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: 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.

The purpose of this study was to assess the contractile and non-contractile content in thigh muscles of patients with Duchenne muscular dystrophy (DMD) and determine the relationship with functional abilities. Magnetic resonance images of the thigh were acquired in 28 boys with DMD and 10 unaffected boys. Muscle strength, timed functional tests, and the Brookes Lower Extremity scale were also assessed. Non-contractile content in the DMD group was significantly greater than in the control group for six muscles, including rectus femoris, biceps femoris-long head and adductor magnus. Non-contractile content in the total thigh musculature assessed by MRI correlated with the Brookes scale (rs=0.75) and supine-up test (rs=0.68), as well as other functional measures. An age-related specific torque increase was observed in the control group (rs=0.96), but not the DMD (rs=0.06). These findings demonstrate that MRI measures of contractile and non-contractile content can provide important information about disease progression in DMD.

Freezing of gait (FOG) is a poorly understood symptom affecting many patients with Parkinson's disease (PD). Despite growing evidence of a behavioral link between anxiety, attention and FOG in PD, no research to date has investigated the neural mechanisms that might explain this relationship. The present study therefore examined resting-state MRI functional connectivity between the amygdala, striatum and frontoparietal attentional control network in PD patients with (freezers: n = 19) and without FOG (non-freezers: n = 21) in the dopaminergic 'off' state. Functional connectivity was subsequently correlated with an objective measure of FOG severity and a subjective scale of affective disorder within each group. Connectivity between the right amygdala and right putamen was significantly increased in freezers compared to non-freezers (p < 0.01). Furthermore, freezers showed increased anti-coupling between the frontoparietal network and left amygdala (p = 0.011), but reduced anti-coupling between this network and the right putamen (p = 0.027) as compared to non-freezers. Key functional connections between the amygdala, putamen and frontoparietal network were significantly associated with FOG severity and a fear of falling. This study provides the first evidence that dysfunctional fronto-striato-limbic processes may underpin the link between anxiety and FOG in PD. It is proposed that freezers have heightened striato-limbic load and reduced top-down attentional control at rest, which when further challenged by the parallel processing demands of walking may precipitate FOG.

ObjectiveTo quantify disease progression in individuals with Duchenne muscular dystrophy (DMD) using magnetic resonance biomarkers of leg muscles.MethodsMRI and magnetic resonance spectroscopy (MRS) biomarkers were acquired from 104 participants with DMD and 51 healthy controls using a prospective observational study design with patients with DMD followed up yearly for up to 6 years. Fat fractions (FFs) in vastus lateralis and soleus muscles were determined with 1H MRS. MRI quantitative T2 (qT2) values were measured for 3 muscles of the upper leg and 5 muscles of the lower leg. Longitudinal changes in biomarkers were modeled with a cumulative distribution function using a nonlinear mixed-effects approach.ResultsMRS FF and MRI qT2 increased with DMD disease duration, with the progression time constants differing markedly between individuals and across muscles. The average age at half-maximal muscle involvement (μ) occurred 4.8 years earlier in vastus lateralis than soleus, and these measures were strongly associated with loss-of-ambulation age. Corticosteroid treatment was found to delay μ by 2.5 years on average across muscles, although there were marked differences between muscles with more slowly progressing muscles showing larger delay.ConclusionsMRS FF and MRI qT2 provide sensitive noninvasive measures of DMD progression. Modeling changes in these biomarkers across multiple muscles can be used to detect and monitor the therapeutic effects of corticosteroids on disease progression and to provide prognostic information on functional outcomes. This modeling approach provides a method to transform these MRI biomarkers into well-understood metrics, allowing concise summaries of DMD disease progression at individual and population levels.ClinicalTrials.gov identifier:NCT01484678.

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BACKGROUND CONTEXT Findings on imaging of noncontractile anatomic abnormalities and the intensity of low back pain have weak associations because of false-positive rates among asymptomatic individuals. This association might be stronger for contractile tissues. PURPOSE The purpose of this study was to examine the relationship between location and reports of pain intensity in the low back and exercise-induced muscle damage to the lumbar paraspinal muscles. STUDY DESIGN Nondiagnostic observational study in a laboratory setting. METHODS Delayed onset muscle soreness was induced in the low back of healthy pain-free volunteers. Measures of pain intensity (100-mm visual analog scale [VAS]) and location (area on the pain diagram) were taken before and 48 hours after exercise. Muscle damage was quantified using mechanical pain thresholds, motor performance deficits, and transverse relaxation time (T2)–weighted magnetic resonance imaging (MRI). Changes pre- to postexercise in signal intensity on T2-weighted imaging within the erector spinae, pain intensity, pain area, mechanical pain threshold, and isometric torque were assessed using paired t tests. Bivariate correlations were conducted to assess associations among muscle damage, pain intensity, and pain drawing area. RESULTS Twenty participants volunteered (11 women; average age, 22.3 years; average body mass index, 23.5) for study participation. Reports of pain intensity at 48 hours ranged from 0 to 59 mm on the VAS. Muscle damage was confirmed by reductions in mechanical threshold (p=.011) and motor performance (p<.001) and by changes in T2-weighted MRI (p=.007). This study was powered to find an association of at least r=0.5 to be statistically significant. Correlations of continuous variables revealed no significant correlations between pain intensity and measures of muscle damage (ranging between −0.075 and 0.151). There was a significant association between the remaining torque deficit at 48 hours and pain area. CONCLUSIONS The results of this study indicate that there was no association between the magnitude of muscle damage in the lumbar erector spinae and reported pain intensity in the low back. In future studies, larger cohorts may report statistically significant associations, but our data suggest that there will be low magnitude potentially indicating limited clinical relevance.