Diagnostic Accuracy of APTw and NOEw MRI Metrics for IDH Mutation and 1p/19q Codeletion Prediction in Gliomas

ABSTRACT

Isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion are key molecular markers for glioma classification. Amide proton transfer weighted (APTw) and nuclear Overhauser effect–weighted (NOEw) markers showed promise for glioma characterization, by probing protein‐related tissue properties. However, their interpretation is confounded by direct water saturation, macromolecules (semi‐solid magnetization transfer—ssMT), and T ₁ relaxation. Here, we aimed to assess the performance of three APTw and NOEw metrics—uncorrected, spillover/ssMT‐corrected (FMC), and fully spillover/ssMT‐ and T ₁ ‐corrected (FMTC)—for glioma stratification. Fifty patients with suspected gliomas were prospectively enrolled (12 IDH‐wild‐type, 38 IDH‐mutant, of which 21 with 1p/19q codeletion). Acquisitions were performed at 3 T using a 3D gradient echo readout with chemical exchange saturation transfer ( B ₁  = 2 μT for APTw, 0.6 μT for NOEw; T _1sat  = 2 s), WASABI (WAter Shift And B1) for B ₀ / B ₁ mapping, and saturation recovery for T ₁ mapping. Glioma subtypes were compared using metrics extracted from manually segmented masks, using two‐tailed Mann–Whitney U tests, and the Benjamini–Hochberg false discovery rate (FDR) correction. Effect sizes were quantified using Cliff's δ with 95% bootstrap confidence intervals and classification performance was assessed by receiver operating characteristic analyses (area under the curve, AUC). IDH‐mutant and wild‐type gliomas differed significantly for the uncorrected APTw metric ( p  = 0.005, AUC = 0.79), with stronger discrimination following correction—APTw‐FMC ( p  < 0.001, AUC = 0.94) and APTw‐FMTC ( p  < 0.001, AUC = 0.96), both with large effect sizes. Only APTw‐FMTC distinguished 1p/19q codeleted from non‐codeleted gliomas before FDR correction (uncorrected p  = 0.01, AUC = 0.74). The NOEw metrics did not differ between any molecular subgroups, likely due to limited sensitivity of this contrast at 3 T. These results suggest that correcting for fluid, ssMT, and T ₁ effects enhances the accuracy of APTw metrics, offering a more robust and biophysically grounded approach to noninvasive glioma diagnosis.