Ishu Arpan1, Rebecca J Willcocks1, Sean C Forbes1, Richard S Finkel1, Donovan J Lott1, William D Rooney1, William T Triplett1, Claudia R Senesac1, Michael J Daniels1, Barry J Byrne1, Erika L Finanger1, Barry S Russman1, Dah-Jyuu Wang1, Gihan I Tennekoon1, Glenn A Walter1, H L Sweeney1, Krista Vandenborne2. 1. From the Departments of Physical Therapy (I.A., R.J.W., S.C.F., D.J.L., W.T.T., C.R.S., K.V.), Physiology and Functional Genomics (G.A.W.), and Pediatrics (B.J.B.), and Molecular Genetics & Microbiology, Powell Gene Therapy Center (B.J.B.), University of Florida, Gainesville; The Children's Hospital of Philadelphia (R.S.F., D.-J.W., G.I.T.), PA; Oregon Health & Science University (W.D.R., E.L.F., B.S.R.), Portland; the Departments of Integrative Biology and Statistics and Data Sciences (M.J.D.), The University of Texas at Austin; Shriners Hospital for Children (B.S.R.), Philadelphia, PA; and the Department of Physiology (H.L.S.), University of Pennsylvania, Philadelphia. 2. From the Departments of Physical Therapy (I.A., R.J.W., S.C.F., D.J.L., W.T.T., C.R.S., K.V.), Physiology and Functional Genomics (G.A.W.), and Pediatrics (B.J.B.), and Molecular Genetics & Microbiology, Powell Gene Therapy Center (B.J.B.), University of Florida, Gainesville; The Children's Hospital of Philadelphia (R.S.F., D.-J.W., G.I.T.), PA; Oregon Health & Science University (W.D.R., E.L.F., B.S.R.), Portland; the Departments of Integrative Biology and Statistics and Data Sciences (M.J.D.), The University of Texas at Austin; Shriners Hospital for Children (B.S.R.), Philadelphia, PA; and the Department of Physiology (H.L.S.), University of Pennsylvania, Philadelphia. kvandenb@phhp.ufl.edu.
Abstract
OBJECTIVE: To evaluate the effects of corticosteroids on the lower extremity muscles in boys with Duchenne muscular dystrophy (DMD) using MRI and magnetic resonance spectroscopy (MRS). METHODS: Transverse relaxation time (T2) and fat fraction were measured by MRI/MRS in lower extremity muscles of 15 boys with DMD (age 5.0-6.9 years) taking corticosteroids and 15 corticosteroid-naive boys. Subsequently, fat fraction was measured in a subset of these boys at 1 year. Finally, MRI/MRS data were collected from 16 corticosteroid-naive boys with DMD (age 5-8.9 years) at baseline, 3 months, and 6 months. Five boys were treated with corticosteroids after baseline and the remaining 11 served as corticosteroid-naive controls. RESULTS: Cross-sectional comparisons demonstrated lower muscle T2 and less intramuscular (IM) fat deposition in boys with DMD on corticosteroids, suggesting reduced inflammation/damage and fat infiltration with treatment. Boys on corticosteroids demonstrated less increase in IM fat infiltration at 1 year. Finally, T2 by MRI/MRS detected effects of corticosteroids on leg muscles as early as 3 months after drug initiation. CONCLUSIONS: These results demonstrate the ability of MRI/MRS to detect therapeutic effects of corticosteroids in reducing inflammatory processes in skeletal muscles of boys with DMD. Our work highlights the potential of MRI/MRS as a biomarker in evaluating therapeutic interventions in DMD.
OBJECTIVE: To evaluate the effects of corticosteroids on the lower extremity muscles in boys with Duchenne muscular dystrophy (DMD) using MRI and magnetic resonance spectroscopy (MRS). METHODS: Transverse relaxation time (T2) and fat fraction were measured by MRI/MRS in lower extremity muscles of 15 boys with DMD (age 5.0-6.9 years) taking corticosteroids and 15 corticosteroid-naive boys. Subsequently, fat fraction was measured in a subset of these boys at 1 year. Finally, MRI/MRS data were collected from 16 corticosteroid-naive boys with DMD (age 5-8.9 years) at baseline, 3 months, and 6 months. Five boys were treated with corticosteroids after baseline and the remaining 11 served as corticosteroid-naive controls. RESULTS: Cross-sectional comparisons demonstrated lower muscle T2 and less intramuscular (IM) fat deposition in boys with DMD on corticosteroids, suggesting reduced inflammation/damage and fat infiltration with treatment. Boys on corticosteroids demonstrated less increase in IM fat infiltration at 1 year. Finally, T2 by MRI/MRS detected effects of corticosteroids on leg muscles as early as 3 months after drug initiation. CONCLUSIONS: These results demonstrate the ability of MRI/MRS to detect therapeutic effects of corticosteroids in reducing inflammatory processes in skeletal muscles of boys with DMD. Our work highlights the potential of MRI/MRS as a biomarker in evaluating therapeutic interventions in DMD.
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