Abstract
Cerebral small vessel disease (cSVD) is associated with vascular cognitive impairment, dementia, and stroke. Blood-brain barrier (BBB) dysfunction is central to its pathophysiology and is involved in the formation of tissue lesions. The spatial heterogeneity of BBB leakage remains largely unclear. This cross-sectional study assessed BBB leakage rate (K(i)), fractional volume of leaking tissue (v(l)), and blood plasma volume (v(p)) in various tissue regions, including gray matter (GM), normal appearing white matter (NAWM), and white matter hyperintensities (WMH) of 59 patients with cSVD and 32 controls using a high spatial resolution dynamic-contrast enhanced MRI protocol. Using regionally averaged measures, patients with cSVD had higher v(l) (p = 0.020) and lower v(p) (p < 0.001) within WMH compared to controls, K(i) did not differ in any region. To evaluate the spatial heterogeneity of leakage in the NAWM, we analyzed 2-mm-wide shells extending outward from WMH edges. This revealed stronger BBB leakage in perilesional NAWM (p = 0.032) of cSVD patients compared to controls, with a striking dip close to the WMH. K(i), v(l), and v(p) increased with distance from WMH edges (all p < 0.001). This pattern of lower BBB leakage in the perilesional NAWM could be caused by local reductions in microvascular blood flow or vessel surface area.