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

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

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.

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Author information

Authors and Affiliations

  1. Nuclear Medicine Unit, Ente Ospedaliero Ospedali Galliera, Genoa, Italy

    Arnoldo Piccardo & Michela Massollo

  2. Neuroradiology Unit, IRCCS Istituto Giannina Gaslini, via G. Gaslini 5, 16147, Genoa, Italy

    Domenico Tortora, Mariasavina Severino, Andrea Rossi & Giovanni Morana

  3. Head-Neck and Neuroscience Department, IRCCS Istituto Giannina Gaslini, Genoa, Italy

    Samantha Mascelli

  4. Neurosurgery Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy

    Gianluca Piatelli & Alessandro Consales

  5. Anaesthesiology Department, Ente Ospedaliero Ospedali Galliera, Genoa, Italy

    Marco Pescetto

  6. Pediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    Veronica Biassoni & Elisabetta Schiavello

  7. Neuro-oncology Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy

    Antonio Verrico, Claudia Milanaccio & Maria Luisa Garrè

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  1. Arnoldo Piccardo
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Corresponding author

Correspondence to Giovanni Morana.

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Conflict of interest

The authors declare that they have no conflict of interest.

This article does not contain any studies with animals performed by any of the authors.

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent was obtained from all individual participants or their legal guardians included in the study, and patient assent was obtained whenever appropriate.

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Andrea Rossi and Giovanni Morana are joint last authors.

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Piccardo, A., Tortora, D., Mascelli, S. et al. Advanced MR imaging and 18F-DOPA PET characteristics of H3K27M-mutant and wild-type pediatric diffuse midline gliomas. Eur J Nucl Med Mol Imaging 46, 1685–1694 (2019). https://doi.org/10.1007/s00259-019-04333-4

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