Relevance of the diffusion tensor imaging along the perivascular space (DTI-ALPS) index in small vessel disease – A study in patients with mild ischaemic stroke

The Diffusion Tensor Imaging along the Perivascular Space (DTI-ALPS) index has been proposed as a non-invasive marker of glymphatic function, but its specific utility in the context of SVD and cognition remains unclear. In 189 patients with mild ischaemic stroke (age 38.8-86.3 years), we computed DTI-ALPS and quantified imaging markers of SVD: enlarged perivascular spaces (PVS), white matter hyperintensities (WMH), and cerebral microbleeds. Cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA). Linear regression models were used to explore the associations between DTI-ALPS, SVD markers and cognition. We found that lower DTI-ALPS values were associated with higher volume of basal ganglia PVS (β = –0.026, 95% CI [–0.052, –0.001]) and with male sex (–0.058, [–0.105, –0.010]). DTI-ALPS was also negatively associated with fractional anisotropy (FA) (–0.062, [–0.084, –0.040]) and mean diffusivity (MD) (–0.056, [–0.092, –0.021]) and positively associated with both neurite density (NDI) (0.033 [0.001,0.065]) and orientation dispersion (ODI) (0.079 [0.061,0.097]) indices. Higher WMH volume predicted lower DTI-ALPS in patients with non-lacunar stroke (–0.079 [–0.118, –0.041]). No associations were observed between DTI-ALPS values and microbleeds or MoCA scores. These findings suggest that, in post-stroke SVD, the DTI-ALPS index may primarily reflect local tissue fluid changes and microstructure damage, rather than serving as a specific, direct indicator of glymphatic function or cognitive impairment. Future research using region-specific and physiologically dynamic imaging approaches may be better suited to capture the glymphatic contributions to stroke and SVD pathology. • After mild stroke, lower DTI-ALPS associated with higher BGPVS volume and male sex. • WMH load also predicted lower DTI-ALPS, particularly in non-lacunar stroke. • DTI-ALPS also showed strong negative associations with FA and MD. • There was no association between DTI-ALPS and patient cognitive scores. • DTI-ALPS may reflect microstructure or fluid changes in SVD, not glymphatic flow.