Selection Approach to Identify the Optimal Biomarker Using Quantitative Muscle MRI and Functional Assessments in Becker Muscular Dystrophy

Neurology. 2021 Aug 3;97(5):e513-e522. doi: 10.1212/WNL.0000000000012233. Epub 2021 Jun 23.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / diagnostic imaging
  • Adult
  • Biomarkers / analysis
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Leg / diagnostic imaging
  • Leg / physiopathology
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Muscle Contraction
  • Muscle, Skeletal / diagnostic imaging*
  • Muscle, Skeletal / physiopathology
  • Muscular Dystrophy, Duchenne / diagnosis*
  • Muscular Dystrophy, Duchenne / diagnostic imaging*
  • Muscular Dystrophy, Duchenne / physiopathology
  • Observer Variation
  • Reproducibility of Results
  • Thigh
  • Walk Test
  • Young Adult


  • Biomarkers