Purpose Skeletal muscles of children with Duchenne muscular dystrophy (DMD) have enhanced susceptibility to damage and progressive lipid infiltration, which contribute to an increase in magnetic resonance proton transverse relaxation time (T2). Therefore, examining T2 changes in individual muscles may be useful for monitoring disease progression in DMD. In this study we utilized mean T2, percent elevated pixels, and T2 heterogeneity to assess changes in composition of dystrophic muscles. In addition, we used fat saturation (fatsat) to distinguish T2 changes due to edema and inflammation from fat infiltration in muscles. Methods Thirty subjects with DMD and 15 age-matched controls underwent T2-weighted imaging of their lower leg using 3-T MR system. T2 maps were developed and four lower leg muscles were manually traced (soleus, medial gastrocnemius, peroneal and tibialis anterior). Mean T2 of the traced regions of interest (ROI), width of T2 histograms, and percent-elevated pixels were calculated. Results We found that even in young children with DMD, muscles had elevated mean T2, were more heterogeneous, and had a greater percent-elevated pixels in the lower leg muscles than controls. T2 measures decreased with fat saturation, but were still higher (p<0.05) in dystrophic muscles than controls. Further, T2 measures showed positive correlations with timed functional tests (r=0.23–0.79). Conclusion The elevated T2 measures with and without fat saturation in all ages of DMD examined (5–15 years) compared to unaffected controls indicate that the dystrophic muscles have increased regions of damage, edema, and fat infiltration. This study shows that T2 mapping provides multiple approaches that can be effectively utilized to characterize muscle tissue in children with DMD even in the early stages of the disease. Therefore, T2 mapping may prove clinically useful in monitoring muscle changes due to disease process or therapeutic interventions in DMD.

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 1H2O 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: 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. Duchenne muscular dystrophy (DMD) is a devastating form of muscular dystrophy caused by the absence of dystrophin, making muscle cell membranes fragile and susceptible to mechanical damage.1,2 Currently, there is no cure for the disease. Corticosteroids have been reported to slow disease progression in DMD.3-7 However, the mechanism by which corticosteroids preserve muscle function in DMD is not fully understood.Among several proposed mechanisms, corticosteroids are thought to reduce inflammation in dystrophic muscles. 8,9 MRI, in particular T2-weighted MRI, is sensitive to alterations in muscle chemistry and structure induced by processes like damage/inflammation and fat infiltration, [10][11][12][13][14][15][16][17] and therefore may have the potential to detect the effects of corticosteroid treatment on dystrophic muscles. Magnetic resonance spectroscopy (MRS) allows quantification of chemical compounds and can separate lipid and water components, allowing a more targeted investigation of skeletal muscles in DMD. 18-21The overall goal of this study was to examine the ability of MRI/MRS to detect the effects of corticosteroids on skeletal muscles in boys with DMD. The specific aims of the study were to (1) perform a cross-sectional comparison between the lower extremity muscles of 5-to 6.9-year-old

Duchenne muscular dystrophy (DMD) is characterized by in increased muscle damage and progressive replacement of muscle by noncontractile tissue. Both of these pathological changes can lengthen the MRI transverse proton relaxation time (T2). The current study measured longitudinal changes in T2 and its distribution in the lower leg of 16 boys with DMD (5–13 years, 15 ambulatory), 15 healthy controls (5–13 years). These muscles were chosen to allow extended longitudinal monitoring, due to their slow progression compared with proximal muscles in DMD. In the soleus muscle of boys with DMD, T2 and the percentage of pixels with an elevated T2 (≥2 SD above control mean T2) increased significantly over one year and two years, while the width of the T2 histogram increased over two years. Changes in soleus T2 variables were significantly greater in 9–13 year old compared with 5–8 year old boys with DMD. Significant correlations between the change in all soleus T2 variables over two years and the change in functional measures over two years were found. MRI measurement of muscle T2 in boys with DMD is sensitive to disease progression and shows promise as a clinical outcome measure.

Evidence indicates that experience-dependent cortical plasticity underlies post-stroke motor recovery of the impaired upper extremity. Motor skill learning in neurologically intact individuals is thought to involve the primary motor cortex, and the majority of studies in the animal literature have studied changes in the primary sensorimotor cortex with motor rehabilitation. Whether changes in engagement in the sensorimotor cortex occur in humans after stroke currently is an area of much interest. The present study conducted a meta-analysis on stroke studies examining changes in neural representations following therapy specifically targeting the upper extremity to determine if rehabilitation-related motor recovery is associated with neural plasticity in the sensorimotor cortex of the lesioned hemisphere. Twenty-eight studies investigating upper extremity neural representations (e.g., TMS, fMRI, PET, or SPECT) were identified, and 13 met inclusion criteria as upper extremity intervention training studies. Common outcome variables representing changes in the primary motor and sensorimotor cortices were used in calculating standardized effect sizes for each study. The primary fixed effects model meta-analysis revealed a large overall effect size (E.S. = 0.84, S.D. = 0.15, 95% C.I. = 0.76 -0.93). Moreover, a fail-safe analysis indicated that 42 null effect studies would be necessary to lower the overall effect size to an insignificant level. These results indicate that neural changes in the sensorimotor cortex of the lesioned hemisphere accompany functional paretic upper extremity motor gains achieved with targeted rehabilitation interventions.