Distinct vulnerable plaque phenotypes underlie perforator and hypoperfusion strokes: multimodal high resolution...

Intracranial atherosclerotic stenosis (ICAS) causes ischemia, predominantly from downstream hemodynamic compromise or perforator artery occlusion. We compared plaque morphology and composition between these mechanisms using high resolution vessel wall imaging (HR-VWI) and optical coherence tomography (OCT).

We enrolled 39 patients with symptomatic ICAS presenting with cerebral infarction or transient ischemic attack (TIA). All patients underwent HR-VWI and OCT. Based on diffusion weighted imaging (DWI) and CT perfusion (CTP), patients were classified as: (1) hypoperfusion type-watershed infarction on DWI or TIA with distal hypoperfusion on CTP; or (2) perforator type-an infarct confined to a single perforator territory on DWI. Plaque features were compared between groups, and multivariable logistic regression identified imaging markers independently associated with perforator-type events.

On HR-VWI, perforator-type plaques more often exhibited intraplaque hemorrhage (IPH; 52.9% vs 13.6%; P=0.008), plaque ulceration (47.1% vs 13.6%; P=0.033), and a higher eccentric index (0.63±0.13 vs 0.48 (IQR 0.34); P=0.028) than hypoperfusion-type plaques. On OCT, perforator-type lesions had thinner fibrous caps (60 µm (IQR 50-80) vs 90±30 µm; P=0.004) and more frequent superficial thrombus (35.3% vs 4.5%; P=0.030) and cholesterol crystals (52.9% vs 18.2%; P=0.022). In multivariable analysis, thinner caps (per 10 µm increase, OR 0.663, 95% CI 0.481 to 0.914, P=0.012) and IPH (OR 9.703, 95% CI 1.508 to 62.429, P=0.017) were independently associated with perforator-type stroke.

Plaques causing perforator artery occlusion showed a vulnerable phenotype characterized by a thin fibrous cap and IPH on multimodal imaging, distinguishing them from plaques underlying hemodynamic ischemia. These features may support mechanism specific risk stratification in ICAS.