Whole-brain magnetic resonance spectroscopic imaging measures are related to disability in ALS

Abstract

Objective: To demonstrate the sensitivity of a recently developed whole-brain magnetic resonance spectroscopic imaging (MRSI) sequence to cerebral pathology and disability in amyotrophic lateral sclerosis (ALS), and compare with measures derived from diffusion tensor imaging.

Methods: Whole-brain MRSI and diffusion tensor imaging were undertaken in 13 patients and 14 age-similar healthy controls. Mean N-acetylaspartate (NAA), fractional anisotropy, and mean diffusivity were extracted from the corticospinal tract, compared between groups, and then in relation to disability in the patient group.

Results: Significant reductions in NAA were found along the course of the corticospinal tracts on whole-brain MRSI. There were also significant changes in fractional anisotropy (decreased) and mean diffusivity (increased) in the patient group, but only NAA showed a significant relationship with disability (r = 0.65, p = 0.01).

Conclusion: Whole-brain MRSI has potential as a quantifiable neuroimaging marker of disability in ALS. It offers renewed hope for a neuroimaging outcome measure with the potential for harmonization across multiple sites in the context of a therapeutic trial.

Figure 1. Regional changes in whole-brain magnetic resonance spectroscopic imaging diffusion tensor imaging in a group of 11 patients with amyotrophic lateral sclerosis and 2 patients with primary lateral sclerosis compared with age-similar healthy controls

Row (A) shows the results of the whole-brain N-acetylaspartate (NAA) analysis, with significant changes in red; (B) shows the results of the fractional anisotropy (FA) analysis on the white-matter skeleton, with skeleton in yellow and significant changes in blue; whereas (C) shows mean diffusivity (MD) results on the white-matter skeleton, with significant changes in green. Decreased NAA is seen throughout the length of the corticospinal tract (CST) (A), reduced FA particularly within the superior CSTs and corpus callosum (B), and increased MD throughout the white matter tracts (C).

Figure 2. Comparison of CST NAA, FA, and MD between patients and controls (A–C), and in relation to disability in the patient group (D–F, 2 patients with PLS are shown as unfilled triangles in each)

Although all 3 measures are significantly different in the patient group, only NAA has a significant relationship with disability. (D) NAA: r = 0.65, p = 0.01; (E) FA: r = −0.03, p = 0.91; (F) MD: r = −0.29, p = 0.32. ALSFRS-R = Amyotrophic Lateral Sclerosis Functional Rating Scale–revised; CST = corticospinal tract; FA = fractional anisotropy; MD = mean diffusivity; NAA = N-acetylaspartate; PLS = primary lateral sclerosis.

Figure 3. t Statistic distributions within the corticospinal tract (CST) (left panel) and optic radiation (right panel) showing increased sensitivity of N-acetylaspartate (NAA) compared with fractional anisotropy (FA) and mean diffusivity (MD) within the CST