bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP185: Apparent Thalamostriate Vein and Brush Sign on Susceptibility-Weighted Imaging as Predictors of Infarct Growth at the Lenticulostriate Artery Territory
Authors: Yoshimura Shota , Yamaguchi Susumu , Matsuo Takayuki
Published: January 2025

Introduction:
Branch atheromatous disease involving the lenticulostriate artery (LSA) is strongly associated with early neurological deterioration. We aimed to investigate whether an apparent thalamostriate vein (TSV) or brush sign on susceptibility-weighted imaging (SWI) can predict infarct growth.

Methods:
Consecutive patients with the small subcortical infarction of the LSA presenting within 24 h of onset were retrospectively evaluated. MRI, including SWI, was performed on admission and within 1 week of admission. An apparent TSV was defined as a difference in the diameter of the TSV between the right and left sides on SWI upon admission. Infarct growth was defined as an increase in infarct size on axial or coronal diffusion-weighted imaging from <15 mm at admission to ≥15 mm at follow-up. Progressive paralysis was defined as an increase in the manual muscle test score by >1 point.

Results:
Of the 76 patients (median age, 76 [67.25–82] years, 48 male) with the small subcortical infarction of the LSA, 22 (median age, 75.5 [64.75–82.5] years, 13 male) presented with an apparent TSV and/or brush sign. On univariable logistic analysis, only the presence of apparent TSV and/or brush sign (OR, 3.12; 95% CI, 1.11–8.73;
p
=0.03) was associated with infarct growth. In multivariable logistic regression analysis, age (OR, 1.07; 95% CI, 1.01–1.14;
p
=0.02) and infarct growth (OR, 4.46; 95% CI, 1.37–14.54;
p
=0.01) were independently associated with progressive paralysis.

Conclusion:
An apparent TSV or brush sign could indicate infarct growth in cases of the small subcortical infarction of the LSA.
Abstract WP187: Graph neural networks for impossible transfemoral access pre-procedural prediction in stroke mechanical thrombectomy
Authors: Canals Pere , Garcia-Tornel Garcia-Camba Alvaro , Ribo Marc
Published: January 2025

Introduction:
3 to 5% of patients undergoing endovascular thrombectomy present impossible catheter access to the occlusion site from transfemoral access (TFA), largely attributed to complex arterial anatomy. Radial access can be an effective bailout strategy, but intraprocedural delays may negatively impact outcomes. Novel image processing algorithms allow for advanced characterization of vascular pathways from baseline neuroimaging, enabling the exploration of predictive models of impossible TFA before arterial puncture.

Methods:
A retrospective cohort of patients with an anterior large vessel occlusion who received thrombectomy from TFA between 2017 and 2023 were included in this study. A previously described automatic vascular analysis software was used to generate centerline graphs from the aorta to the intracranial occlusion site from baseline CTA. ArterialGNet, a graph neural network based on graph attention designed to integrate descriptors of centerline pathways extracted at three different distance scales, was trained for impossible TFA prediction. Five-fold cross validation was used for model derivation. The method was compared to a previously introduced random forest ensemble model with extreme gradient boosting (XGBRF) based on six vascular tortuosity descriptors of the aortic and supra-aortic regions.

Results:
A total of 745 patients (aged 78 years IQR 68-85, 56% women) were included in this study. Patients treated between 2017 to 2022 (n=568, 3.2% with impossible TFA) were used for model training and validation. Patients treated in 2023 (n=177, 3.4% with impossible TFA) were held out for testing. In validation, the best-performing configuration of ArterialGNet achieved a C-statistic of 0.82 (95%CI 0.74-0.90), similar to the baseline model (0.82, 95%CI 0.77-0.88). Comparable outcomes were observed in the final testing for ArterialGNet (0.84, 95%CI: 0.82–0.86). In contrast, the XGBRF model exhibited signs of overfitting (0.65, 95% CI: 0.53–0.78). In final testing, ArterialGNet predicted impossible TFA with a sensitivity of 0.80 (95%CI 0.66-0.94) and a specificity of 0.84 (95%CI 0.76-0.91). Median processing time for ArterialGNet was below 4 min.

Conclusions:
A novel model for impossible TFA prediction was validated with a large dataset. Impossible TFA prediction before arterial puncture may assist in decision support for initial access selection in thrombectomy, reducing intraprocedural delays and potentially improving clinical outcomes.
Abstract WP188: Differential Patterns of Cerebral Atrophy and Clinical Impacts in Cerebral Amyloid Angiopathy and Hypertensive Cerebral Small Vessel Disease
Authors: Wu Juanjuan , Sha Yuhui , Ni Jun , Peng Bin
Published: January 2025

Introduction:
Cerebral amyloid angiopathy (CAA) is an age-related cerebral small vessel disease that can lead to poor outcomes due to cerebral hemorrhage. The same applies to hypertensive cerebral small vessel disease (HTN-CSVD). Cerebral atrophy is a common imaging manifestation of CSVD, but its imaging patterns in both CAA and HTN-CSVD and clinical relevance have not been fully elucidated.

Hypothesis:
Based on the differences in the distribution of affected vessels between CAA and HTN-CSVD, it is hypothesized that there is a spatial distribution difference in cerebral atrophy. This may lead to different clinical characteristics between the two conditions. Previous small sample studies have shown a correlation between medial temporal lobe atrophy and cognitive levels in CAA patients, which still needs further validation.

Methods:
Statistical Parametric Mapping 12 was used to obtain automated, quantitative, voxel-based morphology of cerebral atrophy shown on 5.0T MRI, including total intracranial volume, gray matter volume, white matter volume and cerebrospinal fluid volume. Two-sample t test explores the differences in the spatial distribution characteristics of cerebral atrophy between 36 CAA patients and 51 HTN-CSVD patients. A voxel-wise multiple regression analysis clarifies the correlation between cerebral atrophy and cognitive decline in CAA.

Results:
After adjusting for age, gender, and total intracranial volume, cerebral atrophy differences between CAA and HTN-CSVD were mainly observed in the cortex of bilateral cerebellar hemispheres and vermis (
p
< 0.05 FWE). There is a spatial correlation between cerebral atrophy and cognitive levels in CAA after adjusting for age, gender, and total intracranial volume. Regional brain volume in the left medial temporal lobe, insula, parietal lobe, and thalamus was associated with mini-mental state examination scores (
p
< 0.05 FDR), and cerebral atrophy in the left lateral temporal lobe and right cerebellar hemisphere was associated with Montreal Cognitive Assessment scores (
p
< 0.05 FDR).

Conclusion:
Cerebral atrophy in CAA is predominantly in the cerebellum, compared to HTN-CSVD, and is independently associated with overall cognitive levels prominantly in left temporal lobe. In conclusion, this study provides valuable reference for a better understanding of the differences of cerebral atrophy between CAA and HTN-CSVD, as well as the clinical relevance of cerebral atrophy.
Abstract WP193: Longitudinal Assessment of Vessel Wall Radiomics and Luminal Blood Flow During Evaluation of Intracranial Atherosclerotic Plaques
Authors: Veeturi Sricharan , Pinter Nandor , Mecca Nicholas , Morrish Benjamin , Levy Elad , Siddiqui Adnan , Tutino Vincent
Published: January 2025

Introduction:
Intracranial atherosclerotic disease (ICAD) is a common cause of primary and secondary stroke. Understanding plaque evolution can help in risk stratification and in selecting proper therapies.

Hypothesis:
In this study, we hypothesized that vessel wall radiomics and hemodynamic features correlate with longitudinal change in plaque volume.

Methods:
Patients with ICAD and history of cerebral ischemia were included. Time-of-flight MRA, high-resolution vessel wall imaging (proton density-weighted, PD, and contrast-enhanced T1-weighted, T1CE) and phase-contrast MR-based volumetric flow (NOVA) were collected at multiple time points. MRA was used to segment lumen and perform computational fluid dynamics (CFD). NOVA flow rate used as boundary conditions. Plaques were segmented on PD images from each time point. PD and T1CE scans were co-registered and radiomics features (RFs) were extracted from the first time point from both image types. Plaques were compared between consecutive time points and classified as progressing, stable, or regressing, based on volume change (those <5mm
3
were excluded). ANOVA analysis was done to determine which features were different between the 3 groups of plaques.

Results:
32 plaques from 14 patients were analyzed (12 regressing, 15 stable, 5 progressing). Mean follow-up time of MRI was 11.8 months. Mean plaque size at baseline was 20.94mm3. Average growth in the progression group was 24.33mm
3
. Dual antiplatelet therapy was more frequent in the regression group. 57 RFs were significantly different (p<0.05) between the groups. CFD showed no significant difference in hemodynamics; however, wall shear stress (WSS) was lower and WSS divergence was higher adjacent to regressing plaques.

Conclusion:
We found significant differences in RFs between progressing, stable and regressing plaques, suggesting that vessel wall imaging can be used to better understand plaque evolution.
Abstract WP197: Detection and segmentation of hyperdense middle cerebral artery sign on non-contrast CT using artificial intelligence
Authors: Kim Chi Kyung , Ryu Wi-sun , Oh Kyungmi
Published: January 2025

Background:
The hyperdense artery sign (HAS) in patients with large vessel occlusion (LVO) is associated with outcomes after ischemic stroke. Considering the labor-intensive nature of manual segmentation of HAS, we developed and validated an automated HAS segmentation algorithm on non-contrast brain CT (NCCT) images using a multicenter dataset with independent annotations by two experts.

Methods:
For the training dataset, we included patients with ischemic stroke undergoing concurrent NCCT and CT angiography between May 2011 and December 2022 from six stroke centers. The model was externally validated using a dataset from one stroke center. For the clinical validation dataset, a consecutive series of patients admitted within 24 hours of symptom onset were included between December 2020 and April 2023 from six stroke centers. The model was trained using a 2D U-Net algorithm with manual segmentation by two experts. We constructed models trained on datasets annotated individually by each expert, and an ensemble model using shuffled annotations from both experts. The performance of the models was compared using area under the receiver operating characteristics curve (AUROC), sensitivity, and specificity.

Results:
A total of 673, 365, and 774 patients were included in the training, external validation, and clinical validation datasets, respectively, with mean (SD) ages of 68.8 (13.2), 67.6 (13.4), and 68.8 (13.6) years and male frequencies of 55.0%, 59.5%, and 57.6%. The ensemble model achieved higher AUROC and sensitivity compared to the models trained on annotations from a single expert in the external validation dataset. In the clinical validation dataset, the ensemble model exhibited an AUROC of 0.846 (95% CI, 0.819–0.871), sensitivity of 76.8% (65.1–86.1%), and specificity of 88.5% (85.9–90.8%). The predicted volume of the clot was significantly correlated with infarct volume on follow-up diffusion-weighted imaging (r=0.42; p<0.001).

Conclusion:
Our algorithm promptly and accurately identifies HAS, facilitating the screening of potential patients who may require intervention.
Abstract WP226: Thrombin-Mediated Platelet Activity Predicts Hematoma Expansion After Spontaneous Intracerebral Hemorrhage
Authors: Copenhaver Kaleigh , Silva Pinheiro do Nascimento Juliana , Goldenberger Fernando , Shownkeen Harish , Lindholm Paul , Naidech Andrew
Published: January 2025

Objective:
Hematoma expansion (HE) predicts disability and death after intracerebral hemorrhage (ICH). Platelet activity is essential for coagulation, and the use of anti-platelet medication (e.g., aspirin, NSAIDs) is associated with increased HE. The impact of pre-ICH anti-platelet medication on HE is incompletely understood. Specific biomarkers of platelet activity would improve our understanding of HE and could point towards targeted treatments. We tested the hypothesis that biomarkers of platelet activity predict subsequent HE.

Methods:
We prospectively identified patients with spontaneous ICH within 12 hours of symptom onset and measured whole blood with TEG 6s platelet mapping assays to assess platelet function (Hemonetics Inc.). We assessed heparinase kaolin (HKH) to determine the total platelet activation. We measured activated fibrinogen polymerization (ActF) to determine the fibrinogen component. Hematoma volumes for initial and follow-up CTs were calculated using a validated semi-automated method. HE was calculated by measuring the difference in hematoma volume between scans. We calculated the correlation between HE and platelet activity using Spearman’s rank correlation. We constructed a linear regression model to predict HE from ActF and an ActF by pre-ICH anti-platelet interaction term. The interaction term tests the hypothesis that there is an interaction between ActF and HE that varied with pre-ICH anti-platelet medication.

Results:
There were 38 patients from three metropolitan sites. Fourteen (36.8%) were known to take pre-ICH anti-platelet medication. HKH was negatively correlated with HE (r = -0.30, CI [-0.63, 0.04], P = 0.03), indicating more HKH activity predicted less HE. Results for ActF were dependent upon whether the patient took pre-ICH anti-platelet medication (interaction P = 0.005), where HE was the dependent variable and independent variables included ActF and pre-ICH anti-platelet medication.

Discussion:
Hemostatic biomarkers predicted subsequent HE in patients with ICH. The association of ActF with HE was dependent on aspirin or NSAIDs use. Potential interventions that improve platelet activity in patients that are high risk for HE deserves further study.

Applying for the Mordecai Y. T. Globus New Investigator Award in Stroke
Abstract WP251: Middle meningeal artery embolization using Onyx and particles for chronic subdural hematoma: A single center experience.
Authors: Reid Graham , Noss Eric , Bramlage Luke , Ludwig Bryan , Terry John , Cheng-Ching Esteban
Published: January 2025

Chronic subdural hematoma (cSDH) represents a relatively treatment-resistant pathologic process with a large impact on quality-adjusted life years. This risk is increased in the elderly, and the prevalence is expected to rise as the population ages. Expectant management and classical surgical treatment are associated with increased recurrence rate as well as complications. Middle meningeal artery (MMA) embolization is being utilized more frequently as adjunctive and primary treatment. It has demonstrated beneficial effects on recurrence and progression of cSDH. Here, we present the outcomes of this technique with different embolic agents in our patient population.

IRB approval was obtained for this study. Retrospectively, all patients at a single institution who underwent endovascular MMA embolization with or without open surgical intervention for cSDH were included. Vulnerable populations were excluded. Demographic and medical data were collected at initial, 1-month, and 3-month time points if available and analyzed for differences with unpaired T-test, paired-T test, and chi-square test.

Between 2020 and 2024, a total of 50 patients were treated with MMA embolization for cSDH. Mean age was 73 years. Majority were male. Most were on antithrombotic therapy. Of these, 34 had history of prior SDH, and 38 had history of head trauma. Of the 50 patients, 29 patients underwent combined open surgery and MMA embolization, while 21 underwent MMA embolization alone. The cSDH was bilateral in 23 patients and unilateral in 27 (13 right, 14 left) for a total of 73 cSDHs. Surgical evacuation was performed in 44 cSDHs. Liquid embolic agent (Onyx) was utilized for 32 patients, while particulate embolic agents (250-500 um) were utilized for 18 patients. Of the patients who had follow-up CTs at 1 month, there were 21 cSDHs treated with particles and 39 with Onyx. There was no significant difference in the proportions of patients undergoing surgery in addition to MMA embolization between the groups treated with Onyx and those treated with particle embolization. Additionally, there was no significant difference in the proportions of treated hemispheres with ≥ 50% reduction or ≥ 75% reduction between those treated with Onyx and those treated with particles.

At our institution, there was no difference in reduction of cSDH with Onyx as compared to particle embolization. MMA embolization was associated with no recurrence or progression of cSDH at 3 months.
Abstract WP318: Cancer and Atrial Cardiopathy: A Secondary Analysis of the ARCADIA Clinical Trial
Authors: Navi Babak , Elkind Mitchell , Zhang Cenai , Tirschwell David , Kronmal Richard , Elm Jordan , Broderick Joseph , Gladstone David , Kamel Hooman , Longstreth W
Published: January 2025

Background:
Approximately 50% of ischemic strokes in patients with cancer are classified as cryptogenic after standard evaluation. As cancer and its treatments are associated with increased risk for atrial fibrillation (AF), the pathological substrate for AF—atrial cardiopathy—could be the underlying etiology for some of these cancer-related cryptogenic strokes. However, the relationship between cancer and atrial cardiopathy is uncertain.

Methods:
We conducted a post-hoc cross-sectional analysis of baseline data collected from patients enrolled into the ARCADIA trial from 2018-2023 at 185 North American sites. Patients had to be age 45 years or older with a clinical diagnosis of cryptogenic ischemic stroke within the past 180 days and without AF of any duration. Enrolled patients consented to screening for atrial cardiopathy, the presence of which was required for randomization. Linear regression models were used to examine associations between a history of cancer and the three log-transformed atrial cardiopathy biomarkers: serum N-terminal pro-B-type natriuretic peptide (NT-proBNP), P-wave terminal force in ECG lead V
1
(PTFV
1
), and left atrial diameter index (LADI) on echocardiogram.

Results:
Among 3,745 patients with cryptogenic stroke, 506 (13.5%) had a history of cancer. Patients with, compared to those without, a history of cancer were older (71 versus 65 years) and more often White (88% versus 74%) and non-Hispanic (94% versus 90%). Medical comorbidities were similar between groups. History of cancer was associated with higher median values of NT-proBNP (126 versus 103 pg/mL, p<0.001) and LADI (1.9 versus 1.8 cm/m
2
, p<0.001) but similar median values of PTFV
1
(3000 versus 3025, p=0.08). After adjusting for demographics and tobacco use, no association remained between history of cancer and NT-proBNP (beta-coefficient, -0.09; 95% CI, -0.20 to 0.03), PTFV
1
(beta-coefficient, -0.04; 95% CI, -0.10 to 0.02), or LADI (beta-coefficient, 0.01; 95% CI, -0.01 to 0.04).

Conclusions:
In a multicenter prospective cohort of patients with cryptogenic stroke, history of cancer was not independently associated with selected biomarkers for atrial cardiopathy. These data suggest that, in the absence of apparent AF, cancer and atrial cardiopathy may not be linked in patients with stroke.
Abstract WP32: Impact of External Ventricular Drain Placement Timing on Rerupture and Outcomes in Aneurysmal Subarachnoid Hemorrhage
Authors: Chuck Carlin , Oldam Joseph , Wang Diana , Taman Mazen , Haq Rakin , Gupta Sahil , Voong Viva , Duong Anna , Feler Joshua , Torabi Radmehr , Moldovan Krisztina , Furie Karen , Wolman Dylan , Jayaraman Mahesh , Mahta Ali
Published: January 2025

Introduction:
Urgent external ventricular drain (EVD) placement in aneurysmal subarachnoid hemorrhage (aSAH) is necessary for hydrocephalus treatment. However, it is unclear whether more rapid EVD placement is associated with better neurologic outcomes. In addition, EVD placement before aneurysm securement is thought to decrease aneurysmal transluminal pressure and may increase the risk of aneurysmal rerupture. We sought to better characterize whether the intervals from arrival to EVD placement and from EVD placement to aneurysm treatment were associated with differences in aneurysmal rerupture rates or neurologic outcomes.

Methods:
A retrospective study of a prospectively collected cohort of patients with aSAH presenting from 2015 to 2023 to a single academic center was performed. Multivariate logistic regressions (MLR) were performed to analyze the time from hospital arrival to EVD and both preprocedural aneurysm rerupture as well as poor neurologic outcomes, defined as a modified Rankin scale (mRS) >3 at 3 months. In addition, a similar analysis was performed with time from EVD to aneurysm securement.

Results:
Out of 434 patients with ruptured aSAH, we excluded those who received urgent craniotomy or craniectomy, as well as those who did not undergo angiography due to early mortality or EVD placement due to lack of hydrocephalus, resulting in a cohort of 231 patients (mean [SD] age, 57.6 [13.5]; 67.5% female, 69.3% white). Longer arrival to EVD was associated with an increased risk of preprocedural aneurysmal rerupture (OR 1.93, 95%CI 1.05, 3.66, p=0.038); however, longer EVD to aneurysm securement was not associated with differences in preprocedural aneurysmal rerupture (OR 0.66, 95%CI [0.41, 1.09], p=0.093). On MLR, longer arrival to EVD or longer EVD to aneurysm securement was not associated with differences in 3-month neurologic outcomes (OR 1.13, 95%CI [0.73, 1.75], p=0.6 and OR 0.74, 95%CI [0.51, 1.05], p=0.095, respectively).

Conclusion:
We found that longer arrival to EVD was associated with an increased risk of preprocedural rerupture, but not associated with differences in neurologic outcomes at 3 months. While EVD placement prior to aneurysmal securement is theorized to decrease transluminal pressure and increase rerupture risk, we did not find an association between duration from EVD placement to aneurysm securement and rerupture risk.
Abstract WP347: Evaluating Brain Microvascular Endothelial Cell Dysfunction to Stenosis in a Tissue-Engineered Model of the Blood-Brain Barrier
Authors: Pessell Alexander , Sargur Krishna , Li Yanlin , Demirtas Alp , Zhao Nan , Searson Peter
Published: January 2025

Introduction:
Highly specialized brain microvascular endothelial cells (BMECs) form the first defense of the blood-brain barrier (BBB), regulating the exchange of molecules, cells, and pathogens in and out of the brain. Ischemic stroke, a heterogeneous disease with various etiological subtypes and risk factors, places stress on the BBB. While macroscopic BBB changes in ischemic stroke are observable in animal models, individual cell phenotypical and functional changes remain largely unknown due to poor spatiotemporal resolution. Our objective is to use human-based, tissue-engineered microvessel models to capture these details in response to stenosis, a hallmark of ischemic stroke.

Methods:
Pluripotent stem cells were differentiated into BMECs (iBMECs), validated for BBB phenotype, and seeded into 150 μm channels in collagen I/Matrigel hydrogels. Microvessels were matured for two days under physiological flow (~5 dyne cm
-2
). To model stenosis, a microactuator was mounted on a 3D printed platform and connected to a capillary tube (~1 mm diameter). Barrier function was probed by perfusing microvessels with Lucifer yellow + 70 kDa dextran after 4 h of varied stenosis %, followed by thresholding in ImageJ to track focal leaks. Reactive oxygen species (ROS) generation was assessed using a live cell ROS stain and imaging on the microvessel polar planes with an epifluorescent microscope. The zonula occludens-1 (ZO-1) fluorescent tag on the iBMECs outlined cells for single-cell analyses in CellProfiler using CellPose.

Results and Conclusions:
A tissue-engineered BBB model from the Searson Lab was modified (Fig. 1A) to include a microactuator for inducing adjustable (0-100%) and reversible stenosis during the perfusion of iBMEC&HUVEC microvessels within a hydrogel ECM (Fig. 1B, C). Preliminary results show focal leaks forming immediately after stenosis (Fig. 2A, B), with distribution increasing along the microvessel length as stenosis intensifies (Fig. 2C). Using ZO-1 labeled iBMECs for cell segmentation from epifluorescence images, we found that ROS significantly increases with greater stenosis (Fig. 3A, B), particularly in the center and upstream of microvessels (Fig. 3C). In conclusion, our findings suggest that stenosis disrupts barrier function, with the disruption not always being regionally dependent. We will further investigate whether these changes are due to physical or chemical factors, such as altered wall shear stress or oxygen/glucose bottlenecks.
Abstract WP352: Bezafibrate Treatment Alters Cerebral Energy Metabolism in Female Rats Undergoing Nicotine and Oral Contraceptive Withdrawal
Authors: Sanchez Vicente , Sharma Harry , Raval Ami
Published: January 2025

Introduction:
Women who smoke cigarettes while using oral contraceptives (OC) increase their risk for and severity of stroke compared to nonsmoking women who use OC. Studies published from our laboratory showed that combination of smoking derived nicotine (N) with OC exacerbates the severity of ischemic episodes in females via altering cerebral glucose and fatty acids metabolism. Relinquishing the smoking habit reduces the risk for stroke, however, N+OC withdrawal (NW) for 30 days fails to reduce severity of ischemic brain damage in female rats previously exposed to N+OC. The goal of the current study is to test the efficacy of an FDA-approved lipid-lowering drug Bezafibrate (Bez) in improving brain energy metabolism after nicotine withdrawal.

Methods:
Adult Sprague-Dawley female rats were randomly (n = 6-8/group) exposed to either saline, N (4.5 mg/kg) +/- OC for 16-21 days. To determine the effects of Bez along with N+OC on mitochondrial biogenesis, adult rats exposed to N+/-OC were fed
ad libitum
with either standard chow or 0.15% (w/w) bezafibrate-supplemented chow during 30 days of withdrawal period. At the end of the treatment, brain tissue was harvested to obtain an unbiased global metabolomic profile (performed by Metabolon Inc.) The metabolomic study was complemented with western blot analysis and enzyme activity measurements of key altered pathways. Mitochondrial biogenesis was assessed by western blots of oxidative phosphorylation system subunits and by enzymatic determination of complex activities and citrate synthase.

Results:
Global metabolomic analysis showed that several of the long chain polyunsaturated fatty acids (LCPUFAs) (
e.g.,
docosahexaenoate (DHA; 22:6n3) and arachidonate (20:4n6)) were significantly higher in the N+Bez, OC+Bez, and N+OC+Bez groups when compared to the nicotine group. It is shown that Bez decreases serum lipid levels by activating cellular uptake of fatty acids. These results suggest that Bez treatment is increasing cortical tissue uptake of LCPUFAs in the N and N+OC groups. Enzymatic analysis of electron transport chain complexes showed the activities of NADH dehydrogenase and cytochrome c oxidase were significantly higher in N+Bez and Sal+Bez when compared to nicotine group.

Conclusion:
Bezafibrate could potentially mitigate effects of N+OC on the brain and rescue cerebral energy metabolism. Future studies are needed to evaluate it’s impact on stroke outcomes.
Abstract WP357: Predictors of Reperfusion CBF and its Effects on Outcome After Endovascular Middle Cerebral Artery Occlusion in the SPAN Trial
Authors: Imai Takahiko , Morais Andreia , JIN XUYAN , Aykan Sanem A , Ayata Cenk
Published: January 2025

Introduction:
The rapid recanalization of occluded vessels and the restoration of cerebral blood flow (CBF) are critical for the outcome of stroke. Patients may exhibit poor reperfusion (no-flow) or hyperperfusion (hyperemia) after recanalization, and factors influencing these conditions are not fully understood. The Stroke Preclinical Assessment Network (SPAN) conducted a randomized, controlled, blinded, and highly heterogeneous multi-laboratory trial to identify effective interventions in the stroke animal model. Here, we examined the factors influencing the CBF recovery after filament removal and the effect of reperfusion CBF on stroke outcome in SPAN.

Methods:
Both sexes of C57BL6 healthy young were subjected to 30 or 60-minutes transient endovascular filament middle cerebral artery occlusion (MCAO). For homogeneity of all other factors, we used subjects enrolled at Mass General Hospital only. We measured CBF at 5 (n=128) and 10 minutes (n=88) after filament removal by laser Doppler flowmetry. We first tested whether sex, surgeons, MCAO duration, circadian time (ZT) at MCAO, age, weight, surgical duration, and SPAN treatments (control, fasudil, fingolimod, tocilizumab, uric acid, veliparib) predicted the reperfusion CBF. We then assessed the influence of CBF on tissue (day-2 MRI lesion volume) and behavioral outcomes (acute neurological deficits score and day-7 and 28 corner test) and 30-day mortality. A generalized linear model with backward elimination and a mixed model were used for bivariate and multivariable analyses.

Results:
CBF gradually increased after filament removal between 5 and 10 minutes (p=0.03). In bivariate analyses, CBF was significantly lower in animal that had MCAO in their active circadian phase (ZT12-24) (p=0.04). In multivariable analysis, reperfusion CBF was predicted to be higher in females, after 60 min MCAO, in inactive phase (ZT0-12), and short anesthesia duration. CBF also differed among the three surgeons. Only tocilizumab had lower CBF compared to the control group. Reperfusion CBF did not predict tissue and behavioral outcomes. However, higher CBF was related to lower day-1 weight loss (p<0.01) and lower mortality for 30 days (p<0.01).

Conclusion:
In conclusion, we show that sex, ischemia duration, circadian stage at MCAO, and total anesthesia duration predict the reperfusion CBF after mouse endovascular filament MCAO. We also show that reperfusion CBF can predict mortality, independent of tissue and behavioral outcomes.
Abstract WP383: Targeting CD38 to Alleviate Brain Endothelial Cell Dysfunction and Cognitive Impairment in Vascular Dementia
Authors: Chen Zhili , Yu Mingjing , Chen Jieli , yan tao
Published: January 2025

Background and purpose:
Vascular dementia (VaD) is one of the most common causes of cognitive decline, primarily resulting from cerebrovascular damage. Central to the pathogenesis of VaD are cerebrovascular endothelial cell (CEC) dysfunction, blood-brain barrier (BBB) disruption, and neuroinflammation. CD38, an enzyme involved in neuroinflammation and cellular senescence, has recently been implicated in these processes. However, its specific role in CEC dysfunction within the context of VaD remains poorly understood. We hypothesize that CD38 contributes to CEC dysfunction, BBB disruption, and cognitive decline in VaD, and that inhibiting CD38 could mitigate these pathological effects and improve cognitive outcomes.

Method:
We used a mouse model of VaD induced by bilateral carotid artery stenosis (BCAS). Mice were treated with the selective CD38 inhibitor 78c (10 mg/kg, twice daily for 1 month) to assess its therapeutic potential. CBF, BBB permeability, and cognitive function were evaluated. The expression of CD38, pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), and CEC tight junction proteins were analyzed. In vitro experiments were conducted using CECs to investigate the effects of 78c on TNF-α-induced CD38 expression and inflammatory responses, focusing on the NOX4/eNOS signaling pathway.

Result:
Our results demonstrated that BCAS significantly reduced CBF, increased BBB permeability, and induced cognitive deficits, all of which were accompanied by elevated CD38 expression in CECs and heightened levels of pro-inflammatory cytokines. Treatment with the CD38 inhibitor 78c effectively mitigated these effects, resulting in reduced white matter damage, improved CBF, enhanced expression of CEC tight junction proteins, and decreased neuroinflammation and BBB disruption. In vitro studies further revealed that 78c attenuates TNF-α-induced CD38 expression and inflammatory responses in CECs, likely via the NOX4/eNOS signaling pathway.

Conclusion:
This study identifies CD38 as a crucial mediator of CEC dysfunction in VaD, linking chronic cerebral hypoperfusion to neurovascular damage. Targeting CD38 with the selective inhibitor 78c presents a promising therapeutic strategy for restoring vascular integrity and alleviating cognitive impairment in VaD. These findings not only highlight a novel molecular mechanism underlying VaD progression but also open new avenues for the development of targeted treatments for this debilitating condition.
Abstract WP387: Corraborated Evidence on Change of Metabolome after Ischemic Stroke due to Large Vessel Occlusion
Authors: Sidorov Evgeny , Rout Madhusmita , Xu Chao , Smith Kyle , Sanghera Dharambir
Published: January 2025

Background:
Metabolomics is commonly used to search for acute ischemic stroke (AIS) biomarkers. However, many studies which found metabolite - AIS associations have contradictory findings, which prevents solid conclusion. To obtain corroborative evidence on change of serum metabolome after AIS, our study: (1) focused on patients with large vessel occlusion (LVO), (2) combined cross-sectional and longitudinal study designs, and (3) performed analysis using different metabolome platforms: Nuclear Magnetic Resonance (NMR) and Liquid Chromatography-Mass Spectrometry (LC-MS).

Methods:
In the cross-sectional part of the study, we compared serum metabolome of 84 LVO stroke patients and 82 controls using NMR (250 compounds), with multivariate regression. Samples were collected 48-72 hours after AIS. In the longitudinal part we prospectively analyzed serum metabolome using LC-MS (1554 compounds) on 15 LVO stroke patients at 4 time-points: <24 hours, 48-72 hours, 5-7 days, 80-120 days using mixed regression model. Our hypothesis is that serum metabolites elevated in cross-sectional part would show rising trajectory in longitudinal part, and vice versa. We used age, gender, race as covariates, and the Two-Stage Benjamini&Hochberg procedure for multiple testing.

Results:
All patients and controls had equal characteristics. 18 significant metabolites from the cross-sectional part had 152 corresponding derivatives with significant change in the longitudinal part, which showed 4 patterns of metabolome change after AIS (Table 2). Glycerol, phosphatidylethanolamine (PE), ceramide, phenylalanine were significantly increased in the cross-sectional part, while their derivatives had well-ordered rising trajectory in the longitudinal part during first week, then either continued to increase or decreased. Histidine, tyrosine, valine, glutamine, phosphatidylcholine (PC), sphingomyelin, fatty acids (FA), including monounsaturated, polyunsaturated, and saturated fatty acids were decreased in the cross-sectional part, while their derivatives had well-ordered declining trajectory on the longitudinal part during first week, then either continued to decrease or increased.

Conclusion:
We obtained corroborated evidence that glycerol, PE, ceramide and phenylalanine are increasing, while histidine, tyrosine, valine, glutamine, PC, sphingomyelin, and FA are decreasing after LVO strokes. Future studies should evaluate the clinical impact of these findings.
Abstract WP389: Unraveling Cerebral Cavernous Malformation Pathogenesis: Insights from a Radiation-Induced Endothelial Dysmorphism Model
Authors: Alcazar Roberto , Srinath Abhinav , Tieri David , Vera Cruz Diana , Allaw Sammy , Montas Dominic , Haro Fidel , Pearson Erik , Pytel Peter , Awad Issam , Polster Sean
Published: January 2025

Introduction:
Mouse models have been a valuable tool for studying the molecular mechanisms driving cerebral cavernous malformation (CCM) pathogenesis. However, genetically modified mouse models do not fully recapitulate human CCM disease, and endothelial dysfunction is implicated in multiple disease processes of the brain. Herein, we provide a radiation-induced platform of endothelial dysmorphism and physiologic dysfunction similar to that observed in CCM disease. By analyzing gene expression and pathway alterations in endothelial cells, this model enhances our understanding of the fundamental biological processes at play that are common and different between CCM and endothelial leak.

Methods:
Ten-week-old female C57BL/6 mice underwent irradiation with 40 Gy (@50% isodose) to a 5mm target within the left cerebral hemisphere. Brain parenchymal changes were assessed using contrast-enhanced CT imaging and histology. Endothelial cell RNA extraction and transcriptomic analysis were performed on formalin-fixed, paraffin-embedded coronal tissue sections from radiated and control hemispheres using the a digital spatial profiler system. Ingenuity Pathway Analysis (IPA) was employed to identify affected molecular pathways.

Results:
CT imaging revealed increased blood-brain barrier permeability within the irradiated area. Histologic analysis identified telangiectasias and microhemorrhages, consistent with dysmorphic endothelium and capillary malformations. Gene expression profiles between radiated vs. non-radiated endothelium demonstrated a clear distinction by principal component analysis. Differentially expressed genes were primarily associated with extracellular matrix organization, regulation of the actin cytoskeleton, and pro-inflammatory cytokine response pathways. Upstream analysis predicted TGFB1, TNF, lipopolysaccharide, dexamethasone, and angiotensinogen as potential regulators underlying the observed changes.

Conclusion:
This study elucidates a signature of dysmorphic endothelium in a non-genetically modified mouse model, revealing potential key molecular pathways and regulators that lead to endothelial leak. This model can guide mechanistic-based experimental studies and provide a platform for targeted interventions directed at critical components of CCM pathophysiology and the blood-brain barrier.
Abstract WP63: Bilateral carotid artery stenosis causes synaptic changes in the retina of aged mice
Authors: Barney Spencer , Monga Sheelu , Zuniga-Sanchez Elizabeth , Moruno-Manchon Jose
Published: January 2025

Introduction:
Visual impairments occur frequently in patients with cerebrovascular disease, particularly with carotid artery disease, which contributes to the development of vascular contributions to cognitive impairment and dementias (VCID). However, patients with VCID usually do not realize their vision loss until the postoperative period to improve their arterial circulation. These visual difficulties can be caused by the effects of dementia on the brain or an eye condition. Our study aimed to determine if our mouse model of VCID shows retinal alterations in the eye.

Methodology:
In our lab, we used the bilateral carotid artery stenosis model (BCAS) in aged mice as a model of VCID. We implanted a 0.16 mm diameter micro-coil in each carotid artery in 17-month-old C57BL/6 mice of both sexes. Mice were maintained for two months until they were used for experiments. Then, mice were tested for open field, elevated plus maze, tail suspension, and fear conditioning. After euthanasia, their eyes were analyzed by immunohistochemistry and electron microscopy.

Results:
We did not find significant differences in velocity and distance moved in the open field test, nor the elevated plus maze and tail suspension, but we did observe that BCAS significantly reduced the percentage of freezing time, compared with sham mice. Examination of the retina of the experimental mice revealed that BCAS mice showed a significantly reduced (p=0.02) synaptic layer or outer plexiform layer (OPL) area in the outer retina, compared with sham mice. Interestingly, the OPL in the retina of BCAS mice showed a significant reduction of horizontal cell bodies (p=0.023), an increase in the rod (p=0.054) and cone (p=0.033) sprout length, loss of cone terminals (p=0.037) and a reduction of pre- and post-synaptic protein expression (p=0.06), compared with the retina of sham mice.

Conclusions:
Our study indicates that BCAS mice exhibit cognitive impairment, specifically associated with conditioning memory. However, they do not show anxiety-like behavior. Furthermore, the eyes of BCAS mice show an ectopic distribution of rod and cone synapsis in the retina, which occurs with natural aging and consequently leads to vision loss. Thus, BCAS can exacerbate aging-associated phenotypes in the retina of aged mice. Our study is the first to report vision impairments in aged BCAS mice, which makes it a feasible model to identify the molecular mechanisms that govern visual impairments in VCID patients.
Abstract WP73: Effect of Nurse Driven Stroke Alert Activation on Door to Needle Times
Authors: Mayer Laurie , Yaworski Wendy , Delfino Kristie
Published: January 2025

Background:
Research indicates that quicker response times from onset of stroke symptoms to the initiation of treatment result in better recovery outcomes. The purpose of this study is to determine if consistent nurse-led stroke alert activation improves door to needle (DTN) times, which frequently results in better patient outcomes.

Method:
The method applied was a retrospective review of stroke alert records to evaluate the efficacy of different activation models. The period included in this review was January 2023 through December 2024. Each facility in this study is a primary stroke center with similar stroke alert volumes and treatment rates. The first facility reviewed (Facility “A”) used a physician-driven activation model in which a provider evaluated the patient to confirm appropriateness of neurological needs prior to stroke alert activation. The second facility included for review (Facility “B”) was consistently activating stroke alerts based on nursing evaluation alone. Taking the review a step further, the impact of implementing a nurse-driven activation process on door-to-needle times was included (Facility “C”).

Results:
Facility “A” had a physician-driven activation model. In the time evaluated, the activation average was 29 minutes with an average DTN of 53 minutes. Facility “B” had a consistent nurse-driven activation model. The activation average was 9 minutes with a DTN average of 34 minutes. The 68% faster activation time resulted in a 35% improvement in DTN. Finally, Facility “C” implemented a nurse-driven activation model as a process improvement project. From October 2023 (when process improvement implementation was initiated) through June 2024, their activation time average improved from 13 minutes to 10 minutes (23% improvement) and their DTN average improved from 41 minutes to 33 minutes (19% improvement).

Conclusion:
The implementation of a nurse-driven activation model decreases DTN times. Our data supports that empowering nurses to activate the stroke team based on their independent assessment promotes earlier activation, improves DTN times and ultimately, patient outcomes.
Abstract WP76: Leveraging Digital Health to Improve the Cardiovascular Health of Stroke Survivors: A Nurse-Led Approach
Authors: Meza Burgos Claudia Patricia , Juega Jesus , Francisco Jaume , Santos Alba , Duran Laura , Alvarez-Sabin Jose , SERO LAIA , Ustrell Xavier , Bashir Saima , Molina Carlos , Pagola Jorge
Published: January 2025

Background:
The aim of this study was to determine the impact of a nurse-led digital health intervention targeting cardiovascular risk in patients with cryptogenic stroke, as well as to identify factors associated with whether or not cardiovascular health improves.

Methods:
This is a secondary analysis of an ongoing randomized controlled trial of an digital health intervention that integrates advanced nursing practice to improve cardiovascular health in cryptogenic stroke patients aged 55 years or older, recruited in Spain (SMART THUNDER NCT03169257). The intervention consists of using an activity tracker and a mHealth application. The follow-up period was 12 months. The Life’s Simple 7 (LS7 score) is use to determine cardiovascular risk.

Results:
Out of 116 subjects, 59 participated in the digital health intervention group and 56 received usual care. Among all participants, higher self-reported health literacy (OR = 1.32, 95% CI: 1.166 - 1.501, p = 0.000) and higher self-reported attitude toward technology (OR = 1.26, 95% CI: 1.091 - 1.455, p = 0.002) were associated with and ideal LS7 score at 3 months. Compared with those receiving usual care, participants in the digital health intervention group showed significant improvement of LS7 score from 3 to 12 months (p = 0.013).

Conclusion:
The nurse-led digital health intervention was associated with greater self-improvement of cardiovascular health in stroke patients over time. This study also demonstrated that higher health literacy and a positive attitude towards technology contribute to improved cardiovascular outcomes, allowing us to identify a vulnerable subset of patients that might benefit from a more comprehensive digital health intervention.
Abstract WP78: Improving Quality of Care through the Implementation of a Dietitian-Led Enteral Access Team in the Post-Acute Stroke Population
Authors: Williams Devin , Madigan Carly
Published: January 2025

Introduction:
Dysphagia affects approximately 30-80% of ischemic stroke patients. While most patients recover swallowing functions within a week, 10-50% may experience persistent issues for up to six months post-stroke. Early enteral access is critical for providing hydration, nutrition, and medication to these patients. Stroke patients often require specialized nutritional support through feeding tubes. At a large urban academic comprehensive stroke center, we identified an opportunity to develop a model that supports and streamlines feeding tube placement for this population to enhance care quality and improve patient outcomes.

Methods:
This retrospective study evaluated enteral feeding support in 43 post-acute stroke patients from October 2023 through July 31st. We compared tube placements and outcomes between nursing staff and a dietitian-led enteral access team. Nursing staff used standard NG tube procedures, while the dietitian-led team employed advanced techniques, including an electromagnetic device and bridle retention system to enhance tube stability and reduce need for replacements. We also assessed discharges to acute rehabilitation with bridled small-bore tubes who would have otherwise required PEG placement
.

Results:
Out of 43 patients, 7 patients had NG tubes placed by nursing staff and 36 by the dietitian-led team. All 7 patients required replacement and were ultimately escalated to the dietitian-led team. The dietitian-led team achieved greater tube stability using advanced techniques and required only 1 replacement. A total of 13 patients were discharged to rehabilitation with bridled tubes.

Conclusion:
In conclusion, we found that a dietitian-led enteral access team can maintain high-quality care and satisfaction through advanced enteral tube placement techniques. Additionally, a subset of patients were able to defer PEG placement allowing for additional time for recovery from dysphagia. Future considerations include evaluating nurse workload reduction, decreased hospital stays, and accelerated rehabilitation placement with early, secure enteral access.