title: Reliability of 7T (1) H-MRS measured human prefrontal cortex glutamate, glutamine, and glutathione signals using an adapted echo time optimized PRESS sequence: A between- and within-sessions investigation.
abstract: OBJECTIVE
  To ascertain the mechanisms of neuropsychiatric illnesses and their treatment, accurate and reliable imaging techniques are required; proton magnetic resonance spectroscopy ((1) H-MRS) can noninvasively measure glutamatergic function. Evidence suggests that aberrant glutamatergic signaling plays a role in numerous psychopathologies. Until recently, overlapping glutamatergic signals (glutamate, glutamine, and glutathione) could not easily be separated. However, the advent of novel pulse sequences and higher field magnetic resonance imaging (MRI) allows more precise resolution of overlapping glutamatergic signals, although the question of signal reliability remains undetermined.
  
  
  METHODS
  At 7T MR, we acquired (1) H-MRS data from the medial pregenual anterior cingulate cortex of healthy volunteers (n = 26) twice on two separate days. An adapted echo time optimized point-resolved spectroscopy sequence, modified with the addition of a J-suppression pulse to attenuate N-acetyl-aspartate multiplet signals at 2.49 ppm, was used to excite and acquire the spectra. In-house software was used to model glutamate, glutamine, and glutathione, among other metabolites, referenced to creatine. Intraclass correlation coefficients (ICCs) were computed for within- and between-session measurements.
  
  
  RESULTS
  Within-session measurements of glutamate, glutamine, and glutathione were on average reliable (ICCs ≥0.7). As anticipated, ICCs for between-session values of glutamate, glutamine, and glutathione were slightly lower but nevertheless reliable (ICC >0.62). A negative correlation was observed between glutathione concentration and age (r(24)  = -0.37; P < 0.05), and a gender effect was noted on glutamine and glutathione.
  
  
  CONCLUSIONS
  The adapted sequence provides good reliability to measure glutamate, glutamine, and glutathione signals.
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA.|Institute of Cognitive Neuroscience, University College London, Alexandra House, 17 Queen Square, London, WC1N 3AR, UK.
authors.forename: Níall
authors.initials: N
authors.lastname: Lally
authors.affiliation: Magnetic Resonance Spectroscopy Core Facility, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Li
authors.initials: L
authors.lastname: An
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Dipavo
authors.initials: D
authors.lastname: Banerjee
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Niciu
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Luckenbaugh
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Erica M
authors.initials: EM
authors.lastname: Richards
authors.affiliation: Institute of Cognitive Neuroscience, University College London, Alexandra House, 17 Queen Square, London, WC1N 3AR, UK.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Roiser
authors.affiliation: Magnetic Resonance Spectroscopy Core Facility, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Shen
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Zarate
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Allison C
authors.initials: AC
authors.lastname: Nugent
mesh_terms: D000328:Adult; D000465:Algorithms; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D057054:Molecular Imaging / Q000379:methods; D018377:Neurotransmitter Agents / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism*; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods*; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012815:Signal Processing, Computer-Assisted; D055815:Young Adult
chemical_list: D018377:Neurotransmitter Agents; D005973:Glutamine; D018698:Glutamic Acid; D005978:Glutathione
keywords: glutamatergic; intraclass correlation coefficient; medial prefrontal cortex (mPFC); point resolved spectroscopy; proton magnetic resonance spectroscopy; reliability