Ultra high-field (7tesla) magnetic resonance spectroscopy in Amyotrophic Lateral Sclerosis

PLoS One. 2017 May 12;12(5):e0177680. doi: 10.1371/journal.pone.0177680. eCollection 2017.

Abstract

The main objective of this study was to utilize high field (7T) in vivo proton magnetic resonance imaging to increase the ability to detect metabolite changes in people with ALS, specifically, to quantify levels of glutamine and glutamine separately. The second objective of this study was to correlate metabolic markers with clinical outcomes of disease progression. 13 ALS participants and 12 age-matched healthy controls (HC) underwent 7 Tesla MRI and MRS. Single voxel MR spectra were acquired from the left precentral gyrus using a very short echo time (TE = 5 ms) STEAM sequence. MRS data was quantified using LCModel and correlated to clinical outcome markers. N-acetylaspartate (NAA) and total NAA (tNA, NAA + NAAG) were decreased by 17% in people with ALS compared to HC (P = 0.004 and P = 0.005, respectively) indicating neuronal injury and/or loss in the precentral gyrus. tNA correlated with disease progression as measured by forced vital capacity (FVC) (P = 0.014; Rρ = 0.66) and tNA/tCr correlated with overall functional decline as measured by worsening of the ALS Functional Rating Scale-Revised (ALSFRS-R) (P = 0.004; Rρ = -0.74). These findings underscore the importance of NAA as a reliable biomarker for neuronal injury and disease progression in ALS. Glutamate (Glu) was 15% decreased in people with ALS compared to HC (P = 0.02) while glutamine (Gln) concentrations were similar between the two groups. Furthermore, the decrease in Glu correlated with the decrease in FVC (P = 0.013; Rρ = 0.66), a clinical marker of disease progression. The decrease in Glu is most likely driven by intracellular Glu loss due to neuronal loss and degeneration. Neither choline containing components (Cho), a marker for cell membrane turnover, nor myo-Inositol (mI), a suspected marker for neuroinflammation, showed significant differences between the two groups. However, mI/tNA was correlated with upper motor neuron burden (P = 0.004, Rρ = 0.74), which may reflect a relative increase of activated microglia around motor neurons. In summary, 7T 1H MRS is a powerful non-invasive imaging technique to study molecular changes related to neuronal injury and/or loss in people with ALS.

MeSH terms

  • Adult
  • Aged
  • Amyotrophic Lateral Sclerosis / metabolism*
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / metabolism
  • Female
  • Glutamic Acid / metabolism
  • Glutamine / metabolism
  • Humans
  • Magnetic Resonance Spectroscopy / methods*
  • Male
  • Middle Aged
  • Motor Cortex / metabolism
  • Motor Neurons / metabolism

Substances

  • Glutamine
  • Aspartic Acid
  • Glutamic Acid
  • N-acetylaspartate

Grants and funding

This work was conducted with support from the Harvard NeuroDiscovery Center, Muscular Dystrophy Association Clinical Research Training Grant, Research fellowship from the American Academy of Neurology, and the Anne B. Young neuroscience translational medicine fellowship. Siemens Healtheneers provided support in the form of salaries for authors CT, NS and RS, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.