Abstract
OBJECTIVE: We aimed to evaluate the diagnostic performance of neuroimaging-based machine learning (ML) models for non-invasive prediction of H3K27M mutations in diffuse midline gliomas (DMG). METHODS: Following PRISMA-DTA guidelines, we searched four databases up to May 2025 to identify eligible studies evaluating neuroimaging-based ML for predicting H3K27M mutations in DMG. Study quality was assessed using PROBAST+AI and GRADE. Bivariate random-effects models were used to pool sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). RESULTS: Sixteen studies were included, comprising 2,357 patients in internal validation cohorts and 1,792 patients in external validation cohorts. MRI-based ML models showed strong diagnostic performance in internal validation, with pooled sensitivity of 0.86 (95% CI: 0.79-0.91), specificity of 0.82 (95% CI: 0.75-0.87), and AUC of 0.91 (95% CI: 0.88-0.93). For PET/CT-based ML models, pooled sensitivity was 0.58 (95% CI: 0.44-0.71) and pooled specificity was 0.65 (95% CI: 0.46-0.81), with an AUC of 0.61 (95% CI: 0.57-0.66). MRI-based ML showed significantly higher sensitivity (Z = 3.71; P < 0.01) and AUC (Z = 11.42; P < 0.01) than PET/CT-based ML. Subgroup analysis indicated that MRI-based deep learning (DL) models outperformed conventional machine learning (cML) algorithms (P = 0.01). Models using DNA sequencing as the reference standard showed higher specificity than those using immunohistochemistry (P < 0.001). CONCLUSION: MRI-based ML demonstrates high accuracy and generalizability for non-invasive H3K27M prediction in DMG, seemingly outperforming current PET/CT-based ML. The adoption of DL architectures and DNA sequencing as the reference standard may further improve performance, supporting the clinical utility of MRI-based ML for molecular stratification. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=1078673, identifier CRD420251078673.