Precision of metabolite-selective MRS measurements of glutamate, GABA and glutathione: A review of human brain studies

NMR Biomed. 2024 Mar;37(3):e5071. doi: 10.1002/nbm.5071. Epub 2023 Dec 4.


Single-voxel proton magnetic resonance spectroscopy (SV 1 H-MRS) is an in vivo noninvasive imaging technique used to detect neurotransmitters and metabolites. It enables repeated measurements in living participants to build explanatory neurochemical models of psychiatric symptoms and testing of therapeutic approaches. Given the tight link among glutamate, gamma-amino butyric acid (GABA), glutathione and glutamine within the cellular machinery, MRS investigations of neurocognitive and psychiatric disorders must quantify a network of metabolites simultaneously to capture the pathophysiological states of interest. Metabolite-selective sequences typically provide improved metabolite isolation and spectral modelling simplification for a single metabolite at a time. Non-metabolite-selective sequences provide information on all detectable human brain metabolites, but feature many signal overlaps and require complicated spectral modelling. Although there are short-echo time (TE) MRS sequences that do not use spectral editing and are optimised to target either glutamate, GABA or glutathione, these approaches usually imply a precision tradeoff for the remaining two metabolites. Given the interest in assessing psychiatric and neurocognitive diseases that involve excitation-inhibition imbalances along with oxidative stress, there is a need to survey the literature on the quantification precision of current metabolite-selective MRS techniques. In this review, we locate and describe 17 studies that report on the quality of simultaneously acquired MRS metabolite data in the human brain. We note several factors that influence the data quality for single-shot acquisition of multiple metabolites of interest using metabolite-selective MRS: (1) internal in vivo references; (2) brain regions of interests; (3) field strength of scanner; and/or (4) optimised acquisition parameters. We also highlight the strengths and weaknesses of various SV spectroscopy techniques that were able to quantify in vivo glutamate, GABA and glutathione simultaneously. The insights from this review will assist in the development of new MRS pulse sequences for simultaneous, selective measurements of these metabolites and simplified spectral modelling.

Keywords: gamma-amino butyric acid; glutamate; glutathione; human brain; metabolite-selective pulse sequence; neurocognitive disorders; proton magnetic resonance spectroscopy; psychiatric illnesses.

Publication types

  • Review

MeSH terms

  • Brain* / diagnostic imaging
  • Brain* / metabolism
  • Glutamic Acid* / metabolism
  • Glutamine / metabolism
  • Glutathione / metabolism
  • Humans
  • gamma-Aminobutyric Acid / metabolism


  • Glutamic Acid
  • Glutamine
  • Glutathione
  • gamma-Aminobutyric Acid