Geometry of Terminal Internal Carotid Artery Bifurcation May Be Associated With Middle Cerebral Artery Plaque Ulceration: A Three-Dimensional Rotational Angiography Study

Intracranial atherosclerotic disease (ICAD) is a major cause of ischemic stroke.In patients with symptomatic ICAD, ICAD plaque ulceration as revealed through three-dimensional rotational angiography (3DRA) was associated with repetitive infarctions downstream, indicating possibly repetitive embolization. 1Hence, plaque ulceration represents a vulnerable plaque type in ICAD, and it is imperative to study the contributing factors.Previous studies have revealed the effects of carotid bifurcation geometry, in addition to systemic risk factors, on atherosclerosis in proximal internal carotid artery (ICA). 2,3Regarding ICAD, there is some evidence of the association between proximal artery geometry and early-stage atherosclerosis (e.g., non-stenotic plaque) in middle cerebral artery (MCA). 4However, it would be more clinically relevant to study such associations in patients with advanced ICAD (e.g., high-grade, symptomatic lesions), which bear a much higher stroke risk.In this study, we therefore aimed to investigate the association between terminal ICA bifurcation geometry and MCA-M1 plaque ulceration in patients with symptomatic, high-grade, atherosclerotic MCA-M1 stenosis.In a prospective, cross-sectional study, patients with ischemic stroke or transient ischemic attack within 1 month, attributed to high-grade (60%-99%), atherosclerotic MCA-M1 stenosis confirmed through 3DRA, were recruited.Patients with an ipsilateral hypoplastic anterior cerebral artery (ACA) were excluded.More inclusion/exclusion criteria are provided in Supplementary Meth-ods.This study was approved by the local Ethics Committee (Reference No. 2011.021), and all patients provided written informed consent.Ulcerative MCA-M1 plaque was defined as the invagination of contrast beneath the endoluminal lining or a >90˚ slope at the upstream or downstream plaque shoulder. 1Non-ulcerative plaques were defined as lesions with a smooth or irregular plaque surface. 1 We measured the distance of the plaque from the MCA origin and assessed the geometric features at the terminal ICA bifurcation in 3DRA, including the diameters at the MCA origin, ACA origin, and terminal ICA, and MCA-ACA angle (Figure 1 and Supplementary Methods).We calculated the area ratios of MCA versus ACA origin, MCA origin versus terminal ICA, and MCA+ACA origins versus terminal ICA.Continuous and categorical variables were respectively described using median (interquartile range, IQR) and numbers (percentage) and compared between patients with ulcerative and non-ulcerative plaques, using Wilcoxon rank sum tests and chisquare or Fisher's exact tests.The geometric features of ICA bifurcation with a P<0.05 in univariate analyses were analyzed using multivariate logistic regression for their independent associations with ulcerative MCA-M1 plaque, adjusting for age, sex in Model 1, plus cardiovascular risk factors in Model 2, and plus percent luminal stenosis in MCA-M1 in Model 3.All analyses were conducted using IBM SPSS Statistics v26.0 (IBM Corp., Armonk, NY, USA), with a two-sided P<0.05 considered to represent statistical significance.