Perivascular and parenchymal brain fluid diffusivity in patients with a recent small subcortical infarct.

Purpose: Fluid exchanges between perivascular spaces (PVS) and interstitium may contribute to the pathophysiology of small vessel disease (SVD). We aimed to analyze water diffusivity measures and their relationship with PVS and other SVD imaging markers.

Methods: We enrolled 50 consecutive patients with a recent small subcortical infarct. We collected clinical variables, including vascular risk factors and sleep quality scales. All patients underwent a 3-Tesla MRI with standard structural sequences and multishell-diffusion images to obtain extracellular free water content (FW) and water diffusivity along the perivascular space (ALPS) index. We obtained volumetric measurements of white matter hyperintensities (WMH) and PVS, and the number of lacunes and microbleeds. To analyze the association between PVS, ALPS index, FW, and SVD imaging features, we utilized linear regression models including age, sex, history of hypertension and diabetes, Pittsburgh Sleep Quality Index, WMH, and brain volume.

Results: All patients (mean age 70 years, 36% women) had usable data. FW and PVS were strongly associated in all models (0.008 < Beta < 0.054; P < 0.045). Higher FW was related to the other SVD features in univariable models and remained significant for WMH (1.175 < Beta < 1.262; P < 0.001) and brain volume (Beta < 0.0001; P < 0.002) in multivariable models. ALPS index was not associated with FW, PVS, or any other SVD markers.

Conclusions: The increased extracellular water in SVD suggests that impaired brain fluid exchanges, PVS dilation, and other SVD features are linked. Further investigation is needed to determine the specificity of the ALPS index to PVS diffusion.