Abstract
We aimed to analyze the relationships between brain fluid diffusivity, perivascular spaces (PVS) dilation, and small vessel disease (SVD) severity in 50 patients with a recent small subcortical infarct. We collected clinical variables, including the Pittsburgh Sleep Quality Index (PSQI). The 3-Tesla magnetic resonance imaging (MRI) acquisition included standard structural sequences and multishell-diffusion images to obtain brain fluid estimates, such as extracellular free water (FW) content and water diffusivity along the perivascular space (ALPS ) index. We obtained volumetric measures of brain white matter hyperintensity (WMH) normalized to intracranial volume, and PVS in basal ganglia and white matter regions. We counted lacunes and microbleeds, then calculated a summary SVD score (range 0–4, one point awarded for the presence of each of the four SVD markers). Using linear regression models including age, sex, history of hypertension, diabetes, PSQI, WMH ratio, and brain volume, we found a strong association (0.008 < Beta < 0.054; P < 0.045) between FW and PVS in both regions in all models. Higher FW in normal-appearing white matter was related to all SVD features in univariable models and remained significant for WMH ratio (1.175 < Beta < 1.262; P < 0.001) and brain volume (Beta < 0.0001; P < 0.002) in multivariable models. We found no associations between ALPS index and FW, PVS, or any other SVD markers. The increased extracellular water in SVD suggests impaired brain fluid dynamics, PVS dilation, and other SVD features are linked; the lack of association with ALPS index suggests ALPS is not specific to PVS diffusion.