Abstract
INTRODUCTION: We explored how blood-brain barrier (BBB) leakage rate of gadolinium chelates (K(trans)) and BBB water exchange rate (k(w)) varied in cerebral small vessel disease (cSVD) subtypes. METHODS: Thirty sporadic cSVD, 40 cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and 13 high-temperature requirement factor A serine peptidase 1 (HTRA) -related cSVD subjects were investigated parallel to 40 healthy individuals. Subjects underwent clinical, cognitive, and MRI assessment. RESULTS: In CADASIL, no difference in K(trans), but lower k(w) was observed in multiple brain regions. In sporadic cSVD, no difference in k(w), but higher K(trans) was found in the whole brain and normal-appearing white matter. In HTRA1-related cSVD, both higher K(trans) in the whole brain and lower k(w) in multiple brain regions were observed. In each patient group, the altered BBB measures were correlated with lesion burden or clinical severity. DISCUSSION: In cSVD subtypes, distinct alterations of k(w) and K(trans) were observed. The combination of K(trans) and k(w) can depict the heterogeneous BBB dysfunction. HIGHLIGHTS: We measured BBB leakage to gadolinium-based contrast agent (K(trans)) and water exchange rate (k(w)) across BBB in three subtypes of cSVD. CADASIL is characterized by lower k(w), HTRA1-related cSVD exhibits both higher K(trans) and lower k(w), while sporadic cSVD is distinguished by higher K(trans). There are distinct alterations in k(w) and K(trans) among subtypes of cSVD, indicating the heterogeneous nature of BBB dysfunction.