Impedance alterations in healthy and diseased mice during electrically induced muscle contraction

Alterations in the health of muscles can be evaluated through the use of electrical impedance myography (EIM). To date, however, nearly all work in this field has relied upon the measurement of muscle at rest. To provide an insight into the contractile mechanisms of healthy and disease muscle, we evaluated the alterations in the spectroscopic impedance behavior of muscle during the active process of muscle contraction. The gastrocnemii from a total of 13 mice were studied (five wild type, four muscular dystrophy animals, and four amyotrophic lateral sclerosis animals). Muscle contraction was induced via monophasic current pulse stimulation of the sciatic nerve. Simultaneously, multisine EIM (1 kHz to 1 MHz) and force measurements of the muscle were performed. Stimulation was applied at three different rates to produce mild, moderate, and strong contractions. We identified changes in both single and multifrequency data, as assessed by the Cole impedance model parameters. The processes of contraction and relaxation were clearly identified in the impedance spectra and quantified via derivative plots. Reductions in the center frequency f(c) were observed during the contraction consistent with the increasing muscle fiber diameter. Different EIM stimulation rate-dependencies were also detected across the three groups of animals.Peer ReviewedPostprint (author's final draft

A Comparison of Three Electrophysiological Methods for the Assessment of Disease Status in a Mild Spinal Muscular Atrophy Mouse Model

Objectives: There is a need for better, noninvasive quantitative biomarkers for assessing the rate of progression and possible response to therapy in spinal muscular atrophy (SMA). In this study, we compared three electrophysiological measures: compound muscle action potential (CMAP) amplitude, motor unit number estimate (MUNE), and electrical impedance myography (EIM) 50 kHz phase values in a mild mouse model of spinal muscular atrophy, the Smn1c/c mouse. Methods: Smn1c/c mice (N = 11) and wild type (WT) animals (−/−, N = 13) were measured on average triweekly until approximately 1 year of age. Measurements included CMAP, EIM, and MUNE of the gastrocnemius muscle as well as weight and front paw grip strength. At the time of sacrifice at one year, additional analyses were performed on the animals including serum survival motor neuron (SMN) protein levels and muscle fiber size. Results: Both EIM 50 kHz phase and CMAP showed strong differences between WT and SMA animals (repeated measures 2-way ANOVA, P<0.0001 for both) whereas MUNE did not. Both body weight and EIM showed differences in the trajectory over time (p<0.001 and p = 0.005, respectively). At the time of sacrifice at one year, EIM values correlated to motor neuron counts in the spinal cord and SMN levels across both groups of animals (r = 0.41, p = 0.047 and r = 0.57, p = 0.003, respectively), while CMAP did not. Motor neuron number in Smn1c/c mice was not significantly reduced compared to WT animals. Conclusions: EIM appears sensitive to muscle status in this mild animal model of SMA. The lack of a reduction in MUNE or motor neuron number but reduced EIM and CMAP values support that much of the pathology in these animals is distal to the cell body, likely at the neuromuscular junction or the muscle itself

Age- and Gender-Associated Differences in Electrical Impedance Values of Skeletal Muscle

Electrical impedance measurements of skeletal muscle may be sensitive to age-associated declines in muscle health. In an effort to evaluate this concept further, we performed electrical impedance myography (EIM) using a handheld array on 38 individuals aged 19–50 years and 41 individuals aged 60–85 years. Individuals either had 7 upper extremity or 7 lower extremity muscles measured. The 50 kHz reactance, resistance and phase were used as the major outcome variables. Although the phase values were similar in both groups, both reactance and resistance values were lower in the lower extremities of the older individuals as compared to the younger (−23 ± 6%, p = 0.001 for reactance and −27 ± 7%, p = 0.005 for resistance), whereas changes in upper extremity values were not significantly different (−9 ± 5%, p = 0.096 for reactance and +5 ± 9%, p = 0.55 for resistance). When analyzing the genders separately, it became clear that this reduction in lower extremity values was most pronounced in men and less consistently present in women. These findings suggest that age- and gender-associated differences in muscle condition are detectable using EIM. The relationship of these easily obtained parameters to standard functional, imaging, and pathological markers of sarcopenia deserves further study

Impedance alterations in healthy and diseased mice during electrically induced muscle contraction

Alterations in the health of muscles can be evaluated through the use of electrical impedance myography (EIM). To date, however, nearly all work in this field has relied upon the measurement of muscle at rest. To provide an insight into the contractile mechanisms of healthy and disease muscle, we evaluated the alterations in the spectroscopic impedance behavior of muscle during the active process of muscle contraction. The gastrocnemii from a total of 13 mice were studied (five wild type, four muscular dystrophy animals, and four amyotrophic lateral sclerosis animals). Muscle contraction was induced via monophasic current pulse stimulation of the sciatic nerve. Simultaneously, multisine EIM (1 kHz to 1 MHz) and force measurements of the muscle were performed. Stimulation was applied at three different rates to produce mild, moderate, and strong contractions. We identified changes in both single and multifrequency data, as assessed by the Cole impedance model parameters. The processes of contraction and relaxation were clearly identified in the impedance spectra and quantified via derivative plots. Reductions in the center frequency f(c) were observed during the contraction consistent with the increasing muscle fiber diameter. Different EIM stimulation rate-dependencies were also detected across the three groups of animals.Peer Reviewe

Summary of correlations.

<p>Summary of correlations.</p

Trajectories of change (± standard deviation) over the period of 15 weeks to 52 weeks for the 7 Smn1^c/c animals (in black) and 7 WT animals (in gray) followed for the entire duration.

<p>Data is normalized to baseline with a least squares fit of the data. Only weight and EIM showed significant differences in the trajectories between the groups.</p

Column plots comparing 1-year end point data for WT and SMA animals.

<p>While most of the readily obtained measures, including body weight, paw grip strength, and muscle size are smaller and SMN is markedly reduced, all electrophysiological parameters show only modest differences. In addition, hydroxyproline, a measure of muscle fibrosis, is non-significantly increased in the SMA animals. *<0.05, **<0.01, ***<0.001.</p

A selection of the correlations between various parameters for both animal types combined.

<p>A selection of the correlations between various parameters for both animal types combined.</p