Comparison of amide proton transfer metrics for IDH genotype discrimination in gliomas at low B₁

Amide proton transfer-weighted (APTw) imaging enables tumor characterization by detecting mobile proteins and peptides. Low B₁ levels provide greater spectral selectivity, advantageous for resolving APT signals. However, low B₁ also increases the T₁ dependence of conventional APT metrics, including magnetization transfer ratio asymmetry (MTR_asym), multipool Lorentzian fitting, and inverse difference, despite their different strategies for mitigating confounding effects. This study compared the newly proposed quasi-steady-state (QUASS)-based apparent exchange-dependent relaxation (AREX) with conventional APT metrics for discrimination of IDH genotypes in gliomas under finite radiofrequency irradiation with B₁ of 0.75 μT, a level previously shown to provide good tumor-to-normal tissue contrast. Protein phantoms with varying concentrations were constructed, and glioma patients were prospectively enrolled and classified according to IDH mutation status. QUASS was used to reconstruct steady-state Z-spectra, from which APT metrics were quantified. Statistical analyses included the Mann-Whitney U test, area under the curve (AUC), and DeLong test, with false discovery rate correction. In the phantom study, QUASS-based AREX showed the strongest correlation with egg white concentration among the evaluated APT metrics (r = 0.988, P < 0.001). Among 45 patients (22 IDH-mutant and 23 IDH-wildtype), QUASS-based AREX significantly differentiated IDH genotypes (P = 0.007), whereas MTR_asym, multipool Lorentzian fitting, and inverse difference did not (P = 0.733, 0.250, and 0.087, respectively). QUASS-based AREX achieved the highest AUC of 0.771, significantly outperforming the other metrics (all P < 0.05). Under the saturation parameters used in this study, QUASS-based AREX provided better IDH genotype discrimination than the evaluated conventional APT metrics.