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  Isolation and focal treatment of brain aneurysms using interfacial fluid trapping

  Khoury, Maria; Mekler, Tirosh; Epshtein, Mark; Kreinin, Yevgeniy; Korneyev, Dmitry; Abezgauz, Ludmila; Anagnostakou, Vania; Ramon, Guy Z; Sznitman, Josué; Gounis, Matthew J; et al. (2024-10-04)

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

  Fama, Rosemary; Sassoon, Stephanie A; Müller-Oehring, Eva M; Saranathan, Manojkumar; Pohl, Kilian M; Zahr, Natalie M; Pfefferbaum, Adolf; Sullivan, Edith V (2024-09-27)

  The thalamus, with its reciprocal connections to and from cortical, subcortical, and cerebellar regions, is a central active participant in multiple functional brain networks. Structural MRI studies measuring the entire thalamus without respect to its regional or nuclear divisions report volume shrinkage in diseases including HIV infection, alcohol use disorder (AUD), and their comorbidity (HIV+AUD). Here, we examined relations between thalamic subregions (anterior, ventral, medial, and posterior) and neuropsychological functions (attention/working memory, executive functioning, episodic memory, and motor skills). Volumes of thalamic subregions were derived from automatic segmentations of standard T1 weighted MRIs of 65 individuals with HIV, 189 with AUD, 80 with HIV+AUD comorbidity, and 141 healthy controls (CTRL). Total thalamic volume was smaller and cognitive and motor composite scores were lower in the three diagnostic groups relative to the CTRL group. The AUD and HIV+AUD groups had significantly smaller thalamic subregional volumes than the CTRL group. The HIV+AUD group had smaller anterior thalamic volume than the HIV-only group and smaller ventral thalamic volume than the AUD-only group. In the HIV+AUD group, memory scores correlated with anterior thalamic volumes, attention/working memory scores correlated with posterior and medial thalamic volumes, and motor skill scores correlated with posterior thalamic volumes. Exploratory analyses focused on the HIV+AUD group indicated that within the posterior thalamic region, the pulvinar and medial geniculate nuclei were related to attention/working memory scores, and the pulvinar was related to motor skills scores. This study is novel in locating volume deficits in specific thalamic subregions, in addition to the thalamus as a whole, in HIV, AUD, and their comorbidity and in identifying functional ramifications of these deficits. Taken together, this study highlights the relevance of thalamic subregional volume deficits to dissociable cognitive and motor processes.
• Neuroimaging Applications for the Delivery and Monitoring of Gene Therapy for Central Nervous System Diseases

  Daci, Rrita; Gray-Edwards, Heather L; Shazeeb, Mohammed Salman; Vardar, Zeynep; Vachha, Behroze; Cataltepe, Oguz I; Flotte, Terence R (2024-09-26)

  Neurological disease due to single gene defects represents a targetable entity for adeno-associated virus (AAV) mediated gene therapy. The delivery of AAV-mediated gene therapy to the brain is challenging, owing to the presence of the blood-brain barrier. Techniques in gene transfer, such as convection-enhanced intraparenchymal delivery and image-guided delivery to the cerebrospinal fluid (CSF) spaces of the brain has led the field into highly accurate delivery techniques, which provide correction of genetic defects in specific brain regions or more broadly. These techniques commonly use magnetic resonance imaging (MRI), computed tomography (CT), and fluoroscopic guidance. Even more, the neuroimaging changes evaluated by MRI, MR spectroscopy (MRS), diffusion tensor imaging (DTI), and functional MRI (fMRI) can serve as important biomarkers of therapy effect and overall disease progression. Here, we discuss the role of neuroimaging in delivering AAV vectors and monitoring the effect of gene therapy.
• What Program Directors Think About Resident Recruitment: Results of the 2023 Spring Survey of the Association of Program Directors in Radiology (APDR) Part I

  Garner, Hillary W; Slanetz, Priscilla J; Swanson, Jonathan O; Griffith, Brent D; DeBenedectis, Carolynn M; Gould, Jennifer E; Holm, Tara L; Retrouvey, Michele; Paladin, Angelisa M; Rozenshtein, Anna (2024-09-25)

  Rationale and objectives: The Association of Program Directors in Radiology (APDR) administers an annual survey to assess issues and experiences related to residency program management and education. Our purpose is to provide the response data from the 2023 survey and discuss its insights on the impact of COVID-19 on resident recruitment (Part I) and education (Part II), which can be used to facilitate planning and resource allocation for the evolving needs of programs and their leadership. In Part I, we consider the effects of ERAS preference signaling, the virtual interview format, and the potential of a universal interview release date. Materials and methods: An observational, cross-sectional study of the APDR membership was performed using a web-based survey consisting of 45 questions, 23 of which pertain to virtual recruitment and are discussed in Part I of a two-part survey analysis. All active APDR members (n = 393) were invited to participate in the survey. Results: The response rate was 32% (124 of 393). 83% reported that signaling increased the likelihood of an interview offer. 96% reported only offering virtual interviews; however, 59% intended to offer virtual-only interviews in the future. 53% would adhere to a universal interview release date but an additional 44% would do so depending on the agreed date, Results were tallied using Qualtrics software and qualitative responses were tabulated or summarized as comments. Conclusions: Virtual recruitment is expected to continue for many programs and most respondents would accept a universal interview release date. Preference signaling and geographic signaling are considered positive additions to the application process.
• What Program Directors Think About Resident Education: Results of the 2023 Spring Survey of the Association of Program Directors in Radiology (APDR) Part II

  Garner, Hillary W; Slanetz, Priscilla J; Swanson, Jonathan O; Griffith, Brent D; DeBenedectis, Carolynn M; Gould, Jennifer E; Holm, Tara L; Retrouvey, Michele; Paladin, Angelisa M; Rozenshtein, Anna (2024-09-25)

  Rationale and objectives: The Association of Program Directors in Radiology (APDR) administers an annual survey to assess issues and experiences related to residency program management and education. Response data from the 2023 survey provides insights on the impact of COVID-19 on resident recruitment (Part I) and education (Part II), which can be used to facilitate planning and resource allocation for the evolving needs of programs and their leadership. Materials and methods: An observational, cross-sectional study of the APDR membership was performed using a web-based survey consisting of 45 questions, 12 of which pertain to resident education in the post-pandemic era and are discussed in Part II of a two-part survey analysis. All active APDR members (n = 393) were invited to participate in the survey. Results: The response rate was 32% (124 of 393). Results were tallied using Qualtrics software and qualitative responses were tabulated or summarized as comments. Conclusions: The primary challenges to resident education are faculty burnout, rising case volumes, and remote instruction. However, most program leaders report that in-person readouts are much more common than remote readouts. The ability to offer both in-person and remote AIRP sessions is viewed positively. Most program leaders require Authorized User certification, although many do not think all residents need it. Assessment of procedural competence varies by the type of procedure and is similar to graduates' self-assessment of competence.
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  Exploring Deep Learning Applications using Ultrasound Single View Cines in Acute Gallbladder Pathologies: Preliminary results

  Ge, Connie; Jang, Junbong; Svrcek, Patrick; Fleming, Victoria; Kim, Young H (2024-09-20)

  Rationale and objectives: In this preliminary study, we aimed to develop a deep learning model using ultrasound single view cines that distinguishes between imaging of normal gallbladder, non-urgent cholelithiasis, and acute calculous cholecystitis requiring urgent intervention. Methods: Adult patients presenting to the emergency department between 2017-2022 with right-upper-quadrant pain were screened, and ultrasound single view cines of normal imaging, non-urgent cholelithiasis, and acute cholecystitis were included based on final clinical diagnosis. Longitudinal-view cines were de-identified and gallbladder pathology was annotated for model training. Cines were randomly sorted into training (70%), validation (10%), and testing (20%) sets and divided into 12-frame segments. The deep learning model classified cines as normal (all segments normal), cholelithiasis (normal and non-urgent cholelithiasis segments), and acute cholecystitis (any cholecystitis segment present). Results: A total of 186 patients with 266 cines were identified: Normal imaging (52 patients; 104 cines), non-urgent cholelithiasis (73;88), and acute cholecystitis (61;74). The model achieved a 91% accuracy for Normal vs. Abnormal imaging and an 82% accuracy for Urgent (acute cholecystitis) vs. Non-urgent (cholelithiasis or normal imaging). Furthermore, the model identified abnormal from normal imaging with 100% specificity, with no false positive results. Conclusion: Our deep learning model, using only readily obtained single-view cines, exhibited a high degree of accuracy and specificity in discriminating between non-urgent imaging and acute cholecystitis requiring urgent intervention.
• Predictive value of follow-up infarct volume on functional outcomes in middle cerebral artery M2 segment vessel occlusion stroke treated with mechanical thrombectomy

  Yedavalli, Vivek; Salim, Hamza Adel; Musmar, Basel; Adeeb, Nimer; El Naamani, Kareem; Henninger, Nils; Sundararajan, Sri Hari; Kühn, Anna Luisa; Khalife, Jane; Ghozy, Sherief; et al. (2024-09-13)

  Background: Medium vessel occlusion (MeVO) strokes, particularly affecting the M2 segment of the middle cerebral artery, represent a critical proportion of acute ischemic strokes, posing significant challenges in management and outcome prediction. The efficacy of mechanical thrombectomy (MT) in MeVO stroke may warrant reliable predictors of functional outcomes. This study aimed to investigate the prognostic value of follow-up infarct volume (FIV) for predicting 90-day functional outcomes in MeVO stroke patients undergoing MT. Methods: This multicenter, retrospective cohort study analyzed data from the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry, covering patients with acute ischemic stroke due to M2 segment occlusion treated with MT. We examined the relationship between 90-day functional outcomes, measured by the modified Rankin Scale (mRS), and follow-up infarct volume (FIV), assessed through CT or MRI within 12-36 h post-MT. Results: Among 130 participants, specific FIV thresholds were identified with high specificity and sensitivity for predicting outcomes. A FIV ⩽5 ml was highly specific for predicting favorable and excellent outcomes. The optimal cut-off for both prognostications was identified at ⩽15 ml by the Youden Index, with significant reductions in the likelihood of favorable outcomes observed above a 40 ml threshold. Receiver Operator Curve (ROC) analyses confirmed FIV as a superior predictor of functional outcomes compared to traditional recanalization scores, such as final modified thrombolysis in cerebral infarction score (mTICI). Multivariable analysis further highlighted the inverse relationship between FIV and positive functional outcomes. Conclusions: FIV within 36 h post-MT serves as a potent predictor of 90-day functional outcomes in patients with M2 segment MeVO strokes. Establishing FIV thresholds may aid in the prognostication of stroke outcomes, suggesting a role for FIV in guiding post intervention treatment decisions and informing clinical practice. Future research should focus on validating these findings across diverse patient populations and exploring the integration of FIV measurements with other clinical and imaging markers to enhance outcome prediction accuracy.
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  Mechanical Thrombectomy Versus Intravenous Thrombolysis in Distal Medium Vessel Acute Ischemic Stroke: A Multinational Multicenter Propensity Score-Matched Study

  Salim, Hamza Adel; Yedavalli, Vivek; Musmar, Basel; Adeeb, Nimer; Essibayi, Muhammed Amir; Naamani, Kareem El; Henninger, Nils; Sundararajan, Sri Hari; Kühn, Anna Luisa; Khalife, Jane; et al. (2024-09-13)

  Background and purpose: The management of acute ischemic stroke (AIS) due to distal medium vessel occlusion (DMVO) remains uncertain, particularly in comparing the effectiveness of intravenous thrombolysis (IVT) plus mechanical thrombectomy (MT) versus IVT alone. This study aimed to evaluate the safety and efficacy in DMVO patients treated with either MT-IVT or IVT alone. Methods: This multinational study analyzed data from 37 centers across North America, Asia, and Europe. Patients with AIS due to DMVO were included, with data collected from September 2017 to July 2023. The primary outcome was functional independence, with secondary outcomes including mortality and safety measures such as types of intracerebral hemorrhage. Results: The study involved 1,057 patients before matching, and 640 patients post-matching. Functional outcomes at 90 days showed no significant difference between groups in achieving good functional recovery (modified Rankin Scale 0-1 and 0-2), with adjusted odds ratios (OR) of 1.21 (95% confidence interval [CI] 0.81 to 1.79; P=0.35) and 1.00 (95% CI 0.66 to 1.51; P>0.99), respectively. Mortality rates at 90 days were similar between the two groups (OR 0.75, 95% CI 0.44 to 1.29; P=0.30). The incidence of symptomatic intracerebral hemorrhage was comparable, but any type of intracranial hemorrhage was significantly higher in the MT-IVT group (OR 0.43, 95% CI 0.29 to 0.63; P<0.001). Conclusion: The results of this study indicate that while MT-IVT and IVT alone show similar functional and mortality outcomes in DMVO patients, MT-IVT presents a higher risk of hemorrhagic complications, thus MT-IVT may not routinely offer additional benefits over IVT alone for all DMVO stroke patients. Further prospective randomized trials are needed to identify patient subgroups most likely to benefit from MT-IVT treatment in DMVO.
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  Quantitative reliability assessment of brain MRI volumetric measurements in type II GM1 gangliosidosis patients

  Zoppo, Christopher T; Kolstad, Josephine; Johnston, Jean; D'Souza, Precilla; Kühn, Anna Luisa; Vardar, Zeynep; Peker, Ahmet; Lindsay, Clifford; Rentiya, Zubir S; King, Robert; et al. (2024-09-13)

  Purpose: GM1-gangliosidosis (GM1) leads to extensive neurodegenerative changes and atrophy that precludes the use of automated MRI segmentation techniques for generating brain volumetrics. We developed a standardized segmentation protocol for brain MRIs of patients with type II GM1 and then assessed the inter- and intra-rater reliability of this methodology. The volumetric data may be used as a biomarker of disease burden and progression, and standardized methodology may support research into the natural history of the disease which is currently lacking in the literature. Approach: Twenty-five brain MRIs were included in this study from 22 type II GM1 patients of which 8 were late-infantile subtype and 14 were juvenile subtype. The following structures were segmented by two rating teams on a slice-by-slice basis: whole brain, ventricles, cerebellum, lentiform nucleus, thalamus, corpus callosum, and caudate nucleus. The inter- and intra-rater reliability of the segmentation method was assessed with an intraclass correlation coefficient as well as Sorensen-Dice and Jaccard coefficients. Results: Based on the Sorensen-Dice and Jaccard coefficients, the inter- and intra-rater reliability of the segmentation method was significantly better for the juvenile patients compared to late-infantile (p < 0.01). In addition, the agreement between the two rater teams and within themselves can be considered good with all p-values < 0.05. Conclusions: The standardized segmentation approach described here has good inter- and intra-rater reliability and may provide greater accuracy and reproducibility for neuromorphological studies in this group of patients and help to further expand our understanding of the natural history of this disease.
• A prospective, randomized, controlled, interventional clinical trial to evaluate the safety and efficacy of the medical monopoint reperfusion system for aspiration thrombectomy in acute ischemic stroke patients (SUMMIT MAX): Trial rationale and design

  Dabus, Guilherme; Puri, Ajit S; McGuinness, Ben; Priest, Ryan A; Rai, Ansaar T; Gross, Bradley A; Zaidat, Osama O; Hanel, Ricardo A; Shazam Hussain, M; Shaikh, Hamza A; et al. (2024-09-09)

  Background: Treatment of large vessel occlusion (LVO) using mechanical thrombectomy with or without intravenous thrombolysis has demonstrated better outcomes compared to medical treatment alone. Large-bore aspiration catheters have been recently introduced. Their effectiveness and safety have not been demonstrated in a randomized trial. The SUMMIT MAX study is designed to address this question. Methods: SUMMIT MAX is a randomized controlled trial where the effectiveness and safety of the large-bore Monopoint Reperfusion system (Route 92 Medical, San Mateo, CA), will be compared to the currently largest available FDA-cleared aspiration thrombectomy device the AXS Vecta Aspiration system (Stryker Neurovascular, Fremont, CA). The study is a multi-center, prospective, randomized, controlled, interventional, open label clinical trial. The hypothesis is that the effectiveness measured by the recanalization rate (modified thrombolysis in cerebrovascular infarction - mTICI) and safety measured by symptomatic intracranial hemorrhage rate (sICH) of the medical monopoint reperfusion system is non-inferior to the AXS Vecta Aspiration system. Results: Up to 250 subjects are enrolled with at least 50% of subjects enrolled by US sites. The primary effectiveness endpoint is successful arterial revascularization defined as an mTICI score ≥ 2b after use of the assigned device adjudicated by an independent core lab. The primary safety endpoint is defined as sICH within 24 h (-8/+24) post-procedure. Secondary endpoints include successful arterial revascularization defined as a mTICI score ≥ 2b after use of the assigned device with or without adjunctive therapy; device-related serious adverse events; all asymptomatic hemorrhages; time from groin puncture to final angiogram; and rate of first pass effect defined as mTICI 2b after first pass with the assigned device stratified by age (≤85, ≥ 86). Conclusion: SUMMIT MAX is a randomized controlled trial comparing the effectiveness and safety of a new large bore class of aspiration devices to the currently largest FDA-cleared aspiration device available.
• Encouragement vs. liability: How prompt engineering influences ChatGPT-4's radiology exam performance

  Nguyen, Daniel; MacKenzie, Allison; Kim, Young H (2024-09-06)

  Large Language Models (LLM) like ChatGPT-4 hold significant promise in medical application, especially in the field of radiology. While previous studies have shown the promise of ChatGTP-4 in textual-based scenarios, its performance on image-based response remains suboptimal. This study investigates the impact of prompt engineering on ChatGPT-4's accuracy on the 2022 American College of Radiology In Training Test Questions for Diagnostic Radiology Residents that include textual and visual-based questions. Four personas were created, each with unique prompts, and evaluated using ChatGPT-4. Results indicate that encouraging prompts and those disclaiming responsibility led to higher overall accuracy (number of questions answered correctly) compared to other personas. Personas that threaten the LLM with legal action or mounting clinical responsibility were not only found to score less, but also refrain of answering questions at a higher rate. These findings highlight the importance of prompt context in optimizing LLM responses and the need for further research to integrate AI responsibly into medical practice.
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  A minimally invasive endovascular approach to the cerebellopontine angle cistern enables broad CNS biodistribution of scAAV9-CB-GFP

  Benatti, Hector Ribeiro; Anagnostakou, Vania; Taghian, Toloo; Hall, Erin F; Nath, Sarah; Heilman, Carl B; Beneduce, Brandon M; Leporati, Anita; Raskett, Christopher M; Epshtein, Mark; et al. (2024-08-26)

  Neurological disorders pose a challenge for targeted therapy due to restricted access of therapeutic agents to the central nervous system (CNS). Current methods are limited by procedure-related risks, invasiveness, and insufficient CNS biodistribution. A novel percutaneous transvenous technology, currently in clinical trials for communicating hydrocephalus, offers a minimally invasive approach by providing endovascular access to the cerebrospinal fluid-filled cerebellopontine angle (CPA) cistern. We hypothesized that drug delivery to the CPA cistern could yield widespread CNS distribution. Using an ovine model, we compared the biodistribution of scAAV9-CB-GFP following CPA cistern infusion with previously reported cisterna magna (CM) administration. Targeting both the CPA cistern and CM in sheep, we employed a lumbar spine-inserted microcatheter under fluoroscopy. CPA delivery of AAV9 demonstrated biodistribution and transduction in the cerebral cortices, striatum, thalamus, midbrain, cerebellum, and spinal cord, with minor liver distribution comparable to CM. The favorable safety profile in humans with hydrocephalus suggests that percutaneous endovascular injection into the CPA could offer a clinically safer and minimally invasive delivery system for CNS gene and cell-based therapies.
• Normative Modeling of Thalamic Nuclear Volumes and Characterization of Lateralized Volume Alterations in Alzheimer's Disease Versus Schizophrenia

  Young, Taylor R; Kumar, Vinod Jangir; Saranathan, Manojkumar (2024-08-23)

  Background: Thalamic nuclei facilitate a wide range of complex behaviors, emotions, and cognition and have been implicated in neuropsychiatric disorders including Alzheimer's disease (AD) and schizophrenia. The aim of this work was to establish novel normative models of thalamic nuclear volumes and their laterality indices and investigate their changes in schizophrenia and AD. Methods: Volumes of bilateral whole thalami and 10 thalamic nuclei were generated from T1 MRI data using a state-of-the-art novel segmentation method in healthy control subjects (n=2374) and early mild cognitive impairment (MCI, n=211), late MCI (n=113), AD (n=88), and schizophrenia (n=168). Normative models for each nucleus were generated from healthy control subjects while controlling for sex, intracranial volume, and site. Extreme z-score deviations (|z|>1.96) and z-score distributions were compared across phenotypes. Z-scores were associated with clinical descriptors. Results: Increased infranormal and decreased supranormal z-scores were observed in schizophrenia and AD. Z-score shifts representing reduced volumes were observed in most nuclei in schizophrenia and AD with strong overlap in the bilateral pulvinar, medial dorsal, and centromedian nuclei. Shifts were larger in AD with evidence of a left-sided preference in early MCI while a predilection for right thalamic nuclei was observed in schizophrenia. The right medial dorsal nucleus was associated with disorganized thought and daily auditory verbal hallucinations. Conclusion: In AD, thalamic nuclei are more severely and symmetrically affected while in schizophrenia, the right thalamic nuclei are more affected. We highlight the right medial dorsal nucleus, which may mediate multiple symptoms of schizophrenia and is affected early in the disease course.
• Pretreatment predictors of very poor clinical outcomes in medium vessel occlusion stroke patients treated with mechanical thrombectomy

  Yedavalli, Vivek; Salim, Hamza; Musmar, Basel; Adeeb, Nimer; El Naamani, Kareem; Henninger, Nils; Sundararajan, Sri Hari; Kühn, Anna Luisa; Khalife, Jane; Ghozy, Sherief; et al. (2024-08-19)

  Background: Acute ischemic stroke (AIS) from primary medium vessel occlusions (MeVO) is a prevalent condition associated with substantial morbidity and mortality. Despite the common use of mechanical thrombectomy (MT) in AIS, predictors of poor outcomes in MeVO remain poorly characterized. Methods: In this prospectively collected, retrospectively reviewed, multicenter, multinational study, data from the MAD-MT (Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy) registry were analyzed. The study included 1568 patients from 37 academic centers across North America, Asia, and Europe, treated with MT, with or without intravenous tissue plasminogen activator (IVtPA), between September 2017 and July 2021. Results: Among the 1568 patients, 347 (22.2%) experienced very poor outcomes (modified Rankin score (mRS), 5-6). Key predictors of poor outcomes were advanced age (odds ratio (OR): 1.03; 95% confidence interval (CI): 1.02 to 1.04; p < 0.001), higher baseline National Institutes of Health Stroke Scale (NIHSS) scores (OR: 1.07; 95% CI: 1.05 to 1.10; p < 0.001), pre-operative glucose levels (OR: 1.01; 95% CI: 1.00 to 1.02; p < 0.001), and a baseline mRS of 4 (OR: 2.69; 95% CI: 1.25 to 5.82; p = 0.011). The multivariable model demonstrated good predictive accuracy with an area under the receiver-operating characteristic (ROC) curve of 0.76. Conclusions: This study demonstrates that advanced age, higher NIHSS scores, elevated pre-stroke mRS, and pre-operative glucose levels significantly predict very poor outcomes in AIS-MeVO patients who received MT. These findings highlight the importance of a comprehensive risk assessment in primary MeVO patients for personalized treatment strategies. However, they also suggest a need for cautious patient selection for endovascular thrombectomy. Further prospective studies are needed to confirm these findings and explore targeted therapeutic interventions.
• Creation of a predictive calculator to determine adequacy of occlusion of the woven endobridge (WEB) device in intracranial aneurysms-A retrospective analysis of the WorldWide WEB Consortium database

  Musmar, Basel; Adeeb, Nimer; Gendreau, Julian; Horowitz, Melanie Alfonzo; Salim, Hamza Adel; Sanmugananthan, Praveen; Aslan, Assala; Brown, Nolan J; Cancelliere, Nicole M; McLellan, Rachel M; et al. (2024-08-10)

  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.
• Assessment of Thrombectomy versus Combined Thrombolysis and Thrombectomy in Patients with Acute Ischemic Stroke and Medium Vessel Occlusion

  Dmytriw, Adam A; Ghozy, Sherief; Salim, Hamza Adel; Musmar, Basel; Siegler, James E; Kobeissi, Hassan; Shaikh, Hamza; Khalife, Jane; Abdalkader, Mohamad; Klein, Piers; et al. (2024-08-06)

  Background The combination of intravenous thrombolysis (IVT) with mechanical thrombectomy (MT) may have clinical benefits for patients with medium vessel occlusion. Purpose To examine whether MT combined with IVT is associated with different outcomes than MT alone in patients with acute ischemic stroke (AIS) and medium vessel occlusion. Materials and Methods This retrospective study included consecutive adult patients with AIS and medium vessel occlusion treated with MT or MT with IVT at 37 academic centers in North America, Asia, and Europe. Data were collected from September 2017 to July 2021. Propensity score matching was performed to reduce confounding. Univariable and multivariable logistic regression analyses were performed to test the association between the addition of IVT treatment and different functional and safety outcomes. Results After propensity score matching, 670 patients (median age, 75 years [IQR, 64-82 years]; 356 female) were included in the analysis; 335 underwent MT alone and 335 underwent MT with IVT. Median onset to puncture (350 vs 210 minutes, P < .001) and onset to recanalization (397 vs 273 minutes, P < .001) times were higher in the MT group than the MT with IVT group, respectively. In the univariable regression analysis, the addition of IVT was associated with higher odds of a modified Rankin Scale (mRS) score 0-2 (odds ratio [OR], 1.44; 95% CI: 1.06, 1.96; P = .019); however, this association was not observed in the multivariable analysis (OR, 1.37; 95% CI: 0.99, 1.89; P = .054). In the multivariable analysis, the addition of IVT also showed no evidence of an association with the odds of first-pass effect (OR, 1.27; 95% CI: 0.9, 1.79; P = .17), Thrombolysis in Cerebral Infarction grades 2b-3 (OR, 1.64; 95% CI: 0.99, 2.73; P = .055), mRS scores 0-1 (OR, 1.27; 95% CI: 0.91, 1.76; P = .16), mortality (OR, 0.78; 95% CI: 0.49, 1.24; P = .29), or intracranial hemorrhage (OR, 1.25; 95% CI: 0.88, 1.76; P = .21). Conclusion Adjunctive IVT may not provide benefit to MT in patients with AIS caused by distal and medium vessel occlusion. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Wojak in this issue.
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  Investigating therapeutic nonsense suppression in a neurofibromatosis mouse model

  Wu, Chan; Shazeeb, Mohammed Salman; Mangkalaphiban, Kotchaphorn; Han, George; Peker, Ahmet; Rentiya, Zubir S; Gounis, Matthew J; Jacobson, Allan (2024-08-04)

  Neurofibromatosis type 1 (NF1) is a human genetic disorder caused by variants in the NF1 gene. Plexiform neurofibromas, one of many NF1 manifestations, are benign peripheral nerve sheath tumors occurring in up to 50% of NF1 patients. A substantial fraction of NF1 pathogenetic variants are nonsense mutations, which result in the synthesis of truncated non-functional NF1 protein (neurofibromin). To date, no therapeutics have restored neurofibromin expression or addressed the consequences of this protein's absence in NF1 nonsense mutation patients, but nonsense suppression is a potential approach to the problem. Ataluren is a small molecule drug that has been shown to stimulate functional nonsense codon readthrough in several models of nonsense mutation diseases, as well as in Duchenne muscular dystrophy patients. To test ataluren's potential applicability in nonsense mutation NF1 patients, we evaluated its therapeutic effects using three treatment regimens in a previously established NF1 patient-derived (c.2041C > T; p.Arg681X) nonsense mutation mouse model. Collectively, our experiments indicate that: i) ataluren appeared to slow the growth of neurofibromas and alleviate some paralysis phenotypes, ii) female Nf1-nonsense mutation mice manifested more severe paralysis and neurofibroma phenotypes than male mice, iii) ataluren doses with apparent effectiveness were lower in female mice than in male mice, and iv) age factors also influenced ataluren's effectiveness.
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  Treatment of large intracranial aneurysms using the Woven EndoBridge (WEB): a propensity score-matched analysis

  Musmar, Basel; Salim, Hamza Adel; Adeeb, Nimer; Aslan, Assala; Aljeradat, Bahaa; Diestro, Jose Danilo Bengzon; McLellan, Rachel M; Algin, Oktay; Ghozy, Sherief; Dibas, Mahmoud; et al. (2024-07-31)

  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.
• Off-Label use of Woven EndoBridge device for intracranial brain aneurysm treatment: Modeling of occlusion outcome

  Essibayi, Muhammed Amir; Jabal, Mohamed Sobhi; Musmar, Basel; Adeeb, Nimer; Salim, Hamza; Aslan, Assala; Cancelliere, Nicole M; McLellan, Rachel M; Algin, Oktay; Ghozy, Sherief; et al. (2024-07-26)

  Introduction: The Woven EndoBridge (WEB) device is emerging as a novel therapy for intracranial aneurysms, but its use for off-label indications requires further study. Using machine learning, we aimed to develop predictive models for complete occlusion after off-label WEB treatment and to identify factors associated with occlusion outcomes. Methods: This multicenter, retrospective study included 162 patients who underwent off-label WEB treatment for intracranial aneurysms. Baseline, morphological, and procedural variables were utilized to develop machine-learning models predicting complete occlusion. Model interpretation was performed to determine significant predictors. Ordinal regression was also performed with occlusion status as an ordinal outcome from better (Raymond Roy Occlusion Classification [RROC] grade 1) to worse (RROC grade 3) status. Odds ratios (OR) with 95 % confidence intervals (CI) were reported. Results: The best performing model achieved an AUROC of 0.8 for predicting complete occlusion. Larger neck diameter and daughter sac were significant independent predictors of incomplete occlusion. On multivariable ordinal regression, higher RROC grades (OR 1.86, 95 % CI 1.25-2.82), larger neck diameter (OR 1.69, 95 % CI 1.09-2.65), and presence of daughter sacs (OR 2.26, 95 % CI 0.99-5.15) were associated with worse aneurysm occlusion after WEB treatment, independent of other factors. Conclusion: This study found that larger neck diameter and daughter sacs were associated with worse occlusion after WEB therapy for aneurysms. The machine learning approach identified anatomical factors related to occlusion outcomes that may help guide patient selection and monitoring with this technology. Further validation is needed.
• Symptomatic intracerebral hemorrhage in proximal and distal medium middle cerebral artery occlusion patients treated with mechanical thrombectomy

  Yedavalli, Vivek S; Salim, Hamza Adel; Musmar, Basel; Adeeb, Nimer; Essibayi, Muhammed Amir; ElNaamani, Kareem; Henninger, Nils; Sundararajan, Sri Hari; Kuhn, Anna Luisa; Khalife, Jane; et al. (2024-07-24)

  Background: Acute ischemic stroke (AIS) caused by distal medium vessel occlusions (DMVOs) represents a significant proportion of overall stroke cases. While intravenous thrombolysis (IVT) has been a primary treatment, advancements in endovascular procedures have led to increased use of mechanical thrombectomy (MT) in DMVO stroke patients. However, symptomatic intracerebral hemorrhage (sICH) remains a critical complication of AIS, particularly after undergoing intervention. This study aims to identify factors associated with sICH in DMVO stroke patients undergoing MT. Methods: This retrospective analysis utilized data from the Multicenter Analysis of Distal Medium Vessel Occlusions: Effect of Mechanical Thrombectomy (MAD-MT) registry, involving 37 centers across North America, Asia, and Europe. Middle cerebral artery (MCA) DMVO stroke patients were included. The primary outcome measured was sICH, as defined per the Heidelberg Bleeding Classification. Univariable and multivariable logistic regression were used to identify factors independently associated with sICH. Results: Among 1708 DMVO stroke patients, 148 (8.7%) developed sICH. Factors associated with sICH in DMVO patients treated with MT included older age (adjusted odds ratio (aOR) 1.01, 95% confidence interval (95% CI) 1.00 to 1.03, P=0.048), distal occlusion site (M3, M4) compared with medium occlusions (M2) (aOR 1.71, 95% CI 1.07 to 2.74, P=0.026), prior use of antiplatelet drugs (aOR 2.06, 95% CI 1.41 to 2.99, P<0.001), lower Alberta Stroke Program Early CT Scores (ASPECTS) (aOR 0.75, 95% CI 0.66 to 0.84, P<0.001), higher preoperative blood glucose level (aOR 1.00, 95% CI 1.00 to 1.01, P=0.012), number of passes (aOR 1.27, 95% CI 1.15 to 1.39, P<0.001), and successful recanalization (Thrombolysis In Cerebral Infarction (TICI) 2b-3) (aOR 0.43, 95% CI 0.28 to 0.66, P<0.001). Conclusion: This study provides novel insight into factors associated with sICH in patients undergoing MT for DMVO, emphasizing the importance of age, distal occlusion site, prior use of antiplatelet drugs, lower ASPECTS, higher preoperative blood glucose level, and procedural factors such as the number of passes and successful recanalization. Pending confirmation, consideration of these factors may improve personalized treatment strategies.

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