Association of MRI-Visible Perivascular Spaces with Early White Matter Injury

BACKGROUND AND PURPOSE: MRI-visible perivascular spaces (PVS) are considered markers of cerebral small vessel disease (CSVD) and may reflect dysfunction of brain perivascular drainage. WM integrity assessed with DTI provides a sensitive assessment of early brain injury, related vascular risk factors, and risk of stroke and dementia. We investigated the relationship between PVS and WM integrity in community-dwelling participants.

MATERIALS AND METHODS: Framingham Heart Study (FHS) participants with brain MRI, PVS ratings, and DTI measures were included. PVS were rated in the basal ganglia (BG) and centrum semiovale (CS) and categorized into grades I–IV based on counts. We related PVS burden to global DTI measures (free water fraction [FW], fractional anisotropy [FA], peak skeletonized mean diffusivity [PSMD]), diffusion along perivascular spaces (DTI-ALPS), and voxel-based measures using multivariable linear regression analyses.

RESULTS: Among 3077 participants (57.2 mean age; 53% women), 7% had high-burden PVS in the BG, and 13% had high burden in the CS. High PVS burden in either or both regions was associated with higher global FW, PSMD, lower global FA, and lower DTI-ALPS index in fully adjusted models (P < .001). Voxel analyses revealed significant associations between high PVS burden in both regions and FW involving ascending, descending, interhemispheric, and intrahemispheric tracts (P < .0001) but not with FA.

CONCLUSIONS: PVS burden was associated with early signs of global WM injury after adjustment for vascular risk factors, suggesting that high PVS burden may represent early brain injury related to CSVD or impaired perivascular function.