Quantitative Brain Sodium MRI Depicts Corticospinal Impairment in Amyotrophic Lateral Sclerosis
Aude-Marie Grapperon, Ben Ridley, Annie Verschueren, Adil Maarouf, Sylviane Confort-Gouny, Etienne Fortanier, Lothar Schad, Maxime Guye, Jean-Philippe Ranjeva,  … Show all Authors
Author Affiliations
From the Aix Marseille University, CRMBM, UMR CNRS 7339, 27 Boulevard Jean Moulin, 13005 Marseille, France (A.M.G., B.R., A.V., A.M., S.C., E.F., M.G., J.P.R., W.Z.); APHM, Hôpital de la Timone, Referral Centre for Neuromuscular Diseases and ALS, Marseille, France (A.M.G., A.V., E.F., S.A.); APHM, Hôpital de la Timone, CEMEREM, Marseille, France (B.R., A.M., S.C., M.G., J.P.R., W.Z.); Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany (L.S.); and Aix Marseille University, INSERM, GMGF, Marseille, France (S.A.).
Address correspondence to W.Z. (e-mail: wafaa.zaaraoui@univ-amu.fr).
Published Online:Jun 11 2019https://doi.org/10.1148/radiol.2019182276
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Abstract
Sodium MRI depicts disease-relevant regional alterations in sodium homeostasis in the precentral gyri, corticospinal tracts, and corpus callosum of patients with amyotrophic lateral sclerosis.

Background
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that mainly affects the upper and lower motor neurons. Recent sodium (23Na) MRI studies have shown that abnormal sodium concentration is related to neuronal suffering in neurodegenerative conditions.

Purpose
To use 23Na MRI to investigate abnormal sodium concentrations and map their distribution in the brains of study participants with ALS as compared with healthy control subjects.

Materials and Methods
Twenty-seven participants with ALS (mean age, 54 years ± 10 [standard deviation], eight women) and 30 healthy control subjects (mean age, 50 years ± 10; 16 women) were prospectively recruited between September 2015 and October 2017 and were examined by using conventional proton MRI and sodium MRI at 3 T. Voxel-based statistical mapping was used to compare quantitative whole-brain total sodium concentration (TSC) maps in participants with ALS with those in control subjects and to localize regions of abnormal elevated TSC. Potential overlap of abnormal elevated TSC with regions of atrophy as detected with 1H MRI also was investigated.

Results
Voxel-based statistical mapping analyses revealed higher sodium concentration in motor regions (bilateral precentral gyri, corticospinal tracts, and the corpus callosum) of participants with ALS (two-sample t test, P < .005; age and sex as covariates). In these regions, mean TSC was higher in participants with ALS (mean, 45.6 mmol/L wet tissue ± 3.2) than in control subjects (mean, 41.8 mmol/L wet tissue ± 2.7; P < .001; Cohen d = 1.28). Brain regions showing higher TSC represented a volume of 15.4 cm3 that did not overlap with gray matter atrophy occupying a volume of 16.9 cm3. Elevated TSC correlated moderately with corticospinal conduction failure assessed with transcranial magnetic stimulation in the right upper limb (Spearman ρ = −0.57; 95% confidence interval: −0.78, −0.16; P = .005; n = 23).

Conclusion
Quantitative 23Na MRI is sensitive to alterations of brain sodium homeostasis within disease-relevant regions in patients with amyotrophic lateral sclerosis (ALS). This supports further investigation of abnormal sodium concentration as a potential marker of neurodegenerative processes in patients with ALS that could be used as a secondary endpoint in clinical trials.

© RSNA, 2019

Online supplemental material is available for this article.

Article History
Received: Oct 3 2018
Revision requested: Dec 10 2018
Revision received: Apr 19 2019
Accepted: Apr 29 2019
Published online: June 11 2019
Published in print: Aug 2019
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