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Reliable diagnosis of IDH-mutant glioblastoma by 2-hydroxyglutarate detection: a study by 3-T magnetic resonance spectroscopy

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Abstract

We have previously reported that reliable detection of 2-hydroxyglutarate (2HG) in isocitrate dehydrogenase (IDH)-mutant WHO grade 2 and 3 gliomas is possible utilizing 3.0-T single-voxel magnetic resonance spectroscopy (SVMRS). We set out to determine whether the same method could be applied to detect 2HG in IDH-mutant glioblastoma. Forty-four patients harboring glioblastoma underwent pre-operative MRS evaluation to detect 2HG and other metabolites. Presence of IDH-mutations was determined by IDH1 R132H immunohistochemical analysis and DNA sequencing of surgically obtained tissues. Six out of 44 (13.6%) glioblastomas were IDH-mutant. IDH-mutant glioblastoma exhibited significantly higher accumulation of 2HG (median 3.191 vs. 0.000 mM, p < 0.0001, Mann-Whitney test). A cutoff of 2HG = 0.897 mM achieved high sensitivity (100.0%) and specificity (92.59%) in determining IDH-mutation in glioblastoma. Glioblastoma with high 2HG accumulation did not have significantly longer overall survival than glioblastoma with low 2HG accumulation (p = 0.107, log-rank test). Non-invasive and reliable detection of 2HG in IDH-mutant glioblastoma was possible by 3.0-T SVMRS.

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Acknowledgements

We acknowledge Drs. Kimihiko Nakamura, Taro Nishikawa, Shinya Jinguji, Toshiharu Nomura, and others for the help with imaging.

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  1. Manabu Natsumeda and Kunio Motohashi contributed equally.

Authors and Affiliations

  1. Department of Neurosurgery, Brain Research Institute, University of Niigata, Niigata, Japan

    Manabu Natsumeda, Kunio Motohashi, Takanori Nozawa, Hideaki Abe, Yoshihiro Tsukamoto, Ryosuke Ogura, Masayasu Okada, Tsutomu Kobayashi, Hiroshi Aoki, Kouichirou Okamoto & Yukihiko Fujii

  2. Center for Integrated Brain Science, Brain Research Institute, University of Niigata, Niigata, Japan

    Kunio Motohashi, Hironaka Igarashi, Kouichirou Okamoto & Tsutomu Nakada

  3. Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan

    Takanori Nozawa, Hitoshi Takahashi & Akiyoshi Kakita

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  1. Manabu Natsumeda
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Correspondence to Hironaka Igarashi.

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Ethical approval was obtained in accordance with the human research guidelines of the Institutional Review Board of University of Niigata.

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Natsumeda, M., Motohashi, K., Igarashi, H. et al. Reliable diagnosis of IDH-mutant glioblastoma by 2-hydroxyglutarate detection: a study by 3-T magnetic resonance spectroscopy. Neurosurg Rev 41, 641–647 (2018). https://doi.org/10.1007/s10143-017-0908-y

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