Altered Perivascular Diffusivity in Glioblastoma:Integrating DTI-ALPS Index with Radio-Pathomicand Histopathologic Correlates
Abstract
PURPOSE: Glioblastoma is an aggressive primary brain tumor that often exhibits perivascular invasion. This behavior may directly interfere with glymphatic flow, hindering perivascular drainage routes. This study aims to assess glymphatic dysfunction in glioblastoma by evaluating the DTI-ALPS index, an MRI-based surrogate of glymphatic activity. We additionally correlate mpMRI-derived tumor features with radio-pathomic maps of hypercellularity.
METHODS: We included 368 IDH-wildtype GBM patients from the UCSF-PDGM dataset. Preoperative T1, T1C, FLAIR, ADC, and diffusion tensor imaging (DTI) maps were preprocessed using standard co-registration and intensity normalization protocols. Radio-pathomic maps of tumor cellularity were generated using a previously published model which was trained on spatially aligned autopsy samples. The DTI-ALPS index was computed using DTI maps normalized to the JHU-ICMB-FA template, with ROIs on predefined white matter tracts and categorized by tumor laterality.
RESULTS: The DTI-ALPS index was significantly lower on the ipsilateral side for both the GTR and STR cohorts (p < 0.00001). Furthermore, DTI-ALPS mean and DTI-ALPS ipsilateral showed an inverse association with contrast enhancing and FLAIR hyperintensity volumes (both p < 0.00001) and total cellularity within the contrast enhancing and FLAIR hyperintensity regions (both p < 0.00001). Notably, autopsy tissue analysis revealed SOX2 positive tumor cells in the perivascular spaces. Survival…
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