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

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          Abstract

          Background and Purpose

          Derangements 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.

          Methods

          Ten 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.

          Results

          Maximal 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.

          Conclusion

          Glutamate, 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.

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          Most cited references26

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          Issues of spectral quality in clinical 1H-magnetic resonance spectroscopy and a gallery of artifacts.

          In spite of the facts that magnetic resonance spectroscopy (MRS) is applied as clinical tool in non-specialized institutions and that semi-automatic acquisition and processing tools can be used to produce quantitative information from MRS exams without expert information, issues of spectral quality and quality assessment are neglected in the literature of MR spectroscopy. Even worse, there is no consensus among experts on concepts or detailed criteria of quality assessment for MR spectra. Furthermore, artifacts are not at all conspicuous in MRS and can easily be taken for true, interpretable features. This article aims to increase interest in issues of spectral quality and quality assessment, to start a larger debate on generally accepted criteria that spectra must fulfil to be clinically and scientifically acceptable, and to provide a sample gallery of artifacts, which can be used to raise awareness for potential pitfalls in MRS. Copyright (c) 2004 John Wiley & Sons, Ltd.
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            Resting-state glutamate and GABA concentrations predict task-induced deactivation in the default mode network.

            Deactivation of the human brain's default mode network (DMN) is regarded as suppression of endogenous activity to support exogenous task-related processes. This phenomenon has important functional relevance and insufficient DMN deactivation has been implicated in several neuropsychiatric disorders. However, the neurochemical mechanism of the DMN's deactivation remains largely unknown. In the present study, we test the hypothesis that the major excitatory and inhibitory neurotransmitters, glutamate and GABA, respectively, are associated with DMN deactivation. We used magnetic resonance spectroscopy to measure neurotransmitter concentrations in the posterior cingulate cortex/precuneus (PCC/PCu), a key component of the DMN, and functional magnetic resonance imaging to evaluate DMN deactivation induced by an n-back working memory task. Our results demonstrate significant associations of glutamate and GABA with DMN deactivation. Specifically, high regional GABA concentration in the PCC/PCu area is associated with enhanced deactivation induced by the task in the same region, whereas high glutamate concentration is associated with reduced deactivation. Furthermore, the association between GABA and DMN deactivation increases with the cognitive loads. These neurochemical characteristics of DMN deactivation may provide novel insights toward better understanding of the DMN's functions under normal physiological conditions and dysfunctions in neuropsychiatric disorders.
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              MR spectroscopy of the human brain with enhanced signal intensity at ultrashort echo times on a clinical platform at 3T and 7T.

              Recently, the spin-echo full-intensity acquired localized (SPECIAL) spectroscopy technique was proposed to unite the advantages of short TEs on the order of milliseconds (ms) with full sensitivity and applied to in vivo rat brain. In the present study, SPECIAL was adapted and optimized for use on a clinical platform at 3T and 7T by combining interleaved water suppression (WS) and outer volume saturation (OVS), optimized sequence timing, and improved shimming using FASTMAP. High-quality single voxel spectra of human brain were acquired at TEs below or equal to 6 ms on a clinical 3T and 7T system for six volunteers. Narrow linewidths (6.6 +/- 0.6 Hz at 3T and 12.1 +/- 1.0 Hz at 7T for water) and the high signal-to-noise ratio (SNR) of the artifact-free spectra enabled the quantification of a neurochemical profile consisting of 18 metabolites with Cramér-Rao lower bounds (CRLBs) below 20% at both field strengths. The enhanced sensitivity and increased spectral resolution at 7T compared to 3T allowed a two-fold reduction in scan time, an increased precision of quantification for 12 metabolites, and the additional quantification of lactate with CRLB below 20%. Improved sensitivity at 7T was also demonstrated by a 1.7-fold increase in average SNR (= peak height/root mean square [RMS]-of-noise) per unit-time.
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                Author and article information

                Contributors
                Journal
                Front Neurosci
                Front. Neurosci.
                Frontiers in Neuroscience
                Frontiers Media S.A.
                1662-4548
                1662-453X
                15 September 2020
                2020
                : 14
                : 566643
                Affiliations
                [1] 1Department of Neurology, The Royal Melbourne Hospital , Parkville, VIC, Australia
                [2] 2Department of Medicine and Radiology, The University of Melbourne , Parkville, VIC, Australia
                [3] 3Department of Neurology, The Alfred Hospital , Melbourne, VIC, Australia
                [4] 4Department of Neuroscience, Central Clinical School, Monash University , Melbourne, VIC, Australia
                [5] 5Department of Radiology, The Royal Melbourne Hospital , Parkville, VIC, Australia
                Author notes

                Edited by: Xi-Nian Zuo, Nanning Normal University, China

                Reviewed by: Yuzheng Hu, Zhejiang University, China; Yan Li, University of California, San Francisco, United States

                *Correspondence: Ofer M. Gonen, Ofer.Gonen@ 123456mh.org.au

                This article was submitted to Brain Imaging Methods, a section of the journal Frontiers in Neuroscience

                Article
                10.3389/fnins.2020.566643
                7522573
                32038151
                82cacbe1-77ed-43ea-9279-fb00ae431cc8
                Copyright © 2020 Gonen, Moffat, Kwan, O’Brien, Desmond and Lui.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 28 May 2020
                : 21 August 2020
                Page count
                Figures: 3, Tables: 5, Equations: 0, References: 37, Pages: 9, Words: 0
                Funding
                Funded by: University of Melbourne 10.13039/501100001782
                Funded by: Royal Melbourne Hospital Neuroscience Foundation 10.13039/100012504
                Funded by: National Imaging Facility 10.13039/100015572
                Categories
                Neuroscience
                Original Research

                Neurosciences
                magnetic resonance spectroscopy,steam,default mode network,posterior cingulate cortex,precuneus,reproducibility

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