Longitudinal MR spectroscopy of neurodegeneration in multiple sclerosis with diffusion of the intra-axonal constituent N-acetylaspartate

Neuroimage Clin. 2017 Jun 22:15:780-788. doi: 10.1016/j.nicl.2017.06.028. eCollection 2017.


Multiple sclerosis (MS) is a pathologically complex CNS disease: inflammation, demyelination, and neuroaxonal degeneration occur concurrently and may depend on one another. Current therapies are aimed at the immune-mediated, inflammatory destruction of myelin, whereas axonal degeneration is ongoing and not specifically targeted. Diffusion-weighted magnetic resonance spectroscopy can measure the diffusivity of metabolites in vivo, such as the axonal/neuronal constituent N-acetylaspartate, allowing compartment-specific assessment of disease-related changes. Previously, we found significantly lower N-acetylaspartate diffusivity in people with MS compared to healthy controls (Wood et al., 2012) suggesting that this technique can measure axonal degeneration and could be useful in developing neuroprotective agents. In this longitudinal study, we found that N-acetylaspartate diffusivity decreased by 8.3% (p < 0.05) over 6 months in participants who were experiencing clinical or MRI evidence of inflammatory activity (n = 13), whereas there was no significant change in N-acetylaspartate diffusivity in the context of clinical and radiological stability (n = 6). As N-acetylaspartate diffusivity measurements are thought to more specifically reflect the intra-axonal space, these data suggest that N-acetylaspartate diffusivity can report on axonal health on the background of multiple pathological processes in MS, both cross-sectionally and longitudinally.

Keywords: Axonopathy; DW-MRS, diffusion-weighted magnetic resonance spectroscopy; Diffusion-weighted magnetic resonance spectroscopy; EDSS, Expanded Disability Scale Score; HV, healthy volunteer; ICV, intracranial volume; MS, multiple sclerosis; Multiple sclerosis; NAA, N-acetylaspartate; PASAT, Paced Auditory Symbol Addition Test; T, Tesla; VOI, volume of interest; WM, white matter; White matter.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / analysis
  • Aspartic Acid / metabolism
  • Axons / metabolism*
  • Axons / pathology
  • Brain / metabolism
  • Brain / pathology
  • Female
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Multiple Sclerosis / metabolism*
  • Multiple Sclerosis / pathology
  • Nerve Degeneration / metabolism*
  • Nerve Degeneration / pathology
  • Young Adult


  • Aspartic Acid
  • N-acetylaspartate