Disruption of the Blood–Brain Barrier Predicts Progression of Cerebral Small Vessel Disease White Matter Hyperintensities

Objective The objective of this study was to test if blood–brain barrier (BBB) disruption, detected using dynamic susceptibility contrast (DSC) imaging, would predict progression of white matter hyperintensities (WMHs) over the subsequent year in patients with chronic cerebrovascular disease. Methods The study included patients with a history of stroke and at least early confluence of WMH. Magnetic resonance imaging (MRI) scans performed at baseline (> 3 months from stroke) and again 1 year later were segmented to calculate the WMH volume expressed as a fraction of the total brain volume. Change in WMH volume between the 2 timepoints and progression of WMH were the outcome measures. BBB disruption was measured using DSC imaging on the baseline MRI. WMH masks were dilated by 3 mm to create a mask of the adjacent normal appearing white matter (penumbra). BBB disruption was averaged within the WMH and the penumbra. Results Fifty patients were included; median age was 69 years, and 46% were women. The mean WMH fraction was 1.25% at baseline and 1.36% at 1 year. The mean baseline BBB disruption was 0.20% in the WMH and 0.22% in the penumbra. More severe BBB disruption was associated with greater WMH progression when measured in the WMH ( ß = 0.95, confidence interval CI = 0.39–1.51, r 2 = 0.19, p = 0.001) and in the penumbra ( ß = 0.81, CI = 0.10–1.53, r 2 = 0.10, p = 0.027). The best predictor of progression was BBB disruption in the penumbra with an odds ratio (OR) of 2 (OR = 2, CI = 1.01–3.96, p = 0.046) for each 0.1% increase in BBB disruption. Interpretation More severe BBB disruption was predictive of greater WMH progression in patients with chronic cerebrovascular disease. ANN NEUROL 2025