Preoperative Grading of WHO Grade 3 Gliomas and Comprehensive Glioma Assessment Using APTw MRI: Enhancing Diagnostic Thresholds and Noninvasive Tumor Characterization

Accurate preoperative grading of gliomas is essential for prognostic stratification and surgical planning. However, conventional MRI often struggles to differentiate between WHO Grade 2 and Grade 3 gliomas. This study evaluated the diagnostic value of amide proton transfer-weighted (APTw) imaging, a noninvasive and contrast-free molecular MRI technique, in improving glioma grading. We retrospectively analyzed 57 treatment-naive glioma patients who underwent preoperative APTw imaging and compared APTw signal intensities with histopathological grades and molecular subtypes. Receiver operating characteristic analysis identified an APTw signal intensity threshold of 2.3% that optimally distinguished Grade 2 from Grade 3 gliomas, yielding 75% sensitivity, 80% specificity, and 77.8% accuracy. Applying this threshold corrected presurgical undergrading in five of seven initially misclassified Grade 3 tumors. Mean APTw values were significantly higher in IDH-wild-type gliomas than in IDH-mutant gliomas (AUC 0.94), supporting the role of APTw imaging in molecular stratification. However, within Grade 4 tumors, APTw did not differentiate between IDH-mutant and IDH-wild-type subtypes. In addition, APTw imaging revealed intratumoral heterogeneity not evident on conventional MRI sequences in 43% of cases, suggesting a potential role in guiding biopsy targeting. APTw signal differences also indicated variations in tumor extent that were not captured on conventional imaging. These findings suggest that incorporating APTw imaging into the preoperative workflow can improve glioma grading, reveal biological heterogeneity, and enhance molecular characterization, ultimately supporting more informed clinical decision-making. Wider use of standardized APTw acquisition protocols and multicenter validation of the proposed thresholds may support broader clinical adoption, positioning APTw as a valuable complement to conventional MRI in the individualized management of glioma patients.