Rebecca J Willcocks1, William D Rooney2, William T Triplett1, Sean C Forbes1, Donovan J Lott1, Claudia R Senesac1, Michael J Daniels3, Dah-Jyuu Wang4, Ann T Harrington5, Gihan I Tennekoon5, Barry S Russman6, Erika L Finanger6, Barry J Byrne7, Richard S Finkel8, Glenn A Walter9, H Lee Sweeney10, Krista Vandenborne1. 1. Department of Physical Therapy, University of Florida, Gainesville, FL. 2. Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR. 3. Department of Statistics & Data Sciences and Department of Integrative Biology, University of Texas at Austin, Austin, TX. 4. Division of Neurology and Department of Radiology, the Children's Hospital of Philadelphia, Philadelphia, PA. 5. the Children's Hospital of Philadelphia, Philadelphia, PA. 6. Departments of Pediatrics and Neurology, Oregon Health & Science University, Shriners Hospital for Children, Portland, OR. 7. Department of Pediatrics and Molecular Genetics and Microbiology, Powell Gene Therapy Center University of Florida, Gainesville, FL. 8. Nemours Children's Hospital, University of Central Florida College of Medicine, Orlando, FL. 9. Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL. 10. Department of Physiology, University of Pennsylvania, Philadelphia, PA.
Abstract
OBJECTIVE: The aim of this study was to describe Duchenne muscular dystrophy (DMD) disease progression in the lower extremity muscles over 12 months using quantitative magnetic resonance (MR) biomarkers, collected across three sites in a large cohort. METHODS: A total of 109 ambulatory boys with DMD (8.7 ± 2.0 years; range, 5.0-12.9) completed baseline and 1-year follow-up quantitative MR imaging (transverse relaxation time constant; MRI-T2 ), MR spectroscopy (fat fraction and (1) H2 O T2 ), and 6-minute walk test (6MWT) measurements. A subset of boys completed additional measurements after 3 or 6 months. RESULTS: MRI-T2 and fat fraction increased significantly over 12 months in all age groups, including in 5- to 6.9-year-old boys. Significant increases in vastus lateralis (VL) fat fraction were observed in 3 and 6 months. Even in boys whose 6MWT performance improved or remained stable over 1 year, significant increases in MRI-T2 and fat fraction were found. Of all the muscles examined, the VL and biceps femoris long head were the most responsive to disease progression in boys with DMD. INTERPRETATION: MR biomarkers are responsive to disease progression in 5- to 12.9-year-old boys with DMD and able to detect subclinical disease progression in DMD, even within short (3-6 months) time periods. The measured sensitivity of MR biomarkers in this multicenter study may be critically important to future clinical trials, allowing for smaller sample sizes and/or shorter study windows in this fatal rare disease.
OBJECTIVE: The aim of this study was to describe Duchenne muscular dystrophy (DMD) disease progression in the lower extremity muscles over 12 months using quantitative magnetic resonance (MR) biomarkers, collected across three sites in a large cohort. METHODS: A total of 109 ambulatory boys with DMD (8.7 ± 2.0 years; range, 5.0-12.9) completed baseline and 1-year follow-up quantitative MR imaging (transverse relaxation time constant; MRI-T2 ), MR spectroscopy (fat fraction and (1) H2 O T2 ), and 6-minute walk test (6MWT) measurements. A subset of boys completed additional measurements after 3 or 6 months. RESULTS:MRI-T2 and fat fraction increased significantly over 12 months in all age groups, including in 5- to 6.9-year-old boys. Significant increases in vastus lateralis (VL) fat fraction were observed in 3 and 6 months. Even in boys whose 6MWT performance improved or remained stable over 1 year, significant increases in MRI-T2 and fat fraction were found. Of all the muscles examined, the VL and biceps femoris long head were the most responsive to disease progression in boys with DMD. INTERPRETATION: MR biomarkers are responsive to disease progression in 5- to 12.9-year-old boys with DMD and able to detect subclinical disease progression in DMD, even within short (3-6 months) time periods. The measured sensitivity of MR biomarkers in this multicenter study may be critically important to future clinical trials, allowing for smaller sample sizes and/or shorter study windows in this fatal rare disease.
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