title: MR spectroscopy for in vivo assessment of the oncometabolite 2-hydroxyglutarate and its effects on cellular metabolism in human brain gliomas at 9.4T.
abstract: To examine in vivo metabolic alterations in the isocitrate dehydrogenase (IDH) mutated gliomas using magnetic resonance spectroscopy (MRS) at magnetic field 9.4T.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Neuroradiology, Eberhard-Karls University Tübingen, Tübingen, Germany.|Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, University College London Hospitals, London, UK.|Center for CNS tumors, Comprehensive Cancer Center Tübingen-Stuttgart, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Sotirios
authors.initials: S
authors.lastname: Bisdas
authors.affiliation: Department of Biomedical Magnetic Resonance, Eberhard-Karls University Tübingen, Tübingen, Germany. grzegorz.chadzynski@uni-tuebingen.de.|High-field Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tübingen, Germany. grzegorz.chadzynski@uni-tuebingen.de.
authors.forename: Grzegorz L
authors.initials: GL
authors.lastname: Chadzynski
authors.affiliation: Center for CNS tumors, Comprehensive Cancer Center Tübingen-Stuttgart, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|Department of Neurology & Stroke, Hertie Institute for Clinical Brain Research, Eberhard-Karls University Tübingen, Tübingen, Germany.|Interdisciplinary Division of Neuro-Oncology, University Hospital Tübingen, Hertie Institute for Clinical Brain Research, Eberahrd Karls University, Tübingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Braun
authors.affiliation: Center for CNS tumors, Comprehensive Cancer Center Tübingen-Stuttgart, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|Interdisciplinary Division of Neuro-Oncology, University Hospital Tübingen, Hertie Institute for Clinical Brain Research, Eberahrd Karls University, Tübingen, Germany.|Department of Neuropathology, Eberhard-Karls University Tübingen, Tübingen, Germany.|Center for Personalized Medicine, Eberhard Karls University, Tübingen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Schittenhelm
authors.affiliation: Center for CNS tumors, Comprehensive Cancer Center Tübingen-Stuttgart, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|Interdisciplinary Division of Neuro-Oncology, University Hospital Tübingen, Hertie Institute for Clinical Brain Research, Eberahrd Karls University, Tübingen, Germany.|Center for Personalized Medicine, Eberhard Karls University, Tübingen, Germany.|Department of Neurosurgery, Eberhard-Karls University Tübingen, Tübingen, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Skardelly
authors.affiliation: Department of Biomedical Magnetic Resonance, Eberhard-Karls University Tübingen, Tübingen, Germany.|High-field Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tübingen, Germany.
authors.forename: Gisela E
authors.initials: GE
authors.lastname: Hagberg
authors.affiliation: Department of Biomedical Magnetic Resonance, Eberhard-Karls University Tübingen, Tübingen, Germany.|Clinic for Psychiatry and Psychotherapy, Eberhard-Karls University Tübingen, Tübingen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ethofer
authors.affiliation: High-field Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tübingen, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Pohmann
authors.affiliation: High-field Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tübingen, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Shajan
authors.affiliation: Department of Biomedical Magnetic Resonance, Eberhard-Karls University Tübingen, Tübingen, Germany.|High-field Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tübingen, Germany.
authors.forename: Jörn
authors.initials: J
authors.lastname: Engelmann
authors.affiliation: Center for CNS tumors, Comprehensive Cancer Center Tübingen-Stuttgart, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|Department of Neurology & Stroke, Hertie Institute for Clinical Brain Research, Eberhard-Karls University Tübingen, Tübingen, Germany.|Interdisciplinary Division of Neuro-Oncology, University Hospital Tübingen, Hertie Institute for Clinical Brain Research, Eberahrd Karls University, Tübingen, Germany.|Center for Personalized Medicine, Eberhard Karls University, Tübingen, Germany.|German Cancer Consortium (DKTK), DKFZ partner site Tübingen, Tübingen, Germany.
authors.forename: Ghazaleh
authors.initials: G
authors.lastname: Tabatabai
authors.affiliation: Center for CNS tumors, Comprehensive Cancer Center Tübingen-Stuttgart, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|Department of Neurology & Stroke, Hertie Institute for Clinical Brain Research, Eberhard-Karls University Tübingen, Tübingen, Germany.|Center for Personalized Medicine, Eberhard Karls University, Tübingen, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Ziemann
authors.affiliation: Department of Neuroradiology, Eberhard-Karls University Tübingen, Tübingen, Germany.|Center for CNS tumors, Comprehensive Cancer Center Tübingen-Stuttgart, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.|Center for Personalized Medicine, Eberhard Karls University, Tübingen, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Ernemann
authors.affiliation: Department of Biomedical Magnetic Resonance, Eberhard-Karls University Tübingen, Tübingen, Germany.|High-field Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tübingen, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Scheffler
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics*; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005977:Glutarates / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D057054:Molecular Imaging / Q000379:methods; D009154:Mutation / Q000235:genetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D005977:Glutarates; C019417:alpha-hydroxyglutarate; D000429:Alcohol Oxidoreductases; C023858:2-hydroxyglutarate dehydrogenase
keywords: human brain tumors; isocitrate dehydrogenase; magnetic resonance spectroscopy; neurooncology; neuroradiology