An optimal 1H-MRS technique at 7T: Proof-of-principle in Chronic Multiple Sclerosis and Neuromyelitis Optica Brain Lesions and Normal Appearing Brain Tissue

Abstract

AbstractMagnetic 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 NAA was lower in lesions compared to normal appearing brain white matter (NAWM) with reciprocal findings for Inositol. An unexpected subtlety revealed by our technique was that total NAA differences were 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 Inositol between lesion and NAWM sites, nor were there any differences between MS and AQP4Ab-NMOSD for a priori hypotheses. Post-hoc testing did however reveal greater total NAA in MS compared to AQP4Ab-NMOSD NAWM. Post-hoc testing also 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 Inositol concentration differences in AQP4Ab-NMOSD brain lesions versus NAWM and the important influence of NAAG differences between lesions and normal appearing white matter in MS.