Longitudinal Quantitative MRI Provides Responsive Outcome Measures for Early and Late Muscle Changes in ALS

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Introduction/Aims Studies have demonstrated the potential of muscle MRIs to measure disease progression in ALS. However, the responsiveness and utility of quantitative muscle MRIs in an ALS clinical trial remain unknown. This study aimed to determine the responsiveness of quantitative muscle MRIs to measure disease progression in ALS. Methods Longitudinal quantitative muscle MRIs were obtained in an ALS study that delivered human neural progenitor cells to the spinal cord (NCT02943850). Participants underwent MRIs at baseline, 1, 3, 6, 9, and 12 months. MRI measures included fat fraction (ff), water T2 (T 2m), cross‐sectional area (CSA), and remaining muscle area (RMA). Non‐MRI measures included strength via Accurate Test of Limb Isometric Strength (ATLIS) and the ALSFRS‐R. Standardized response means (SRM) were calculated at 1, 3, 6, and 12 months. Results Significant increases in muscle FF and decreases in CSA and RMA were seen as early as 1 month from baseline. At 6 months, the most responsive measures were muscle FF (SRMthigh = 1.85, SRMcalf = 1.39), T 2m (SRMthigh = 1.2, SRMcalf = 1.71), CSA (SRMthigh = −1.58, SRMcalf = −1.14), RMA (SRMthigh = −1.77, SRMcalf = −1.28), and strength tested via ATLIS (SRMknee extension = −1.79, SRMknee flexion = −1.3). The ALSFRS‐R was the least responsive at 6 months (SRM = −0.85). Muscle FF and T 2m correlated with ALSFRS‐R leg subscores and MRI measures demonstrated varying degrees of correlation with strength. Discussion High responsiveness and low variability make quantitative muscle MRI a novel and complementary outcome measure for ALS clinical trials.