Venous disruption affects white matter integrity through increased interstitial fluid in cerebral small vessel disease

Deep medullary veins (DMVs) participate in the drainage of surrounding white matter. In cerebral small vessel disease (CSVD), disrupted DMVs were often observed together with damaged white matter, but the phenomenon lacked validation and explanation. We hypothesized that venous disruption might cause white matter damage through increased interstitial fluid resulting from hemodynamic alteration, and we designed a comprehensive multi-modality MRI study to testify our hypothesis. Susceptibility-weighted imaging was used to investigate the characteristics of DMVs and derive DMVs scores. Free water elimination diffusion tensor imaging model was used to analyze interstitial fluid fraction (fraction of free water, fFW) and white matter integrity (tissue fractional anisotropy, FAt). Totally, 104 CSVD patients were included. Total DMVs score was associated with FAt of DMVs drainage area. The effect of total DMVs score on FAt was mediated by fFW, after controlling for age, sex, hypertension, regional cerebral blood flow and lacune numbers. The relationships between DMVs score, fFW and FAt were also significant in most DMVs drainage subregions. Therefore, we discovered the DMVs disruption - increased interstitial fluid - white matter damage link in CSVD patients, which was independent of arterial perfusion variations.