Clinical Trial

. 2014 Sep 9;83(11):974-80.

doi: 10.1212/WNL.0000000000000775. Epub 2014 Aug 6.

Examination of effects of corticosteroids on skeletal muscles of boys with DMD using MRI and MRS

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

Affiliations

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.

PMID: 25098537
PMCID: PMC4162304
DOI: 10.1212/WNL.0000000000000775

Clinical Trial

Examination of effects of corticosteroids on skeletal muscles of boys with DMD using MRI and MRS

Ishu Arpan et al. Neurology. 2014.

. 2014 Sep 9;83(11):974-80.

doi: 10.1212/WNL.0000000000000775. Epub 2014 Aug 6.

Authors

Affiliations

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.

PMID: 25098537
PMCID: PMC4162304
DOI: 10.1212/WNL.0000000000000775

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.

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Figures

**Figure 1. Cross-sectional comparisons of MRI T2 between corticosteroid-treated and corticosteroid-naive boys with Duchenne muscular dystrophy**
Comparison of T2 by imaging in the lower leg muscles (A) and thigh muscles (B) of boys with Duchenne muscular dystrophy (DMD) on corticosteroid treatment (CS) and corticosteroid-naive boys (CS-naive). T2 values were lower in all the muscles examined in boys with DMD on corticosteroid therapy except for the gracilis (Gra) muscle. Values are represented as mean ± SEM; **p ≤ 0.01 and *p ≤ 0.05. BFLH = biceps femoris long head; MG = medial gastrocnemius; Per = peroneals; Sol = soleus; TA = tibialis anterior; TP = tibialis posterior; VL = vastus lateralis.

**Figure 2. Cross-sectional comparisons of MRS T2 between corticosteroid-treated and corticosteroid-naive boys with Duchenne muscular dystrophy**
An example gradient echo image of the lower leg with voxel placement in the soleus (Sol) muscle is depicted with the corresponding spectra acquired during the spectroscopic relaxometry scan. (A) Cross-sectional comparisons of T2 by spectroscopy between corticosteroid-treated boys (CS) and corticosteroid-naive boys (CS-naive) with Duchenne muscular dystrophy. (B) T2 values for both the Sol and vastus lateralis (VL) muscles were lower in CS boys compared to CS-naive boys, indicating less damage in the muscles of boys on corticosteroid treatment. Values are represented as mean ± SEM; **p ≤ 0.01 and *p ≤ 0.05. MRS = magnetic resonance spectroscopy; TE = echo time.

**Figure 3. Cross-sectional and longitudinal comparisons of fat fraction between corticosteroid-treated and corticosteroid-naive boys with Duchenne muscular dystrophy**
(A) ¹H–magnetic resonance spectroscopy spectrum from the soleus (Sol) muscle of a boy with Duchenne muscular dystrophy (DMD) depicts water and lipid peaks. (B) Cross-sectional comparisons of fat fraction in the Sol and vastus lateralis (VL) muscles between corticosteroid-treated (CS) and corticosteroid-naive boys (CS-naive) with DMD. (C) Longitudinal changes in fat fraction over 1 year in the Sol and VL muscles of boys in 2 groups. Values are represented as mean ± SEM; **p ≤ 0.01 and *p ≤ 0.05.

**Figure 4. Effects of corticosteroid initiation on MRI T2 of lower leg muscles in boys with Duchenne muscular dystrophy**
Comparison of absolute change in MRI T2 with respect to baseline in lower leg muscles of corticosteroid-treated boys with Duchenne muscular dystrophy (CS) and corticosteroid-naive boys (CS-naive) at 3 months (A) and 6 months (B). Values are represented as mean ± SEM; **p ≤ 0.01 and *p ≤ 0.05. MG = medial gastrocnemius; Per = peroneals; Sol = soleus; TA = tibialis anterior; TP = tibialis posterior.

See this image and copyright information in PMC

Comment in

Quantitative MRI in muscular dystrophy: An indispensable trial endpoint?
Hollingsworth KG. Hollingsworth KG. Neurology. 2014 Sep 9;83(11):956-7. doi: 10.1212/WNL.0000000000000785. Epub 2014 Aug 6. Neurology. 2014. PMID: 25098536 No abstract available.

References

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Examination of effects of corticosteroids on skeletal muscles of boys with DMD using MRI and MRS

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Examination of effects of corticosteroids on skeletal muscles of boys with DMD using MRI and MRS

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