Cereb Circ Cogn Behav. 2026 Jan 13;10:100528. doi: 10.1016/j.cccb.2026.100528. eCollection 2026.
ABSTRACT
BACKGROUND: Subtle blood-brain barrier (BBB) leakage has been detected in small vessel disease (SVD). While established methods rely on gadolinium-based contrast agents (GBCA), diffusion-weighted arterial spin labelling (DW-ASL) is a promising alternative which assesses water exchange rate (k ) without injected contrast. However, DW-ASL has not been widely applied in sporadic SVD. We aimed to determine how k varied with GBCA BBB leakage measures, baseline and 1-year change in SVD burden.
METHODS: We recruited patients with mild ischaemic stroke (lacunar or cortical) all characterised for SVD features. We assessed k using DW-ASL and GBCA measures of BBB leakage (permeability-surface area product (PS), blood plasma volume and exchange rate of GBCA) using dynamic-contrast enhanced MRI. We used separate linear regression models to assess how k varied with GBCA-derived metrics, baseline and 1-year change in WMH volume in co-variate-adjusted analyses.
RESULTS: We included 24 with complete MRI (61±10 years; 71% male). Patients with higher k tended to have more severe baseline SVD (e.g. subcortical grey matter (SGM): B=14.59 min-1/%WMH volume, 95% confidence interval (95%CI)=-1.00,28.18, p=0.04) and greater 1-year increase (B=0.0013 %WMH volume increase/min-1, 95%CI=-0.0001, 0.0026, p=0.06). We generally found k and GBCA BBB leakage measures were not meaningfully associated (e.g. SGM k ∼PS: B=-0.23 min-1/10-4 min-1, 95%CI=-7.47, 7.01, p=0.95).
CONCLUSION: BBB water exchange estimated using DW-ASL tended to be greater with higher WMH burden and progression, suggesting k may be a sensitive measure of BBB dysfunction in SVD. However, non-concordance between k and GBCA metrics suggests the two methods probe different aspects of BBB function.
PMID:41631279 | PMC:PMC12860635 | DOI:10.1016/j.cccb.2026.100528