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Objective  Several studies have demonstrated that compromised blood–brain barrier (BBB) integrity may play a pivotal role in the pathogenesis of individual cerebral small vessel disease (cSVD) markers, but the association between BBB permeability and total magnetic resonance imaging (MRI) cSVD burden remains unclear. This study aimed to investigate the relationship between BBB permeability and total MRI cSVD burden.    Methods  Consecutive participants without symptomatic stroke history presented for physical examination were enrolled in this cross-sectional study. The presence of lacunes, white matter hyperintensities (WMH), cerebral microbleeds, and enlarged perivascular spaces was recorded in an ordinal score (range 0–4). We used dynamic contrast-enhanced-MRI and Patlak pharmacokinetic model to quantify BBB permeability in the normal-appearing white matter (NAWM), WMH, cortical gray matter (CGM), and deep gray matter (DGM).    Results  All 99 participants averaged 70.33 years old (49–90 years). Multivariable linear regression analyses adjusted for age, sex, and vascular risk factors showed that leakage rate and area under the leakage curve in the NAWM, WMH, CGM, and DGM were positively associated with total MRI cSVD burden (all  P  < 0.01). Moreover, fractional blood plasma volumes in the NAWM, CGM, and DGM were negatively associated with total MRI cSVD burden (all  P  < 0.05).    Conclusion  This study verified that compromised BBB integrity is associated with total MRI cSVD burden, suggesting that BBB dysfunction may be a critical contributor to the pathogenesis of cSVD. Longitudinal studies are required to determine whether there is a causal relationship between BBB permeability and total MRI cSVD burden.

Compromised Blood–Brain Barrier Integrity Is Associated With Total Magnetic Resonance Imaging Burden of Cerebral Small Vessel Disease