Validation of automated DTI-ALPS and free water index as potential survival stratification markers in IDH-wildtype glioblastoma

PURPOSE: Diffusion MRI-based indirect indices of neurofluid dynamics, such as diffusion tensor imaging along the perivascular space (DTI-ALPS) and extracellular free water (FW), have been reported to have prognostic implications in glioblastoma. However, their clinical utility, replicability, and the relation between the tumor burden remain insufficiently investigated with inconsistent results hindering its integration into routine imaging. METHODS: Two datasets of isocitrate dehydrogenase-wildtype (IDHwt) glioblastoma were retrieved from The Cancer Imaging Archive (UPENN = 200, UCSF = 125). The automated DTI-ALPS (aDTI-ALPS) and the FW index was used as an indirect indicator of glymphatic function. Prognostic significance was assessed using Kaplan-Meier analysis along with log-rank test, and multivariable Cox regression including aDTI-ALPS and clinical variables such as age, and extent of resection. Associations between MRI indices and tumor characteristics were also evaluated. RESULTS: A higher aDTI-ALPS index was associated with longer survival (P = 0.024 and 0.018 for both datasets, respectively; log-rank test), indicating its prognostic significance. Multivariable Cox analysis revealed low aDTI-ALPS as an independent factor for poor prognosis (hazard ratio (HR), 1.352; P = 0.050 and hazard ratio, 1.616; P = 0.044, respectively). Low FW index was associated with longer survival in UPENN. Additionally, the aDTI-ALPS index showed no correlation with tumor volume or tumor laterality, and the HR was smaller than molecular markers. CONCLUSION: Automated DTI-ALPS and the free water index may serve as reproducible prognostic factors in IDH-wildtype glioblastoma, while showing no significant correlation with tumor burden.