Peritumoral brain zone oxygen extraction fraction is associated with tumor Ki-67 index in untreated glioblastoma

Abstract Background The non-contrast-enhancing peritumoral brain zone (PBZ) contributes to glioblastoma progression but remains incompletely characterized by structural MRI. We tested whether PBZ oxygen extraction fraction (OEF) derived from dynamic susceptibility contrast (DSC) MRI is associated with the Ki‑67 proliferation index at the patient level. Methods In this retrospective analysis, we analyzed 80 adults with untreated IDH-wildtype glioblastoma with preoperative DSC and diffusion MRI. Mean values of paired regions of interest were extracted from non-contrast-enhancing T2/FLAIR-hyperintense PBZ, the contrast-enhancing tumor core, and contralateral normal-appearing white matter (NAWM). PBZ and CE to NAWM ratios for OEF, capillary transit time heterogeneity, cerebral metabolic rate of oxygen, cerebral blood volume, and apparent diffusion coefficient were computed after ComBat harmonization. These ratios were subsequently correlated with Ki-67 using Spearman’s rank correlation. Results PBZ OEF demonstrated a positive correlation with Ki-67 (Spearman ρ = 0.27, P = .014). In contrast, other PBZ and all CE imaging ratios were not associated with Ki-67 after multiple testing. In regression models including CE OEF, PBZ OEF remained associated with Ki‑67 (P = .041) and improved model fit (ΔR2 = 0.094). Conclusions Higher DSC-derived PBZ OEF ratio was modestly but significantly associated with higher tumor Ki-67 in untreated IDH-wildtype glioblastoma, suggesting that PBZ OEF captures physiologic variation in non-contrast-enhancing tissue beyond the contrast-enhancing tumor core. Given the lack of spatial co-registration between PBZ and pathology sampling, prospective validation with spatially matched histology and outcome endpoints is warranted.