Simultaneous quantification of GABA, Glx and GSH in the neonatal human brain using magnetic resonance spectroscopy
Balance between inhibitory and excitatory neurotransmitter systems and the protective role of the major antioxidant glutathione (GSH) are central to early healthy brain development. Disruption has been implicated in the early life pathophysiology of psychiatric disorders and neurodevelopmental condi...
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Elsevier
2021-06-01
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Series: | NeuroImage |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S105381192100207X |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yanez Lopez Maria Anthony N. Price Nicolaas A.J. Puts Emer J. Hughes Richard A.E. Edden Grainne M. McAlonan Tomoki Arichi Enrico De Vita |
spellingShingle |
Yanez Lopez Maria Anthony N. Price Nicolaas A.J. Puts Emer J. Hughes Richard A.E. Edden Grainne M. McAlonan Tomoki Arichi Enrico De Vita Simultaneous quantification of GABA, Glx and GSH in the neonatal human brain using magnetic resonance spectroscopy NeuroImage Edited-MRS Neonate GABA Glutamate GSH |
author_facet |
Yanez Lopez Maria Anthony N. Price Nicolaas A.J. Puts Emer J. Hughes Richard A.E. Edden Grainne M. McAlonan Tomoki Arichi Enrico De Vita |
author_sort |
Yanez Lopez Maria |
title |
Simultaneous quantification of GABA, Glx and GSH in the neonatal human brain using magnetic resonance spectroscopy |
title_short |
Simultaneous quantification of GABA, Glx and GSH in the neonatal human brain using magnetic resonance spectroscopy |
title_full |
Simultaneous quantification of GABA, Glx and GSH in the neonatal human brain using magnetic resonance spectroscopy |
title_fullStr |
Simultaneous quantification of GABA, Glx and GSH in the neonatal human brain using magnetic resonance spectroscopy |
title_full_unstemmed |
Simultaneous quantification of GABA, Glx and GSH in the neonatal human brain using magnetic resonance spectroscopy |
title_sort |
simultaneous quantification of gaba, glx and gsh in the neonatal human brain using magnetic resonance spectroscopy |
publisher |
Elsevier |
series |
NeuroImage |
issn |
1095-9572 |
publishDate |
2021-06-01 |
description |
Balance between inhibitory and excitatory neurotransmitter systems and the protective role of the major antioxidant glutathione (GSH) are central to early healthy brain development. Disruption has been implicated in the early life pathophysiology of psychiatric disorders and neurodevelopmental conditions including Autism Spectrum Disorder.Edited magnetic resonance spectroscopy (MRS) methods such as HERMES have great potential for providing important new non-invasive insights into these crucial processes in human infancy. In this work, we describe a systematic approach to minimise the impact of specific technical challenges inherent to acquiring MRS data in a neonatal population, including automatic segmentation, full tissue-correction and optimised GABA+ fitting and consider the minimum requirements for a robust edited-MRS acquisition. With this approach we report for the first time simultaneous GABA+, Glx (glutamate + glutamine) and GSH concentrations in the neonatal brain (n = 18) in two distinct regions (thalamus and anterior cingulate cortex (ACC)) using edited MRS at 3T.The improved sensitivity provided by our method allows specific regional neurochemical differences to be identified including: significantly lower Glx and GSH ratios to total creatine in the thalamus compared to the ACC (p < 0.001 for both), and significantly higher GSH levels in the ACC following tissue-correction (p < 0.01). Furthermore, in contrast to adult GABA+ which can typically be accurately fitted with a single peak, all neonate spectra displayed a characteristic doublet GABA+ peak at 3 ppm, indicating a lower macromolecule (MM) contribution to the 3 ppm signal in neonates. Relatively high group-level variance shows the need to maximise voxel size/acquisition time in edited neonatal MRS acquisitions for robust estimation of metabolites.Application of this method to study how these levels and balance are altered by early-life brain injury or genetic risk can provide important new knowledge about the pathophysiology underlying neurodevelopmental disorders. |
topic |
Edited-MRS Neonate GABA Glutamate GSH |
url |
http://www.sciencedirect.com/science/article/pii/S105381192100207X |
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doaj-a41cccde7d4449f0a82f0a1ca620bf9e2021-04-26T05:53:59ZengElsevierNeuroImage1095-95722021-06-01233117930Simultaneous quantification of GABA, Glx and GSH in the neonatal human brain using magnetic resonance spectroscopyYanez Lopez Maria0Anthony N. Price1Nicolaas A.J. Puts2Emer J. Hughes3Richard A.E. Edden4Grainne M. McAlonan5Tomoki Arichi6Enrico De Vita7Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King's College London, London, United KingdomCentre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King's College London, London, United KingdomDepartment of Forensic and Neurodevelopmental Sciences, Sackler Institute for Translational Neurodevelopment, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United KingdomCentre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King's College London, London, United KingdomRussell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, United StatesDepartment of Forensic and Neurodevelopmental Sciences, Sackler Institute for Translational Neurodevelopment, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; MRC Centre for Neurodevelopmental Disorders, King's College London, London, United Kingdom; NIHR-Maudsley Biomedical Research, King's College London, United KingdomCentre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom; Department of Bioengineering, Imperial College London, South Kensington Campus, London, United KingdomCentre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom; Biomedical Engineering Department, School of Biomedical Engineering and Imaging Sciences, St Thomas’ Hospital, Westminster Bridge Road, Lambeth Wing, 3rd Floor, London SE1 7EH, United Kingdom; Corresponding author.Balance between inhibitory and excitatory neurotransmitter systems and the protective role of the major antioxidant glutathione (GSH) are central to early healthy brain development. Disruption has been implicated in the early life pathophysiology of psychiatric disorders and neurodevelopmental conditions including Autism Spectrum Disorder.Edited magnetic resonance spectroscopy (MRS) methods such as HERMES have great potential for providing important new non-invasive insights into these crucial processes in human infancy. In this work, we describe a systematic approach to minimise the impact of specific technical challenges inherent to acquiring MRS data in a neonatal population, including automatic segmentation, full tissue-correction and optimised GABA+ fitting and consider the minimum requirements for a robust edited-MRS acquisition. With this approach we report for the first time simultaneous GABA+, Glx (glutamate + glutamine) and GSH concentrations in the neonatal brain (n = 18) in two distinct regions (thalamus and anterior cingulate cortex (ACC)) using edited MRS at 3T.The improved sensitivity provided by our method allows specific regional neurochemical differences to be identified including: significantly lower Glx and GSH ratios to total creatine in the thalamus compared to the ACC (p < 0.001 for both), and significantly higher GSH levels in the ACC following tissue-correction (p < 0.01). Furthermore, in contrast to adult GABA+ which can typically be accurately fitted with a single peak, all neonate spectra displayed a characteristic doublet GABA+ peak at 3 ppm, indicating a lower macromolecule (MM) contribution to the 3 ppm signal in neonates. Relatively high group-level variance shows the need to maximise voxel size/acquisition time in edited neonatal MRS acquisitions for robust estimation of metabolites.Application of this method to study how these levels and balance are altered by early-life brain injury or genetic risk can provide important new knowledge about the pathophysiology underlying neurodevelopmental disorders.http://www.sciencedirect.com/science/article/pii/S105381192100207XEdited-MRSNeonateGABAGlutamateGSH |