MRI contrast accumulation in features of cerebral small vessel disease: blood-brain barrier dysfunction or elevated vascular density?

BACKGROUND

White matter lesions (WML) and dilated perivascular spaces (PVS) are features of small vessel disease (SVD), commonly observed in aging and dementia, with unknown pathophysiology. Human studies have documented contrast accumulation within and in proximity of SVD-lesions. However, whether such observations mainly reflect excessive blood-brain barrier (BBB) leakage, or altered microvascular density in the investigated regions, remains unclear.

METHODS

To evaluate the roles of BBB leakage and vascular density in aging and SVD, dynamic contrast enhanced (DCE) MRI was used to estimate the permeability-surface area product (PS) and fractional plasma volume ([Formula: see text]) in normal-appearing brain tissue and in proximity of and within WML and PVS in a population-based cohort (N = 56; 34/22 m/f; age 64 to 84 years). Analysis of variance (ANOVA) was used to assess regional differences in PS and [Formula: see text] and analysis of covariance (ANCOVA) was used to assess regional differences in PS with [Formula: see text] and vascular risk as covariates.

RESULTS

Pronounced increases in PS and [Formula: see text] were observed from normal-appearing white matter (NAWM) to WML peripheries to WMLs. Similar PS and [Formula: see text]increases were observed from basal ganglia (BG) to BG-PVS. Further, PS in NAWM and white matter (WM) PVS were found to increase with cortex-to-ventricular depth. However, ANCOVA models with [Formula: see text] as a covariate showed that variance in PS was mainly explained by vp (η2=0.17 to η2=0.35; all p < 10- 3), whereas the effect of region was only borderline-significant when comparing NAWM, WML peripheries and WML (p = 0.03) and non-significant for the other comparisons (p > 0.29).

CONCLUSIONS

Our findings support the notion that contrast leakage across the BBB accumulates within and in proximity of SVD-related lesions. However, high contrast accumulation may mainly reflect high vascularization, and to a lesser degree than previously recognized BBB dysfunction.