Beyond plaque morphology: a multimodal imaging model combining structural vulnerability and functional reserve predicts stroke recurrence in symptomatic intracranial atherosclerosis.

BACKGROUND: Symptomatic intracranial atherosclerotic disease (ICAD) is associated with a high risk of recurrent ischemic stroke, and improved risk stratification approaches are needed. The aim of this study was to develop a multimodal imaging model integrating high-resolution vessel wall imaging (HR-VWI)-derived plaque vulnerability with the cerebral collateral cascade (CCC) framework to predict long-term stroke recurrence in ICAD. METHODS: In this retrospective cohort study, patients with anterior-circulation ICAD underwent computed tomography angiography (CTA), CT perfusion (CTP), and HR-VWI. CCC status was assessed across arterial collaterals, tissue perfusion, and venous outflow (CCC+, CCCmixed, CCC-). HR-VWI metrics including plaque burden and enhancement ratio were quantified. Independent predictors were identified using Firth-corrected Cox models. The performance of single-modality (plaque-only or CCC-only) and integrated multimodal prediction models was evaluated using receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis, and DeLong's test. RESULTS: Among 89 patients (median follow-up 30.0 months), 20 experienced recurrent stroke. The recurrence group demonstrated significantly higher plaque burden, enhancement ratio, and hypoperfusion volume (all P<0.05). Recurrence rate was higher in the CCC- group (64.3%) than in the CCC+ group (5.3%, P<0.001). Multivariable analysis identified plaque enhancement ratio [adjusted hazard ratio (aHR) =2.52, P=0.005], plaque burden (aHR =1.07, P=0.013), and CCC- profile (aHR =3.39, P=0.005) as independent predictors. The multimodal model integrating these predictors demonstrated improved discriminative performance [area under the ROC curve (AUC) =0.829], outperforming the best plaque-only model (AUC =0.735, P<0.05). CONCLUSIONS: This multimodal model synergistically combines structural plaque vulnerability and functional hemodynamic reserve, providing a potentially useful tool for stratifying long-term recurrence risk in symptomatic ICAD.