Heterogeneous blood‐brain barrier dysfunction in cerebral small vessel diseases
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.