Dynamic susceptibility contrast-MRI parameters, ADC values, and the T2-FLAIR mismatch sign are useful to differentiate between H3-mutant and H3-wild-type high-grade midline glioma.

• Diffuse midline glioma, H3K27-altered (DMG-A), showed a significantly lower normalized relative cerebral blood flow and volume compared with H3K27-wild-type counterparts (DMG-W). • T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign was significantly more frequent in DMG-A compared to DMG-W. • Indicators that combined DSC parameters, ADC values, and T2-FLAIR mismatch sign, with or without age, are useful to distinguish the two tumors.