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In vivo 2-hydroxyglutarate-proton magnetic resonance spectroscopy (3 T, PRESS technique) in treatment-naïve suspect lower-grade gliomas: feasibility and accuracy in a clinical setting

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Abstract

Isocitrate dehydrogenase 1/2 (IDH1/2) mutations are often detected in lower-grade gliomas (LGG) and result into 2-hydroxyglutarate (2HG) synthesis. Prior studies showed that 2HG can be detected in vivo using magnetic resonance spectroscopy (MRS), but its accuracy and translational impact are still under investigation.

Purpose

To investigate the clinical feasibility of MRS for in vivo detection and quantification of 2HG on consecutive treatment-naïve suspect LGG patients and to compare MRS accuracy with tissue IDH1/2 analysis.

Methods

MRS spectra at 3 T were acquired with 1H-MRS single-voxel PRESS 2HG-tailored sequences with TE 30 (group 1) or TE 97 (groups 2A and B). Voxel sizes were 1.5 × 1.5 × 1.5 cm3 for group 1 (n = 13) and group 2A (n = 14) and 2 × 2 × 2 cm3 for group 2B (n = 32). Multiple metabolites’ concentrations were analyzed with LCModel. Tumors were assessed for IDH status and main molecular markers. 2HG levels in urine/blood were measured by liquid chromatography–mass spectrometry.

Results

The larger voxel TE 97 sequence resulted in highest specificity (100%), sensitivity (79%), and accuracy (87%). Urine and blood 2HG did not result predictive.

Conclusion

Our data confirm that 2 × 2 × 2-cm3 voxel TE 97 MRS shows high accuracy for 2HG detection, with good sensitivity and 100% specificity in distinguishing IDH mutant gliomas. Main limits of the technique are small tumor volume and low cellularity. Integrating 2HG-MRS with other metabolites may help non-invasive diagnosis of glioma, prognostic assessment, and treatment planning in clinical setting.

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Acknowledgements

We thank Federico Riccardi Sirtori (Oncology Unit, Nerviano Medical Sciences, Nerviano (MI)) for dosing 2HG in biological fluids and Ruben Gianeri (Unit of Neuroradiology, FONDAZIONE IRCCS ISTITUTO NEUROLOGICO CARLO BESTA) for the help with MR imaging. We absolutely thank our patients.

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Authors and Affiliations

  1. Unit of Neuroradiology, Fondazione Irccs Istituto Neurologico Carlo Besta, Via Celoria 11, Milan, Italy

    Valeria Cuccarini, Luigi Antelmi, Anna Nigri & Maria Grazia Bruzzone

  2. Neuropathology, Fondazione Irccs Istituto Neurologico Carlo Besta, Milan, Italy

    Bianca Pollo & Chiara Calatozzolo

  3. Unit of Molecular Neuro-Oncology, Fondazione Irccs Istituto Neurologico Carlo Besta, Milan, Italy

    Rosina Paterra, Marica Eoli, Gaetano Finocchiaro & Elena Anghileri

  4. Department Neurosurgery Department, Fondazione Irccs Istituto Neurologico Carlo Besta, Milan, Italy

    Francesco DiMeco

  5. Department of Research and Clinical Development, Scientific Directorate, Fondazione Irccs Istituto Neurologico Carlo Besta, Milan, Italy

    Greta Brenna & Irene Tramacere

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  1. Valeria Cuccarini
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  2. Luigi Antelmi
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Correspondence to Elena Anghileri.

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The Institutional Ethics Committee approved the study (protocol n. 419/2014), which conforms to the Declaration of Helsinki. Informed consent was obtained from all participants.

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Cuccarini, V., Antelmi, L., Pollo, B. et al. In vivo 2-hydroxyglutarate-proton magnetic resonance spectroscopy (3 T, PRESS technique) in treatment-naïve suspect lower-grade gliomas: feasibility and accuracy in a clinical setting. Neurol Sci 41, 347–355 (2020). https://doi.org/10.1007/s10072-019-04087-9

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