Electrical impedance myography for assessment of Duchenne muscular dystrophy
Researchers continue to seek more effective tools for evaluating the effect of therapy in DMD, regardless of age. For example, biopsies evaluating dystrophin expression can provide evidence of drug effect at the cellular level.7 Magnetic resonance imaging (MRI) has also been used to evaluate the health of DMD muscle.8 Importantly, a recent longitudinal study demonstrated MRI's high sensitivity to disease progression as measured by the amount of fat deposition using the Dixon technique, even in boys younger than 7 years.10 However, MRI is relatively expensive, requires identical acquisition protocols across centers, is restricted to mainly lower extremity muscles in this population, and can be difficult to perform in younger children, those with behavioral problems, or those with advanced disease.
Electrical impedance myography (EIM) represents another potential method for assessing the effect of therapy in DMD that does not have these limitations.11 In EIM, the evaluator places a small 4‐electrode array over a muscle of interest connected to a multifrequency impedance‐measuring device (Fig 1).12 A very low‐intensity alternating current at a range of frequencies (approximately 1kHz to 1MHz) is passed across the outer 2 electrodes; the inner 2 electrodes measure the resulting voltages. Alterations in the muscle's structure and composition, including myocyte hypertrophy and atrophy, inflammation, edema, and connective tissue and fat deposition will impact the measured impedances.13 Our underlying hypothesis is that EIM is sensitive to changes in the biophysical properties of muscle due to DMD progression as well as to the effects of therapy. EIM has several additional potential advantages, including being entirely painless, being rapid to apply to a variety of upper and lower body muscles at the bedside, and providing numerical data that do not require complex image analysis. Evaluator training is also straightforward, and high reproducibility of measurements is possible.16 Importantly, cross‐sectional data obtained in both mdx and wild‐type mice as well as in DMD and healthy boys demonstrate marked differences in EIM values between healthy and dystrophin‐deficient muscle.11
In this 2‐year, nonblinded, longitudinal study, we evaluated alterations in EIM values in a group of boys with DMD and compared changes to those of aged‐matched healthy boys. Functional measures as well as quantitative ultrasound data (discussed in our companion article)17 were also obtained. Our goal was to identify the character of EIM change in healthy children versus those with DMD. In addition, we separately evaluated alterations in a subset of DMD boys initiated on corticosteroids to determine whether EIM is sensitive to the therapeutic impact of that class of medications.