Sotirios Bisdas1,2,3, Grzegorz L Chadzynski4,5, Christian Braun3,6,7, Jens Schittenhelm3,7,8,9, Marco Skardelly3,7,9,10, Gisela E Hagberg11,12, Thomas Ethofer11,13, Rolf Pohmann12, G Shajan12, Jörn Engelmann11,12, Ghazaleh Tabatabai3,6,7,9,14, Ulf Ziemann3,6,9, Ulrike Ernemann1,3,9, Klaus Scheffler11,12. 1. Department of Neuroradiology, Eberhard-Karls University Tübingen, Tübingen, Germany. 2. Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, University College London Hospitals, London, UK. 3. Center for CNS tumors, Comprehensive Cancer Center Tübingen-Stuttgart, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany. 4. Department of Biomedical Magnetic Resonance, Eberhard-Karls University Tübingen, Tübingen, Germany. grzegorz.chadzynski@uni-tuebingen.de. 5. High-field Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tübingen, Germany. grzegorz.chadzynski@uni-tuebingen.de. 6. Department of Neurology & Stroke, Hertie Institute for Clinical Brain Research, Eberhard-Karls University Tübingen, Tübingen, Germany. 7. Interdisciplinary Division of Neuro-Oncology, University Hospital Tübingen, Hertie Institute for Clinical Brain Research, Eberahrd Karls University, Tübingen, Germany. 8. Department of Neuropathology, Eberhard-Karls University Tübingen, Tübingen, Germany. 9. Center for Personalized Medicine, Eberhard Karls University, Tübingen, Germany. 10. Department of Neurosurgery, Eberhard-Karls University Tübingen, Tübingen, Germany. 11. Department of Biomedical Magnetic Resonance, Eberhard-Karls University Tübingen, Tübingen, Germany. 12. High-field Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tübingen, Germany. 13. Clinic for Psychiatry and Psychotherapy, Eberhard-Karls University Tübingen, Tübingen, Germany. 14. German Cancer Consortium (DKTK), DKFZ partner site Tübingen, Tübingen, Germany.
Abstract
PURPOSE: To examine in vivo metabolic alterations in the isocitrate dehydrogenase (IDH) mutated gliomas using magnetic resonance spectroscopy (MRS) at magnetic field 9.4T. MATERIALS AND METHODS: Spectra were acquired with a 9.4T whole-body scanner with the use of a custom-built head coil (16 channel transmit and 31 channel receive). A modified stimulated echo acquisition mode (STEAM) sequence was used for localization. Eighteen patients with brain tumors of probable glial origin participated in this study. The study was performed in accordance with the guidelines of the local Ethics Committee. RESULTS: The increased spectral resolution allowed us to directly address metabolic alterations caused by the specific pathophysiology of IDH mutations including the presence of the oncometabolite 2-hydroxglutarate (2HG) and a significant decrease of the pooled glutamate and glutamine (20%, P = 0.024), which probably reflects an attempt to replenish α-ketoglutarate lost by conversion to 2HG. We also observed significantly reduced glutathione (GSH) levels (39%, P = 0.019), which could be similarly caused by depletion of dihydronicotinamide-adenine dinucleotide phosphate (NADPH) during this conversion in IDH mutant gliomas. CONCLUSION: We demonstrate that MRS at 9.4T provides a noninvasive measure of 2HG in vivo, which may be used for therapy planning and prognostication, and may provide insights into related pathophysiologic metabolic alterations associated with IDH mutations. J. MAGN. RESON. IMAGING 2016;44:823-833.
PURPOSE: To examine in vivo metabolic alterations in the isocitrate dehydrogenase (IDH) mutated gliomas using magnetic resonance spectroscopy (MRS) at magnetic field 9.4T. MATERIALS AND METHODS: Spectra were acquired with a 9.4T whole-body scanner with the use of a custom-built head coil (16 channel transmit and 31 channel receive). A modified stimulated echo acquisition mode (STEAM) sequence was used for localization. Eighteen patients with brain tumors of probable glial origin participated in this study. The study was performed in accordance with the guidelines of the local Ethics Committee. RESULTS: The increased spectral resolution allowed us to directly address metabolic alterations caused by the specific pathophysiology of IDH mutations including the presence of the oncometabolite 2-hydroxglutarate (2HG) and a significant decrease of the pooled glutamate and glutamine (20%, P = 0.024), which probably reflects an attempt to replenish α-ketoglutarate lost by conversion to 2HG. We also observed significantly reduced glutathione (GSH) levels (39%, P = 0.019), which could be similarly caused by depletion of dihydronicotinamide-adenine dinucleotide phosphate (NADPH) during this conversion in IDH mutant gliomas. CONCLUSION: We demonstrate that MRS at 9.4T provides a noninvasive measure of 2HG in vivo, which may be used for therapy planning and prognostication, and may provide insights into related pathophysiologic metabolic alterations associated with IDH mutations. J. MAGN. RESON. IMAGING 2016;44:823-833.
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