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 agesimilar 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 5 0.65, p 5 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. Neurology â 2013;80:610-615 GLOSSARY ALS 5 amyotrophic lateral sclerosis; ALSFRS-R 5 Amyotrophic Lateral Sclerosis Functional Rating Scale-revised; CST 5 corticospinal tract; DTI 5 diffusion tensor imaging; FA 5 fractional anisotropy; LMN 5 lower motor neuron; MD 5 mean diffusivity; MIDAS 5 Metabolite Imaging and Data Analysis System; MRSI 5 magnetic resonance spectroscopic imaging; NAA 5 N-acetylaspartate; OR 5 optic radiation; PLS 5 primary lateral sclerosis; TBSS 5 tract-based spatial statistics; WM 5 white matter.

Role of diffusion tensor imaging or magnetic resonance spectroscopy in the diagnosis and disability assessment of amyotrophic lateral sclerosis

“…Other studies [10] have reported that FA and NAA within the entire white matter are significantly decreased in ALS patients compared with controls, and our results are in accordance with the decrease in the FA or NAA/Cr for each side. However, we failed to show a significant change in the NAA on either side.…”

“…Furthermore, advanced MRI measurements are needed to explore ALS, including whole-brain magnetic resonance spectroscopic imaging (MRSI) [10]. ALS could be better understood if the research community developed a perfect ALS animal model.…”

High-field MRS in clinical drug development

“…In a well-received recent paper [14] and Editorial [15,16], Neurology applauded this study which yielded unique information about NAA distribution along motor tracts in patients with ALS, which was superior in reflecting motor defects than the previously much-lauded DTI --tractography. What is wrong with this approach?…”

Further development of biomarkers in amyotrophic lateral sclerosis

“…The combination of NAA and myo-inositol may improve the specificity of the test, but further studies are needed [164]. Using whole-brain resonance spectroscopic imaging, NAA levels are significantly associated with a degree of disability [165]. Recent advances in proton magnetic resonance spectroscopy ( 1 H-MRS) allow for the direct quantification of GABA (gamma-aminobutyric acid) in the cortex [166].…”