Heterogeneous blood-brain barrier dysfunction in cerebral small vessel diseases

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.