IMG-113. Lower DTI-ALPS Index Associates with Higher Tumor Cellularity and Contrast-Enhancing Volume in Glioblastoma

Abstract Glioblastoma (GBM) is an aggressive primary brain tumor with the unique ability to infiltrate along the blood vessels. This invasive 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 and comparing it with radio-pathomic derived cellularity metrics. We included 218 IDH-wildtype GBM patients who underwent gross total resection (GTR) from the UCSF-PDGM dataset. Preoperative T1, T1C, FLAIR, ADC, and diffusion tensor imaging (DTI) maps were first co-registered, with each image being aligned to the FLAIR. Qualitative images were intensity normalized using the standard deviation within a mask of the brain. Radio-pathomic maps of tumor cellularity were generated using a previously published model which was trained on spatially aligned autopsy samples and uses clinical MR images to predict the underlying tumor pathology. The DTI-ALPS index was computed using DTI maps normalized to the JHU-ICMB-FA template, with ROIs placed on predefined white matter tracts and categorized by tumor laterality. The DTI-ALPS index was significantly lower in patients with tumor ipsilateral to the hemisphere compared to the contralateral side (p<0.00001). Furthermore, DTI-ALPS mean and DTI-ALPS ipsilateral showed an inverse association with contrast enhancing volume (p<0.00001) and total cellularity within the contrast enhancing region (p<0.00001). Our findings suggest that GBM-associated perivascular invasion disrupts glymphatic flow, as evidenced by a significantly lower DTI-ALPS index in the tumor-affected hemisphere. The inverse correlation between the ALPS index and both tumor volume and cellularity highlight the extent to which GBM alters perivascular fluid dynamics. These results underscore the potential role of glymphatic dysfunction in GBM progression.