Association of Glymphatic Imaging Markers With Clinical Outcomes and Cerebral Small Vessel Disease Burden After Intracerebral Hemorrhage.

OBJECTIVE

The glymphatic system plays a critical role in cerebral metabolite clearance and white matter injury. However, its clinical relevance in intracerebral hemorrhage (ICH) remains poorly understood. This study aimed to investigate imaging-based glymphatic markers in relation to functional outcomes and cerebral small vessel disease (CSVD) burden in patients with ICH.

METHODS

We included 70 patients with acute supratentorial ICH who underwent diffusion tensor imaging (DTI). Glymphatic-related imaging parameters were derived using magnetic resonance imaging (MRI), including DTI-ALPS, free water (FW) fraction, and relative perivascular space (PVS) volume. CSVD burden was assessed using relative white matter hyperintensity (WMH) volume and number of lacunes. Functional independence was defined as a 3-month modified Rankin Scale score of 0-2.

RESULTS

In fully adjusted logistic regression models, higher FW in deep WM was associated with a lower likelihood of functional independence at 3 months (OR = 0.59; 95% CI, 0.36-0.98; p = 0.041), with consistent findings across sequential models. Linear regression analyses further demonstrated that greater relative WMH volume was significantly associated with increased FW in deep WM (β = 0.143; 95% CI, 0.008-0.277; p = 0.038) and with smaller relative PVS volume in fully adjusted models. Neither FW association remained statistically significant after FDR correction. The FW-outcome association was also nonsignificant after adjustment for WMH burden, and the exploratory mediation analysis showed no statistically significant indirect effect.

INTERPRETATION: Contralateral FW showed nominal associations with functional outcome and WMH burden and may reflect diffuse CSVD-related white matter injury. Its independent prognostic and mediating roles remain unestablished and require validation in larger longitudinal studies.