Glucose Hypometabolic Pattern and Prediction of Isocitrate Dehydrogenase Status in Non-Contrast-Enhanced Glioma Using...

Background/Objectives:¹⁸F-fluorodeoxyglucose positron emission tomography (FDG PET) reflects glucose metabolism but has limited diagnostic value for gliomas because of its high physiological uptake in the normal brain. This study visualized and characterized patterns of hypometabolism in non-contrast-enhanced gliomas using Z-score analysis and explored its potential for estimating isocitrate dehydrogenase (IDH) status. Methods: We retrospectively analyzed 116 patients with non-contrast-enhanced supratentorial gliomas, classified according to the 2021 World Health Organization classification (26 glioblastomas, IDH-wildtype; 54 astrocytomas, IDH-mutant; and 36 oligodendrogliomas, IDH-mutant and 1p/19q-codeleted). Z-score maps of FDG images were generated using a normal database. Tumor-associated hypometabolic regions (Z < -2) were analyzed, focusing on the proportion of severely hypometabolic regions (Z6-: Z < -6) and sphericity. Results: The mean Z-score differed significantly among the three subtypes, with the highest value observed in glioblastomas and the lowest in astrocytomas (p < 0.001). IDH-mutant gliomas showed a higher proportion of Z6- regions (p < 0.001) and higher sphericity (p = 0.009) than IDH-wildtype gliomas. In multivariable logistic regression, both the proportion of Z6- and sphericity were independent predictors of IDH status. Their combination demonstrated a strong discriminative performance for IDH status (area under the receiver operating characteristic curve = 0.839). On visual assessment, tumors with both small Z6- extent and low sphericity were primarily IDH-wildtype (75%), whereas the absence of both features indicated IDH-mutant status (94.8%). Conclusions: Z-score-based analysis enables the objective visualization and quantification of tumor-associated hypometabolic regions in non-contrast-enhanced gliomas, providing a potentially useful imaging biomarker for estimating IDH status.