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

Autor: Diaz F; Board of Governors Regenerative Medicine Institute, Cedars-Siniai Medical Center, Los Angeles, California, USA.; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California, USA., Thornton JS; Neuroradiological Academic Unit, UCL Queen Square Institute of Neurology, London, UK., Wastling SS; Neuroradiological Academic Unit, UCL Queen Square Institute of Neurology, London, UK., Asaab A; Neuroradiological Academic Unit, UCL Queen Square Institute of Neurology, London, UK., Morrow JM; Queen Square Centre for Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK., Zafeiropoulos N; Neuroradiological Academic Unit, UCL Queen Square Institute of Neurology, London, UK., Bresee C; Biostatistics Shared Resources, Cedars-Sinai Medical Center, Los Angeles, California, USA., Allred P; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California, USA.; Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, USA., Avalos P; Board of Governors Regenerative Medicine Institute, Cedars-Siniai Medical Center, Los Angeles, California, USA., Lewis RA; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California, USA., Baloh RH; Board of Governors Regenerative Medicine Institute, Cedars-Siniai Medical Center, Los Angeles, California, USA.; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California, USA.; Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, USA., Svendsen CN; Board of Governors Regenerative Medicine Institute, Cedars-Siniai Medical Center, Los Angeles, California, USA.
Jazyk: angličtina
Zdroj: Muscle & nerve [Muscle Nerve] 2024 Nov 29. Date of Electronic Publication: 2024 Nov 29.
DOI: 10.1002/mus.28306
Abstrakt: 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 (SRM thigh  = 1.85, SRM calf  = 1.39), T 2m (SRM thigh  = 1.2, SRM calf  = 1.71), CSA (SRM thigh  = -1.58, SRM calf  = -1.14), RMA (SRM thigh  = -1.77, SRM calf  = -1.28), and strength tested via ATLIS (SRM knee extension  = -1.79, SRM knee 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.
(© 2024 Wiley Periodicals LLC.)
Databáze: MEDLINE
Externí odkaz: