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

Neuroimage. 2021 Sep:238:118225. doi: 10.1016/j.neuroimage.2021.118225. Epub 2021 May 30.

Abstract

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.

Keywords: Magnetic resonance spectroscopy; Multiple Sclerosis; Neuroinflammatory disorders; Neuromyelitis optica; Ultra-high field MRI.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aquaporin 4 / immunology
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / analysis
  • Autoantibodies / analysis
  • Autoantigens / immunology
  • Brain Chemistry*
  • Female
  • Gliosis / diagnostic imaging
  • Gliosis / metabolism
  • Gliosis / pathology
  • Glutamates / analysis
  • Humans
  • Inositol / analysis
  • Magnetic Resonance Spectroscopy / instrumentation
  • Magnetic Resonance Spectroscopy / methods*
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / diagnostic imaging
  • Multiple Sclerosis, Relapsing-Remitting / metabolism*
  • Multiple Sclerosis, Relapsing-Remitting / pathology
  • Nerve Tissue Proteins / immunology
  • Neuromyelitis Optica / diagnostic imaging
  • Neuromyelitis Optica / immunology
  • Neuromyelitis Optica / metabolism*
  • Neuromyelitis Optica / pathology
  • Young Adult

Substances

  • AQP4 protein, human
  • Aquaporin 4
  • Autoantibodies
  • Autoantigens
  • Glutamates
  • Nerve Tissue Proteins
  • Aspartic Acid
  • Inositol
  • N-acetylaspartate
  • N-acetylglutamic acid