Background: FLAIR lesion burden is an established biomarker in small vessel disease. To examine its role in intracranial atherosclerosis, we studied ischemic lesion burden throughout the brain at baseline or enrollment in the SAMMPRIS trial and also on serial MRIs in the medical arm, investigating its relationship with recurrent stroke.
Methods: We performed blinded measurement of lesion burden on baseline and followup FLAIR and DWI images. Baseline FLAIR and DWI lesion volume and FLAIR vascular hyperintensities (FVH) were analyzed with respect to baseline variables including prior history, co-morbidities and angiographic measures and also correlated with subsequent ischemic stroke in the territory of the stenotic artery.
Results: Of 451 SAMMPRIS subjects, baseline MRI included DWI in 309 (69%) with FLAIR in 293 (65%). Ischemic lesion burden on baseline FLAIR was median 2.7 cc (0-87.0) cc, with greater extent in those older than 60 years (p=0.03) and those on anti-thrombotics (p=0.01). Increased FLAIR lesion burden showed a trend towards worse collateral status by angiography (p=0.10). The presence of FVH in 72/194 (37%) anterior circulation stenoses reflected more robust collateral status (p=0.002). Corresponding baseline DWI lesion volume was median 5.16 cc (range 0-71.8). Baseline FLAIR lesion burden predicted subsequent stroke in the territory (HR 1.028 [95% CI 1.013-1.043], p=0.0002) in both medical and endovascular therapy arms, whereas baseline DWI size was not predictive of subsequent stroke in the territory. Serial FLAIR in the medical arm revealed interval burden growth in 31/47 (66%), whereas only 13/47 (28%) had clinical stroke outcomes.
Conclusions: FLAIR MRI is a potent biomarker of ischemic lesion burden that reflects prior strokes and collateral status. Baseline FLAIR lesion burden throughout the brain may identify stroke risk in intracranial atherosclerosis. “Silent” ischemic lesion progression on serial MRI in this study may have clinical sequelae, such as cognitive impairment, and deserves greater scrutiny.