Altered perivascular diffusivity in glioblastoma: integrating DTI-ALPS index with radio-pathomic and histopathologic correlates. J Neurooncol 2026 Feb 21;177(1)
Date
02/21/2026Pubmed ID
41721916Pubmed Central ID
PMC12924826DOI
10.1007/s11060-026-05458-xScopus ID
2-s2.0-105030585109 (requires institutional sign-in at Scopus site)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. DTI-ALPS metrics were not independently associated with overall survival after adjustment for clinical covariates.
CONCLUSION: Our findings suggest that GBM-associated perivascular invasion disrupts glymphatic function, as evidenced by a significantly lower DTI-ALPS index in the tumor-affected hemisphere. The inverse correlation between the DTI-ALPS index and both volume and cellularity metrics highlights the extent to which GBM alters perivascular fluid dynamics.
Author List
Nath B, Bobholz SA, Kim DC, Lowman AK, Duenweg SR, Winiarz A, Chao B, Kyereme F, Barrett M, Reecher HM, Connelly J, Mrachek EKS, Jacobsohn J, Krucoff MO, Tanhehco E, Agarwal M, Destiche D, Banerjee A, LaViolette PSAuthors
Mohit Agarwal MD Associate Professor in the Radiology department at Medical College of WisconsinAnjishnu Banerjee PhD Associate Professor in the Data Science Institute department at Medical College of Wisconsin
Samuel Bobholz PhD Assistant Professor in the Radiology department at Medical College of Wisconsin
Jennifer M. Connelly MD Professor in the Neurology department at Medical College of Wisconsin
Savannah R. Duenweg Research Scientist I in the Radiology department at Medical College of Wisconsin
Max O. Krucoff BS, MD Associate Professor in the Neurosurgery department at Medical College of Wisconsin
Peter LaViolette PhD Vice Chair, Professor in the Radiology department at Medical College of Wisconsin
Hope M. Reecher BS, MD Postdoctoral Researcher in the Radiology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AdultAged
Brain Neoplasms
Diffusion Tensor Imaging
Female
Follow-Up Studies
Glioblastoma
Humans
Male
Middle Aged
