Person:

Sanchez, Benjamin

The positioning of electrodes in electrical impedance myography (EIM) is critical for accurately assessing disease progression and effectiveness of treatment. In human and animal trials for neuromuscular disorders, inconsistent electrode positioning adds errors to the muscle impedance. Despite its importance, how the reproducibility of resistance and reactance, the two parameters that define EIM, are affected by changes in electrode positioning remains unknown. In this paper, we present a novel approach founded on biophysical principles to study the reproducibility of resistance and reactance to electrode misplacements. The analytical framework presented allows the user to quantify a priori the effect on the muscle resistance and reactance using only one parameter: the uncertainty placing the electrodes. We also provide quantitative data on the precision needed to position the electrodes and the minimum muscle length needed to achieve a pre-specified EIM reproducibility. The results reported here are confirmed with finite element model simulations and measurements on five healthy subjects. Ultimately, our data can serve as normative values to enhance the reliability of EIM as a biomarker and facilitate comparability of future human and animal studies.

Objectives: Non-invasive and effort independent biomarkers are needed to better assess the effects of drug therapy on healthy muscle and that affected by muscular dystrophy (mdx). Here we evaluated the use of multi-frequency electrical impedance for this purpose with comparison to force and histological parameters. Methods: Eight wild-type (wt) and 10 mdx mice were treated weekly with RAP-031 activin type IIB receptor at a dose of 10 mg kg−1 twice weekly for 16 weeks; the investigators were blinded to treatment and disease status. At the completion of treatment, impedance measurements, in situ force measurements, and histology analyses were performed. Results: As compared to untreated animals, RAP-031 wt and mdx treated mice had greater body mass (18% and 17%, p < 0.001 respectively) and muscle mass (25% p < 0.05 and 22% p < 0.001, respectively). The Cole impedance parameters in treated wt mice, showed a 24% lower central frequency (p < 0.05) and 19% higher resistance ratio (p < 0.05); no significant differences were observed in the mdx mice. These differences were consistent with those seen in maximum isometric force, which was greater in the wt animals (p < 0.05 at > 70 Hz), but not in the mdx animals. In contrast, maximum force normalized by muscle mass was unchanged in the wt animals and lower in the mdx animals by 21% (p < 0.01). Similarly, myofiber size was only non-significantly higher in treated versus untreated animals (8% p = 0.44 and 12% p = 0.31 for wt and mdx animals, respectively). Conclusions: Our findings demonstrate electrical impedance of muscle reproduce the functional and histological changes associated with myostatin pathway inhibition and do not reflect differences in muscle size or volume. This technique deserves further study in both animal and human therapeutic trials.