title: Reproducibility measurement of glutathione, GABA, and glutamate: Towards in vivo neurochemical profiling of multiple sclerosis with MR spectroscopy at 7T.
abstract: To determine the reproducibility of a comprehensive single-session measurement of glutathione (GSH), γ-aminobutyric acid (GABA), glutamate, and other biochemicals implicated in the pathophysiology of multiple sclerosis (MS) in the human brain with1H magnetic resonance spectroscopy (MRS).
  
  
  
  Five healthy subjects were studied twice in separate 1-hour sessions at 7T. One MS patient was also scanned once. GSH and GABA were measured with J-difference editing using a semilocalized by adiabatic selective refocusing sequence (semi-LASER, TE = 72 msec). A stimulated echo acquisition mode sequence (STEAM, TE = 10 msec) was used to detect glutamate along with the overall biochemical profile. Spectra were quantified with LCModel. Quantification accuracy was assessed through Cramer-Rao lower bounds (CRLB). Reproducibility of the metabolite quantification was tested using coefficients of variation (CoV).
  
  
  
  CRLB were ≤7% for GSH, GABA, and glutamate and average CoV of 7.8 ± 3.2%, 9.5 ± 7.0%, and 3.2 ± 1.7% were achieved, respectively. The average test/retest concentration differences at this measurement reproducibility and quantification accuracy were smaller for GABA and glutamate than intersubject variations in metabolite content with CoV ratios of 0.6 and 0.8, respectively. As proof of principle, GSH, GABA, and glutamate were also detected in an MS patient.
  
  
  
  GSH, GABA, glutamate, and other metabolites relevant in MS can be quantified at 7T with high accuracy and reproducibility in a single 1-hour session. This methodology might serve as a clinical research tool to investigate biochemical markers associated with MS.
  
  
  
  2 J. Magn. Reson. Imaging 2017;45:187-198.
authors.affiliation: Department of Radiology and Biomedical Imaging, Yale University, New Haven, Connecticut, USA.
authors.forename: Hetty
authors.initials: H
authors.lastname: Prinsen
authors.affiliation: Department of Radiology and Biomedical Imaging, Yale University, New Haven, Connecticut, USA.|Department of Biomedical Engineering, Yale University, New Haven, Connecticut, USA.
authors.forename: Robin A
authors.initials: RA
authors.lastname: de Graaf
authors.affiliation: Department of Radiology and Biomedical Imaging, Yale University, New Haven, Connecticut, USA.|Department of Psychiatry, Yale University, New Haven, Connecticut, USA.
authors.forename: Graeme F
authors.initials: GF
authors.lastname: Mason
authors.affiliation: Department of Neurology, Yale University, New Haven, Connecticut, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pelletier
authors.affiliation: Department of Radiology and Biomedical Imaging, Yale University, New Haven, Connecticut, USA.|Department of Neurology, Yale University, New Haven, Connecticut, USA.
authors.forename: Christoph
authors.initials: C
authors.lastname: Juchem
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D057054:Molecular Imaging / Q000379:methods; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D018377:Neurotransmitter Agents; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D005978:Glutathione
keywords: 7 Tesla; brain; human; magnetic resonance spectroscopy; multiple sclerosis; reproducibility