNIS Editorial Board., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Flow diversion has become a standard treatment for cerebral aneurysms. However, major drawbacks include the need for dual antiplatelet therapy after implant and delayed complete occlusion of the aneurysm, which occurs when new tissue growth excludes the aneurysm from the parent artery. Biomimetic surface modifications such as the phosphorylcholine polymer (Shield surface modification) represent major advances in reducing thrombogenicity of these devices. However, in vitro studies have raised concerns that this modification may also delay endothelialization of flow diverters., Methods: Bare metal Pipeline, Pipeline Shield, and Vantage with Shield devices were implanted in the common carotid arteries (CCAs) of 10 rabbits (two in the left CCA, one in the right CCA). Following implant and at 5, 10, 15, and 30 days, the devices were imaged with high-frequency optical coherence tomography and conventional angiography to evaluate tissue growth. At 30 days the devices were explanted and their endothelial growth was assessed with scanning electron microscopy (SEM) at five locations along their length using a semi-quantitative score., Results: The average tissue growth thickness (ATGT) was not different between the three devices. Neointima was apparent at 5 days and all devices demonstrated similar ATGT at each time point. On SEM, no difference was found in the endothelium scores between the device types., Conclusion: In vivo, neither the Shield surface modification nor the device design (Vantage) altered the longitudinal healing of the flow diverter., Competing Interests: Competing interests: CTZ, RMK, ME, and VA declare no competing interests. MJG: (1) Consultant on a fee-per-hour basis for Alembic LLC, Astrocyte Pharmaceuticals, BendIt Technologies, Cerenovus, Imperative Care, Jacob’s Institute, Medtronic Neurovascular, Mivi Neurosciences, phenox GMbH, Q’Apel, Route 92 Medical, Scientia, Simcerre, Stryker Neurovascular, Stryker Sustainability Solutions, Wallaby Medical; holds stock in Imperative Care, InNeuroCo, Galaxy Therapeutics, Neurogami and Synchron. (2) Research support from the NIH, the United States – Israel Binational Science Foundation, Anaconda, ApicBio, Arsenal Medical, Axovant, Balt, Cerenovus, Ceretrieve, CereVasc, Cook Medical, Galaxy Therapeutics, Gentuity, Gilbert Foundation, Imperative Care, InNeuroCo, Insera, Jacob’s Institute, Magneto, MicroBot, Microvention, Medtronic Neurovascular, MIVI Neurosciences, Naglreiter MDDO, Neurogami, Q’Apel, Philips Healthcare, Progressive Medical, Pulse Medical, Rapid Medical, Route 92 Medical, Scientia, Stryker Neurovascular, Syntheon, ThrombX Medical, Wallaby Medical, the Wyss Institute and Xtract Medical. (3) Associate Editor of Basic Science on the JNIS Editorial Board. MJG is the guarantor of the study., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Endovascular interventions are increasingly becoming the preferred approach for treating strokes and cerebral artery diseases. These procedures rely on sophisticated angiographical imaging guidance, which encounters challenges because of limited contrast and spatial resolution. Achieving a more precise visualization of the underlying arterial pathology and neurovascular implants is crucial for accurate procedural decision-making. In a human study involving 32 patients, we introduced the clinical application of a miniaturized endovascular neuro optical coherence tomography ( n OCT) imaging probe. This technology was designed to navigate the tortuous paths of the cerebrovascular circulation and to offer high-resolution imaging in situ. The n OCT probe is compatible with standard neurovascular microcatheters, integrating with the procedural workflow used in clinical routine. Equipped with a miniaturized optical fiber and a distal lens, the probe illuminates the tissue and collects the backscattered, near-infrared light. While rotating the fiber and the lens at high speed, the probe is rapidly retracted, creating a spiral-shaped light pattern to comprehensively capture the arterial wall and implanted devices. Using n OCT, we demonstrated volumetric microscopy of cerebral arteries in patients undergoing endovascular procedures. We imaged the anterior and posterior circulation of the brain, including distal segments of the internal carotid and middle-cerebral arteries, as well as the vertebral, basilar, and posterior cerebral arteries. We captured a broad spectrum of neurovascular pathologies, such as brain aneurysms, ischemic stroke, arterial stenoses, dissections, and intracranial atherosclerotic disease. n OCT offered artifact-free, high-resolution visualizations of intracranial artery pathology and neurovascular devices.

Intracranial atherosclerotic disease (ICAD) involves the build-up of atherosclerotic plaques in cerebral arteries, significantly contributing to stroke worldwide. Diagnosing ICAD entails various techniques that measure arterial stenosis severity. Digital subtraction angiography, CT angiography, and magnetic resonance angiography are established methods for assessing stenosis. High-resolution MRI offers additional insights into plaque morphology including plaque burden, hemorrhage, remodeling, and contrast enhancement. These metrics and plaque traits help identify symptomatic plaques. Techniques like transcranial Doppler, CT perfusion, computational fluid dynamics, and quantitative MRA analyze blood flow restrictions due to ICAD. Intravascular ultrasound or optical coherence tomography have a very high spatial resolution and can assess the structure of the arterial wall and the plaque from the lumen of the target vascular territory. Positron emission tomography could further detect inflammation markers. This review aims to provide a comprehensive overview of the spectrum of current modalities for atherosclerotic plaque analysis and risk stratification., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The 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. We aimed to evaluate the potential of a DNA-reacting surface to aid the retention of both the main clot and small fragments within the thrombectomy device to improve the potential of MT procedures., Methods: Device-suitable alloy samples were coated with 15 different compounds and put in contact with extracellular DNA or with human peripheral whole blood, to compare their binding to DNA versus blood elements in vitro. Clinical-grade MT devices were coated with two selected compounds and evaluated in functional bench tests to study clot retrieval efficacy and quantify distal emboli using an M1 occlusion model., Results: Binding properties of samples coated with all compounds were increased for DNA (≈3-fold) and decreased (≈5-fold) for blood elements, as compared with the bare alloy samples in vitro. Functional testing showed that surface modification with DNA-binding compounds improved clot retrieval and significantly reduced distal emboli during experimental MT of large vessel occlusion in a three-dimensional model., Conclusion: Our results suggest that clot retrieval devices coated with DNA-binding compounds can considerably improve the outcome of the MT procedures in stroke patients., Competing Interests: Competing interests: CS salary is supported by a grant from the French National Research Agency (ANR). GC received research support from the French National Research Agency (ANR) and from the incubator Cardiovascular Lab. CS, GC, MA and AN are the inventors of a pending patent related to this work (WO2021EP64257). GC and AN are the scientific co-founders of a company related to this work (KAPTO Medical). MJG: 1. Consultant on a fee-per-hour basis for Alembic LLC, Astrocyte Pharmaceuticals, BendIt Technologies, Cerenovus, Imperative Care, Jacob’s Institute, Medtronic Neurovascular, Mivi Neurosciences, phenox GMbH, Q’Apel, Route 92 Medical, Scientia, Stryker Neurovascular, Stryker Sustainability Solutions, Wallaby Medical; holds stock in Imperative Care, InNeuroCo, Galaxy Therapeutics, Neurogami, and Synchron; 2. Research support from the NIH, the United States–Israel Binational Science Foundation, Anaconda, ApicBio, Arsenal Medical, Axovant, Balt, Cerenovus, Ceretrieve, CereVasc LLC, Cook Medical, Galaxy Therapeutics, Gentuity, Gilbert Foundation, Imperative Care, InNeuroCo, Insera, Jacob’s Institute, Magneto, MicroBot, Microvention, Medtronic Neurovascular, MIVI Neurosciences, Naglreiter MDDO, Neurogami, Philips Healthcare, Progressive Medical, Pulse Medical, Rapid Medical, Route 92 Medical, Scientia, Stryker Neurovascular, Syntheon, ThrombX Medical, Wallaby Medical, the Wyss Institute and Xtract Medical; 3. Associate Editor of Basic Science on the JNIS Editorial Board. MM owns shares of the company Nobil Bio Ricerche srl. GI are employees of Nobil Bio Ricerche srl., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Preclinical testing of intracranial stents is currently performed in the peripheral circulation, and rarely in the basilar artery of the dog., Objective: To test the feasibility of intracranial stenting in the middle cerebral artery (MCA) of the dog and explore the use of MRI to detect thromboembolic complications., Methods: Six purpose-bred cross-hound dogs were used for proof-of-concept stenting of both MCAs in each animal. Immediately following the procedure, the animals were imaged with MRI. MRI was repeated weekly for 1 month. After the final angiography at 30 days, the animals were euthanized for pathological assessment of the stents and the brain., Results: We successfully deployed 12 stents in the MCAs of all animals. We deployed three techniques for microcatheterization of the MCA-namely, directly through the internal carotid artery (ICA), using anastomotic arteries from the external carotid artery, or via the contralateral ICA through the anterior communicating artery. Two iatrogenic perforations of the ICA with formation of an arteriovenous fistula occurred, without clinical sequelae, which spontaneously resolved on follow-up. All animals tolerated the procedure and completed the follow-up surveillance. MRI revealed procedural thromboembolic induced areas of restricted diffusion, and only one instance of a delayed thromboembolic lesion during surveillance. At follow-up angiography, the devices were all patent., Conclusion: We describe a new preclinical model of intracranial stenting in the MCA. Such a model may prove useful for evaluating new surface modifications., Competing Interests: Competing interests: MJG: 1. Consultant on a fee-per-hour basis for Alembic LLC, Astrocyte Pharmaceuticals, BendIt Technologies, Cerenovus, Imperative Care, Jacob’s Institute, Medtronic Neurovascular, Mivi Neurosciences, phenox GMbH, Q’Apel, Route 92 Medical, Scientia, Stryker Neurovascular, Stryker Sustainability Solutions, Wallaby Medical; holds stock in Imperative Care, InNeuroCo, Galaxy Therapeutics and Neurogami; 2. Research support from the NIH, the United States – Israel Binational Science Foundation, Anaconda, ApicBio, Arsenal Medical, Axovant, Balt, Cerenovus, Ceretrieve, CereVasc LLC, Cook Medical, Galaxy Therapeutics, Gentuity, Gilbert Foundation, Imperative Care, InNeuroCo, Insera, Jacob’s Institute, Magneto, MicroBot, Microvention, Medtronic Neurovascular, MIVI Neurosciences, Naglreiter MDDO, Neurogami, Philips Healthcare, Progressive Medical, Pulse Medical, Rapid Medical, Route 92 Medical, Scientia, Stryker Neurovascular, Syntheon, ThrombX Medical, Wallaby Medical, the Wyss Institute and Xtract Medical; 3. Associate editor of basic science on the JNIS editorial board. RV: grants from the NIH, Leducq Foundation, 4C Medical, 4Tech, Abbott Vascular, Ablative Solutions, Absorption Systems, Advanced NanoTherapies, Aerwave Medical Inc, Alivas, Amgen Inc, Asahi Medical, Aurios Medical, Avantec Vascular, BD Bioscences, Biosensors, Biotronik, Biotyx Medical, Bolt Medical Inc, Boston Scientific, Canon Inc, Cardiac Implants LLC, Cardiawave, CardioMech, Cardionomic, CeloNova BioSciences Inc, Cerus Endovascular Inc, Chansu Vascular Technologies LLC, Children’s National Medical Center, Concept Medical, Cook Medical, Cooper Health, Cormaze Technologies GmbH, CRL/AccelLab, CroíValve, CSI, DexCom Inc, Edwards Lifesciences, Elucid Bioimaging, eLum Technologies Inc, Emboline Inc, Endotronix, Envision, Filterlex, Imperative Care Inc, Innovative Cardiovascular Solutions LLC, Intact Vascular Inc, Interface Biolgics, InterShunt Technologies Inc, Invatin Technologies, Lahav CRO, LimFlow, L & J Biosciences, Lutonix, Lyra Therapeutics Inc, Mayo Clinic, Maywell, MD Start, MedAlliance, Medanex Clinic, Medtronic plc, Mercator Limited, MicroPort, MicroVention, Neovasc Inc, Nephronyx Ltd, Nova Vascular, Nyra Medical, Occultech, Olympus Therapeutics, OhioHealth, OrbusNeich, Ossio, phenox Inc, Pi-Cardia, Polares Medical, PolyVascular, Profusa Inc, ProKidney LLC, Protembis, Pulse Biosciences Inc, Qool Therapeutics, Recombinetics, ReCor Medical Inc, Regencor Inc, Renata Medical, Restore Medical Ltd, Ripple Therapeutics, Rush University, Sanofi SA, Shockwave Medical, Sahajanand Medical Technologies Limited, SoundPipe, Spartan Micro, SpectraWAVE Inc, Surmodics Inc, Terumo Corporation, Jacobs Institute, Transmural Systems LLC, Transverse Medical Inc, TruLeaf Medical, University of California, San Francisco, University of Pennsylvania Medical Center, Vascudyne Inc, Vesper, Vetex Medical, WhiteSwell, WL Gore and Associates Inc, and Xeltis and personal fees from Abbott Vascular, Boston Scientific, CeloNova BioSciences Inc, OrbusNeich, Terumo Corporation, W. L. Gore and Associates Inc, Edwards Lifesciences, Cook Medical, CSI, ReCor Medical, Sino Medical Sciences Technology Inc, Surmodics Inc, Bard BD, Medtronic plc, and Xeltis outside the submitted work. ASP: 1. Consultant for Medtronic Neurovascular, Stryker NeurovascularBalt, Q’Apel Medical, Cerenovus, Microvention, Imperative Care, Agile, Merit, CereVasc and Arsenal Medical; 2. Research grants from NIH, Microvention, Cerenovus, Medtronic Neurovascular and Stryker Neurovascular; 3. Stockholder: InNeuroCo, Agile, Perfuze, Galaxy, and NTI. AHS: consulting fees: Amnis Therapeutics, Apellis Pharmaceuticals, Inc., Boston Scientific, Canon Medical Systems USA, Inc., Cardinal Health 200, LLC, Cerebrotech Medical Systems, Inc., Cerenovus, Cerevatech Medical, Inc., Cordis, Corindus, Inc., Endostream Medical, Ltd, Imperative Care, Integra, IRRAS AB, Medtronic, MicroVention, Minnetronix Neuro, Inc., Penumbra, Q’Apel Medical, Inc., Rapid Medical, Serenity Medical, Inc., Silk Road Medical, StimMed, LLC, Stryker Neurovascular, Three Rivers Medical, Inc., VasSol, Viz.ai, Inc., W.L. Gore and Associates. Leadership or fiduciary role in other board, society, committee or advocacy group: Past secretary of the board of the Society of NeuroInterventional Surgery (2020-2021), chair of the Cerebrovascular Section of the AANS/CNS. Stock or stock options: Adona Medical, Inc., Amnis Therapeutics, Bend IT Technologies, Ltd., BlinkTBI, Inc, Buffalo Technology Partners, Inc., Cardinal Consultants, LLC, Cerebrotech Medical Systems, Inc, Cerevatech Medical, Inc., Cognition Medical, CVAID Ltd., E8, Inc., Endostream Medical, Ltd, Imperative Care, Inc., Instylla, Inc., International Medical Distribution Partners, Launch NY, Inc., NeuroRadial Technologies, Inc., Neurotechnology Investors, Neurovascular Diagnostics, Inc., PerFlow Medical, Ltd., Q’Apel Medical, Inc., QAS.ai, Inc., Radical Catheter Technologies, Inc., Rebound Therapeutics Corp. (purchased 2019 by Integra Lifesciences, Corp), Rist Neurovascular, Inc. (purchased 2020 by Medtronic), Sense Diagnostics, Inc., Serenity Medical, Inc., Silk Road Medical, Adona Medical, Inc., Amnis Therapeutics, Bend IT Technologies, Ltd., BlinkTBI, Inc, Buffalo Technology Partners, Inc., Cardinal Consultants, LLC, Cerebrotech Medical Systems, Inc, Cerevatech Medical, Inc., Cognition Medical, CVAID Ltd., E8, Inc., Endostream Medical, Ltd, Imperative Care, Inc., Instylla, Inc., International Medical Distribution Partners, Launch NY, Inc., NeuroRadial Technologies, Inc., Neurotechnology Investors, Neurovascular Diagnostics, Inc., PerFlow Medical, Ltd., Q’Apel Medical, Inc., QAS.ai, Inc., Radical Catheter Technologies, Inc., Rebound Therapeutics Corp. (purchased 2019 by Integra Lifesciences, Corp), Rist Neurovascular, Inc. (Purchased 2020 by Medtronic), Sense Diagnostics, Inc., Serenity Medical, Inc., Silk Road Medical, SongBird Therapy, Spinnaker Medical, Inc., StimMed, LLC, Synchron, Inc., Three Rivers Medical, Inc., Truvic Medical, Inc., Tulavi Therapeutics, Inc., Vastrax, LLC, VICIS, Inc., Viseon, Inc. Other financial or non-financial interests: National PI/Steering Committees: Cerenovus EXCELLENT and ARISE II Trial; Medtronic SWIFT PRIME, VANTAGE, EMBOLISE and SWIFT DIRECT Trials; MicroVention FRED Trial and CONFIDENCE Study; MUSC POSITIVE Trial; Penumbra 3D Separator Trial, COMPASS Trial, INVEST Trial, MIVI neuroscience EVAQ Trial; Rapid Medical SUCCESS Trial; InspireMD C-GUARDIANS IDE Pivotal Trial., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: High-frequency optical coherence tomography (HF-OCT) is an intravascular imaging method that allows for volumetric imaging of flow diverters in vivo., Objective: To examine the hypothesis that a threshold for both volume and area of communicating malapposition can be predictive of early aneurysm occlusion., Methods: Fifty-two rabbits underwent elastase aneurysm formation, followed by treatment with a flow diverter. At the time of implant, HF-OCT was acquired to study the rate and degree of communicating malapposition. Treated aneurysms were allowed to heal for either 90 or 180 days and euthanized following catheter angiography. Healing was dichotomized into aneurysm remnant or neck remnant/complete occlusion. Communicating malapposition was measured by HF-OCT using a semi-automatic algorithm able to detect any points where the flow diverter was more than 50 µm from the vessel wall. This was then summed across image slices to either a volume or area. Finally, a subsampled population was used to train a statistical classifier for the larger dataset., Results: No difference in occlusion rate was found between device type or follow-up time (p=0.28 and p=0.67, respectively). Both volume and area of malapposition were significantly lower in aneurysms with a good outcome (p<0.001, both). From the statistical model, a volume of less than 0.56 mm 3 or a normalized area less than 0.69 as quantified by HF-OCT was predictive of occlusion (p<0.001, each)., Conclusions: HF-OCT allows for measurements of both volume and area of malapposition and, from these measurements, an accurate prediction for early aneurysm occlusion can be made., Competing Interests: Competing interests: ASP: consultant for Medtronic Neurovascular, Stryker Neurovascular, Balt, Q’Apel Medical, Cerenovus, Microvention, Imperative Care, Agile, Merit, CereVasc, and Arsenal Medical; research grants from NIH, Microvention, Cerenovus, Medtronic Neurovascular, and Stryker Neurovascular; holds stocks in InNeuroCo, Agile, Perfuze, Galaxy and NTI. JMA and HGD are employees of Stryker Neurovascular. GJU is an employee of Gentuity. MJG: has been a consultant on a fee-per-hour basis for Alembic LLC, Astrocyte Pharmaceuticals, BendIt Technologies, Cerenovus, Imperative Care, Jacob’s Institute, Medtronic Neurovascular, Mivi Neurosciences, phenox GMbH, Q’Apel, Route 92 Medical, Scientia, Stryker Neurovascular, Stryker Sustainability Solutions, Wallaby Medical; holds stock in Imperative Care, InNeuroCo, Galaxy Therapeutics and Neurogami; and has received research support from the National Institutes of Health (NIH), the United States – Israel Binational Science Foundation, Agile, Anaconda, ApicBio, Arsenal Medical, Axovant, Balt, Cerenovus, Ceretrieve, CereVasc LLC, Cook Medical, Galaxy Therapeutics, Gentuity, Gilbert Foundation, Imperative Care, InNeuroCo, Insera, Jacob’s Institute, Magneto, MicroBot, Microvention, Medtronic Neurovascular, MIVI Neurosciences, Naglreiter MDDO, Neurogami, Philips Healthcare, Progressive Medical, Pulse Medical, Rapid Medical, Route 92 Medical, Scientia, Stryker Neurovascular, Syntheon, ThrombX Medical, Wallaby Medical, the Wyss Institute and Xtract Medical. MJG is associate editor of Basic Science on the JNIS editorial board. MSS: has been a consultant on a fee-per-hour basis for Sanofi; and has research support from Sio Gene Therapies, Inozyme, the National Institutes of Health (NIH), Gilbert Foundation, and Massachusetts Life Science Center., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Diagnosing and treating acute ischemic stroke patients within a narrow timeframe is challenging. Time needed to access the occluded vessel and initiate thrombectomy is dictated by the availability of information regarding vascular anatomy and trajectory. Absence of such information potentially impacts device selection, procedure success, and stroke outcomes. While the cervical vessels allow neurointerventionalists to navigate devices to the occlusion site, procedures are often encumbered due to tortuous pathways. The purpose of this retrospective study was to determine how neurointerventionalists consider the physical nature of carotid segments when evaluating a procedure's difficulty., Methods: Seven neurointerventionalists reviewed 3D reconstructions of CT angiograms of left and right carotid arteries from 49 subjects and rated the perceived procedural difficulty on a three-point scale (easy, medium, difficult) to reach the targeted M1. Twenty-two vessel metrics were quantified by dividing the carotids into 5 segments and measuring the radius of curvature, tortuosity, vessel radius, and vessel length of each segment., Results: The tortuosity and length of the arch-cervical and cervical regions significantly impacted difficulty ratings. Additionally, two-way interaction between the radius of curvature and tortuosity on the arch-cervical region was significant (p < 0.0001) wherein, for example, at a given arch-cervical tortuosity, an increased radius of curvature reduced the perceived case difficulty., Conclusions: Examining the vessel metrics and providing detailed vascular data tailored to patient characteristics may result in better procedure preparation, facilitate faster vessel access time, and improve thrombectomy outcomes. Additionally, documenting these correlations can enhance device design to ensure they suitably function under various vessel conditions., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MSS: 1. Consultant on a fee-per-hour basis for Sanofi; 2. Research support from Massachusetts Life Science Center and the Breast Cancer Research Foundation. ASP: 1. Consultant for Medtronic Neurovascular, Stryker NeurovascularBalt, Q’Apel Medical, Cerenovus, Microvention, Imperative Care, Agile, Merit, CereVasc and Arsenal Medical; 2. Research grants from NIH, Microvention, Cerenovus, Medtronic Neurovascular and Stryker Neurovascular; 3. Stockholder: InNeuroCo, Agile, Perfuze, Galaxy and NTI. MJG: 1. Consultant on a fee-per-hour basis for Alembic LLC, Astrocyte Pharmaceuticals, BendIt Technologies, Cerenovus, Imperative Care, Jacob’s Institute, Medtronic Neurovascular, Mivi Neurosciences, phenox GMbH, Q’Apel, Route 92 Medical, Scientia, Stryker Neurovascular, Stryker Sustainability Solutions, Wallaby Medical; 2. holds stock in Imperative Care, InNeuroCo, Galaxy Therapeutics and Neurogami; 3. Research support from the NIH, the United States – Israel Binational Science Foundation, Anaconda, ApicBio, Arsenal Medical, Axovant, Balt, Cerenovus, Ceretrieve, CereVasc LLC, Cook Medical, Galaxy Therapeutics, Gentuity, Gilbert Foundation, Imperative Care, InNeuroCo, Insera, Jacob’s Institute, Magneto, MicroBot, Microvention, Medtronic Neurovascular, MIVI Neurosciences, Naglreiter MDDO, Neurogami, Philips Healthcare, Progressive Medical, Pulse Medical, Rapid Medical, Route 92 Medical, Scientia, Stryker Neurovascular, Syntheon, ThrombX Medical, Wallaby Medical, the Wyss Institute and Xtract Medical; 4. Associate Editor of Basic Science on the JNIS Editorial Board., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Super large-bore aspiration (SLBA) has shown high rates of complete clot ingestion., Objective: To report the initial clinical feasibility, safety, and efficacy of this novel SLBA insert combination-super large-bore ingestion of clot (SLIC) technique for stroke., Methods: We performed a retrospective review of three comprehensive stroke center databases. The SLIC technique entails a triaxial assembly of an 8 Fr 0.106″ Base Camp catheter, 0.088″ catheter extender (HiPoint), and an insert catheter (Tenzing 8) that completely consumes the inner diameter of the 0.088″ SLBA catheter. The HiPoint catheter is delivered over the Tenzing 8 to the face of the embolus, which is withdrawn, while aspirating through the Base Camp and HiPoint catheters as a single assembly., Results: Thirty-three consecutive patients with large vessel occlusion were treated with SLIC. The median age was 70 years (30-91) and 17 were male (51.5%). The median presenting National Institutes of Health Stroke Scale score and Alberta Stroke Program Early CT score was 21 (1-34) and 8 (5-10), respectively. There was 100% success in delivering the 0.088″ catheter to the site of the occlusion. The successful revascularization rate (modified Thrombolysis in Cerebral Infarction (mTICI) score ≥2B) was 100% within a single pass in most cases (82%). Final mTICI ≥2C was achieved in 94.1% of occlusions, with 73.5% mTICI 3 recanalization. The rate of first pass effect in achieving excellent reperfusion (mTICI ≥2C) was 70.5%. There were no adverse events or postprocedural symptomatic hemorrhages., Conclusions: Our initial experience with the SLIC technique resulted in achieving a first pass effect (mTICI ≥2C) in 70.5%. Navigation of the SLBA catheter extender over the Tenzing insert was successful and safe in this early experience., Competing Interests: Competing interests: FM, GMC, JS, ALK, VN, and VA declare no competing interest. GD: Has served as a paid consultant for Medtronic, Penumbra, Stryker, Cerenovus, Microvention, InNeuroCo, Route 92 Medical; has received honoraria for lectures from Medtronic, Penumbra, and Microvention; has served on the Data and Safety Monitoring Board (DSMB) for RIST, and is the treasurer of the Society of Neurointerventional Surgery (SNIS). RAH: Has received resesarch funding from the NIH, Interline Endowment, Microvention, Stryker and CNX; has received consulting fees from Medtronic, Balt, Stryker, Q’Apel, Codman, Cerenovus, Microvention, Imperative Care, Phenox, Rapid Medical; has participated on the DSMB or advisory boards for MICI, eLum, Three Rivers, Shape Medical; and is an investor/stockholder in InNeuroCo, Cerebrotech, eLum, Endostream, Three Rivers Medical Inc, Scientia, RisT, BlinkTBI, and Corindus. MJG: Has been a consultant on a fee-per-hour basis for Alembic LLC, Astrocyte Pharmaceuticals, BendIt Technologies, Cerenovus, Imperative Care, Jacob’s Institute, Medtronic Neurovascular, Mivi Neurosciences, phenox GMbH, Q’Apel, Route 92 Medical, Stryker Neurovascular, Wallaby Medical; holds stock in Imperative Care, InNeuroCo, Galaxy Therapeutics, and Neurogami; and has received research support from the National Institutes of Health (NIH), the United States – Israel Binational Science Foundation, Anaconda, ApicBio, Arsenal Medical, Axovant, Balt, Cerenovus, Ceretrieve, CereVasc LLC, Cook Medical, Galaxy Therapeutics, Gentuity, Gilbert Foundation, Imperative Care, InNeuroCo, Insera, Jacob’s Institute, Magneto, Microvention, Medtronic Neurovascular, MIVI Neurosciences, Naglreiter MDDO, Neurogami, Philips Healthcare, Progressive Medical, Pulse Medical, Rapid Medical, Route 92 Medical, Stryker Neurovascular, Syntheon, ThrombX Medical, Wallaby Medical, the Wyss Institute, and Xtract Medical. MJG is associate editor of basic science on the JNIS editorial board. ASP: consultant for Medtronic Neurovascular, Stryker NeurovascularBalt, Q’Apel Medical, Cerenovus, Microvention, Imperative Care, Agile, Merit, CereVasc, and Arsenal Medical; research grants from NIH, Microvention, Cerenovus, Medtronic Neurovascular, and Stryker Neurovascular; hold stocks in InNeuroCo, Agile, Perfuze, Galaxy and NTI., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

Objectives: Cell-free hemoglobin in the cerebrospinal fluid (CSF-Hb) may be one of the main drivers of secondary brain injury after aneurysmal subarachnoid hemorrhage (aSAH). Haptoglobin scavenging of CSF-Hb has been shown to mitigate cerebrovascular disruption. Using digital subtraction angiography (DSA) and blood oxygenation-level dependent cerebrovascular reactivity imaging (BOLD-CVR) the aim was to assess the acute toxic effect of CSF-Hb on cerebral blood flow and autoregulation, as well as to test the protective effects of haptoglobin., Methods: DSA imaging was performed in eight anesthetized and ventilated sheep (mean weight: 80.4 kg) at baseline, 15, 30, 45 and 60 minutes after infusion of hemoglobin (Hb) or co-infusion with haptoglobin (Hb:Haptoglobin) into the left lateral ventricle. Additionally, 10 ventilated sheep (mean weight: 79.8 kg) underwent BOLD-CVR imaging to assess the cerebrovascular reserve capacity., Results: DSA imaging did not show a difference in mean transit time or cerebral blood flow. Whole-brain BOLD-CVR compared to baseline decreased more in the Hb group after 15 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.01 vs -0.01 ± 0.02) and remained diminished compared to Hb:Haptoglobin group after 30 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.01 vs 0.0 ± 0.01), 45 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.01 vs 0.01 ± 0.02) and 60 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.02 vs 0.01 ± 0.01)., Conclusion: It is demonstrated that CSF-Hb toxicity leads to rapid cerebrovascular reactivity impairment, which is blunted by haptoglobin co-infusion. BOLD-CVR may therefore be further evaluated as a monitoring strategy for CSF-Hb toxicity after aSAH., Competing Interests: Declaration of Competing Interest MH and DJS are inventors on a patent application on the use of haptoglobin in aneurysmal subarachnoid hemorrhage (WO2020/234195). MH, DJS, RMB, and KA are inventors on a patent application on the use of hemopexin and haptoglobin in aneurysmal subarachnoid hemorrhage (PCT/EP2022/052203). Haptoglobin has been provided free of charge by CSL Behring in the framework of an Innosuisse collaboration with the University of Zurich., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The 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., Methods: In 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., Results: Of 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., Conclusion: We 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., Competing Interests: Competing interests: VA, ME, RMK, and AV declare no competing interest. GJU is an employee of Gentuity LLC. ASP: consultant for Medtronic Neurovascular and Stryker Neurovascular; research grants from Medtronic Neurovascular and Stryker Neurovascular. MJG has been a consultant on a fee-per-hour basis for Alembic LLC, Astrocyte Pharmaceuticals, BendIt Technologies, Cerenovus, Imperative Care, Jacob's Institute, Medtronic Neurovascular, Mivi Neurosciences, phenox GMbH, Q’Apel, Route 92 Medical, Stryker Neurovascular, Wallaby Medical; holds stock in Imperative Care, InNeuroCo, Galaxy Therapeutics and Neurogami; and has received research support from the Research support from the National Institutes of Health (NIH), the United States – Israel Binational Science Foundation, Anaconda, ApicBio, Arsenal Medical, Axovant, Balt, Cerenovus, Ceretrieve, CereVasc LLC, Cook Medical, Galaxy Therapeutics, Gentuity, Gilbert Foundation, Imperative Care, InNeuroCo, Insera, Jacob’s Institute, Magneto, Microvention, Medtronic Neurovascular, MIVI Neurosciences, Naglreiter MDDO, Neurogami, Philips Healthcare, Progressive Medical, Pulse Medical, Rapid Medical, Route 92 Medical, Stryker Neurovascular, Syntheon, ThrombX Medical, Wallaby Medical, the Wyss Institute and Xtract Medical. MJG is Associate Editor of Basic Science on the JNIS Editorial Board., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

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 <0.0001) and reduced the final normalized infarct volume as compared to controls (0.99 versus 0.88, control versus OMX-IS drug, P <0.0001). Among slow evolvers, OMX-IS treatment delayed infarct progression by approximately 45 minutes; however, this did not reach statistical significance ( 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.

Mechanical thrombectomy to treat large vessel occlusions (LVO) causing a stroke is one of the most effective treatments in medicine, with a number needed to treat to improve clinical outcomes as low as 2.6. As the name implies, it is a mechanical solution to a blocked artery and modeling these mechanics preclinically for device design, regulatory clearance and high-fidelity physician training made clinical applications possible. In vitro simulation of LVO is extensively used to characterize device performance in representative vascular anatomies with physiologically accurate hemodynamics. Embolus analogues, validated against clots extracted from patients, provide a realistic simulated use experience. In vitro experimentation produces quantitative results such as particle analysis of distal emboli generated during the procedure, as well as pressure and flow throughout the experiment. Animal modeling, used mostly for regulatory review, allows estimation of device safety. Other than one recent development, nearly all animal modeling does not incorporate the desired target organ, the brain, but rather is performed in the extracranial circulation. Computational modeling of the procedure remains at the earliest stages but represents an enormous opportunity to rapidly characterize and iterate new thrombectomy concepts as well as optimize procedure workflow. No preclinical model is a perfect surrogate; however, models available can answer important questions during device development and have to date been successful in delivering efficacious and safe devices producing excellent clinical outcomes. This review reflects on the developments of preclinical modeling of mechanical thrombectomy with particular focus on clinical translation, as well as articulate existing gaps requiring additional research., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Diagnosis of cerebrovascular disease includes vascular neuroimaging techniques such as computed tomography (CT) angiography, magnetic resonance (MR) angiography (with or without use of contrast agents) and catheter digital subtraction angiography (DSA). These techniques provide mostly information about the vessel lumen. Vessel wall imaging with MR seeks to characterize cerebrovascular pathology, but with resolution that is often insufficient for small lesions. Intravascular imaging techniques such as ultrasound and optical coherence tomography (OCT), used for over a decade in the peripheral circulation, is not amendable to routine deployment in the intracranial circulation due to vessel caliber and tortuosity. However, advances in OCT technology including the probe profile, stiffness and unique distal rotation solution, holds the promise for eventual translation of OCT into the clinical arena. As such, it is apropos to review this technology and present the rationale for utilization of OCT in the cerebrovasculature., (Copyright © 2021 IBRO. Published by Elsevier Ltd. All rights reserved.)