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

Abstract

PURPOSE:

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.

METHODS:

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.

RESULTS:

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).

CONCLUSIONS:

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.

• Authors: Arnoldo Piccardo, Domenico Tortora, Samantha Mascelli, Mariasavina Severino, Gianluca Piatelli, Alessandro Consales, Marco Pescetto, Veronica Biassoni, Elisabetta Schiavello, Michela Massollo, Antonio Verrico, Claudia Milanaccio, Maria Luisa Garrè, Andrea Rossi, Giovanni Morana
• Journal: European journal of nuclear medicine and molecular imaging (Eur J Nucl Med Mol Imaging) Vol. 46 Issue 8 Pg. 1685-1694 (Jul 2019) ISSN: 1619-7089 [Electronic] Germany
• PMID: 31030232 (Publication Type: Comparative Study, Evaluation Study, Journal Article)

Chemical References

• Histones
• Radiopharmaceuticals
• fluorodopa F 18
• Dihydroxyphenylalanine

Topics

• Adolescent
• Brain Neoplasms (diagnostic imaging, genetics)
• Child
• Child, Preschool
• Diffusion Magnetic Resonance Imaging (methods, standards)
• Dihydroxyphenylalanine (analogs & derivatives)
• Female
• Glioma (diagnostic imaging, genetics)
• Histones (genetics)
• Humans
• Magnetic Resonance Spectroscopy (methods, standards)
• Male
• Mutation
• Perfusion Imaging (methods, standards)
• Positron-Emission Tomography (methods, standards)
• Radiopharmaceuticals