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Objective: The Woven EndoBridge (WEB) device was approved to treat wide-necked bifurcation aneurysms. The device is designed as an intrasaccular flow disruptor covering aneurysm widths up to 10 mm. Although prior studies combined all aneurysm sizes, it is known that aneurysms behave differently in response to endovascular treatment based on their size. Therefore, the authors' objective was to identify ideal middle cerebral artery (MCA) aneurysm width and neck sizes most suitable for WEB treatment., Methods: The WorldWideWEB consortium is a large multicenter retrospective database that analyzes intracranial aneurysms treated with the WEB device. In this study, all unruptured MCA bifurcation aneurysms with available measurements were included. Cutoff values based on aneurysm width and neck in relation to aneurysm occlusion status were measured using the receiver operating characteristic (ROC) curve. Propensity score matching (PSM) was then used to compare treatment outcomes between aneurysms smaller and larger than the cutoff value for both width and neck size., Results: The ideal cutoff values for MCA bifurcation aneurysm width and neck were 6.1 mm and 4.6 mm, respectively. On PSM, 87 matched pairs were compared based on width size (≤ 6.1 mm and > 6.1 mm), and 77 matched pairs were compared based on neck size (≤ 4.6 mm and > 4.6 mm). There was a significant difference in adequate aneurysm occlusion between aneurysms smaller and larger than those cutoff values for both widths (93% vs 76%, p = 0.0017) and neck sizes (90% vs 70%, p = 0.0026). The retreatment rate was also significantly higher for larger aneurysms in both parameters., Conclusions: This study shows that MCA bifurcation aneurysms ≤ 6.1 mm in width and ≤ 4.6 mm in neck size are significantly better candidates for WEB treatment, leading to improved occlusion status and reduced retreatment rate, which are important considerations when using WEB devices.

HIV disease remains prevalent in the United States and is particularly prevalent in sub-Saharan Africa. Recent investigations revealed that mitochondrial dysfunction in kidney contributes to HIV-associated nephropathy (HIVAN) in Tg26 transgenic mice. We hypothesized that nicotinamide adenine dinucleotide (NAD) deficiency contributes to energetic dysfunction and progressive tubular injury. We investigated metabolomic mechanisms of HIVAN tubulopathy. Tg26 and wild-type (WT) mice were treated with the farnesoid X receptor (FXR) agonist INT-747 or nicotinamide riboside (NR) from 6 to 12 wk of age. Multiomic approaches were used to characterize kidney tissue transcriptomes and metabolomes. Treatment with INT-747 or NR ameliorated kidney tubular injury, as shown by serum creatinine, the tubular injury marker urinary neutrophil-associated lipocalin, and tubular morphometry. Integrated analysis of metabolomic and transcriptomic measurements showed that NAD levels and production were globally downregulated in Tg26 mouse kidneys, especially nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD salvage pathway. Furthermore, NAD-dependent deacetylase sirtuin3 activity and mitochondrial oxidative phosphorylation activity were lower in ex vivo proximal tubules from Tg26 mouse kidneys compared with those of WT mice. Restoration of NAD levels in the kidney improved these abnormalities. These data suggest that NAD deficiency might be a treatable target for HIVAN. NEW & NOTEWORTHY The study describes a novel investigation that identified nicotinamide adenine dinucleotide (NAD) deficiency in a widely used HIV-associated nephropathy (HIVAN) transgenic mouse model. We show that INT-747, a farnesoid X receptor agonist, and nicotinamide riboside (NR), a precursor of nicotinamide, each ameliorated HIVAN tubulopathy. Multiomic analysis of mouse kidneys revealed that NAD deficiency was an upstream metabolomic mechanism contributing to HIVAN tubulopathy.

Introduction: High-resolution magnetic resonance imaging (HR-MRI) allows for detailed visualization of intracranial atherosclerotic plaques. Radiomics can be used as a tool for objective quantification of the plaque's characteristics. We analyzed the radiomics features (RFs) obtained from 7 T HR-MRI of patients with intracranial atherosclerotic disease (ICAD) to determine distinct characteristics of culprit and non-culprit plaques., Methods: Patients with stroke due to ICAD underwent HR-MRI. Culprit plaques in the vascular territory of the stroke were identified. Degree of stenosis, area degree of stenosis and plaque burden were calculated. A three-dimensional segmentation of the plaque was performed, and RFs were obtained. A machine learning model for prediction and identification of culprit plaques using significantly different RFs was evaluated., Results: The study included 33 patients with ICAD as stroke etiology. Univariate analysis revealed 24 RFs in pre-contrast MRI, 21 in post-contrast MRI, 13 RFs that were different between pre and post contrast MRIs. Additionally, six shape-based RFs significantly differed from culprit and non-culprit plaques. The random forest model achieved an accuracy rate of 81% (88% sensitivity and 75% specificity) in identifying culprit plaques in the independent testing dataset. This model successfully identified the culprit plaques in all patients during the testing phase., Discussion: Symptomatic plaques had a distinct signature RFs compared to other plaques within the same subject. A machine learning model built with RFs successfully identified the symptomatic atherosclerotic plaques in most cases. Radiomics is a promising tool for stratification of plaques in patients with ICAD.

HIV disease remains prevalent in the USA and chronic kidney disease remains a major cause of morbidity in HIV-1-positive patients. Host double-stranded RNA (dsRNA)-activated protein kinase (PKR) is a sensor for viral dsRNA, including HIV-1. We show that PKR inhibition by compound C16 ameliorates the HIV-associated nephropathy (HIVAN) kidney phenotype in the Tg26 transgenic mouse model, with reversal of mitochondrial dysfunction. Combined analysis of single-nucleus RNA-seq and bulk RNA-seq data revealed that oxidative phosphorylation was one of the most downregulated pathways and identified signal transducer and activator of transcription (STAT3) as a potential mediating factor. We identified in Tg26 mice a novel proximal tubular cell cluster enriched in mitochondrial transcripts. Podocytes showed high levels of HIV-1 gene expression and dysregulation of cytoskeleton-related genes, and these cells dedifferentiated. In injured proximal tubules, cell-cell interaction analysis indicated activation of the pro-fibrogenic PKR-STAT3-platelet-derived growth factor (PDGF)-D pathway. These findings suggest that PKR inhibition and mitochondrial rescue are potential novel therapeutic approaches for HIVAN., Competing Interests: TY, KL, AR, BS, KM, YI, YZ, SS, BJ, XY, XW, VT, PS, ML, KO, CW, JK No competing interests declared

Background: Endovascular treatment with the woven endobridge (WEB) device has been widely utilized for managing intracranial aneurysms. However, predicting the probability of achieving adequate occlusion (Raymond-Roy classification 1 or 2) remains challenging., Objective: Our study sought to develop and validate a predictive calculator for adequate occlusion using the WEB device via data from a large multi-institutional retrospective cohort., Methods: We used data from the WorldWide WEB Consortium, encompassing 356 patients from 30 centers across North America, South America, and Europe. Bivariate and multivariate regression analyses were performed on a variety of demographic and clinical factors, from which predictive factors were selected. Calibration and validation were conducted, with variance inflation factor (VIF) parameters checked for collinearity., Results: A total of 356 patients were included: 124 (34.8%) were male, 108 (30.3%) were elderly (≥65 years), and 118 (33.1%) were current smokers. Mean maximum aneurysm diameter was 7.09 mm (SD 2.71), with 112 (31.5%) having a daughter sac. In the multivariate regression, increasing aneurysm neck size (OR 0.706 [95% CI: 0.535-0.929], p  = 0.13) and partial aneurysm thrombosis (OR 0.135 [95% CI: 0.024-0.681], p  = 0.016) were found to be the only statistically significant variables associated with poorer likelihood of achieving occlusion. The predictive calculator shows a c -statistic of 0.744. Hosmer-Lemeshow goodness-of-fit test indicated a satisfactory model fit with a p -value of 0.431. The calculator is available at: https://neurodx.shinyapps.io/WEBDEVICE/., Conclusion: The predictive calculator offers a substantial contribution to the clinical toolkit for estimating the likelihood of adequate intracranial aneurysm occlusion by WEB device embolization., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The Woven EndoBridge (WEB) device is primarily used for treating wide-neck intracranial bifurcation aneurysms under 10 mm. Limited data exists on its efficacy for large aneurysms. We aim to assess angiographic and clinical outcomes of the WEB device in treating large versus small aneurysms. We conducted a retrospective review of the WorldWide WEB Consortium database, from 2011 to 2022, across 30 academic institutions globally. Propensity score matching (PSM) was employed to compare small and large aneurysms on baseline characteristics. A total of 898 patients were included. There was no significant difference observed in clinical presentations, smoking status, pretreatment mRS, presence of multiple aneurysms, bifurcation location, or prior treatment between the two groups. After PSM, 302 matched pairs showed significantly lower last follow-up adequate occlusion rates (81% vs 90%, p = 0.006) and higher retreatment rates (12% vs 3.6%, p < 0.001) in the large aneurysm group. These findings may inform treatment decisions and patient counseling. Future studies are needed to further explore this area., (© 2024. The Author(s).)

Background: Utilizing an endovascular rat glioma model, this study aimed to analyze the efficacy of intra-arterial (IA) carboplatin and bevacizumab delivery with blood-brain barrier breakdown (BBBB) for glioblastoma treatment., Methods: C6-glioma cells were stereotactically injected into the left frontal lobe of Wistar rats. Tumor growth was confirmed on day 8 via MRI. On day 9, a microcatheter was navigated under fluoroscopy from the left femoral artery to the left internal carotid artery. A volume of 2.25 mL of 25% mannitol was administered, followed by either 10 mg/kg of bevacizumab or 2.4 mg/kg of carboplatin. Serial MRI was obtained post-treatment to assess tumor response via analysis of tumor size and radiomics. Histology was analyzed after termination., Results: Control tumor rats and IA mannitol treated tumor rats had fatal tumor growths, with survival until 19.75±2.21 and 36.3±15.1 days, respectively. Carboplatin and bevacizumab treated rats lived >40 days, after which they were euthanized. From serial MRI and histology, IA carboplatin treated rats exhibited tumor regression and resolution by day 35. In IA bevacizumab treated rats, there was tumor regression near the basal ganglia of the brain, closer to the IA chemotherapy injection site, which had reorganized growth patterns. From MRI, 29 unique radiomic features were significantly different between control and treated tumors (notably for total energy and skewness), and treatment responders had a distinct, early manifesting radiomic profile., Conclusion: IA carboplatin and bevacizumab treatment resulted in varying degrees of tumor suppression, validating the first endovascular C6 glioma model as a reliable method to assess new IA therapies., Competing Interests: Competing interests: JL: Research Support: The Society of Vascular and Interventional Neurology Pilot Research Grant, and the Thomas F. Frawley MD Research Fellowship Award. BAS: None. AAB: None. S-SKC: None. BD: None. SB: None. BRL: None. VJ: None. EIL: Board Membership: Stryker, NeXtGen Biologics, MedX Health, Cognition Medical, EndoStream; Consultancy: Claret Medical, GLG Consulting, Guidepoint, Imperative Care, Medtronic, Rebound Therapeutics, StimMed; Employment: University at Buffalo Neurosurgery Inc; Expert Testimony: renders medical/legal opinions as an expert witness; Stock/Stock Options: NeXtGen Biologics, Cognition Medical, Rapid Medical, Claret Medical, Imperative Care, Rebound Therapeutics, StimMed. VMT: Financial Interest/Investor/Stock Options/Ownership: Neurovascular Diagnostics, Inc, QAS.ai, Inc. Grant Support: Brain Aneurysm Foundation, National Science Foundation Award No. 1746694, NIH NINDS award R43 NS115314-0, clinical and translational science institute grant from the national Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR001412 to the University at Buffalo. Consultant/Advisory Board: Canon Medical Systems America. AHS: Financial Interest/Investor/Stock Options/Ownership: 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, 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. Consultant/Advisory Board: National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR001412 to the University at Buffalo., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Despite the numerous studies evaluating the occlusion rates of aneurysms following WEB embolization, there are limited studies identifying predictors of occlusion. Our purpose was to identify predictors of aneurysm occlusion and the need for retreatment., Materials and Methods: This is a review of a prospectively maintained database across 30 academic institutions. We included patients with previously untreated cerebral aneurysms embolized using the WEB who had available intraprocedural data and long-term follow-up., Results: We studied 763 patients with a mean age of 59.9 (SD, 11.7) years. Complete aneurysm occlusion was observed in 212/726 (29.2%) cases, and contrast stasis was observed in 485/537 (90.3%) of nonoccluded aneurysms. At the final follow-up, complete occlusion was achieved in 497/763 (65.1%) patients, and retreatment was required for 56/763 (7.3%) patients. On multivariable analysis, history of smoking, maximal aneurysm diameter, and the presence of an aneurysm wall branch were negative predictors of complete occlusion (OR, 0.5, 0.8, and 0.4, respectively). Maximal aneurysm diameter, the presence of an aneurysm wall branch, posterior circulation location, and male sex increase the chances of retreatment (OR, 1.2, 3.8, 3.0, and 2.3 respectively). Intraprocedural occlusion resulted in a 3-fold increase in the long-term occlusion rate and a 5-fold decrease in the retreatment rate ( P < .001), offering a specificity of 87% and a positive predictive value of 85% for long-term occlusion., Conclusions: Intraprocedural occlusion can be used to predict the chance of long-term aneurysm occlusion and the need for retreatment after embolization with a WEB device. Smoking, aneurysm size, and the presence of an aneurysm wall branch are associated with decreased chances of successful treatment., (© 2024 by American Journal of Neuroradiology.)

Aneurysm wall enhancement (AWE) has the potential to be used as an imaging biomarker for the risk stratification of intracranial aneurysms (IAs). Radiomics provides a refined approach to quantify and further characterize AWE's textural features. This study examines the performance of AWE quantification combined with clinical information in detecting symptomatic IAs. Ninety patients harboring 104 IAs (29 symptomatic and 75 asymptomatic) underwent high-resolution magnetic resonance imaging (HR-MRI). The assessment of AWE was performed using two different methods: 3D-AWE mapping and composite radiomics-based score (RadScore). The dataset was split into training and testing subsets. The testing set was used to build two different nomograms using each modality of AWE assessment combined with patients' clinical information and aneurysm morphological data. Finally, each nomogram was evaluated on an independent testing set. A total of 22 radiomic features were significantly different between symptomatic and asymptomatic IAs. The 3D-AWE mapping nomogram achieved an area under the curve (AUC) of 0.77 (63% accuracy, 78% sensitivity, and 58% specificity). The RadScore nomogram exhibited a better performance, achieving an AUC of 0.83 (77% accuracy, 89% sensitivity, and 73% specificity). The comprehensive analysis of IAs with the quantification of AWE data through radiomic analysis, patient clinical information, and morphological aneurysm metrics achieves a high accuracy in detecting symptomatic IA status., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Transcriptomic profiling has emerged as a powerful tool for exploring the molecular landscape of ischemic stroke clots and providing insights into the pathophysiological mechanisms underlying stroke progression and recovery. In this study, we aimed to investigate the relationship between stroke clot transcriptomes and stroke thrombectomy outcome, as measured by early neurological improvement (ENI) 30 (i.e., a 30% reduction in NIHSS at 24 h post-thrombectomy)., Hypothesis: We hypothesized that there exist distinct clot gene expression patterns between good and poor neurological outcomes., Methods: Transcriptomic analysis of 32 stroke clots retrieved by mechanical thrombectomy was conducted. Transcriptome data of these clots were analyzed to identify differentially expressed genes (DEGs), defined as those with a log(fold-change) ≥ 1.5 and q < 0.05 between samples with good and poor early neurological outcomes. Gene ontology and bioinformatics analyses were performed on genes with p < 0.01 to identify enriched biological processes and Ingenuity Pathway Analysis canonical pathways. Moreover, AUC analysis assessed the predictive power of DEGs for 90-day function outcome (mRS ≤ 2) and cellular composition of clot was predicted using CIBERSORT. We also assessed whether differential enrichment of immune cell types could indicate patient survival., Results: A total of 41 DEGs were identified. Bioinformatics showed that enriched biological processes and pathways emphasized the chronic immune response and matrix metalloproteinase inhibition. Moreover, 25 of the DEGs were found to be significant predictors of 90-day mRS. These genes were indicative of monocytes enrichment and neutrophil depletion in patients with poorer outcomes., Conclusion: Our study revealed a distinct gene expression pattern and dysregulated biological pathways associated with ENI. This expression pattern was also predictive of long-term outcome, suggesting a biological link between those ENIs and 90-day mRS., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The treatment of intracranial aneurysms is dictated by its risk of rupture in the future. Several clinical and radiological risk factors for aneurysm rupture have been described and incorporated into prediction models. Despite the recent technological advancements in aneurysm imaging, linear length and visible irregularity with a bleb are the only radiological measure used in clinical prediction models. The purpose of this article is to summarize both the standard imaging techniques, including their limitations, and the advanced techniques being used experimentally to image aneurysms. It is expected that as our understanding of advanced techniques improves, and their ability to predict clinical events is demonstrated, they become an increasingly routine part of aneurysm assessment. It is important that neurovascular specialists understand the spectrum of imaging techniques available., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The Woven EndoBridge (WEB) device has been widely used to treat intracranial wide neck bifurcation aneurysms. Initial studies have demonstrated that approximately 90% of patients have same or improved long-term aneurysm occlusion after the initial 6-month follow up. The aim of this study is to assess the long-term follow-up in aneurysms that have achieved complete occlusion at 6 months. We also compared the predictive value of different imaging modalities used. This is an analysis of a prospectively maintained database across 13 academic institutions. We included patients with previously untreated cerebral aneurysms embolized using the WEB device who achieved complete occlusion at first follow-up and had available long-term follow-up. A total of 95 patients with a mean age of 61.6 ± 11.9 years were studied. The mean neck diameter and height were 3.9 ± 1.3 mm and 6.0 ± 1.8 mm, respectively. The mean time to first and last follow-up was 5.4 ± 1.8 and 14.1 ± 12.9 months, respectively. Out of all the aneurysms that were completely occluded at 6 months, 84 (90.3%) showed complete occlusion at the final follow-up, and 11(11.5%) patients did not achieve complete occlusion. The positive predictive value (PPV) of complete occlusion at first follow was 88.4%. Importantly, this did not differ between digital subtraction angiography (DSA), magnetic resonance angiography (MRA), or computed tomography angiography (CTA). This study underlines the importance of repeat imaging in patients treated with the WEB device even if complete occlusion is achieved short term. Follow-up can be performed using DSA, MRA or CTA with no difference in positive predictive value., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Assessing clot composition on prethrombectomy computed tomography (CT) imaging may help in stroke treatment planning. In this study we seek to use microCT imaging of fabricated blood clots to understand the relationship between CT radiographic signals and the biological makeup., Methods: Clots (n = 10) retrieved by mechanical thrombectomy (MT) were collected, and 6 clot analogs of varying RBC composition were made. We performed paired microCT and histological image analysis of all 16 clots using a ScanCo microCT 100 (4.9 µm resolution) and standard H&E staining (imaged at 40×). From these data types, first order statistic (FOS) radiomics were computed from microCT, and percent composition of RBCs (%RBC) was computed from histology. Polynomial and linear regression (LR) were used to build statistical models based on retrieved thrombus microCT and %RBC that were evaluated for their ability to predict the %RBC of clot analogs from mean HU. Correlation analyses of microCT FOS with composition were completed for both retrieved clots and analogs., Results: The LR model fits relating MT-retrieved clot %RBC with mean (R 2  = 0.625, p = 0.006) and standard deviation (R 2  = 0.564, p < 0.05) in HUs on microCT were significant. Similarly, LR models relating analog histological %RBC to analog protocol %RBC (R 2  = 0.915, p = 0.003) and mean HUs on microCT (R 2  = 0.872, p = 0.007) were also significant. When the LR model built using MT-retrieved clots was used to predict analog %RBC from mean HUs, significant correlation was observed between predictions and actual histological %RBC (R 2  = 0.852, p = 0.009). For retrieved clots, significant correlations were observed for energy and total energy with %RBC and %FP (|R| > 0.7, q < 0.01). Analogs further demonstrated significant correlation between FOS energy, total energy, variance and %WBC (|R| > 0.9, q < 0.01)., Conclusion: MicroCT can be used to build models that predict AIS clot composition from routine CT parameters and help us to better understand radiomic signatures associated with clot composition and first pass outcomes. In future work, such observations can be used to better infer clot composition and inform thrombectomy prognostics from pretreatment CTs., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background and Objectives: Histologic and transcriptomic analyses of retrieved stroke clots have identified features associated with patient outcomes. Previous studies have demonstrated the predictive capacity of histology or expression features in isolation. Few studies, however, have investigated how paired histologic image features and expression patterns from the retrieved clots can improve understanding of clot pathobiology and our ability to predict long-term prognosis. We hypothesized that computational models trained using clot histomics and mRNA expression can predict early neurological improvement (ENI) and 90-day functional outcome (modified Rankin Scale Score, mRS) better than models developed using histological composition or expression data alone., Methods: We performed paired histological and transcriptomic analysis of 32 stroke clots. ENI was defined as a delta-National Institutes of Health Stroke Score/Scale > 4, and a good long-term outcome was defined as mRS ≤2 at 90 days after procedure. Clots were H&E-stained and whole-slide imaged at 40×. An established digital pathology pipeline was used to extract 237 histomic features and to compute clot percent composition (%Comp). When dichotomized by either the ENI or mRS thresholds, differentially expressed genes were identified as those with absolute fold-change >1.5 and q < 0.05. Machine learning with recursive feature elimination (RFE) was used to select clot features and evaluate computational models for outcome prognostication., Results: For ENI, RFE identified 9 optimal histologic and transcriptomic features for the hybrid model, which achieved an accuracy of 90.8% (area under the curve [AUC] = 0.98 ± 0.08) in testing and outperformed models based on histomics (AUC = 0.94 ± 0.09), transcriptomics (AUC = 0.86 ± 0.16), or %Comp (AUC = 0.70 ± 0.15) alone. For mRS, RFE identified 7 optimal histomic and transcriptomic features for the hybrid model. This model achieved an accuracy of 93.7% (AUC = 0.94 ± 0.09) in testing, also outperforming models based on histomics (AUC = 0.90 ± 0.11), transcriptomics (AUC = 0.55 ± 0.27), or %Comp (AUC = 0.58 ± 0.16) alone., Conclusion: Hybrid models offer improved outcome prognostication for patients with stroke. Identified digital histology and mRNA signatures warrant further investigation as biomarkers of patient functional outcome after thrombectomy., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background: The Woven EndoBridge (WEB) devices have been used for treating wide neck bifurcation aneurysms (WNBAs) with several generational enhancements to improve clinical outcomes. The original device dual-layer (WEB DL) was replaced by a single-layer (WEB SL) device in 2013. This study aimed to compare the effectiveness and safety of these devices in managing intracranial aneurysms., Methods: A multicenter cohort study was conducted, and data from 1,289 patients with intracranial aneurysms treated with either the WEB SL or WEB DL devices were retrospectively analyzed. Propensity score matching was utilized to balance the baseline characteristics between the two groups. Outcomes assessed included immediate occlusion rate, complete occlusion at last follow-up, retreatment rate, device compaction, and aneurysmal rupture., Results: Before propensity score matching, patients treated with the WEB SL had a significantly higher rate of complete occlusion at the last follow-up and a lower rate of retreatment. After matching, there was no significant difference in immediate occlusion rate, retreatment rate, or device compaction between the WEB SL and DL groups. However, the SL group maintained a higher rate of complete occlusion at the final follow-up. Regression analysis showed that SL was associated with higher rates of complete occlusion (OR: 0.19; CI: 0.04 to 0.8, p = 0.029) and lower rates of retreatment (OR: 0.12; CI: 0 to 4.12, p = 0.23)., Conclusion: The WEB SL and DL devices demonstrated similar performances in immediate occlusion rates and retreatment requirements for intracranial aneurysms. The SL device showed a higher rate of complete occlusion at the final follow-up., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The Woven EndoBridge (WEB) device is frequently used for the treatment of intracranial aneurysms. Postoperative management, including the use of aspirin, varies among clinicians and institutions, but its impact on the outcomes of the WEB has not been thoroughly investigated., Methods: This was a retrospective, multicenter study involving 30 academic institutions in North America, South America, and Europe. Data from 1492 patients treated with the WEB device were included. Patients were categorized into two groups based on their postoperative use of aspirin (aspirin group: n=1124, non-aspirin group: n=368). Data points included patient demographics, aneurysm characteristics, procedural details, complications, and angiographic and functional outcomes. Propensity score matching (PSM) was applied to balance variables between the two groups., Results: Prior to PSM, the aspirin group exhibited significantly higher rates of modified Rankin scale (mRS) mRS 0-1 and mRS 0-2 (89.8% vs 73.4% and 94.1% vs 79.8%, p<0.001), lower rates of mortality (1.6% vs 8.6%, p<0.001), and higher major compaction rates (13.4% vs 7%, p<0.001). Post-PSM, the aspirin group showed significantly higher rates of retreatment (p=0.026) and major compaction (p=0.037) while maintaining its higher rates of good functional outcomes and lower mortality rates. In the multivariable regression, aspirin was associated with higher rates of mRS 0-1 (OR 2.166; 95% CI 1.16 to 4, p=0.016) and mRS 0-2 (OR 2.817; 95% CI 1.36 to 5.88, p=0.005) and lower rates of mortality (OR 0.228; 95% CI 0.06 to 0.83, p=0.025). However, it was associated with higher rates of retreatment (OR 2.471; 95% CI 1.11 to 5.51, p=0.027)., Conclusions: Aspirin use post-WEB treatment may lead to better functional outcomes and lower mortality but with higher retreatment rates. These insights are crucial for postoperative management after WEB procedures, but further studies are necessary for validation., 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: Embolization and stereotactic radiosurgery (SRS) have increasingly been used to treat complex arteriovenous malformations (AVMs). We studied outcomes of AVM patients treated through a multidisciplinary approach, examined the effect of embolization on SRS success, and analyzed predictors of treatment failure., Methods: We retrospectively reviewed a prospectively maintained database of patients with AVMs treated with Gamma Knife (Leksell) SRS over an 11-year period. Patients with incomplete medical records and follow-up <2 years were excluded. Demographics, clinical presentation, previous rupture history, angiographic nidus size, Spetzler-Martin (S-M) grade, adjunctive endovascular embolization and microsurgical resection, radiologic evidence of obliteration and hemorrhage, and clinical outcomes (modified Rankin Scale [mRS] scores) were recorded. Radiosurgery-related details including nidus volume and number of sessions and radiosurgery-, embolization-, and resection-associated complications were also recorded., Results: Eighty-three patients (mean age, 41.0 ± 21.3 years) were included. Mean reduction in AVM nidus target volume with endovascular embolization was 66.0 ± 19.7%. S-M grade reduction was achieved in 51.6% cases. Total obliteration after SRS was achieved in 56 AVMs (67.5%) after 2 years, and in 38 (86.4%) after 4 years. Two (2.4%) patients had rehemorrhage after SRS. Overall complication rate was 3.6%. Median angiographic follow-up was 55.5 months. Favorable outcomes (mRS = 0-2) were seen in 77.1%. SRS target volume was an independent predictor of treatment failure regardless of pre-SRS embolization., Conclusions: High AVM obliteration rates were achieved with judicious use of radiosurgery alone or with embolization. Embolization reduced target nidus volume by an average of 66%. SRS target volume was an independent predictor of treatment failure., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Biological interpretability of ischemic stroke clot imaging remains challenging., Objective: To carry out paired CT/micro-CT imaging of ischemic stroke clots retrieved by thrombectomy with the aim of identifying interpretable image features that are correlated among pretreatment image modalities and post-treatment histopathology., Methods: We performed multimodal CT imaging and histology for 10 stroke clots retrieved by mechanical thrombectomy. Clots were manually segmented from co-registered, pretreatment CT angiography (CTA) and non-contrast CT (NCCT). For the same cases, retrieved clots were iodine-stained, and imaged with a ScanCo micro-CT 100 (4.9 µm resolution). Afterwards, clots were subjected to histological processing (hematoxylin and eosin staining) and whole slide scanned (40X). Clot radiomic features (RFs) (n=93 per modality, 279 total) were extracted using PyRadiomics and histological composition was computed using Orbit Image Analysis. Correlation analysis was used to test associations between micro-CT and CTA (or NCCT) RFs as well as between RFs and histological composition. Statistical significance was considered at R≥0.65 and q<0.05., Results: From paired RF correlation analysis, we identified 23 scale-invariant RFs with significant correlation between micro-CT and CTA (18), and micro-CT and NCCT (5). Correlation of unpaired RFs identified 377 positively and 36 negatively correlated RFs between micro-CT and CTA, and 168 positively and 41 negatively correlated RFs between micro-CT and NCCT. Scale-invariant RFs computed from CTA and NCCT demonstrated significant correlation with red blood cell and fibrin-platelet components, while micro-CT RFs were found to be correlated with white blood cell percent composition., Conclusion: Multimodal CT, radiomic, and histological analysis of stroke clots can help to bridge the gap between pretreatment imaging and clot pathobiology., Competing Interests: Competing interests: AHS: Research funding: National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR001412 to the University at Buffalo. Consultant/Advisory Board: Cerenovus, Penumbra, Q’Apel Medical, Inc., Stryker Neurovascular. 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; MIVI neuroscience EVAQ Trial. Board membership: Secretary, Society of NeuroInterventional Surgery (SNIS) Board of Directors. Financial Interest/Investor/Stock Options/Ownership: Neurovascular Diagnostics, Inc., QAS.ai, Inc. VMT – Research funding: National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR001412 to the University at Buffalo. Financial Interest/Investor/Stock Options/Ownership: Neurovascular Diagnostics, Inc., QAS.ai, Inc., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Stiffened arteries are a pathology of atherosclerosis, hypertension, and coronary artery disease and a key risk factor for cardiovascular disease events. The increased stiffness of arteries triggers a phenotypic switch, hypermigration, and hyperproliferation of vascular smooth muscle cells (VSMCs), leading to neointimal hyperplasia and accelerated neointima formation. However, the mechanism underlying this trigger remains unknown. Our analyses of whole-transcriptome microarray data from mouse VSMCs cultured on stiff hydrogels simulating arterial pathology identified 623 genes that were significantly and differentially expressed (360 upregulated and 263 downregulated) relative to expression in VSMCs cultured on soft hydrogels. Functional enrichment and gene network analyses revealed that these stiffness-sensitive genes are linked to cell cycle progression and proliferation. Importantly, we found that survivin, an inhibitor of apoptosis protein, mediates stiffness-dependent cell cycle progression and proliferation as determined by gene network and pathway analyses, RT-qPCR, immunoblotting, and cell proliferation assays. Furthermore, we found that inhibition of cell cycle progression did not reduce survivin expression, suggesting that survivin functions as an upstream regulator of cell cycle progression and proliferation in response to ECM stiffness. Mechanistically, we found that the stiffness signal is mechanotransduced via the FAK-E2F1 signaling axis to regulate survivin expression, establishing a regulatory pathway for how the stiffness of the cellular microenvironment affects VSMC behaviors. Overall, our findings indicate that survivin is necessary for VSMC cycling and proliferation and plays a role in regulating stiffness-responsive phenotypes., Competing Interests: The authors have no conflicts to disclose., (© 2023 Author(s).)

Objective: The Woven EndoBridge (WEB) device is an intrasaccular flow disruptor designed for wide-necked bifurcation aneurysms. These aneurysms may require the use of a concomitant stent. The objective of this study was to determine the clinical and radiological outcomes of patients undergoing stent-assisted WEB treatment. In addition, the authors also sought to determine the predictors of a concomitant stent in aneurysms treated with the WEB device., Methods: The data for this study were taken from the WorldWideWEB Consortium, an international multicenter cohort including patients treated with the WEB device. Aneurysms were classified into two groups based on treatment: stent-assisted WEB and WEB device alone. The authors compared clinical and radiological outcomes of both groups. Univariable and multivariable binary logistic regression analyses were performed to determine factors that predispose to stent use., Results: The study included 691 intracranial aneurysms (31 with stents and 660 without stents) treated with the WEB device. The adequate occlusion status did not differ between the two groups at the latest follow-up (83.3% vs 85.6%, p = 0.915). Patients who underwent stenting had more thromboembolic (32.3% vs 6.5%, p < 0.001) and procedural (16.1% vs 3.0%, p < 0.001) complications. Aneurysms treated with a concomitant stent had wider necks, greater heights, and lower dome-to-neck ratios. Increasing neck size was the only significant predictor for stent use., Conclusions: This study demonstrates that there is no difference in the degree of aneurysm occlusion between the two groups; however, complications were more frequent in the stent group. In addition, a wider aneurysm neck predisposes to stent assistance in WEB-treated aneurysms.

Background: The Woven EndoBridge (WEB) device is a novel intrasaccular flow disruptor tailored for bifurcation aneurysms. We aim to describe the degree of aneurysm occlusion at the latest follow-up, and the rate of complications of aneurysms treated with the WEB device stratified according to rupture status., Methods: Our data were taken from the WorldWideWeb Consortium, an international multicenter cohort including patients treated with the WEB device. Aneurysms were classified into two groups: ruptured and unruptured. We compared clinical and radiologic outcomes of both groups. Propensity score matching (PSM) was done to match according to age, gender, bifurcation, location, prior treatment, neck, height, dome width, daughter sac, incorporated branch, pretreatment antiplatelets, and last imaging follow-up., Results: The study included 676 patients with 691 intracranial aneurysms (529 unruptured and 162 ruptured) treated with the WEB device. The PSM analysis had 55 pairs. In both the unmatched (85.8% vs 84.3%, p=0.692) and matched (94.4% vs 83.3%, p=0.066) cohorts there was no significant difference in the adequate occlusion rate at the last follow-up. Likewise, there were no significant differences in both ischemic and hemorrhagic complications between the two groups. There was no documented aneurysm rebleeding after WEB device implantation., Conclusion: There was no significant difference in both the radiologic outcomes and complications between unruptured and ruptured aneurysms. Our findings support the feasibility of treatment of ruptured aneurysms with the WEB device., Competing Interests: Competing interests: JDBD: Honoraria from Medtronic. Travel grant from Microvention. MD: No relevant relationships NA: No relevant relationships RWR: Grants from National Institutes of Health, Heitman foundation, Society of vascular and interventional neurology; Advisory board participation for Rapid medical; Site PI for Microvention and Penumbra JEV: No relevant relationships AG : No relevant relationships SVL: No relevant relationships LR: No relevant relationships AAB: No relevant relationships ES: No relevant relationships KP: No relevant relationships KEL: No relevant relationships GS : No relevant relationships MAM: No relevant relationships IL: No relevant relationships PMR: No relevant relationships JAV: Fees from MicroVention for proctoring cases for new physician users of the Woven EndoBridge device; Medtronic travel expense VŽ: Participation on the data safety monitoring board or advisory board for KBC Sestre Milosrdnice, Zagreb / OB Nova Gradiška MUH: No relevant relationships CR: No relevant relationships HR: No relevant relationships VMT: No relevant relationships SM: No relevant relationships SG: No relevant relationships PH: No relevant relationships NA: No relevant relationships JDR: No relevant relationships YR: No relevant relationships CMS: No relevant relationships OG: No relevant relationships MP: No relevant relationships ALK: No relevant relationships CM: No relevant relationships SE: No relevant relationships RMS: Supported by the NREF, Joe Niekro Foundation, Brain Aneurysm Foundation, Bee Foundation, and the National Institutes of Health (R01NS111119-01A1, UL1TR002736, and KL2TR002737) through the Miami Clinical and Translational Science Institute, from the National Center for Advancing Translational Sciences and the National Institute on Minority Health and Health Disparities. AH: Consulting or speaker fees from Medtronic, MicroVention, Stryker, Penumbra, Cerenovus, Genentech, GE Healthcare, Scientia, Balt, Viz.ai, Insera Therapeutics, Proximie, NeuroVasc, NovaSignal, Vesalio, and Galaxy Therapeutics. AS: No relevant relationships AN: No relevant relationships JJ: Consulting and speaker fees from Cerenovus MP: No relevant relationships JS: No relevant relationships CPF: No relevant relationships MBB: No relevant relationships MM: Grants from Balt, Medtronic, MicroVention, and Stryker. MMS: No relevant relationships JB: No relevant relationships BTJ: No relevant relationships RAD: No relevant relationships TH: No relevant relationships RT: Medtronic Stocks CU: No relevant relationships BL : No relevant relationships PP: No relevant relationships ASP: Grants from NIH, Microvention, Cerenovus, Medtronic and Stryker; Consulting fees from Neurovascular, Stryker NeurovascularBalt, Q’Apel Medical, Cerenovus, Microvention, Imperative Care, Agile, Merit, CereVasc and Arsenal Medical; stock options from InNeuroCo, Agile, Perfuze, Galaxy and NTI GP: No relevant relationships CJG: Grants to institution from Medtronic and Penumbra; consulting fees from Stryker and MicroVention. HA: Proctoring fees from MicroVention. Grants to institution from the National Institutes of Health; consulting fees from Amnis Therapeutics, Apellis Pharmaceuticals, Boston Scientific, Canon Medical Systems, Cardinal Health 200, Cerebrotech Medical Systems, Cerenovus, Cerevatech Medical, Cordis, Corindus, EndoStream Medical, Imperative Care, Integra, IRRAS, Medtronic, MicroVention, Minnetronix Neuro, Penumbra, Q’Apel Medical, Rapid Medical, Serenity Medical, Silk Road Medical, StimMed, Stryker Neurovascular, Three Rivers Medical, VasSol, Viz.ai, and W.L. Gore & Associates; payment for participation on the steering committees for the 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; stock or stock options in Adona Medical, Amnis Therapeutics, Bend IT Technologies, BlinkTBI, Buffalo Technology Partners, Cardinal Consultants, Cerebrotech Medical Systems, Cerevatech Medical, Cognition Medical, CVAID, E8, EndoStream Medical, Imperative Care, Instylla, International Medical Distribution Partners, Launch NY, NeuroRadial Technologies, Neurotechnology Investors, Neurovascular Diagnostics, Perflow Medical, Q’Apel Medical, QAS.ai, Radical Catheter Technologies, Rebound Therapeutics (purchased in 2019 by Integra Lifesciences), Rist Neurovascular (purchased in 2020 by Medtronic), Sense Diagnostics, Serenity Medical, Silk Road Medical, Songbird Therapy, Spinnaker Medical, StimMed, Synchron, Three Rivers Medical, Truvic Medical, Tulavi Therapeutics, Vastrax, VICIS, and Viseon AFD: Consulting fees from Cerenovus, Penumbra, Medtronic, Stryker, Oculus, and Koswire. No relevant relationships RD: No relevant relationships PK: No relevant relationships. VK: No relevant relationships. PL: No relevant relationships SB: No relevant relationships CJS: Participation on the data safety monitoring board or advisory board for Zoll Circulation JK: No relevant relationships PJ: No relevant relationships ST: No relevant relationships FC: No relevant relationships NL: Honoraria for lectures from Cerenovus, Stryker, and CrossMed. MAA: Funding to institution from MicroVention for WEBIT trial; proctoring fees from MicroVention. HHC: No relevant relationships CC: Consulting fees from MicroVention, Stryker, Medtronic, MIVI, and Cerenovus. ABP: Grant to institution from Medtronic; consulting fees from MicroVention, Medtronic, and Q’Apel; workstation for research from Siemens AAD: No relevant relationships, (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Determining stroke etiology is crucial for secondary prevention, but intensive workups fail to classify ~30% of strokes that are cryptogenic., Objective: To examine the hypothesis that the transcriptomic profiles of clots retrieved during mechanical thrombectomy are unique to strokes of different subtypes., Methods: We isolated RNA from the clots of 73 patients undergoing mechanical thrombectomy. Samples of sufficient quality were subjected to 100-cycle, paired-end RNAseq, and transcriptomes with less than 10 million unique reads were excluded from analysis. Significant differentially expressed genes (DEGs) between subtypes (defined by the Trial of Org 10 172 in Acute Stroke Treatment) were identified by expression analysis in edgeR. Gene ontology enrichment analysis was used to study the biologic differences between stroke etiologies., Results: In all, 38 clot transcriptomes were analyzed; 6 from large artery atherosclerosis (LAA), 21 from cardioembolism (CE), 5 from strokes of other determined origin, and 6 from cryptogenic strokes. Among all comparisons, there were 816 unique DEGs, 174 of which were shared by at least two comparisons, and 20 of which were shared by all three. Gene ontology analysis showed that CE clots reflected high levels of inflammation, LAA clots had greater oxidoreduction and T-cell processes, and clots of other determined origin were enriched for aberrant platelet and hemoglobin-related processes. Principal component analysis indicated separation between these subtypes and showed cryptogenic samples clustered among several different groups., Conclusions: Expression profiles of stroke clots were identified between stroke etiologies and reflected different biologic responses. Cryptogenic thrombi may be related to multiple etiologies., Competing Interests: Competing interests: VMT: Financial Interest/Investor/Stock Options/Ownership: Neurovascular Diagnostics, Inc., QAS.ai, Inc. Grant Support: National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR001412 through the University at Buffalo, Cummings Foundation. SF: None. AC: None. TRP: None. AM: None. HHR: None. AAD: None. LDC: None. MW: None. EIL: None. KEP: None. AHS: Financial Interest/Investor/Stock Options/Ownership: Neurovascular Diagnostics, Inc., QAS.ai, Inc. Consultant/Advisory Board: Cerenovus, Penumbra, Q’Apel Medical, Inc., Stryker Neurovascular. National PI/Steering Committees: Cerenovus EXCELLENT and ARISE II Trial; Medtronic SWIFT PRIME, VANTAGE, EMBOLISE and SWIFT DIRECT Trials; MicroVention FRED Trial & CONFIDENCE Study; MUSC POSITIVE Trial; Penumbra 3D Separator Trial, COMPASS Trial; MIVI neuroscience EVAQ Trial. Board membership: Secretary, Society of NeuroInterventional Surgery (SNIS) Board of Directors. Grant Support: National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR001412 through the University at Buffalo. Cummings Foundation., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Several studies have shown promising outcomes of the Woven EndoBridge (WEB) device for the treatment of wide-necked intracranial bifurcation aneurysms. This is a multicenter study attempts to explore the changes in trends and treatment outcomes over time for WEB embolization of intracranial aneurysms. The WorldWideWEB consortium is a retrospective multicenter collaboration of data from international centers spanning from January 2011 and June 2021, with no limitations on aneurysm location or rupture status. Both bifurcation and sidewall aneurysms were included. These patients were stratified based on treatment year into five treatment intervals: 2011-2015 (N = 66), 2016-2017 (N = 77), 2018 (N = 66), 2019 (N = 300), and 2020-2021 (N = 173). Patient characteristics and angiographic and clinical outcomes were compared between these time intervals. This study comprised 671 patients (median age 61.4 years; 71.2% female) with 682 intracranial aneurysms. Over time, we observed an increasing tendency to treat patients presenting with ruptured aneurysms and aneurysms with smaller neck, diameter, and dome widths. Furthermore, we observed a trend towards more off-label use of the WEB for sidewall aneurysms and increased adoption of transradial access for WEB deployment. Moreover, the proportion of patients with adequate WEB occlusion immediately and at last follow-up was significantly higher in more recent year cohorts, as well as lower rates of compaction and retreatment. Mortality and complications did not differ over time. This learning curve study suggests improved experience using the WEB for the treatment of intracranial aneurysms and has yielded higher rates of adequate occlusion over time., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Computed tomography angiography (CTA) is the most widely used imaging modality for intracranial aneurysm (IA) management, yet it remains inferior to digital subtraction angiography (DSA) for IA detection, particularly of small IAs in the cavernous carotid region. The authors evaluated a deep learning pipeline for segmentation of vessels and IAs from CTA using coregistered, segmented DSA images as ground truth., Methods: Using 50 paired CTA-DSA images, the authors trained (n = 27), validated (n = 3), and tested (n = 20) a deep learning model (3D DeepMedic) for cerebrovasculature segmentation from CTA. A landmark-based coregistration algorithm was used for registration and upsampling of CTA images to paired DSA images. Segmented vessels from the DSA were used as the ground truth. Accuracy of the model for vessel segmentation was evaluated using conventional metrics (dice similarity coefficient [DSC]) and vessel segmentation-specific metrics, like connectivity-area-length (CAL). On the test cases (20 IAs), 3 expert raters attempted to detect and segment IAs. For each rater, the authors recorded the rate of IA detection, and for detected IAs, raters segmented and calculated important IA morphology parameters to quantify the differences in IA segmentation by raters to segmentations by DeepMedic. The agreement between raters, DeepMedic, and ground truth was assessed using Krippendorf's alpha., Results: In testing, the DeepMedic model yielded a CAL of 0.971 ± 0.007 and a DSC of 0.868 ± 0.008. The model prediction delineated all IAs and resulted in average error rates of < 10% for all IA morphometrics. Conversely, average IA detection accuracy by the raters was 0.653 (undetected IAs were present to a significantly greater degree on the ICA, likely due to those in the cavernous region, and were significantly smaller). Error rates for IA morphometrics in rater-segmented cases were significantly higher than in DeepMedic-segmented cases, particularly for neck (p = 0.003) and surface area (p = 0.04). For IA morphology, agreement between the raters was acceptable for most metrics, except for the undulation index (α = 0.36) and the nonsphericity index (α = 0.69). Agreement between DeepMedic and ground truth was consistently higher compared with that between expert raters and ground truth., Conclusions: This CTA segmentation network (DeepMedic trained on DSA-segmented vessels) provides a high-fidelity solution for CTA vessel segmentation, particularly for vessels and IAs in the carotid cavernous region.

Background: The Woven EndoBridge (WEB) device has Food and Drug Administration approval for treatment of wide-necked intracranial bifurcation aneurysms. The WEB device has been shown to result in adequate occlusion in bifurcation aneurysms overall, but its usefulness in the individual bifurcation locations has been evaluated separately only in few case series, which were limited by small sample sizes., Objective: To compare angiographic and clinical outcomes after treatment of bifurcation aneurysms at various locations, including anterior communicating artery (AComA), anterior cerebral artery (ACA) bifurcation distal to AComA, basilar tip, internal carotid artery (ICA) bifurcation, and middle cerebral artery (MCA) bifurcation aneurysms using the WEB device., Methods: A retrospective cohort analysis was conducted at 22 academic institutions worldwide to compare treatment outcomes of patients with intracranial bifurcation aneurysms using the WEB device. Data include patient and aneurysm characteristics, procedural details, angiographic and functional outcomes, and complications., Results: A total of 572 aneurysms were included. MCA (36%), AComA (35.7%), and basilar tip (18.9%) aneurysms were most common. The rate of adequate aneurysm occlusion was significantly higher for basilar tip (91.6%) and ICA bifurcation (96.7%) aneurysms and lower for ACA bifurcation (71.4%) and AComA (80.6%) aneurysms (p=0.04)., Conclusion: To our knowledge, this is the most extensive study to date that compares the treatment of different intracranial bifurcation aneurysms using the WEB device. Basilar tip and ICA bifurcation aneurysms showed significantly higher rates of aneurysm occlusion than other locations., Competing Interests: Competing interests: The following authors serve on the editorial board of JNIS, JDBD, AG, AFD, FCA, and PK., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Several translational animal models have been described assessing intra-arterial (IA) treatments for malignant gliomas. We describe the first endovascular animal model that allows testing of IA drug delivery as a first-line treatment, which is difficult to do in actual patients. We report a unique protocol for vascular access and IA delivery in the rat model that, unlike prior reports, does not require direct puncture and opening of proximal cerebrovasculature which carries risk of ischemia in the animal brain post-delivery., Methods: Wistar rats underwent left femoral artery catherization with a Balt Magic 1.2F catheter or Marathon Flow directed 1.5F Microcatheter with an Asahi Chikai 0.008 micro-guidewire which was navigated to the left internal carotid artery under x-ray. 25% mannitol was administered to test blood brain barrier breakdown (BBBB). Additional rats were implanted with C6 glioma cells in the left frontal lobe. C6 Glioma-Implanted Rats (C6GRs) were monitored for overall survival and tumor growth. Tumor volumes from MRI images were calculated utilizing 3D slicer. Additional rats underwent femoral artery catheterization with Bevacizumab, carboplatin, or irinotecan injected into the left internal carotid artery to test feasibility and safety., Results: A successful endovascular access and BBBB protocol was established. BBBB was confirmed with positive Evans blue staining. 10 rats were successfully implanted with C6 gliomas with confirmed growths on MRI. Overall survival was 19.75 ± 2.21 days. 5 rats were utilized for the development of our femoral catheterization protocol and BBBB testing. With regards to IA chemotherapy dosage testing, control rats tolerated targeted 10 mg/kg of bevascizumab, 2.4 mg/kg of carboplatin, and 15 mg/kg of irinotecan IA ICA injections without any complications., Conclusions: We present the first endovascular IA rat glioma model that allows selective catheterization of the intracranial vasculature and assessment of IA therapies for gliomas without need for access and sacrifice of proximal cerebrovasculature.

Purpose: Radiomics features (RFs) extracted from CT images may provide valuable information on the biological structure of ischemic stroke blood clots and mechanical thrombectomy outcome. Here, we aimed to identify RFs predictive of thrombectomy outcomes and use clot histomics to explore the biology and structure related to these RFs., Methods: We extracted 293 RFs from co-registered non-contrast CT and CTA. RFs predictive of revascularization outcomes defined by first-pass effect (FPE, near to complete clot removal in one thrombectomy pass), were selected. We then trained and cross-validated a balanced logistic regression model fivefold, to assess the RFs in outcome prediction. On a subset of cases, we performed digital histopathology on the clots and computed 227 histomic features from their whole slide images as a means to interpret the biology behind significant RF., Results: We identified 6 significantly-associated RFs. RFs reflective of continuity in lower intensities, scattered higher intensities, and intensities with abrupt changes in texture were associated with successful revascularization outcome. For FPE prediction, the multi-variate model had high performance, with AUC = 0.832 ± 0.031 and accuracy = 0.760 ± 0.059 in training, and AUC = 0.787 ± 0.115 and accuracy = 0.787 ± 0.127 in cross-validation testing. Each of the 6 RFs was related to clot component organization in terms of red blood cell and fibrin/platelet distribution. Clots with more diversity of components, with varying sizes of red blood cells and fibrin/platelet regions in the section, were associated with RFs predictive of FPE., Conclusion: Upon future validation in larger datasets, clot RFs on CT imaging are potential candidate markers for FPE prediction., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Infarct volume measured from 2,3,5-triphenyltetrazolium chloride (TTC)-stained brain slices is critical to in vivo stroke models. In this study, we developed an interactive, tunable, software that automatically computes whole-brain infarct metrics from serial TTC-stained brain sections., Methods: Three rat ischemic stroke cohorts were used in this study (Total n  = 91 rats; Cohort 1 n  = 21, Cohort 2 n  = 40, Cohort 3 n  = 30). For each, brains were serially-sliced, stained with TTC and scanned on both anterior and posterior sides. Ground truth annotation and infarct morphometric analysis (e.g., brain-V brain , infarct-V infarct , and non-infarct-V non-infarct volumes) were completed by domain experts. We used Cohort 1 for brain and infarct segmentation model development ( n  = 3 training cases with 36 slices [18 anterior and posterior faces], n  = 18 testing cases with 218 slices [109 anterior and posterior faces]), as well as infarct morphometrics automation. The infarct quantification pipeline and pre-trained model were packaged as a standalone software and applied to Cohort 2, an internal validation dataset. Finally, software and model trainability were tested as a use-case with Cohort 3, a dataset from a separate institute., Results: Both high segmentation and statistically significant quantification performance (correlation between manual and software) were observed across all datasets. Segmentation performance: Cohort 1 brain accuracy = 0.95/f1-score = 0.90, infarct accuracy = 0.96/f1-score = 0.89; Cohort 2 brain accuracy = 0.97/f1-score = 0.90, infarct accuracy = 0.97/f1-score = 0.80; Cohort 3 brain accuracy = 0.96/f1-score = 0.92, infarct accuracy = 0.95/f1-score = 0.82. Infarct quantification (cohort average): V brain (ρ = 0.87, p  < 0.001), V infarct (0.92, p  < 0.001), V non-infarct (0.80, p  < 0.001), %infarct (0.87, p  = 0.001), and infarct:non-infact ratio (ρ = 0.92, p  < 0.001)., Conclusion: Tectonic Infarct Analysis software offers a robust and adaptable approach for rapid TTC-based stroke assessment., Competing Interests: The authors declare the following conflict of interests: BAS, S-SKC, SMMJS, TDJ, AAB, AM, CK, DP, LG, RMK, MG: None. AHS: Financial Interest/Investor/Stock Options/Ownership: 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., 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. Consultant/Advisory Board: 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, Rebound Therapeutics Corp., Serenity Medical, Inc., Silk Road Medical, StimMed, LLC, Stryker Neurovascular, Three Rivers Medical, Inc., VasSol, Viz.ai, Inc., W.L. Gore & Associates. National PI/Steering Committees: Cerenovus EXCELLENT and ARISE II Trial; Medtronic SWIFT PRIME, VANTAGE, EMBOLISE and SWIFT DIRECT Trials; MicroVention FRED Trial & 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. Board membership: Secretary, Society of NeuroInterventional Surgery (SNIS) Board of Directors. Grant Support: clinical and translational science institute grant from the national Center for Advancing Translational Sciences of the 10.13039/100000002National Institutes of Health under award number UL1TR001412 to the 10.13039/100008209University at Buffalo. VMT: Financial Interest/Investor/Stock Options/Ownership: Neurovascular Diagnostics, Inc., QAS.ai, Inc. Grant Support: 10.13039/100013490Brain Aneurysm Foundation, 10.13039/100000001National Science Foundation Award No. 1746694, 10.13039/100000002NIH 10.13039/100000065NINDS award R43 NS115314-0, clinical and translational science institute grant from the national Center for Advancing Translational Sciences of the 10.13039/100000002National Institutes of Health under award number UL1TR001412 to the 10.13039/100008209University at Buffalo., (©2023PublishedbyElsevierLtd.)

Background: Few studies have explored the association between stroke thrombectomy (ST) volume and hospital accreditation with clinical outcomes., Objective: To assess the association of ST case volume and accreditation status with in-hospital mortality and home discharge disposition using the national Medicare Provider Analysis and Review (MEDPAR) database., Methods: Rates of hospital mortality, home discharge disposition, and hospital stay were compared between accredited and non-accredited hospitals using 2017-2018 MEDPAR data. The association of annual ST case volume with mortality and home disposition was determined using Pearson's correlation. Median rate of mortality and number of ST cases at hospitals within the central quartiles were estimated., Results: A total of 29 355 cases were performed over 2 years at 847 US centers. Of these, 354 were accredited. There were no significant differences between accredited and non-accredited centers for hospital mortality (14.8% vs 14.5%, p=0.34) and home discharge (12.1% vs 12.0%, p=0.78). A significant positive correlation was observed between thrombectomy volume and home discharge (r=0.88; 95% CI 0.58 to 0.97, p=0.001). A significant negative relationship was found between thrombectomy volume and mortality (r=-0.86; 95% CI -0.97 to -0.49, p=0.002). Within the central quartiles, the median number of ST cases at hospitals with mortality was 24/year, and the median number of ST cases at hospitals with home discharge rate was 23/year., Conclusion: A higher volume of ST cases was associated with lower mortality and higher home discharge rate. No significant differences in mortality and discharge disposition were found between accredited and non-accredited hospitals., Competing Interests: Competing interests: Competing Interests: MW, VMT, JMC, VL, DP, TRP, AM: None. BRL: Neurosurgery Research and Education Foundation grant contribution to University at Buffalo Neurosurgery Department. MM: grant: NIHR21NS109575 (did not fund this study); consultant: Medtronic, Cerenovus; leadership or fiduciary role in other board, society, committee, or advocacy group; Assistant Editor: Technical Videos, JNIS Editorial Board; Stock options: BrainQ, Endostream, Serenity Medical, SynchronATR: Consulting agreement: Stryker, Cerenovus, MicroVentionJM: Grants/non-salary research support from Stryker, MicroVention, and Penumbra (PI on their trials); Consulting fees: Cerebrotech, Viseon, Endostream, Vastrax, RIST, Synchron, Viz.ai, Perflow, and CVAid; Payment or honoraria: Invited speaker at Barrow Neurological Institute Grand Rounds (March 2020); Leadership or fiduciary role in other board, society, committee or advocacy group: Associate Editor, Editorial Board JNIS, President-Elect, Board of Directors SNIS; Stock or stock options: Cerebrotech, Imperative Care, Endostream, Viseon, BlinkTBI, Myra Medical, Serenity, Vastrax, NTI, RIST, Viz.ai, Synchron, Radical, and Truvic.AST: Stock: Bend IT Technologies, Ltd., BlinkTBI, Inc, Cardinal Consultants, LLC, Cerebrotech Medical Systems, Inc, Endostream Medical, Ltd, Imperative Care, Inc., Instylla, Inc., Neurotechnology Investors, Q’Apel Medical, Inc., Radical Catheter Technologies, Inc., Rist Neurovascular, Inc. (Purchased 2020 by Medtronic), Serenity Medical, Inc., Spinnaker Medical, Inc., Synchron, Inc., Three Rivers Medical, Inc., Truvic Medical, Inc., Tulavi Therapeutics, Inc., Vastrax, LLC, VICIS, Inc., Viz AI; Consultant/Advisory Board: Cerebrotech Medical Systems, Inc., Endostream Medical, Ltd, Imperative Care, Medtronic, Serenity Medical, Inc., Three Rivers Medical, Inc., Viz.ai, Inc.; National PI/Steering Committees: COMPASS, POSITIVE, LARGE trialsKVS: Consulting Fees: Boston Scientific, Canon Medical Systems USA, Inc., MicroVention, Medtronic, Stryker Neurovascular. Payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational event: Canon Medical Systems USA Inc. Stock or stock options: Boston Scientific, Access Closure Inc, Niagara Gorge Medical.JMD: Consulting fees; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events; support for attending meetings and/or travel: Medtronic. Patents planned, issued, or pending: QAS.ai. Participation on a Data Safety Monitoring Board or Advisory Board: NIH NIHDS Strokenet. Stock or stock options: Synchron, Cerebrotech, QAS.aiEIL: Consulting fees: Claret Medical, GLG Consulting, Guidepoint Global, Imperial Care, Medtronic, Rebound, StimMed, Misionix, Mosiac, Clarion, IRRAS. Payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events: Medtronic; Payment for expert testimony: for rendering medical/legal opinions as an expert. Support for attending meetings and/or travel: Reimbursement for travel and food for some meetings with the CNS and ABNS. Stock or stock options: NeXtGen Biologics, RAPID Medical, Claret Medical, Cognition Medical, Imperative Care, Rebound Therapeutics, StimMed, Three Rivers Medical.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 & 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 & 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.)

After detection, identifying which intracranial aneurysms (IAs) will rupture is imperative. We hypothesized that RNA expression in circulating blood reflects IA growth rate as a surrogate of instability and rupture risk. To this end, we performed RNA sequencing on 66 blood samples from IA patients, for which we also calculated the predicted aneurysm trajectory (PAT), a metric quantifying an IA's future growth rate. We dichotomized dataset using the median PAT score into IAs that were either more stable and more likely to grow quickly. The dataset was then randomly divided into training ( n = 46) and testing cohorts ( n = 20). In training, differentially expressed protein-coding genes were identified as those with expression (TPM > 0.5) in at least 50% of the samples, a q -value < 0.05 (based on modified F-statistics with Benjamini-Hochberg correction), and an absolute fold-change ≥ 1.5. Ingenuity Pathway Analysis was used to construct networks of gene associations and to perform ontology term enrichment analysis. The MATLAB Classification Learner was then employed to assess modeling capability of the differentially expressed genes, using a 5-fold cross validation in training. Finally, the model was applied to the withheld, independent testing cohort ( n = 20) to assess its predictive ability. In all, we examined transcriptomes of 66 IA patients, of which 33 IAs were "growing" (PAT ≥ 4.6) and 33 were more "stable". After dividing dataset into training and testing, we identified 39 genes in training as differentially expressed (11 with decreased expression in "growing" and 28 with increased expression). Model genes largely reflected organismal injury and abnormalities and cell to cell signaling and interaction. Preliminary modeling using a subspace discriminant ensemble model achieved a training AUC of 0.85 and a testing AUC of 0.86. In conclusion, transcriptomic expression in circulating blood indeed can distinguish "growing" and "stable" IA cases. The predictive model constructed from these differentially expressed genes could be used to assess IA stability and rupture potential.

Background: Following detection, rupture risk assessment for intracranial aneurysms (IAs) is critical. Towards molecular prognostics, we hypothesized that circulating blood RNA expression profiles are associated with IA risk., Methods: We performed RNA sequencing on 68 blood samples from IA patients. Here, patients were categorized as either high or low risk by assessment of aneurysm size (≥ 5 mm = high risk) and Population, Hypertension, Age, Size, Earlier subarachnoid hemorrhage, Site (PHASES) score (≥ 1 = high risk). Modified F-statistics and Benjamini-Hochberg false discovery rate correction was performed on transcripts per million-normalized gene counts. Protein-coding genes expressed in ≥ 50% of samples with a q value < 0.05 and an absolute fold-change ≥ 2 were considered significantly differentially expressed. Bioinformatics in Ingenuity Pathway Analysis was performed to understand the biology of risk-associated expression profiles. Association was assessed between gene expression and risk via Pearson correlation analysis. Linear discriminant analysis models using significant genes were created and validated for classification of high-risk cases., Results: We analyzed transcriptomes of 68 IA patients. In these cases, 31 IAs were large (≥ 5 mm), while 26 IAs had a high PHASES score. Based on size, 36 genes associated with high-risk IAs, and two were correlated with the size measurement. Alternatively, based on PHASES score, 76 genes associated with high-risk cases, and nine of them showed significant correlation to the score. Similar ontological terms were associated with both gene profiles, which reflected inflammatory signaling and vascular remodeling. Prediction models based on size and PHASES stratification were able to correctly predict IA risk status, with > 80% testing accuracy for both., Conclusions: Here, we identified genes associated with IA risk, as quantified by common clinical metrics. Preliminary classification models demonstrated feasibility of assessing IA risk using whole blood expression., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Studying the relationship between hemodynamics and local intracranial aneurysm (IA) pathobiology can help us understand the natural history of IA. We characterized the relationship between the IA wall appearance, using intraoperative imaging, and the hemodynamics from CFD simulations., Methods: Three-dimensional geometries of 15 IAs were constructed and used for CFD. Two-dimensional intraoperative images were subjected to wall classification using a machine learning approach, after which the wall type was mapped onto the 3D surface. IA wall regions included thick (white), normal (purple-crimson), and thin/translucent (red) regions. IA-wide and local statistical analyses were performed to assess the relationship between hemodynamics and wall type., Results: Thin regions of the IA sac had significantly higher WSS, Normalized WSS, WSS Divergence and Transverse WSS, compared to both normal and thick regions. Thicker regions tended to co-locate with significantly higher RRT than thin regions. These trends were observed on a local scale as well. Regression analysis showed a significant positive correlation between WSS and thin regions and a significant negative correlation between WSSD and thick regions., Conclusion: Hemodynamic simulation results were associated with the intraoperatively observed IA wall type. We consistently found that elevated WSS and WSS Norm were associated with thin regions of the IA wall rather than thick and normal regions.

Background and Purpose: Flow diversion has gradually become a standard treatment for intracranial aneurysms of the anterior circulation. Recently, the off-label use of the flow diverters to treat posterior circulation aneurysms has also increased despite initial concerns of rupture and the suboptimal results. This study aimed to explore the change in complication rates and treatment outcomes across time for posterior circulation aneurysms treated using flow diversion and to further evaluate the mechanisms and variables that could potentially explain the change and outcomes., Materials and Methods: A retrospective review using a standardized data set at multiple international academic institutions was performed to identify patients with ruptured and unruptured posterior circulation aneurysms treated with flow diversion during a decade spanning January 2011 to January 2020. This period was then categorized into 4 intervals., Results: A total of 378 procedures were performed during the study period. Across time, there was an increasing tendency to treat more vertebral artery and fewer large vertebrobasilar aneurysms ( P = .05). Moreover, interventionalists have been increasingly using fewer overlapping flow diverters per aneurysm ( P = .07). There was a trend toward a decrease in the rate of thromboembolic complications from 15.8% in 2011-13 to 8.9% in 2018-19 ( P = .34)., Conclusions: This multicenter experience revealed a trend toward treating fewer basilar aneurysms, smaller aneurysms, and increased usage of a single flow diverter, leading to a decrease in the rate of thromboembolic and hemorrhagic complications., (© 2022 by American Journal of Neuroradiology.)

Introduction: Genome wide association studies (GWAS) have identified multiple regions that confer genetic risk for the polyarticular/oligoarticular forms of juvenile idiopathic arthritis (JIA). However, genome-wide scans do not identify the cells impacted by genetic polymorphisms on the risk haplotypes or the genes impacted by those variants. We have shown that genetic variants driving JIA risk are likely to affect both innate and adaptive immune functions. We provide additional evidence that JIA risk variants impact innate immunity., Materials and Methods: We queried publicly available H3K4me1/H3K27ac ChIP-seq data in CD14+ monocytes to determine whether the linkage disequilibrium (LD) blocks incorporating the SNPs that tag JIA risk loci showed enrichment for these epigenetic marks. We also queried monocyte/macrophage GROseq data, a functional readout of active enhancers. We defined the topologically associated domains (TADs) encompassing enhancers on the risk haplotypes and identified genes within those TADs expressed in monocytes. We performed ontology analyses of these genes to identify cellular processes that may be impacted by these variants. We also used whole blood RNAseq data from the Genotype-Tissue Expression (GTEx) data base to determine whether SNPs lying within monocyte GROseq peaks influence plausible target genes within the TADs encompassing the JIA risk haplotypes., Results: The LD blocks encompassing the JIA genetic risk regions were enriched for H3K4me1/H3K27ac ChIPseq peaks (p=0.00021 and p=0.022) when compared to genome background. Eleven and sixteen JIA were enriched for resting and activated macrophage GROseq peaks, respectively risk regions (p=0.04385 and p=0.00004). We identified 321 expressed genes within the TADs encompassing the JIA haplotypes in human monocytes. Ontological analysis of these genes showed enrichment for multiple immune functions. Finally, we found that SNPs lying within the GROseq peaks are strongly associated with expression levels of plausible target genes in human whole blood., Conclusions: These findings support the idea that both innate and adaptive immunity are impacted by JIA genetic risk variants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Crinzi, Haley, Poppenberg, Jiang, Tutino and Jarvis.)

Background The Woven EndoBridge (WEB) device was explicitly designed for wide-neck intracranial bifurcation aneurysms. Small-scale reports have evaluated the off-label use of WEB devices for the treatment of sidewall aneurysms, with promising outcomes. Purpose To compare the angiographic and clinical outcomes of the WEB device for the treatment of sidewall aneurysms compared with the treatment of bifurcation aneurysms. Materials and Methods A retrospective review of the WorldWideWEB Consortium, a synthesis of retrospective databases spanning from January 2011 to June 2021 at 22 academic institutions in North America, South America, and Europe, was performed to identify patients with intracranial aneurysms treated with the WEB device. Characteristics and outcomes were compared between bifurcation and sidewall aneurysms. Propensity score matching (PSM) was used to match by age, pretreatment ordinal modified Rankin Scale score, ruptured aneurysms, location of aneurysm, multiple aneurysms, prior treatment, neck, height, dome width, daughter sac, and incorporated branch. Results A total of 683 intracranial aneurysms were treated using the WEB device in 671 patients (median age, 61 years [IQR, 53-68 years]; male-to-female ratio, 1:2.5). Of those, 572 were bifurcation aneurysms and 111 were sidewall aneurysms. PSM was performed, resulting in 91 bifurcation and sidewall aneurysms pairs. No significant difference was observed in occlusion status at last follow-up, deployment success, or complication rates between the two groups. Conclusion No significantly different outcomes were observed following the off-label use of the Woven EndoBridge, or WEB, device for treatment of sidewall aneurysms compared with bifurcation aneurysms. The correct characterization of the sidewall aneurysm location, neck angle, and size is crucial for successful treatment and lower retreatment rate. © RSNA, 2022 See also the editorial by Hetts in this issue.

Background: The mechanisms and outcomes in coronavirus disease (COVID-19)-associated stroke are unique from those of non-COVID-19 stroke., Objective: To describe the efficacy and outcomes of acute revascularization of large vessel occlusion (LVO) in the setting of COVID-19 in an international cohort., Methods: We conducted an international multicenter retrospective study of consecutively admitted patients with COVID-19 with concomitant acute LVO across 50 comprehensive stroke centers. Our control group constituted historical controls of patients presenting with LVO and receiving a mechanical thrombectomy between January 2018 and December 2020., Results: The total cohort was 575 patients with acute LVO; 194 patients had COVID-19 while 381 patients did not. Patients in the COVID-19 group were younger (62.5 vs 71.2; P < .001) and lacked vascular risk factors (49, 25.3% vs 54, 14.2%; P = .001). Modified thrombolysis in cerebral infarction 3 revascularization was less common in the COVID-19 group (74, 39.2% vs 252, 67.2%; P < .001). Poor functional outcome at discharge (defined as modified Ranklin Scale 3-6) was more common in the COVID-19 group (150, 79.8% vs 132, 66.7%; P = .004). COVID-19 was independently associated with a lower likelihood of achieving modified thrombolysis in cerebral infarction 3 (odds ratio [OR]: 0.4, 95% CI: 0.2-0.7; P < .001) and unfavorable outcomes (OR: 2.5, 95% CI: 1.4-4.5; P = .002)., Conclusion: COVID-19 was an independent predictor of incomplete revascularization and poor outcomes in patients with stroke due to LVO. Patients with COVID-19 with LVO were younger, had fewer cerebrovascular risk factors, and suffered from higher morbidity/mortality rates., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Objective: The paradigm for intracranial aneurysm (IA) treatment is shifting toward a hybrid approach involving open and endovascular techniques. The authors chronicled the evolution of IA treatment by retrospectively examining a large series of IA cases treated by a single dual-trained neurosurgeon, focusing on evolving technology relative to the choice of treatment options, perioperative morbidity, and mortality., Methods: The aneurysm database at the authors' institution was searched to identify consecutive patients treated with endovascular or open microsurgical approaches by one neurosurgeon during an 18-year time span. Patients were included regardless of IA rupture status, location or morphology, or treatment modality. Data collected were baseline clinical characteristics, aneurysm size, treatment modality, operative complications, in-hospital mortality, and retreatment rate., Results: A total of 1858 patients with 2002 IA treatments were included in the study. Three-hundred fifty IAs (17.5%) were ruptured. Open microsurgery was performed in 504 aneurysms (25.2%) and endovascular surgery in 1498 (74.8%). Endovascular IA treatments trended toward a growing use of flow diversion during the last 11 years. In-hospital mortality was 1.7% overall, including 7.0% in ruptured and 0.5% in unruptured cases. The overall complication rate was 3.3%, including 3.4% for microsurgical cases and 3.3% for endovascular cases. The rate of retreatment was 3.6% after clipping and 10.7% for endovascular treatment., Conclusions: This study demonstrates complementary use of open and endovascular approaches for IA treatment. By customizing treatment to the patient, comparable rates of procedural complications, mortality, and retreatment were achieved for both endovascular and microsurgical approaches.

Background: The value of clot imaging in patients with emergent large vessel occlusion (ELVO) treated with thrombectomy is unknown., Methods: We performed retrospective analysis of clot imaging (clot density, perviousness, length, diameter, distance to the internal carotid artery (ICA) terminus and angle of interaction (AOI) between clot and the aspiration catheter) of consecutive cases of middle cerebral artery (MCA) occlusion and its association with first pass effect (FPE, TICI 2c-3 after a first attempt)., Results: Patients ( n  = 90 total) with FPE had shorter clot length (9.9 ± 4.5 mm vs. 11.7 ± 4.6 mm, P = 0.07), shorter distance from ICA terminus (11.0 ± 7.1 mm vs. 14.7 ± 9.8 mm, P = 0.048), higher perviousness (39.39 ± 29.5 vs 25.43 ± 17.6, P = 0.006) and larger AOI (153.6 ± 17.6 vs 140.3 ± 23.5, P = 0.004) compared to no-FPE patients. In multivariate analysis, distance from ICA terminus to clot ≤13.5 mm (odds ratio (OR) 11.05, 95% confidence interval (CI) 2.65-46.15, P = 0.001), clot length ≤9.9 mm (OR 7.34; 95% CI 1.8-29.96, P = 0.005), perviousness ≥ 19.9 (OR 2.54, 95% CI 0.84-7.6, P = 0.09) and AOI ≥ 137°^ (OR 6.8, 95% CI 1.55-29.8, P = 0.011) were independent predictors of FPE. The optimal cut off derived using Youden's index was 6.5. The area under the curve of a score predictive of FPE success was 0.816 (0.728-0.904, P < 0.001). In a validation cohort ( n  = 30), sensitivity, specificity, positive and negative predictive value of a score of 6-10 were 72.7%, 73.6%, 61.5% and 82.3%., Conclusions: Clot imaging predicts the likelihood of achieving FPE in patients with MCA ELVO treated with the aspiration-first approach.

Objective: The Pipeline Embolization Device (PED) has prompted a paradigm shift in the approach to posterior circulation aneurysms. The year 2021 marks a decade since FDA approval of this flow diverter, and during this time operators have adapted to its off-label uses. The authors examined whether case selection, practice trends, and patient outcomes have changed over this 10-year period., Methods: This study is a retrospective review of consecutive posterior circulation aneurysms managed with the PED at four academic institutions in the US between January 1, 2011, and January 1, 2021. Factors related to case selection, rates of aneurysm occlusion, or complications were identified and evaluated. Angiographic outcomes as well as thromboembolic and hemorrhagic complications were investigated., Results: This study included 117 patients (median age 60 years). At a median follow-up of 12 months, adequate occlusion (> 90%) was attained in 73.2% of aneurysms. Aneurysm occlusion rates were similar over the study interval. Thromboembolic and hemorrhagic complications were reported in 12.0% and 6.0% of the procedures, respectively. There was a nonsignificant trend toward a decline in the rate of thromboembolic (14.1% in 2011-2015 vs 9.4% in 2016-2021, p = 0.443) and hemorrhagic (9.4% in 2011-2015 vs 1.9% in 2016-2021, p = 0.089) complications., Conclusions: The authors observed a trend toward a decline in the rate of thromboembolic and hemorrhagic complications with improved operator experience in using the PED for posterior circulation aneurysms. The use of single-device PED flow diversion significantly increased, as did the tendency to treat smaller aneurysms and observe large unruptured fusiform/dolichoectatic lesions. These findings reflect changes attributable to evolving judgment with maturing experience in PED use.

Background: Optimal outcomes after large-vessel occlusion (LVO) stroke are highly dependent on prompt diagnosis, effective communication, and treatment, making LVO an attractive avenue for the application of artificial intelligence (AI), specifically machine learning (ML). Our objective is to conduct a systematic review to describe existing AI applications for LVO strokes, delineate its effectiveness, and identify areas for future AI applications in stroke treatment and prognostication., Methods: A systematic review was conducted by searching the PubMed, Embase, and Scopus databases. After deduplication, studies were screened by title and abstract. Full-text studies were screened for final inclusion based on prespecified inclusion and exclusion criteria. Relevant data were extracted from each study., Results: Of 11,512 resultant articles, 40 were included. Of 30 studies with reported ML algorithms, the most commonly used ML algorithms were convolutional neural networks in 10 (33.3%), support vector machines in 10 (33.0%), and random forests in 9 (30.0%). Studies examining triage favored direct transport to a stroke center and predicted improved outcomes. ML techniques proved vastly accurate in identifying LVO on computed tomography. Applications of AI to patient selection for thrombectomy are lacking, although some studies determine individual patient eligibility for endovascular treatment with high accuracy. ML algorithms have reasonable accuracy in predicting clinical and angiographic outcomes and associated factors., Conclusions: AI has shown promise in the diagnosis and triage of patients with acute stroke. However, the role of AI in the management and prognostication remains limited and warrants further research to help in decision support., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Genome-wide association studies (GWAS) have identified numerous stroke-associated SNPs. To understand how SNPs affect gene expression related to increased stroke risk, we studied epigenetic landscapes surrounding 26 common, validated stroke-associated loci. Methods: We mapped the SNPs to linkage disequilibrium (LD) blocks and examined H3K27ac, H3K4me1, H3K9ac, and H3K4me3 histone marks and transcription-factor binding-sites in pathologically relevant cell types (hematopoietic and vascular cells). Hi-C data were used to identify topologically associated domains (TADs) encompassing the LD blocks and overlapping genes. Results: Fibroblasts, smooth muscle, and endothelial cells showed significant enrichment for enhancer-associated marks within stroke-associated LD blocks. Genes within encompassing TADs reflected vessel homeostasis, cellular turnover, and enzymatic activity. Conclusions: Stroke-associated genetic variants confer risk predominantly through vascular cells rather than hematopoietic cell types.

Objective: Transradial access (TRA) is commonly utilized in neurointerventional procedures. This study compared the technical and clinical outcomes of the use of TRA versus those of transfemoral access (TFA) for intracranial aneurysm embolization with the Woven EndoBridge (WEB) device., Methods: This is a secondary analysis of the Worldwide WEB Consortium, which comprises multicenter data related to adult patients with intracranial aneurysms who were managed with the WEB device. These aneurysms were categorized into two groups: those who were treated with TRA or TFA. Patient and aneurysm characteristics and technical and clinical outcomes were compared between groups. Propensity score matching (PSM) was used to match groups according to the following baseline characteristics: age, sex, subarachnoid hemorrhage, aneurysm location, bifurcation aneurysm, aneurysm with incorporated branch, neck width, aspect ratio, dome width, and elapsed time since the last follow-up imaging evaluation., Results: This study included 682 intracranial aneurysms (median [interquartile range] age 61.3 [53.0-68.0] years), of which 561 were treated with TFA and 121 with TRA. PSM resulted in 65 matched pairs. After PSM, both groups had similar characteristics, angiographic and functional outcomes, and rates of retreatment, thromboembolic and hemorrhagic complications, and death. TFA was associated with longer procedure length (median 96.5 minutes vs 72.0 minutes, p = 0.006) and fluoroscopy time (28.2 minutes vs 24.8 minutes, p = 0.037) as compared with TRA. On the other hand, deployment issues were more common in those treated with TRA, but none resulted in permanent complications., Conclusions: TRA has comparable outcomes, with shorter procedure and fluoroscopy time, to TFA for aneurysm embolization with the WEB device.

Hemodynamics plays a key role in the natural history of intracranial aneurysms (IAs). However, studies exploring the association between aneurysmal hemodynamics and the biological and mechanical characteristics of the IA wall in humans are sparse. In this review, we survey the current body of literature, summarize the studies' methodologies and findings, and assess the degree of consensus among them. We used PubMed to perform a systematic review of studies that explored the association between hemodynamics and human IA wall features using different sources. We identified 28 publications characterizing aneurysmal flow and the IA wall: 4 using resected tissues, 17 using intraoperative images, and 7 using vessel wall magnetic resonance imaging (MRI). Based on correlation to IA tissue, higher flow conditions, such as high wall shear stress (WSS) with complex pattern and elevated pressure, were associated with degenerated walls and collagens with unphysiological orientation and faster synthesis. MRI studies strongly supported that low flow, characterized by low WSS and high blood residence time, was associated with thicker walls and post-contrast enhancement. While significant discrepancies were found among those utilized intraoperative images, they generally supported that thicker walls coexist at regions with prolonged residence time and that thinner regions are mainly exposed to higher pressure with complex WSS patterns. The current body of literature supports a theory of two general hemodynamic-biologic mechanisms for IA development. One, where low flow conditions are associated with thickening and atherosclerotic-like remodeling, and the other where high and impinging flow conditions are related to wall degeneration, thinning, and collagen remodeling., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)