An In-vivo 1H-MRS short-echo time technique at 7T: Quantification of metabolites in chronic multiple sclerosis and neuromyelitis optica brain lesions and normal appearing brain tissue
George Tackley,
Yazhuo Kong,
Rachel Minne,
Silvia Messina,
Anderson Winkler,
Ana Cavey,
Rosie Everett,
Gabriele C DeLuca,
Andrew Weir,
Matthew Craner,
Irene Tracey,
Jacqueline Palace,
Charlotte J Stagg,
Uzay Emir
Affiliations
George Tackley
Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, United Kingdom; Cardiff University Brain Research Imaging Centre (CUBRIC), Cardiff University, CF24 4HQ, United Kingdom; Corresponding author.
Yazhuo Kong
Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, United Kingdom; CAS Key Laboratory of Behavioural Science, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China
Rachel Minne
School of Health Sciences, Purdue University, 550 Stadium Mall Drive, West Lafayette, IN 47907, (765) 494-1419, United States
Silvia Messina
Division of Clinical Neurology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, United Kingdom
Anderson Winkler
Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, United Kingdom; National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD, United States
Ana Cavey
Division of Clinical Neurology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, United Kingdom
Rosie Everett
Division of Clinical Neurology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, United Kingdom
Gabriele C DeLuca
Division of Clinical Neurology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, United Kingdom
Andrew Weir
Division of Clinical Neurology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, United Kingdom
Matthew Craner
Division of Clinical Neurology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, United Kingdom
Irene Tracey
Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, United Kingdom
Jacqueline Palace
Division of Clinical Neurology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, United Kingdom
Charlotte J Stagg
Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, United Kingdom; MRC Brain Network Dynamics Unit, University of Oxford, Oxford, OX1 3TH, United Kingdom
Uzay Emir
Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, United Kingdom; School of Health Sciences, Purdue University, 550 Stadium Mall Drive, West Lafayette, IN 47907, (765) 494-1419, United States; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, United States
Magnetic Resonance Spectroscopy (MRS) allows for the non-invasive quantification of neurochemicals and has the potential to differentiate between the pathologically distinct diseases, multiple sclerosis (MS) and AQP4Ab-positive neuromyelitis optica spectrum disorder (AQP4Ab-NMOSD). In this study we characterised the metabolite profiles of brain lesions in 11 MS and 4 AQP4Ab-NMOSD patients using an optimised MRS methodology at ultra-high field strength (7T) incorporating correction for T2 water relaxation differences between lesioned and normal tissue.MS metabolite results were in keeping with the existing literature: total N-acetylaspartate (NAA) was lower in lesions compared to normal appearing brain white matter (NAWM) with reciprocal findings for myo-Inositol. An unexpected subtlety revealed by our technique was that total NAA differences were likely driven by NAA-glutamate (NAAG), a ubiquitous CNS molecule with functions quite distinct from NAA though commonly quantified together with NAA in MRS studies as total NAA. Surprisingly, AQP4Ab-NMOSD showed no significant differences for total NAA, NAA, NAAG or myo-Inositol between lesion and NAWM sites, nor were there any differences between MS and AQP4Ab-NMOSD for a priori hypotheses. Post-hoc testing revealed a significant correlation between NAWM Ins:NAA and disability (as measured by EDSS) for disease groups combined, driven by the AP4Ab-NMOSD group.Utilising an optimised MRS methodology, our study highlights some under-explored subtleties in MRS profiles, such as the absence of myo-Inositol concentration differences in AQP4Ab-NMOSD brain lesions versus NAWM and the potential influence of NAAG differences between lesions and normal appearing white matter in MS.
