Neuroanatomical substrates of perivascular space index: a morphometric and tractography study.

Background and objectives: The diffusion tensor image analysis along the perivascular space (DTI-ALPS) index is an important imaging biomarker for assessing glymphatic system function. However, the cortical and white matter metrics associated with changes in the DTI-ALPS index have not been fully elucidated, and the relationship between these two types of metrics remains controversial. Methods: We computed the index in 815 healthy participants from the AOMIC dataset. Surface-based morphometry (SBM) and correlational tractography were employed to identify cortical morphometric features and white matter tracts that were correlated with the DTI-ALPS index. Tract-to-region connectome analysis was then performed to identify significant tracts, and correlations between tract microstructural integrity and connected cortical morphometry were analyzed. Results: The SBM results revealed positive correlations between the DTI-ALPS index and sulcal depth in the precentral, parsopercularis, postcentral, and supramarginal gyri as well as with local gyrification in the superior frontal and lateral orbitofrontal cortices. Tractography showed that the DTI-ALPS index positively correlated with fractional anisotropy (FA) and negatively with mean diffusivity (MD) in the corpus callosum, bilateral fornices, and corticospinal tracts. These tracts exhibited structural connectivity with the aforementioned cortical regions, and MD in several connected tracts positively correlated with regional sulcal depth. Discussion: This study identified cortical and white matter correlates of DTI-ALPS variability in a healthy young-adult cohort. These findings provide novel insights into mechanisms underlying DTI-ALPS index decline in aging and neurological disorders.