TY - JOUR
T1 - Muscle MRI quantifies disease progression in amyotrophic lateral sclerosis
AU - Klickovic, Uros
AU - Zampedri, Luca
AU - Zafeiropoulos, Nick
AU - Ziff, Oliver J
AU - Sinclair, Christopher Dj
AU - Wastling, Stephen
AU - Dudziec, Magdalena
AU - Allen, Jodie
AU - Trimmel, Karin
AU - Howard, Robin S
AU - Malaspina, Andrea
AU - Sharma, Nikhil
AU - Sidle, Katie Cl
AU - Shah, Sachit
AU - Nasel, Christian
AU - Yousry, Tarek A
AU - Greensmith, Linda
AU - Morrow, Jasper M
AU - Thornton, John S
AU - Fratta, Pietro
N1 - Publisher Copyright:
© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group.
PY - 2025/3/25
Y1 - 2025/3/25
N2 - BACKGROUND AND OBJECTIVES: Quantitative and operator-independent biomarkers of disease progression are urgently needed in amyotrophic lateral sclerosis (ALS) research. We assess the potential of skeletal muscle MRI as a sensitive and reliable outcome measure for future ALS clinical trials.METHODS: In this longitudinal cohort study, muscle MRI of head-neck, upper and lower limb regions, alongside clinical and functional assessments, were acquired at three time points over the individual maximum observation period (iMOP) of 1 year in 20 patients with ALS and 16 healthy controls. Quantitative MRI parameters cross-sectional area (CSA), volume (VOL), fat fraction, functional rest muscle area and water T2 (T2m) were correlated with changes in clinical disease severity (functional rating scales and myometry).RESULTS: Among 20 patients with ALS, 17 completed follow-up. Progressive muscle atrophy (CSA, VOL) was observed at hand (rs=0.66), head-neck (partial η²=0.47) and lower-limb level (thighs: η²=0.56, calves: η²=0.54) over iMOP. MRI changes correlated with leg muscle strength (knee extension: r=0.77; plantar flexion: r=0.78), hand grip strength (r=0.71) and functional rating scales (r=0.68).INTERPRETATION: Our findings demonstrate the effectiveness of muscle MRI as a sensitive neuroimaging biomarker of disease progression in ALS, highlighting its potential application in clinical trials.
AB - BACKGROUND AND OBJECTIVES: Quantitative and operator-independent biomarkers of disease progression are urgently needed in amyotrophic lateral sclerosis (ALS) research. We assess the potential of skeletal muscle MRI as a sensitive and reliable outcome measure for future ALS clinical trials.METHODS: In this longitudinal cohort study, muscle MRI of head-neck, upper and lower limb regions, alongside clinical and functional assessments, were acquired at three time points over the individual maximum observation period (iMOP) of 1 year in 20 patients with ALS and 16 healthy controls. Quantitative MRI parameters cross-sectional area (CSA), volume (VOL), fat fraction, functional rest muscle area and water T2 (T2m) were correlated with changes in clinical disease severity (functional rating scales and myometry).RESULTS: Among 20 patients with ALS, 17 completed follow-up. Progressive muscle atrophy (CSA, VOL) was observed at hand (rs=0.66), head-neck (partial η²=0.47) and lower-limb level (thighs: η²=0.56, calves: η²=0.54) over iMOP. MRI changes correlated with leg muscle strength (knee extension: r=0.77; plantar flexion: r=0.78), hand grip strength (r=0.71) and functional rating scales (r=0.68).INTERPRETATION: Our findings demonstrate the effectiveness of muscle MRI as a sensitive neuroimaging biomarker of disease progression in ALS, highlighting its potential application in clinical trials.
UR - http://www.scopus.com/inward/record.url?scp=105001260756&partnerID=8YFLogxK
U2 - 10.1136/jnnp-2024-335571
DO - 10.1136/jnnp-2024-335571
M3 - Journal article
C2 - 40132878
SN - 0022-3050
JO - Journal of Neurology, Neurosurgery and Psychiatry
JF - Journal of Neurology, Neurosurgery and Psychiatry
ER -