Magnetic Resonance Assessment of Hypertrophic and Pseudo-Hypertrophic Changes in Lower Leg Muscles of Boys with Duchenne Muscular Dystrophy and Their Relationship to Functional Measurements.

INTRODUCTION: The primary objectives of this study were to evaluate contractile and non-contractile content of lower leg muscles of boys with Duchenne muscular dystrophy (DMD) and determine the relationships between non-contractile content and functional abilities. METHODS: Lower leg muscles of thirty-two boys with DMD and sixteen age matched unaffected controls were imaged. Non-contractile content, contractile cross sectional area and non-contractile cross sectional area of lower leg muscles (tibialis anterior, extensor digitorum longus, peroneal, medial gastrocnemius and soleus) were assessed by magnetic resonance imaging (MRI). Muscle strength, timed functional tests and the Brooke lower extremity score were also assessed. RESULTS: Non-contractile content of lower leg muscles (peroneal, medial gastrocnemius, and soleus) was significantly greater than control group (p<0.05). Non-contractile content of lower leg muscles correlated with Brooke score (rs = 0.64-0.84) and 30 feet walk (rs = 0.66-0.80). Dorsiflexor (DF) and plantarflexor (PF) specific torque was significantly different between the groups. DISCUSSION: Overall, non-contractile content of the lower leg muscles was greater in DMD than controls. Furthermore, there was an age dependent increase in contractile content in the medial gastrocnemius of boys with DMD. The findings of this study suggest that T1 weighted MR images can be used to monitor disease progression and provide a quantitative estimate of contractile and non-contractile content of tissue in children with DMD.

Magnetic resonance imaging and spectroscopy assessment of lower extremity skeletal muscles in boys with Duchenne muscular dystrophy: a multicenter cross sectional study.

INTRODUCTION: Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder that results in functional deficits. However, these functional declines are often not able to be quantified in clinical trials for DMD until after age 7. In this study, we hypothesized that (1)H2O T2 derived using (1)H-MRS and MRI-T2 will be sensitive to muscle involvement at a young age (5-7 years) consistent with increased inflammation and muscle damage in a large cohort of DMD subjects compared to controls. METHODS: MR data were acquired from 123 boys with DMD (ages 5-14 years; mean 8.6 SD 2.2 years) and 31 healthy controls (age 9.7 SD 2.3 years) using 3-Tesla MRI instruments at three institutions (University of Florida, Oregon Health & Science University, and Children's Hospital of Philadelphia). T2-weighted multi-slice spin echo (SE) axial images and single voxel 1H-MRS were acquired from the lower leg and thigh to measure lipid fraction and (1)H2O T2. RESULTS: MRI-T2, (1)H2O T2, and lipid fraction were greater (p<0.05) in DMD compared to controls. In the youngest age group, DMD values were different (p<0.05) than controls for the soleus MRI-T2, (1)H2O T2 and lipid fraction and vastus lateralis MRI-T2 and (1)H2O T2. In the boys with DMD, MRI-T2 and lipid fraction were greater (p<0.05) in the oldest age group (11-14 years) than the youngest age group (5-6.9 years), while 1H2O T2 was lower in the oldest age group compared to the young age group. DISCUSSION: Overall, MR measures of T2 and lipid fraction revealed differences between DMD and Controls. Furthermore, MRI-T2 was greater in the older age group compared to the young age group, which was associated with higher lipid fractions. Overall, MR measures of T2 and lipid fraction show excellent sensitivity to DMD disease pathologies and potential therapeutic interventions in DMD, even in the younger boys.

Assessment of intramuscular lipid and metabolites of the lower leg using magnetic resonance spectroscopy in boys with Duchenne muscular dystrophy.

The purpose of this study was to use proton magnetic resonance spectroscopy to assess intramuscular lipid and metabolites of lower leg muscles in boys with Duchenne muscular dystrophy (DMD) and determine its relationship with strength and functional ability. Spectroscopic measurements were obtained from four muscles of the lower leg in 25 boys with DMD (9.2±3.1 years) and 10 healthy boys (10.2±2.6 years). Lipid fractions and metabolite concentrations were also determined. Muscle strength, a timed functional test, and the Modified Brooke Lower Extremity Functional Scale were also determined. Lipid fractions were higher (p<0.01) for the DMD group than healthy subjects for all muscles, and lipid fraction was found to be greater in the older DMD boys. The peroneal muscle demonstrated a significant difference in lipid fraction in all DMD age groups. Lipid fractions in all muscles correlated with functional measures (r=0.52-0.70, p<0.001), with smaller inverse correlations with the strength measure (r=-0.36 to -0.56, p<0.05). These findings provide quantifiable information regarding intramuscular lipid and metabolite levels of different muscles across various age groups in boys with DMD and may be used in determining the effect of interventions in future clinical trials.

Metabolic costs of isometric force generation and maintenance of human skeletal muscle.

During isometric contractions, no true work is performed, so the force-time integral (FTI) is often used to approximate isometric work. However, the relationship between FTI and metabolic cost is not as linear. We tested the hypothesis that this nonlinearity was due to the cost of attaining a given force being greater than that of maintaining it. The ATP consumed per contraction in the human medial gastrocnemius muscle (n = 6) was determined by use of (31)P-NMR spectroscopy during eight different electrical stimulation protocols. Each protocol consisted of 8 trains of a single frequency (20 or 80 Hz) and duration (300, 600, 1,200, or 1,800 ms) performed under ischemic conditions. The cost of force generation was determined from the ATP turnover during the short-duration trains that did not attain a steady force level. Estimates of the cost of force maintenance at each frequency were determined by subtracting the ATP turnover during the shorter-duration trains from the turnover during the long-duration trains. The force generation phase of an isometric contraction was indeed more metabolically costly than the force maintenance phase during both 20- and 80-Hz stimulation. Thus the mean rate of ATP hydrolysis appeared to decline as contraction duration increased. Interestingly, the metabolic costs of maintaining force during 20-Hz and 80-Hz stimulation were comparable, although different levels of force were produced.