Clinicians and physicists interested in amyotrophic lateral sclerosis (ALS) patient care and/or ALS research and physicists interested in X-nuclei MRI development and in vivo applications.

Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease that induces a death of upper (in brain) and lower (in spine) motor neurons. To date, diagnosis and management of ALS is only based on clinical and electrophysiological exploration. A high variability is seen in patient presentation and evolution, with a survival delay from few months to a decade. Current explorations lack to individually assess disease progression. Moreover, even if central nervous system (CNS) is involved in ALS, conventional MRI fails to show brain abnormalities. Thus, to depict the CNS impairment in ALS, advanced MRI techniques are required. Brain sodium MRI, a technique that previously showed its ability to detect neuronal death^1,2, seems to be of major interest in ALS.MR scans were performed on a 3T Verio system (Siemens, Germany) in 4 ALS patients and 20 healthy controls (12F/8M, median age 54 yo). The patient disability level was evaluated by the revised ALS functional rating scale (ALSFRS-R). The disease progression rate was calculated using the following formula: (48 - ALSFRS-R)/disease duration. 23Na MRI was acquired using a double-tuned ²³Na-¹H volume head coil (RapidBiomedical, Germany) and a 3D density-adapted radial projection reconstruction pulse sequence³ (TE=200μs/TR=120ms, 17000 projections and 369 samples per projection, 3.6mm³ isotropic resolution, acquisition time = 34min) with two tubes filled with 50 mM of sodium placed in the FOV to serve for external references (Fig.1). High-resolution proton MRI 3D-MPRAGE (TR=2300ms/TE=3ms/TI=900ms, 160 slices, 1mm³ isotropic resolution) was obtained using a 32-element ¹H head coil (Siemens). The optimized post-processing pipeline is described in Fig.2 and allowed to obtain maps of spatial distribution of sodium accumulation resulting from the statistical mapping analyses in each patient compared to data from the healthy controls (SPM12, ANOVA, p=0.001, k=20)Clinical data of ALS patients are shown in Fig. 3. Statistical mapping analyses showed brain sodium accumulation in primary motor cortex (Brodmann area (BA) 4) in 3 out of 4 patients. Other regions showing sodium accumulation were the left fronto-temporal area (Patient 2) and the left thalamus (Patient 1). Maps of spatial distribution of sodium accumulation in ALS patients compared to healthy controls are shown in Fig. 4.Primary motor cortex was involved in 3 out of 4 patients. This result is in accordance with the clinical presentation of these 3 patients (Patient 1, 2 and 4), all suffering from upper motor neuron impairment. Moreover, Patient 3, who had lower motor neuron signs in bulbar area and right upper-limb, but did not have upper motor neuron signs yet, did not present any sodium abnormal brain accumulation. Interestingly, Patient 2, who had the lowest ALSFRS-R and the highest disease progression rate, had the most important and widespread accumulation of sodium, including the right and left BA4 and the right fronto-temporal area.This preliminary study suggests that sodium accumulation, which is an indicator of neuronal injury, could be a marker of ALS diagnosis and disease progression.