Simultaneous quantification of GABA, Glx and GSH in the neonatal human brain using magnetic resonance spectroscopy
Year: 2021
Type: article
Study design: Observational Study
Abstract: 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.
Source: NeuroImage
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,300
Funders: Autism Speaks, South London and Maudsley NHS Foundation Trust, Wellcome Trust, King's College Hospital NHS Foundation Trust, European Federation of Pharmaceutical Industries and Associations, Simons Foundation Autism Research Initiative, NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research, Action Medical Research, National Institute for Health and Care Research, Department of Health and Social Care, King's College London, European Commission, Medical Engineering Centre King’s College London, Innovative Medicines Initiative, National Institutes of Health, Medical Engineering Centre, King’s College London, Sackler Institute for Translational Neurodevelopment, King's College London, Medical Research Council, Engineering and Physical Sciences Research Council, Menzies Centre for Australian Studies, King's College London, University of London, Centre For Medical Engineering, King’s College London, National Institute of Biomedical Imaging and Bioengineering, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1054121244, G1190881904, G1211483440, G1247657515, King's College London Medical Engineering Centre of Research Excellence, G1435826916, Intellectual and Developmental Disabilities Research Centers 2020, G296025267, MRC Centre for Neurodevelopmental Disorders, Resource for Quantitative Functional FMRI, Development of brain activity and motor control in early human life, G4345436876, G4668817743, G5139571028, G5296857752, G5543596241, G5701184066, MRC Transition Support Award CSF Tomoki Arichi, G5893523844, G5935007269, G60524263, Autism Innovative Medicine Studies – 2 – Trials, MRC Centre for Neurodevelopmental Disorders, G7070717597, G7587803570, G8303168876, G8775246936, Simultaneous Hadamard Editing of GABA and Glutathione, G9000057464, MRI Resource for Physiologic, Metabolic and Anatomic Biomarkers, Universal Edited MRS at 3T, G938335843, G961285871
OpenAlex ID: W3135639410