Unveiling intratumoral heterogeneity and isocitrate dehydrogenase status in gliomas: a simultaneous fluorine-18 fluorodeoxyglucose PET/MRI study based on 2021 WHO classification

Objectives To evaluate the diagnostic utility of simultaneous fluorine-18 fluorodeoxyglucose ( 18 F-FDG) PET/MRI quantitative parameters in characterizing glioma heterogeneity and predicting isocitrate dehydrogenase (IDH) mutation status, based on the 2021 WHO Classification. Methods Twenty-five patients with histopathologically confirmed gliomas underwent preoperative simultaneous 18 F-FDG PET/MRI. Forty-one biopsy foci were analyzed. Maximum standardized uptake value (SUV max ), normalized SUV (nSUV) ratios, minimum apparent diffusion coefficient, perfusion index, and cerebral blood flow (CBF), were measured. Patients were stratified into low-grade and high-grade groups (including molecular glioblastoma), according to the 2021 WHO criteria. Generalized estimating equations (GEE) were used alongside standard nonparametric tests to account for clustered biopsy data. Results High-grade tumors exhibited significantly higher SUV and lower minimum apparent diffusion coefficient values compared to low-grade tumors ( P < 0.001). While perfusion parameters showed limited significance in standard unadjusted analyses, GEE analysis revealed them as highly significant predictors for high-grade status. IDH-wildtype (IDH-wt) tumors demonstrated significantly higher perfusion values ( P < 0.001) and tumor-to-white matter metabolic ratios (nSUV). Receiver operating characteristic analysis confirmed high diagnostic performance for SUV max area under the curve (AUC) = 0.938 and CBF (AUC = 0.875) in discriminating tumor grade. Similarly, nSUV1 (AUC = 0.873) and CBF (AUC = 0.825) proved effective for predicting IDH-wt status. Conclusion Simultaneous 18 F-FDG PET/MRI provides complementary metabolic and functional information for glioma characterization. When intratumoral heterogeneity is accounted for using GEE, perfusion parameters emerge as robust biomarkers for predicting high-grade histology and IDH-wt status. These findings support a multimodal approach to guide stereotactic biopsies to the most aggressive intratumoral foci.