Assessment OF aged <i>mdx</i> mice by electrical impedance myography and magnetic resonance imaging

Wu, Jim S.; Li, Jia; Greenman, Robert L.; Bennett, D.; Geisbush, Tom; Rutkove, Seward B.

doi:10.1002/mus.24573

Cited by 19 publications

(19 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…With the further development of the technique (for example, the custom-designed EIM apparatus), we may evaluate a variety of different surface muscles to gain a more global evaluation of the disease in the dog model; (4) in this study, we have focused on correlating the pathological findings with the EIM data, there is a need to determine whether the EIM data relate well with the results of physiological assays such as muscle force measurement, gait analysis and activity monitoring in dogs [12, 17, 18]; results in mdx mice (Seward B. Rutkove, unpublished results) and ALS mice suggest a relationship between muscle force measurement and impedance values [26]. Similarly, it will be worthwhile to compare EIM with muscle ultrasound and MRI [38, 40]; (5) as a cross-sectional study, we only selected two age groups. To establish a robust natural history profile for the entire population of normal and affected dogs, we are obligated to conduct longitudinal follow-up studies on a large cohort of dogs; (6) as our ultimate goal is to develop an effective therapy for DMD, it will be necessary to implement the EIM assay in preclinical therapy studies to help quantify the efficacy of novel experimental interventions.…”

Section: Discussionmentioning

confidence: 99%

Non-invasive evaluation of muscle disease in the canine model of Duchenne muscular dystrophy by electrical impedance myography

et al. 2017

Self Cite

View full text Add to dashboard Cite

Dystrophin-deficient dogs are by far the best available large animal models for Duchenne muscular dystrophy (DMD), the most common lethal childhood muscle degenerative disease. The use of the canine DMD model in basic disease mechanism research and translational studies will be greatly enhanced with the development of reliable outcome measures. Electrical impedance myography (EIM) is a non-invasive painless procedure that provides quantitative data relating to muscle composition and histology. EIM has been extensively used in neuromuscular disease research in both human patients and rodent models. Recent studies suggest that EIM may represent a highly reliable and convenient outcome measure in DMD patients and the mdx mouse model of DMD. To determine whether EIM can be used as a biomarker of disease severity in the canine model, we performed the assay in fourteen young (~6.6-m-old; 6 normal and 8 affected) and ten mature (~16.9-m-old; 4 normal and 6 affected) dogs of mixed background breeds. EIM was well tolerated with good inter-rater reliability. Affected dogs showed higher resistance, lower reactance and phase. The difference became more straightforward in mature dogs. Importantly, we observed a statistically significant correlation between the EIM data and muscle fibrosis. Our results suggest that EIM is a valuable objective measurement in the canine DMD model.

show abstract

Section: Discussionmentioning

confidence: 99%

Non-invasive evaluation of muscle disease in the canine model of Duchenne muscular dystrophy by electrical impedance myography

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…All in vivo animal work reported to date, for example, in amyotrophic lateral sclerosis and muscular dystrophy mice, has been performed on adult animals and has used surface electrode arrays, analogous to those used in human studies (Ahad and Rutkove, 2010; Ahad et al, 2009; Ahad and Rutkove, 2009; Li et al, 2014a; Li et al, 2014d; Li et al, 2013; Li et al, 2012; Wu et al, 2015). Prior studies have demonstrated that subcutaneous tissue contributes little to the measurement of EIM reactance(Sung et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

The neuromuscular impact of symptomatic SMN restoration in a mouse model of spinal muscular atrophy

Arnold

McGovern

Sanchez

et al. 2016

Neurobiology of Disease

Self Cite

View full text Add to dashboard Cite

Background Significant advances in the development of SMN-restoring therapeutics have occurred since 2010 when very effective biological treatments were reported in mouse models of spinal muscular atrophy. As these treatments are applied in human clinical trials, there is pressing need to define quantitative assessments of disease progression, treatment stratification, and therapeutic efficacy. The electrophysiological measures Compound Muscle Action Potential and Motor Unit Number Estimation are reliable measures of nerve function. In both the SMNΔ7 mouse and a pig model of spinal muscular atrophy, early SMN restoration results in preservation of electrophysiological measures. Currently, clinical trials are underway in patients at post-symptomatic stages of disease progression. In this study, we present results from both early and delayed SMN restoration using clinically-relevant measures including electrical impedance myography, compound muscle action potential, and motor unit number estimation to quantify the efficacy and time-sensitivity of SMN-restoring therapy. Methods SMAΔ7 mice were treated via intracerebroventricular injection with antisense oligonucleotides targeting ISS-N1 to increase SMN protein from the SMN2 gene on postnatal day 2, 4, or 6 and compared with sham-treated spinal muscular atrophy and control mice. Compound muscle action potential and motor unit number estimation of the triceps surae muscles were performed at day 12, 21, and 30 by a single evaluator blinded to genotype and treatment. Similarly, electrical impedance myography was measured on the biceps femoris muscle at 12 days for comparison. Results Electrophysiological measures and electrical impedance myography detected significant differences at 12 days between control and late-treated (4 or 6 days) and sham-treated spinal muscular atrophy mice, but not in mice treated at 2 days(p<0.01). EIM findings paralleled and correlated with compound muscle action potential and motor unit number estimation (r=0.61 and r=0.50, respectively, p<0.01). Longitudinal measures at 21 and 30 days show that symptomatic therapy results in reduced motor unit number estimation associated with delayed normalization of compound muscle action potential. Conclusions The incomplete effect of symptomatic treatment is accurately identified by both electrophysiological measures and electrical impedance myography. There is strong correlation between these measures and with weight and righting reflex. This study predicts that measures of compound muscle action potential, motor unit number estimation, and electrical impedance myography are promising biomarkers of treatment stratification and effect for future spinal muscular atrophy trials. The ease of application and simplicity of electrical impedance myography compared with standard electrophysiological measures may be particularly valuable in future pediatric clinical trials.

show abstract

“…One study showed consistent and significant differences in 50 kHz phase reactance and resistance values between wild-type and mdx mice [8]. In this animal model, EIM values also correlated to muscle fiber size, the amount of connective tissue deposition [8], and also to T2 signal on magnetic resonance imaging (MRI) [92]. EIM has also shown sensitivity to the impact of myostatin inhibition in both wildtype and mdx mice [93].…”

Section: Duchenne Muscular Dystrophymentioning

confidence: 86%

Electrical Impedance Myography and Its Applications in Neuromuscular Disorders

2017

Self Cite

View full text Add to dashboard Cite

Electrical impedance myography (EIM) refers to the specific application of electrical bioimpedance techniques for the assessment of neuromuscular disorders. In EIM, a weak, high-frequency electrical current is applied to a muscle or muscle group of interest and the resulting voltages measured. Among its advantages, the technique can be used noninvasively across a variety of disorders and requires limited subject cooperation and evaluator training to obtain accurate and repeatable data. Studies in both animals and human subjects support its potential utility as a primary diagnostic tool, as well as a biomarker for clinical trial or individual patient use. This review begins by providing an overview of the current state and technological advances in electrical impedance myography and its specific application to the study of muscle. We then provide a summary of the clinical and preclinical applications of EIM for neuromuscular conditions, and conclude with an evaluation of ongoing research efforts and future developments.

show abstract

Assessment OF aged mdx mice by electrical impedance myography and magnetic resonance imaging

Abstract: Given the low cost of EIM and the simplicity of application, it may be a valuable alternative to muscle MRI in Duchenne muscular dystrophy, where simple cumulative indices of muscle health are being sought.

Cited by 19 publications

References 29 publications

Non-invasive evaluation of muscle disease in the canine model of Duchenne muscular dystrophy by electrical impedance myography

Non-invasive evaluation of muscle disease in the canine model of Duchenne muscular dystrophy by electrical impedance myography

The neuromuscular impact of symptomatic SMN restoration in a mouse model of spinal muscular atrophy

Electrical Impedance Myography and Its Applications in Neuromuscular Disorders

Contact Info

Product

Resources

About