title: Multicenter prospective longitudinal study of magnetic resonance biomarkers in a large duchenne muscular dystrophy cohort.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Physical Therapy, University of Florida, Gainesville, FL.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Willcocks
authors.affiliation: Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR.
authors.forename: William D
authors.initials: WD
authors.lastname: Rooney
authors.affiliation: Department of Physical Therapy, University of Florida, Gainesville, FL.
authors.forename: William T
authors.initials: WT
authors.lastname: Triplett
authors.affiliation: Department of Physical Therapy, University of Florida, Gainesville, FL.
authors.forename: Sean C
authors.initials: SC
authors.lastname: Forbes
authors.affiliation: Department of Physical Therapy, University of Florida, Gainesville, FL.
authors.forename: Donovan J
authors.initials: DJ
authors.lastname: Lott
authors.affiliation: Department of Physical Therapy, University of Florida, Gainesville, FL.
authors.forename: Claudia R
authors.initials: CR
authors.lastname: Senesac
authors.affiliation: Department of Statistics & Data Sciences and Department of Integrative Biology, University of Texas at Austin, Austin, TX.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Daniels
authors.affiliation: Division of Neurology and Department of Radiology, the Children's Hospital of Philadelphia, Philadelphia, PA.
authors.forename: Dah-Jyuu
authors.initials: DJ
authors.lastname: Wang
authors.affiliation: the Children's Hospital of Philadelphia, Philadelphia, PA.
authors.forename: Ann T
authors.initials: AT
authors.lastname: Harrington
authors.affiliation: the Children's Hospital of Philadelphia, Philadelphia, PA.
authors.forename: Gihan I
authors.initials: GI
authors.lastname: Tennekoon
authors.affiliation: Departments of Pediatrics and Neurology, Oregon Health & Science University, Shriners Hospital for Children, Portland, OR.
authors.forename: Barry S
authors.initials: BS
authors.lastname: Russman
authors.affiliation: Departments of Pediatrics and Neurology, Oregon Health & Science University, Shriners Hospital for Children, Portland, OR.
authors.forename: Erika L
authors.initials: EL
authors.lastname: Finanger
authors.affiliation: Department of Pediatrics and Molecular Genetics and Microbiology, Powell Gene Therapy Center University of Florida, Gainesville, FL.
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Byrne
authors.affiliation: Nemours Children's Hospital, University of Central Florida College of Medicine, Orlando, FL.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Finkel
authors.affiliation: Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL.
authors.forename: Glenn A
authors.initials: GA
authors.lastname: Walter
authors.affiliation: Department of Physiology, University of Pennsylvania, Philadelphia, PA.
authors.forename: H Lee
authors.initials: HL
authors.lastname: Sweeney
authors.affiliation: Department of Physical Therapy, University of Florida, Gainesville, FL.
authors.forename: Krista
authors.initials: K
authors.lastname: Vandenborne
mesh_terms: D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005080:Exercise Test; D006801:Humans; D007866:Leg / Q000473:pathology*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology*; D020388:Muscular Dystrophy, Duchenne / Q000473:pathology* / Q000503:physiopathology
chemical_list: D015415:Biomarkers