Reproducibility of Glutamate, Glutathione, and GABA Measurements in vivo by Single-Voxel STEAM Magnetic Resonance Spectroscopy at 7-Tesla in Healthy Individuals.

Ofer M Gonen,Bradford A Moffat,Patrick Kwan,Elaine Lui,Terence J O’Brien,Patricia M Desmond

doi:10.3389/fnins.2020.566643

Abstract

Background and PurposeDerangements in brain glutamate, glutathione, and γ-amino butyric acid (GABA) are implicated in a range of neurological disorders. Reliable methods to measure these compounds non-invasively in vivo are needed. We evaluated the reproducibility of their measurements in brain regions involved in the default mode network using quantitative MRS at 7-Tesla in healthy individuals.MethodsTen right-handed healthy volunteers underwent 7-Tesla MRI scans on 2 separate days, not more than 2 weeks apart. On each day two scanning sessions took place, with a re-positioning break in between. High-resolution isotropic anatomical scans were acquired prior to each scan, followed by single-voxel 1H-MRS using the STEAM pulse sequence on an 8 mL midline cubic voxel, positioned over the posterior cingulate and precuneus regions. Concentrations were corrected for partial-volume effects.ResultsMaximal Cramér-Rao lower bounds for glutamate, glutathione, and GABA were 2.0, 8.0, and 14.0%, respectively. Mean coefficients of variation within sessions were 5.9 ± 4.8%, 9.3 ± 7.6%, and 11.5 ± 8.8%, and between sessions were 4.6 ± 4.5%, 8.3 ± 5.7%, and 9.2 ± 8.7%, respectively. The mean (±SD) Dice’s coefficient for voxel overlap was 90 ± 4% within sessions and 86 ± 7% between sessions.ConclusionGlutamate, glutathione, and GABA can be reliably quantified using STEAM MRS at 7-Tesla from the posterior cingulate and precuneus cortices of healthy human subjects. STEAM MRS at 7-Tesla may be used to study the metabolic behavior of this important resting-state hub in various disease states.

Highlights

Glutamate and γ-amino butyric acid (GABA) are the major excitatory and inhibitory neurotransmitters in the human brain, respectively (Kocsis and Mattson, 1996; Benarroch, 2010)
All participants completed the two scans separated by 4–14 days
Mean ± standard deviation (SD) concentrations of glutamate, GSH, and GABA scaled to unsuppressed water were 10.18 ± 1.00 mM, FIGURE 2 | Example of a spectrum

Summary

Introduction

Glutamate and γ-amino butyric acid (GABA) are the major excitatory and inhibitory neurotransmitters in the human brain, respectively (Kocsis and Mattson, 1996; Benarroch, 2010). Glutathione (GSH) is the most important free radical scavenging compound in the brain and is thought to be implicated in a wide range of neurological disorders, including epilepsy, multiple sclerosis, Parkinson’s disease, and motor neuron disease (Rae and Williams, 2017). Interest in quantitative MRS of the human brain is increasing due to its importance in evaluating drugs that potentially affect these metabolites. Derangements in brain glutamate, glutathione, and γ-amino butyric acid (GABA) are implicated in a range of neurological disorders. We evaluated the reproducibility of their measurements in brain regions involved in the default mode network using quantitative MRS at 7-Tesla in healthy individuals

Methods

Results

Conclusion