Correlation between Multiparametric MR Imaging and Molecular Genetics in Pontine Pediatric High-Grade Glioma

BACKGROUND AND PURPOSE: Molecular profiling is a crucial feature in the “integrated diagnosis” of CNS tumors. We aimed to determine whether radiomics could distinguish molecular types of pontine pediatric high-grade gliomas that have similar/overlapping phenotypes on conventional anatomic MR images.

MATERIALS AND METHODS: Baseline MR images from children with pontine pediatric high-grade gliomas were analyzed. Retrospective imaging studies included standard precontrast and postcontrast sequences and DTI. Imaging analyses included median, mean, mode, skewness, and kurtosis of the ADC histogram of the tumor volume based on T2 FLAIR and enhancement at baseline. Histone H3 mutations were identified through immunohistochemistry and/or Sanger or next-generation DNA sequencing. The log-rank test identified imaging factors prognostic of survival from the time of diagnosis. Wilcoxon rank-sum and Fisher exact tests compared imaging predictors among groups.

RESULTS: Eighty-three patients had pretreatment MR imaging and evaluable tissue sampling. The median age was 6 years (range, 0.7–17 years); 50 tumors had a K27M mutation in H3-3A, and 11, in H3C2/3. Seven tumors had histone H3 K27 alteration, but the specific gene was unknown. Fifteen were H3 wild-type. Overall survival was significantly higher in H3C2/3- compared with H3-3A-mutant tumors (P = .003) and in wild-type tumors compared with any histone mutation (P = .001). Lower overall survival was observed in patients with enhancing tumors (P = .02) compared with those without enhancement. H3C2/3-mutant tumors showed higher mean, median, and mode ADC_total values (P < .001) and ADC_enhancement (P < .004), with lower ADC_total skewness and kurtosis (P < .003) relative to H3-3A-mutant tumors.

CONCLUSIONS: ADC histogram parameters are correlated with histone H3 mutation status in pontine pediatric high-grade glioma.