Advanced MR imaging and ¹⁸F-DOPA PET characteristics of H3K27M-mutant and wild-type pediatric diffuse midline gliomas

The aim of this study was to investigate MRI-derived diffusion weighted imaging (DWI), ¹H-MR spectroscopy (¹H-MRS) and arterial spin labeling (ASL) perfusion imaging in comparison with ¹⁸F-dihydroxyphenylalanine (DOPA) PET with respect to diagnostic evaluation of pediatric diffuse midline gliomas (DMG) H3K27M-mutant and wild-type.

We retrospectively analyzed 22 pediatric patients with DMG histologically proved and molecularly classified as H3K27M-mutant (12 subjects) and wild-type (10 subjects) who underwent DWI, ¹H-MRS, and ASL performed within 2 weeks of ¹⁸F-DOPA PET. DWI-derived relative minimum apparent diffusion coefficient (rADC min), ¹H-MRS data [choline/N-acetylaspartate (Cho/NAA), choline/creatine (Cho/Cr), and presence of lactate] and relative ASL-derived cerebral blood flow max (rCBF max) were compared with ¹⁸F-DOPA uptake Tumor/Normal tissue (T/N) and Tumor/Striatum (T/S) ratios, and correlated with histological and molecular features of DMG. Statistics included Pearson's chi-square and Mann-Whitney U tests, Spearman's rank correlation and receiver operating characteristic (ROC) analysis.

The highest degrees of correlation among different techniques were found between T/S, rADC min and Cho/NAA ratio (p < 0.01), and between rCBF max and rADC min (p < 0.01). Significant differences between histologically classified low- and high-grade DMG, independently of H3K27M-mutation, were found among all imaging techniques (p ≤ 0.02). Significant differences in terms of rCBF max, rADC min, Cho/NAA and ¹⁸F-DOPA uptake were also found between molecularly classified mutant and wild-type DMG (p ≤ 0.02), even though wild-type DMG included low-grade astrocytomas, not present among mutant DMG. When comparing only histologically defined high-grade mutant and wild-type DMG, only the ¹⁸F-DOPA PET data T/S demonstrated statistically significant differences independently of histology (p < 0.003). ROC analysis demonstrated that T/S ratio was the best parameter for differentiating mutant from wild-type DMG (AUC 0.94, p < 0.001).

Advanced MRI and ¹⁸F-DOPA PET characteristics of DMG depend on histological features; however, ¹⁸F-DOPA PET-T/S was the only parameter able to discriminate H3K27M-mutant from wild-type DMG independently of histology.