Frank Diaz, John S Thornton, Stephen S Wastling, Abeer Asaab, Jasper M Morrow, Nick Zafeiropoulos, Catherine Bresee, Peggy Allred, Pablo Avalos, Richard A Lewis, Robert H Baloh, Clive N Svendsen
{"title":"Longitudinal Quantitative MRI Provides Responsive Outcome Measures for Early and Late Muscle Changes in ALS.","authors":"Frank Diaz, John S Thornton, Stephen S Wastling, Abeer Asaab, Jasper M Morrow, Nick Zafeiropoulos, Catherine Bresee, Peggy Allred, Pablo Avalos, Richard A Lewis, Robert H Baloh, Clive N Svendsen","doi":"10.1002/mus.28306","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction/aims: </strong>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.</p><p><strong>Methods: </strong>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 <sub>2m</sub>), 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.</p><p><strong>Results: </strong>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<sub>thigh</sub> = 1.85, SRM<sub>calf</sub> = 1.39), T <sub>2m</sub> (SRM<sub>thigh</sub> = 1.2, SRM<sub>calf</sub> = 1.71), CSA (SRM<sub>thigh</sub> = -1.58, SRM<sub>calf</sub> = -1.14), RMA (SRM<sub>thigh</sub> = -1.77, SRM<sub>calf</sub> = -1.28), and strength tested via ATLIS (SRM<sub>knee extension</sub> = -1.79, SRM<sub>knee flexion</sub> = -1.3). The ALSFRS-R was the least responsive at 6 months (SRM = -0.85). Muscle FF and T <sub>2m</sub> correlated with ALSFRS-R leg subscores and MRI measures demonstrated varying degrees of correlation with strength.</p><p><strong>Discussion: </strong>High responsiveness and low variability make quantitative muscle MRI a novel and complementary outcome measure for ALS clinical trials.</p>","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":"171-182"},"PeriodicalIF":2.8000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Muscle & Nerve","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/mus.28306","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/29 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍：
Muscle & Nerve is an international and interdisciplinary publication of original contributions, in both health and disease, concerning studies of the muscle, the neuromuscular junction, the peripheral motor, sensory and autonomic neurons, and the central nervous system where the behavior of the peripheral nervous system is clarified. Appearing monthly, Muscle & Nerve publishes clinical studies and clinically relevant research reports in the fields of anatomy, biochemistry, cell biology, electrophysiology and electrodiagnosis, epidemiology, genetics, immunology, pathology, pharmacology, physiology, toxicology, and virology. The Journal welcomes articles and reports on basic clinical electrophysiology and electrodiagnosis. We expedite some papers dealing with timely topics to keep up with the fast-moving pace of science, based on the referees'' recommendation.
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