Association of plaque characteristics with long-term stroke recurrence in patients with intracranial atherosclerotic disease: a 3D high-resolution MRI-based cohort study

Objectives To evaluate the predictive ability of plaque characteristics for long-term stroke recurrence among patients with symptomatic intracranial atherosclerotic disease (ICAD). Methods This cohort study included 132 patients with acute ischemic stroke (AIS) attributed to ICAD who were recruited between July 2017 and December 2020 and followed until stroke recurrence or December 2021. Plaque surface irregularity, degree of stenosis, plaque burden, remodeling ratio, enhancement ratio, and intraplaque hemorrhage were assessed with 3-dimensional high-resolution magnetic resonance vessel wall imaging (3D HR-MRI). Data were analyzed using Cox models, receiver operating characteristic (ROC) curves, and Kaplan–Meier survival analysis. Results Of the 132 patients, during a median follow-up of 2.8 years, stroke recurrence occurred in 35 patients. The multivariable-adjusted hazard ratio (95% confidence interval) of stroke recurrence was 3.15 (1.34–7.42) per 10% increase in plaque burden and 2.17 (1.27–3.70) for enhancement ratio. The area under the curve (AUC) to predict stroke recurrence was 0.725 (95% CI 0.629–0.822) for plaque burden, 0.692 (95% CI 0.593–0.792) for enhancement ratio, and only 0.595 (95% CI 0.492–0.699) for the Essen stroke risk score. The Kaplan–Meier survival analysis further demonstrated significant differences in survival of free recurrent stroke between patients with plaque burden or enhancement ratio below and above the optimum cut-offs (both p < 0.001). Conclusion Higher plaque burden and enhancement ratio are independent risk factors for long-term stroke recurrence among patients with symptomatic ICAD, and valuable imaging markers for predicting and stratifying risk of stroke recurrence. Clinical relevance statement In patients with symptomatic ICAD, the results of this high-resolution magnetic resonance vessel wall imaging study have potential implications for optimal management of intracranial plaques and secondary prevention of stroke recurrence based on plaque burden and enhancement ratio. Key Points • Identification of intracranial plaque characteristics responsible for stroke recurrence is essential to preventing stroke recurrence in patients with symptomatic intracranial atherosclerotic disease. • Higher plaque burden and enhancement ratio are independent risk factors for stroke recurrence. • Plaque burden and enhancement ratio are valuable imaging markers in the prediction and stratification of the risk of stroke recurrence. Supplementary Information The online version contains supplementary material available at 10.1007/s00330-023-10278-y.

Sensitized flow compensation was applied to suppress intraluminal blood signals originating from the arteries.Low refocusing flip angles (90 • ) were used to increase flow-void effects and decrease image.The contrast enhanced T1-VISTA parameters were the same with those of precontrast T1-VISTA.

Image analysis
The evaluation of MR vessel wall imaging was independently conducted by two experienced neuroradiologists, using medical imaging viewer software (Extended MR WorkSpace, Philips Medical Systems).Image quality was graded using a four-point scale (1, poor; 2, marginal; 3, good; and 4, excellent) based on the overall signal-to-noise ratio and the clarity of the vessel wall boundaries [1], and the images with image quality ≥3 were qualified for analysis.
Atherosclerotic plaques on MR vessel wall imaging were identified using a previously reported definition, i.e., the presence of focal wall thickening with or without significant luminal stenosis [2].A plaque was considered a culprit plaque when it was (a) the only lesion within the vascular territory of the stroke or (b) the most stenotic lesion when multiple plaques were present within the same vascular territory of the stroke [2].
The culprit plaque characteristics, including plaque surface irregularity, lumen stenosis, plaque burden, remodeling ratio, enhancement ratio and intraplaque hemorrhage, were analyzed.The normal vessel segments proximal to the culprit plaques were assessed as reference values.Plaque surface irregularity was defined as a discontinuity of the plaque juxtaluminal surface, and regularity defined as smooth inner wall [3].The vessel area (VA) and lumen area (LA) were automatically calculated by manually tracing the outer vessel and lumen contours.The wall area (WA ) was the difference between vessel area and lumen area.The stenosis degree was calculated as: (1-lesion lumen area/reference lumen area) ×100% [4].
Plaque burden was calculated as: wall area (WA )/vessel area (VA) ×100% [5].The schematic diagram regarding the measurement of the plaque burden is shown in Figure S1.Remodeling ratio was calculated as the ratio of the lesion vessel area to the reference vessel area [4].
Enhancement ratio was measured at the slice of greatest enhancement, using adjacent gray matter (in a region of ～ 15 mm 2 ) to normalize signal intensity.Enhancement ratio was calculated as: [signal of plaque (post-contrast)/signal of gray matter (post-contrast)-signal of plaque (pre-contrast)/signal of gray matter (pre-contrast)]/[signal of plaque (precontrast)/signal of gray matter (pre-contrast)] [6].Intraplaque hemorrhage was defined as >150% signal relative to nearby muscles on pre-contrast T1-weighted images [6].
After two months of the initial evaluation, we randomly selected images of 30 patients to evaluate the inter-reader agreement in the assessments of plaque characteristics.There was excellent inter-observer agreement for the identification and measurement of plaque characteristics.The intraclass correlation coefficient (ICC) values were 0.951 (95% CI 0.858-0.980)for degree of stenosis, 0.939 (95% CI 0.821-0.975)for plaque burden, 0.952 (95% CI 0.881-0.979)for enhancement ratio, and 0.933 (95% CI 0.866-0.967)for remodeling ratio.The Kappa values were 0.83 for surface irregularity, and 1.0 for intraplaque hemorrhage.

Outcome assessment
The main outcome of this study was occurrence of a recurrent ischemic stroke in the same vascular territory during follow-up.The recurrent stroke was defined as a new neurological deficit or a sudden deterioration of a previous deficit which occurred over 21 days after the onset of the initial event and was attributable to a confirmed new cerebral infarct relevant to clinical symptoms in the same vascular territory as the initial event on brain imaging [7].
Patients were followed up via face-to-face or telephone interviews until occurrence of recurrent stroke or 31 December 2021, whichever came first.The recurrent stroke was diagnosed and confirmed by the routine head MRI scan, including DWI.The detailed information about the recurrence of stroke, risk factors and current medical treatment were recorded.

Figure S1 .
Figure S1.The schematic diagram regarding measurement of the plaque burden.

Table S1 .
Predictive parameters of plaque burden, enhancement ratio, and ESRS for stroke recurrence ESRS: Essen stroke risk score; AUC: Area under the curve.Eur Radiol (2023) Lv Y, Ma X, Zhao W et al.