Purpose: This study aimed to explore the relationship between serum inflammatory biomarkers and the carotid atherosclerotic plaque characteristics, given prior evidence suggesting a key role of inflammation in the development of atherosclerosis. Methods: In this prospective study, patients with carotid atherosclerotic plaque were recruited. Serum high-sensitivity CRP (Hs-CRP), homocysteine (Hcy) concentrations, and neutrophil-to-lymphocyte ratio (NLR) were obtained for all enrolled patients. Carotid atherosclerosis characteristics (such as intraplaque hemorrhage [IPH] and lipid-rich necrotic core [LRNC]) were determined by three-dimensional high-resolution vessel wall imaging. The associations between Hs-CRP, Hcy, NLR, and plaque characteristics were assessed. Results: In total, 128 patients (84.4% men; mean age, 58.0 ± 8.7 years) were included. Multivariate logistic regression indicated that increased Hs-CRP levels were associated with the presence of LRNC (OR = 1.23, 95% CI: 1.07–1.40, p = 0.003) and IPH (OR = 1.26, 95% CI: 1.10–1.45, p = 0.001). Multivariate linear regression confirmed a significant correlation between Hs-CRP level (β = 3.24, 95% CI: 0.66–5.81, p = 0.014) and the IPH volume. For plaque burden, higher Hs-CRP levels were associated with larger max normalized wall index (NWI) (β = 0.01, 95% CI: 0.00–0.02, p = 0.005) and larger Max wall thickness (β = 0.08, 95% CI: 0.02–0.14, p = 0.006). NLR and Hcy levels did not show significant associations with the carotid plaque characteristics. Conclusions: Elevated Hs-CRP levels were found to be closely associated with plaque burden and vulnerable plaque characteristics. The relationship between the elevated Hs-CRP and plaque vulnerability highlights its potential role in risk stratification and early intervention strategies. Further validation in larger, multicenter population studies is required to confirm these associations.

Background and Aims: High-risk carotid plaque features may contribute to atherosclerotic ischemic stroke beyond stenosis severity. PlaqueRADS is a multimodal grading system integrating plaque vulnerability markers, but its patterns using CTA plus vessel wall imaging (VWI) across stroke etiologies remain unclear. We aimed to compare PlaqueRADS distributions across etiologic subtypes and explore whether ipsilateral scoring provides insights into ESUS mechanisms. Methods: We retrospectively studied patients with unilateral anterior circulation ischemic stroke at a single center who underwent CTA+VWI and met diagnostic criteria for cardioembolic (CE) or large-artery atherosclerotic (LAA) per TOAST, and ESUS per 2022 criteria excluding high-risk PFO. PlaqueRADS was independently scored by three radiologists, excluding cases without bilaterally evaluable arteries. Between-group comparisons were performed using Wilcoxon rank-sum tests, and ipsilateral–contralateral paired analyses with Wilcoxon signed-rank and Sign tests at different PlaqueRADS thresholds. Results: Among 163 patients (CE=71, LAA=48, ESUS=44), ipsilateral PlaqueRADS ≥3 was more frequent in LAA (64.6%) and CE (45.07%) than in ESUS (27.3%). Ipsilateral scores were higher in LAA vs CE (p<0.001) and LAA vs ESUS (p<0.001), while ESUS vs CE did not differ (p=0.145). Within-etiology analyses showed ipsilateral enrichment in CE (p=0.0015) and LAA (p=0.004), but not in ESUS (p=0.97). In exploratory analyses of ESUS, no cutoff reached statistical significance; however, PlaqueRADS ≥4 occurred exclusively ipsilaterally (4/44 vs 0/44). Descriptive analysis of those 4 ESUS patients showed median age 71 years, universal smoking, 3/4 hypertensive, and preserved cardiac features, consistent with an atherothrombotic profile; however, one developed paroxysmal AF. During follow-up, 22% of ESUS patients developed new AF, and PFO prevalence remained higher than in CE/LAA despite exclusion of high-risk cases. Conclusion: LAA exhibits the highest ipsilateral PlaqueRADS burden, while CE patients also show non-negligible atherosclerotic findings. ESUS remains heterogeneous, overall resembling CE, but ~9% harbor unilateral high-risk PlaqueRADS (≥4), compatible with an atherothrombotic phenotype. Standardized PlaqueRADS scoring using VWI may refine ESUS classification and guide trial design by identifying patients less likely to benefit from anticoagulation over antiplatelet strategies. Validation in larger cohorts is warranted.

Diseases of the arterial wall are best diagnosed using vessel wall magnetic resonance imaging (MRI) since luminal imaging does not show the extent of wall pathology. Intracranial and extracranial carotid artery pathology such as atherosclerosis, dissections, vasculitis, and occlusions can lead to clinically significant events such as stroke. Direct visualization of the arterial wall pathology using vessel wall MRI can direct clinical diagnosis and management. This review highlights the importance of carotid and intracranial vessel wall MRI and their clinical applications in neurovascular pathologies. Recent developments such as the carotid Plaque-Reporting and Data System risk scoring and intracranial vasculopathy differentiation using vessel wall MRI are reviewed. Technical requirements of vessel wall MRI sequences for clinical diagnosis and future diagnostic approaches such as stroke etiology reclassification are also discussed.

Many biomedical data exhibit intrinsic graph-like properties, making graph neural networks (GNNs) widely adopted modeling tools. The brain arterial network (BAN) represents the most complex arterial network in humans, where conventional GNNs struggle to capture critical long-range relationships. Recent graph transformers have enabled modeling of these long-range dependencies through attention mechanisms; however, they face challenges in incorporating hierarchical information, especially when strong anatomical priors exist within the graph structure. While some approaches have attempted to integrate hierarchical information into graph transformers, they primarily focus on node feature aggregation, despite BAN's most clinically significant features residing in edges rather than nodes. To address these limitations, we propose a hierarchical graph transformer (HGT) with edge-aware structural encoding that better incorporates anatomical and multi-scale structural information. Our approach achieves state-of-the-art performance across all 11 tasks. This work lays the foundation for individualized risk assessment that complements traditional systemic risk evaluation methods.

BackgroundThe relationship between serum inflammatory biomarkers, carotid atherosclerotic plaque characteristics, and the recurrence of ischemic events remains a subject of ongoing debate.PurposeTo investigate whether the combination of carotid atherosclerotic plaque burden and serum inflammatory biomarkers could help predict ipsilateral ischemic stroke recurrence.Material and MethodsPatients with cerebral infarction were prospectively recruited and received three-dimensional vessel wall imaging (VWI). Baseline serum level of high-sensitivity C-reactive protein (hs-CRP) and the neutrophil-to-lymphocyte ratio (NLR) was recorded. Plaque burden was independently measured by two trained readers. Stroke recurrence was assessed at 1 year after discharge. Factors associated with stroke recurrence were analyzed. Receiver operating characteristic curves were used to calculate areas under the curve (AUCs) of inflammatory biomarkers and plaque burden for predicting stroke recurrence.ResultsA total of 56 patients were included, with recurrence in nine patients. hs-CRP (odds ratio [OR] = 1.60, 95% confidence interval [CI] = 1.17-2.19; P = 0.017) and carotid normalized wall index (NWI) (OR = 1.08, 95% CI = 1.01-1.16; P = 0.023) were found associated with stroke recurrence. Multivariate logistic regression showed that hs-CRP (OR = 1.67, 95% CI = 1.17-2.38; P = 0.005) and NWI (OR = 1.10, 95% CI = 1.01-1.20, P = 0.023) remained associated with stroke recurrence. Hs-CRP (AUC = 0.806; P = 0.002) and NWI (AUC = 0.738; P <0.001) were predictors of stroke recurrence. The combination of hs-CRP with NWI (AUC = 0.811, P <0.001) demonstrated the best performance in terms of predicting stroke recurrence.ConclusionBoth hs-CRP and NWI were independently associated with stroke recurrence. The combination of hs-CRP and NWI may be a good predictor of 1-year stroke recurrence.

Background Cerebrovascular disease (CVD) and Alzheimer's disease (AD) share common risk factors and often coexist. This study investigates the relationship between cerebral arterial features and cognitive decline in patients with clinical AD dementia and amnestic mild cognitive impairment (MCI) using quantitative analysis of Time-Of-Flight (TOF) magnetic resonance angiography (MRA). Methods 131 patients (101 AD dementia, 30 amnestic MCI) underwent baseline TOF-MRA and cognitive assessments and 24-month follow-up cognitive tests. Total distal arterial length was measured using a custom-designed semi-automatic intracranial vascular map construction software. Associations between total distal arterial length and cognitive changes were analyzed using multiple linear regression and repeated measures analysis of covariance. Results Shorter total distal arterial length was significantly associated with greater 2-year decline in Montreal Cognitive Assessment (MoCA) scores over 2 years (r = 0.199, p = 0.020). This association remained significant after adjusting for various confounding factors, including age, sex, education, brain parenchymal fraction, white matter hyperintensities, ApoE4 status, and vascular risk factors. Similar trends were observed for Mini-Mental State Examination (MMSE) scores, although not reaching statistical significance. Conclusions Quantitative measurements of cerebral vasculature on TOF-MRA are independently associated with cognitive decline in patients with clinical AD dementia and amnestic MCI. This suggests that reduced cerebral blood flow may contribute to cognitive decline in these patients, highlighting the potential role of vascular factors in AD progression. These findings support the use of quantitative cerebral arterial measurements as a potential imaging biomarker for cognitive decline in AD.

Background:Contrast enhancement (CE) of intracranial atherosclerotic plaques is a valuable biomarker for identifying culprit plaques in ischemic stroke, but current assessment methods are limited by qualitative approaches and artifact susceptibility. Purpose:To develop and validate a semi-automated method for visualization and quantification of CE intensity and volume, and evaluate its accuracy and scan-rescan reproducibility. Study type:Retrospective. Population:Two patient groups with intracranial atherosclerotic diseases were included: Group A (n=37, 82 plaques) for developing and validating the CE map against expert review, and Group B (n=11, 23 plaques) for assessing scan-rescan reproducibility. Field Strength/Sequence:3.0 T, 3D time-of-flight gradient echo sequence and T1-weighted fast spin echo sequences, before and after Gadolinium contrast injection. Assessment:A 3D quantitative CE map was developed that incorporated dedicated multicontrast, multi-planar preprocessing, image intensity normalization, adjustment for enhancement artifacts, and derivation of a signal intensity threshold. Statistical Tests:Receiver operating characteristic curve analysis determined the optimal CE threshold. Sensitivity, specificity, and Cohen's kappa assessed agreement between the quantitative CE map and manual review. Spearman's correlation evaluated CE volume quantification. Intraclass correlation coefficient (ICC) and coefficient of variance (CV) assessed reproducibility. Results:The optimal signal intensity threshold for post-contrast maps was 0.4 plus the median plaque wall intensity on pre-contrast maps. The area under the curve for CE detection was 0.91 (95% CI: 0.87-0.94), with sensitivity and specificity of 0.83 and 0.90. CE volume measurements strongly correlated with expert measurements (Spearman's rho=0.82, p<0.001). Enhancement ratio showed high reproducibility (ICC=0.92, 95% CI: 0.82-0.96), and CE detection demonstrated robust agreement (kappa=0.82, 95% CI: 0.55-1). Data Conclusion:The proposed CE map demonstrated good accuracy compared to expert review and high scan-rescan reproducibility, enabling comprehensive assessment of CE presence, intensity, and volume for evaluating plaque vulnerability in intracranial atherosclerotic disease.

OBJECTIVE:Carotid plaque disruption with release of atheroembolic debris and consequent brain infarction is the primary mechanism for brain injury in patients with carotid stenosis. Disease severity is quantified traditionally by the degree of stenosis, although it is not an accurate marker of stroke risk. It has been proposed that biomechanical forces acting on a carotid plaque may render it vulnerable to rupture by causing adverse remodeling of its morphology or by direct disruption. We conducted a systematic review to assess the forces acting on carotid plaques and their relationship to adverse plaque outcomes. METHODS:A literature search for studies reporting measurements of flow-related biomechanical forces acting on carotid atherosclerotic plaques was conducted using PubMed, Embase, and Web of Science. Studies were included if they reported on human carotid plaques, used patient-specific geometry, measured forces on or in the atherosclerotic lesions, and reported on carotid plaque-related adverse outcomes. RESULTS:Of 5635 articles screened, 154 met eligibility criteria. Forces were computed using patient-specific arterial geometry derived from multiple imaging modalities, mainly magnetic resonance imaging (58.4%) and ultrasound examination (25.3%). Methodologies used to quantify the forces included computational fluid dynamics (31.8%), finite element analysis (10.4%), fluid-structure interaction models (27.3%), in vivo measurements (29.9%), and in vitro assessments (0.6%). Wall shear stress (WSS) and plaque wall stress (PWS) were the most frequently measured forces, in 72.1% and 45.5% of studies, respectively. Principal PWS (n = 15 studies) and WSS (n = 21 studies) were elevated in patients with adverse outcomes. PWS levels of >160 kPa had a sensitivity of >80% and specificity of >75% in identifying patients with adverse events. Increasing PWS was associated with subsequent ischemic cerebrovascular events (HR=hazard ratio, 12.98 per 1 kPa increase; P = .02). WSS levels of >50 dyn/cm2 had a sensitivity of 100% and specificity of 67% in differentiating patients with adverse events (plaque rupture, cerebral infarction, stroke, or transient ischemic attack) compared with those without. CONCLUSIONS:There is heterogeneity in sample size, study design, imaging protocols, image processing methodology, forces assessed, and adverse carotid plaque-related outcomes measured in the literature. Despite these limitations, increasing PWS and WSS were associated with adverse plaque outcomes consistently and predicted adverse outcomes with moderate to high degrees of sensitivity and specificity. Because the information available is heterogenous, these relationships need to be confirmed in larger prospective studies.

BACKGROUND:Inflammation and immune dysregulation are thought to drive residual cardiovascular disease risk among persons living with human immunodeficiency virus (HIV) (PLWH) despite effective viral suppression with antiretroviral therapy (ART). METHODS:We investigated differences in carotid inflammation and atherosclerosis in a longitudinal cohort of virally suppressed PLWH (N = 50; on stable ART with CD4 > 250 cells/mm3, viral load < 200 copies/mL for > 6 months) and HIV-uninfected controls (N = 51) matched for age, sex, hypertension, diabetes, smoking, hyperlipidemia, and family history of premature coronary artery disease (CAD). Participants were ≥ 40 years old at enrollment. Measures of carotid vascular inflammation (Ktrans), neovascularization (Vp), and wall thickness were assessed at baseline, 1 year, and change over 1 year by dynamic contrast-enhanced magnetic resonance imaging (MRI). RESULTS:Among 101 participants, 8% were women, 42% had hypertension, 52% had hyperlipidemia, 16% had diabetes, and 48% had a family history of CAD. Both PLWH and control participants demonstrated a reduction in systolic and diastolic blood pressures and total cholesterol over 1 year; however, the difference was not significant by HIV status. PLWH had a significant reduction in triglycerides compared with controls (-48.8 vs 12.8 mg/dL, p = 0.026). HIV was not associated with baseline, follow up, or change in markers of systemic inflammation assessed by plasma cytokines, nor vascular inflammation as assessed by Ktrans, Vp, carotid wall thickness, or percent wall volume (a measure of plaque burden). CONCLUSION:In contrast to other studies of treated and virally suppressed PLWH, HIV infection was not associated with carotid inflammation or plaque in our hypothesis-generating study.

BACKGROUND:Carotid atherosclerosis is a major contributor to the etiology of ischemic stroke. Although intraplaque hemorrhage (IPH) is known to increase stroke risk and plaque burden, its long-term effects on plaque dynamics remain unclear. This study aimed to evaluate the long-term impact of IPH on carotid plaque burden progression using deep learning-based segmentation on multi-contrast magnetic resonance vessel wall imaging (VWI). METHODS:28 asymptomatic subjects with carotid atherosclerosis underwent an average of 4.7±0.6 VWI scans over 5.8±1.1 years. Deep learning pipelines were used to segment the carotid vessel walls and IPH. Bilateral plaque progression was analyzed using correlation coefficients and generalized estimating equations. Associations between IPH occurrence, IPH volume, and plaque burden (%WV) progression were evaluated using linear mixed-effect models. RESULTS:IPH was detected in 23/50 of the arteries at any time point. Of arteries without IPH at baseline, 11/39 developed new IPH that persisted, while 5/11 arteries with baseline IPH exhibited it throughout the study. Bilateral plaque growth was significantly correlated (r = 0.54, p<0.001), but this symmetry was weakened in cases with IPH (r = 0.1, p = 0.62). Moreover, IPH presence or development at any point was associated with a 2.3% absolute increase in %WV on average within the affected artery (p<0.001). The volume of IPH was also positively associated with increased %WV (p = 0.005). CONCLUSION:Deep learning-based segmentation pipelines were utilized to identify IPH, quantify IPH volume, and measure their effects on carotid plaque burden during long-term follow-up. Findings demonstrated that IPH may persist for extended periods. While arteries without IPH demonstrated minimal progression under contemporary treatment, the presence of IPH and greater IPH volume significantly accelerated long-term plaque growth.

Background:The clinical manifestations of cerebrovascular disease are known to differ between the Chinese and United States (U.S.) populations as do the plaque features on imaging. Objectives:The aim of this study was to investigate and compare the histological features of excised carotid plaques from Chinese and U.S. patients. Methods:Carotid endarterectomy specimens collected from two prospective studies were included. The entire plaque was serially sectioned (10 μm thickness) at 0.5-1 mm intervals. Hematoxylin and eosin staining and Mallory's trichrome staining were performed. The morphology and components of the plaques were measured and compared between the two groups. Results:A total of 1,152 histological sections from 75 Chinese patients and 1,843 sections from 111 U.S. patients were analyzed. The Chinese group had significantly smaller minimum lumen diameters (median: 1.1 vs. 1.3 mm, p=0.046) and a larger percent wall volume (median: 74% vs. 70%, p=0.018) than the U.S. group. After adjusting for confounding factors, carotid plaques in the Chinese population were more likely to have more lipid pools (β=10.0%, 95%CI: 4.9 to 15.9%), more recent intraplaque hemorrhage (IPH; β=8.4%, 95%CI: 4.5 to 12.7%), and less late IPH (β=-8.2%, 95%CI: -11.3 to -5.4), and fewer fibrous cap disruptions (45% vs. 67%, p=0.061). Chinese plaques were more homogeneous and had a higher percentage of plaques with features of xanthomas than did U.S. plaques (20% vs 2.7%, p<0.001). Conclusions:The histology of Chinese plaques differs significantly from that of U.S. plaques, suggesting substantial differences in the pathophysiology of atherosclerotic cerebrovascular disease between Chinese and North American populations, which could enhance the gap in racial pathology comparison, indicating a need for a different management approach.

OBJECTIVE:To investigate the potential value of serum inflammatory markers combined with carotid plaque characteristics for predicting subsequent recurrent ischemic events. METHODS:Patients with cerebral infarction localized to the internal carotid artery territory were recruited. Carotid MRI examinations were performed, and the plaque characteristics were evaluated at baseline. Serum samples were obtained, and clinical characteristics were documented at baseline. All participants received clinical follow-up 1 year after discharge. Recurrent ipsilateral ischemic stroke was considered the clinical endpoint. Logistic regression analyses were employed to assess the correlations between serum inflammatory biomarkers, plaque characteristics, and the endpoint. The diagnostic performances were evaluated using receiver operating characteristic curves. DeLong's test was used to compare the areas under the curve (AUCs) of the models. RESULTS:In total, 89 patients (84.3% men; mean age, 56.57 ± 9.05 years) with recent anterior circulation (carotid territory) cerebral hemisphere ischemia were included. Sixteen patients presented with an endpoint within the 1-year follow-up. Multivariate logistic regression demonstrated that the normalized wall index, intraplaque hemorrhage, lipid-rich necrotic core, and high-sensitivity C-reactive protein (Hs-CRP) were associated with the endpoint. The model combining plaque characteristics and Hs-CRP had the highest diagnostic performance with an AUC of 0.855. CONCLUSIONS:Serum Hs-CRP level and plaque characteristics may provide complementary information for predicting recurrent stroke. The combination of these two indicators may be a better potential predictor of the population at high risk of stroke recurrence.

Purpose Intraplaque haemorrhage (IPH) is a well-known risk factor for faster plaque progression (volume increase); however, its etiology is unclear. We aimed at determining what other local plaque- and systemic factors contribute to plaque progression and to the development and progression of IPH. Methods We examined 98 asymptomatic participants with carotid plaque using serial multi-contrast magnetic resonance imaging. We measured the percent of wall volume (%WV=100 x [wall volume] / [total vessel volume]) and measured IPH and calcification volumes. We used generalized estimating equations-based regression to analyze predictors of %WV change and new IPH while accounting for covariates (sex, age and statin use), and multiple non-independent observations per participant. Results Total follow-up was 1.8 ± 0.8 years on average. The presence of IPH (β: 0.6 %/y, p = 0.033) and calcification (β: 1.2 %/y, p = 0.028) were each associated with faster plaque progression. New IPH, detected on a subsequent scan in 4 % of arteries that did not initially have IPH, was associated with larger calcification (odds ratio [OR]: 2.6 per 1-SD increase, p = 0.038) and higher pulse pressure (OR: 2.3 per 1-SD increase, p = 0.016). Larger calcification was associated with greater increases in pulse pressure (β: 1.4 mm Hg/y per 1-SD increase, p = 0.040). Conclusions IPH and calcification are each independently associated with faster plaque progression. The association of carotid calcification to increased pulse pressure and new IPH development suggests a possible mechanism by which calcification drives IPH development and plaque progression.

PurposeTo develop an automated deep learning model for MRI-based segmentation and detection of intracranial arterial calcification.MethodsA novel deep learning model under the variational autoencoder framework was developed. A theoretically grounded dissimilarity loss was proposed to refine network features extracted from MRI and restrict their complexity, enabling the model to learn more generalizable MR features that enhance segmentation accuracy and robustness for detecting calcification on MRI.ResultsThe proposed method was compared with nine baseline methods on a dataset of 113 subjects and showed superior performance (for segmentation, Dice similarity coefficient: 0.620, area under precision-recall curve [PR-AUC]: 0.660, 95% Hausdorff Distance: 0.848 mm, Average Symmetric Surface Distance: 0.692 mm; for slice-wise detection, F1 score: 0.823, recall: 0.764, precision: 0.892, PR-AUC: 0.853). For clinical needs, statistical tests confirmed agreement between the true calcification volumes and predicted values using the proposed approach. Various MR sequences, namely T1, time-of-flight, and SNAP, were assessed as inputs to the model, and SNAP provided unique and essential information pertaining to calcification structures.ConclusionThe proposed deep learning model with a dissimilarity loss to reduce feature complexity effectively improves MRI-based identification of intracranial arterial calcification. It could help establish a more comprehensive and powerful pipeline for vascular image analysis on MRI.

BACKGROUND AND PURPOSE: The circle of Willis (COW) is a crucial mechanism for cerebral collateral circulation. This proof-of-concept study aims to develop and assess an analysis method to characterize the hemodynamics of the arterial segments in the COW by using arterial spin-labeling (ASL) based non-contrast-enhanced dynamic MR angiography (dMRA). MATERIALS AND METHODS: The developed analysis method uses a graph model, bootstrap strategy, and ensemble learning methodologies to determine the time curve shift from ASL dMRA to estimate the flow direction within the COW. The performance of the method was assessed on 52 subjects, by using the flow direction, either antegrade or retrograde, derived from 3D phase-contrast MR imaging as the reference. RESULTS: A total of 340 arterial segments in the COW were evaluated, among which 30 (8.8%) had retrograde flow according to 3D phase-contrast MRI. The ASL dMRA-based flow direction estimation has an accuracy, sensitivity, and specificity of 95.47%, 80%, and 96.34%, respectively. CONCLUSIONS: Using ASL dMRA and the developed image analysis method to estimate the flow direction in COW is feasible. This study provides a new method to assess the hemodynamics of the COW, which could be useful for the diagnosis and study of cerebrovascular diseases.

The clinical significance of measuring vessel wall thickness is widely acknowledged. Recent advancements have enabled high-resolution 3D scans of arteries and precise segmentation of their lumens and outer walls; however, most existing methods for assessing vessel wall thickness are 2D. Despite being valuable, reproducibility and accuracy of 2D techniques depend on the extracted 2D slices. Additionally, these methods fail to fully account for variations in wall thickness in all dimensions. Furthermore, most existing approaches are difficult to be extended into 3D and their measurements lack spatial localization and are primarily confined to lumen boundaries. We advocate for a shift in perspective towards recognizing vessel wall thickness measurement as inherently a 3D challenge and propose adapting the Laplacian method as an outstanding alternative. The Laplacian method is implemented using convolutions, ensuring its efficient and rapid execution on deep learning platforms. Experiments using digital phantoms and vessel wall imaging data are conducted to showcase the accuracy, reproducibility, and localization capabilities of the proposed approach. The proposed method produce consistent outcomes that remain independent of centerlines and 2D slices. Notably, this approach is applicable in both 2D and 3D scenarios. It allows for voxel-wise quantification of wall thickness, enabling precise identification of wall volumes exhibiting abnormal wall thickness. Our research highlights the urgency of transitioning to 3D methodologies for vessel wall thickness measurement. Such a transition not only acknowledges the intricate spatial variations of vessel walls, but also opens doors to more accurate, localized, and insightful diagnostic insights.

Background Hypertension‐induced impairment of the cerebral artery network contributes to cognitive impairment. Characterizing the structure and function of cerebral arteries may facilitate the understanding of hypertension‐related pathological mechanisms and lead to the development of new indicators for cognitive impairment. Purpose To investigate the associations between morphological features of the intracranial arteries distal to the circle of Willis on time‐of‐flight MRA (TOF‐MRA) and cognitive performance in a hypertensive cohort. Study Type Prospective observational study. Population 189 hypertensive older males (mean age 64.9 ± 7.2 years). Field Strength/Sequence TOF‐MRA sequence with a 3D spoiled gradient echo readout and arterial spin labeling perfusion imaging sequence with a 3D stack‐of‐spirals fast spin echo readout at 3T. Assessment The intracranial arteries were segmented from TOF‐MRA and the total length of distal arteries (TLoDA) and number of arterial branches (NoB) were calculated. The mean gray matter cerebral blood flow (GM‐CBF) was extracted from arterial spin labeling perfusion imaging. The cognitive level was assessed with short‐term and long‐term delay‐recall auditory verbal learning test (AVLT) scores, and with montreal cognitive assessment. Statistical Tests Univariable and multivariable linear regression were used to analyze the associations between TLoDA, NoB, GM‐CBF and the cognitive assessment scores, with P < 0.05 indicating significance. Results TLoDA ( r = 0.314) and NoB ( r = 0.346) were significantly correlated with GM‐CBF. Multivariable linear regression analyses showed that TLoDA and NoB, but not GM‐CBF ( P = 0.272 and 0.141), were significantly associated with short‐term and long‐term delay‐recall AVLT scores. These associations remained significant after adjusting for GM‐CBF. Data Conclusion The TLoDA and NoB of distal intracranial arteries on TOF‐MRA are significantly associated with cognitive impairment in hypertensive subjects. Level of Evidence 2 Technical Efficacy Stage 3

Introduction: Defining the specific underlying pathophysiology of ischemic stroke is critical for minimizing the risk of recurrent events with personalized secondary prevention treatments. A notable portion of ischemic strokes are classified as embolic stroke of undetermined source (ESUS), leaving these patients without optimal treatment tailored to their pathophysiology. Hypothesis: Standard clinically collected data can reliably reclassify a substantial portion of ESUS patients into either a large artery atherosclerotic (LAA) or cardioembolic (CE) cause. Methods: A statistical model was developed to discriminate LAA from CE using a retrospective cohort of ischemic stroke patients treated at the University of Washington. A total of 189 patients were included (79 CE and 61 LAA to train the model, 49 ESUS patients to assess reclassification). Sixteen candidate predictors were collected across several sources: clinical risk factors, blood tests, echocardiography, ECG, and neurovascular imaging (Table 1). The LASSO (least absolute shrinkage and selection operator) was used to select important predictors in a penalized logistic regression model with stroke etiology (LAA vs. CE) as the outcome. ESUS patients were considered reclassified if the model-based probability of CE or LAA was at least 75%. Results: Of 189 patients, the mean (SD) age was 68 (14) years and 40% were women. The LASSO selected 12 predictors to discriminate CE vs. LAA (Table 1), with a corresponding cross-validated C-statistic = 0.87 (95% CI: 0.82-0.94). When the model was applied to the 49 ESUS patients, 23 (47%) were reclassified to LAA and 6 (12%) to CE. Conclusions: A multivariate model based on standard clinical data can separate LAA from CE with a high degree of discrimination. Applying this model led to reclassification to either LAA or CE in 59% of ESUS patients. Such approaches may enable more personalized secondary prevention strategies, but need to be tested in future trials.

PURPOSE:Atherosclerotic plaques of carotid artery (CA) and middle cerebral artery (MCA) are important causes of acute ischemic stroke (AIS). This study was designed to jointly assess the plaque distribution and features of CA and MCA in AIS patients with pial infarction (PI) and perforating artery infarction (PAI), and to investigate the associations between plaque characteristics and ischemic infarction patterns. METHODS:Imaging data of sixty-five patients from a cross-sectional study were reviewed. All the patients had acute infarction in the MCA territory on diffusion weighted imaging (DWI) and underwent CA and MCA vessel wall imaging (VWI). The CA and MCA plaque presence and high-risk features on the ipsilateral side of infarction were analyzed. The brain infarction lesions were divided into PI group vs. non-PI group, and PAI group vs. non-PAI group. Different plaque distribution types and plaque features were compared in each two groups, and their associations were investigated using binary logistic regression. RESULTS:Sixty-five patients (mean age, 54.6 ± 10.1 years; 61 men) were included. The CA high-risk plaque (OR: 5.683 [1.409-22.929], P = 0.015) and MCA plaque presence (OR: 3.949 [1.397-11.162], P = 0.010) were significantly associated with PI. MCA plaques that involved the orifice of the perforating arteries were significantly associated with PAI (OR: 15.167 [1.851-124.257], P = 0.011). CONCLUSION:CA and MCA plaques show distinct distribution and high-risk features in patients with PI and PAI. Combined intracranial and extracranial arteries imaging should be considered for the evaluation of the symptomatic ischemic patients.

Recent studies report that the rate of recurrent stroke is highest in the stages immediately following cerebral infarction and decreases over time in patients with atherosclerotic carotid stenosis. The purpose of this study was to identify temporal differences in early stage carotid plaque components from acute cerebrovascular ischemic events using carotid MRI. Carotid plaque images were obtained on 3 T MRI from 128 patients enrolled in MR-CAS. Among the 128 subjects, 53 were symptomatic and 75 asymptomatic. The symptomatic patients were classified into three groups based on interval from onset of symptoms to the date of the carotid MRI (Group <14 days; 15-30 days; and > 30 days). The volume of each plaque component was identified and quantified from MR images. The presence of juxtaluminal loose matrix/inflammation (LM/I) was identified as a possible indicator of inflammation on the luminal side. Plaque components were compared between groups using the Wilcoxon rank-sum or the Chi-square test. Patient characteristics and carotid plaque morphology were similar among all four groups. The median volume of LM/I in Group >30 days was significantly lower than in other groups (0 mm3 vs 12.3 mm3 and 18.1 mm3; p = 0.003). In addition, the prevalence of juxtaluminal LM/I decreased over time (ptrend = 0.002). There were no statistically significant differences in other plaque components between the symptomatic groups. The volume of LM/I was significantly smaller in Group >30 days and prevalence of juxtaluminal LM/I in the atherosclerotic carotid plaque was high in the early stages after events. This suggests that carotid plaques undergo rapid evolution after an acute cerebrovascular ischemic event.