Objective
We assessed changes in quantitative muscle ultrasound data in boys with Duchenne muscular dystrophy (DMD) and healthy controls to determine if ultrasound can serve as a biomarker of disease progression. Two approaches were used: grey scale level (GSL), measured from the ultrasound image, and quantitative backscatter analysis (QBA) measured directly from the received echoes.
Methods
GSL and QBA were obtained from six unilateral arm/leg muscles in 36 boys with DMD and 28 healthy boys (age 2–14 years) for up to 2 years. We used a linear mixed-effects model with random intercept and slope terms to compare trajectories of GSL, QBA, and functional assessments. We analyzed separately a subset of boys who initiated corticosteroids.
Results
Compared to healthy boys, increasing GSL in DMD boys >7.0 years was first identified at 6 months (e.g., anterior forearm slope difference of 1.16 arbitrary units/month p=0.004, 95% confidence interval (CI) [0.38,1.94]); in boys ≤7 years, differences in GSL first appeared at 12 months (0.82 arbitrary units /month, p=0.04 95%CI [0.075,1.565] in rectus femoris). QBA performed similarly to GSL (e.g., DMD boys >7 years of 0.41dB/month, p=0.01, 95%CI [0.096,0.72] in anterior forearm at 6 months). US identified differences earlier than functional measures including 6-minute walk and supine-to-stand tests. However, neither QBA nor GSL showed an effect of corticosteroid initiation.
Interpretation
QBA performs similarly to GSL and both appear more sensitive than functional assessments for detecting muscle deterioration in DMD. Additional studies will be required to determine if quantitative muscle ultrasound can detect therapeutic efficacy.
Objective
Sensitive, objective and easily applied methods for evaluating disease progression and response to therapy are needed for clinical trials in Duchenne muscular dystrophy (DMD). In this study, we evaluated whether electrical impedance myography (EIM) could serve this purpose.
Methods
In this non-blinded study, 36 boys with DMD and 29 age-similar healthy boys underwent multifrequency EIM measurements for up to 2 years on 6 muscles unilaterally along with functional assessments. A linear mixed-effects model with random intercept and slope terms was used for the analysis of multifrequency EIM values and functional measures. Seven DMD boys were initiated on corticosteroids; these data were analyzed using a piecewise linear mixed-effects model.
Results
In boys >7.0 years, a significant difference in the slope of EIM phase-ratio trajectories in the upper extremity was observed by 6 months of -0.074/month, p=0.023, 95% confidence interval (CI)[−0.013,−0.14]); at two years, this difference was −0.048/month, p<0.0001 95%CI[−0.028,−0.068]. In boys ≤7.0 years, differences appeared at 6 months in gastrocnemius (EIM phase-slope −0.83°/kHz-month, p=0.007 95%CI[−0.26,−1.40]). EIM outcomes showed significant differences earlier than functional tests. Initiation of corticosteroids significantly improved the slope of EIM phase-ratio (0.057/month, p=0.00019 95%CI[0.028,0.086]) and EIM phase-slope (0.14°/kHz-month, p=0.013 95%CI[0.028,0.25]), consistent with corticosteroids’ known clinical benefit.
Interpretation
EIM detects deterioration in muscles of both younger and older boys by 6 months; it also identifies the therapeutic effect of corticosteroid initiation. Since EIM is rapid to apply, painless, and requires minimal operator training, the technique deserves to be further evaluated as a biomarker in DMD clinical therapeutic trials.
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