TY - JOUR
T1 - Selection Approach to Identify the Optimal Biomarker Using Quantitative Muscle MRI and Functional Assessments in Becker Muscular Dystrophy
AU - van de Velde, Nienke M.
AU - Hooijmans, Melissa T.
AU - Sardjoe Mishre, Aashley S. D.
AU - Keene, Kevin R.
AU - Koeks, Zaïda
AU - Veeger, Thom T. J.
AU - Alleman, Iris
AU - van Zwet, Erik W.
AU - Beenakker, Jan-Willem M.
AU - Verschuuren, Jan J. G. M.
AU - Kan, Hermien E.
AU - Niks, Erik H.
N1 - Publisher Copyright: Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
PY - 2021/8/3
Y1 - 2021/8/3
N2 - OBJECTIVE: To identify the best quantitative fat-water MRI biomarker for disease progression of leg muscles in Becker muscular dystrophy (BMD) by applying a stepwise approach based on standardized response mean (SRM) over 24 months, correlations with baseline ambulatory tests, and reproducibility. METHODS: Dixon fat-water imaging was performed at baseline (n = 24) and 24 months (n = 20). Fat fractions (FF) were calculated for 3 center slices and the whole muscles for 19 muscles and 6 muscle groups. Contractile cross-sectional area (cCSA) was obtained from the center slice. Functional assessments included knee extension and flexion force and 3 ambulatory tests (North Star Ambulatory Assessment [NSAA], 10-meter run, 6-minute walking test). MRI measures were selected using SRM (≥0.8) and correlation with all ambulatory tests (ρ ≤ -0.8). Measures were evaluated based on intraclass correlation coefficient (ICC) and SD of the difference. Sample sizes were calculated assuming 50% reduction in disease progression over 24 months in a clinical trial with 1:1 randomization. RESULTS: Median whole muscle FF increased between 0.2% and 2.6% without consistent cCSA changes. High SRMs and strong functional correlations were found for 8 FF but no cCSA measures. All measures showed excellent ICC (≥0.999) and similar SD of the interrater difference. Whole thigh 3 center slices FF was the best biomarker (SRM 1.04, correlations ρ ≤ -0.81, ICC 1.00, SD 0.23%, sample size 59) based on low SD and acquisition and analysis time. CONCLUSION: In BMD, median FF of all muscles increased over 24 months. Whole thigh 3 center slices FF reduced the sample size by approximately 40% compared to NSAA.
AB - OBJECTIVE: To identify the best quantitative fat-water MRI biomarker for disease progression of leg muscles in Becker muscular dystrophy (BMD) by applying a stepwise approach based on standardized response mean (SRM) over 24 months, correlations with baseline ambulatory tests, and reproducibility. METHODS: Dixon fat-water imaging was performed at baseline (n = 24) and 24 months (n = 20). Fat fractions (FF) were calculated for 3 center slices and the whole muscles for 19 muscles and 6 muscle groups. Contractile cross-sectional area (cCSA) was obtained from the center slice. Functional assessments included knee extension and flexion force and 3 ambulatory tests (North Star Ambulatory Assessment [NSAA], 10-meter run, 6-minute walking test). MRI measures were selected using SRM (≥0.8) and correlation with all ambulatory tests (ρ ≤ -0.8). Measures were evaluated based on intraclass correlation coefficient (ICC) and SD of the difference. Sample sizes were calculated assuming 50% reduction in disease progression over 24 months in a clinical trial with 1:1 randomization. RESULTS: Median whole muscle FF increased between 0.2% and 2.6% without consistent cCSA changes. High SRMs and strong functional correlations were found for 8 FF but no cCSA measures. All measures showed excellent ICC (≥0.999) and similar SD of the interrater difference. Whole thigh 3 center slices FF was the best biomarker (SRM 1.04, correlations ρ ≤ -0.81, ICC 1.00, SD 0.23%, sample size 59) based on low SD and acquisition and analysis time. CONCLUSION: In BMD, median FF of all muscles increased over 24 months. Whole thigh 3 center slices FF reduced the sample size by approximately 40% compared to NSAA.
UR - http://www.scopus.com/inward/record.url?scp=85113711729&partnerID=8YFLogxK
U2 - https://doi.org/10.1212/WNL.0000000000012233
DO - https://doi.org/10.1212/WNL.0000000000012233
M3 - Article
C2 - 34162720
SN - 0028-3878
VL - 97
SP - e513-e522
JO - Neurology
JF - Neurology
IS - 5
ER -