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

Abstract

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.

Fibrogenesis in LAMA2-Related Muscular Dystrophy Is a Central Tenet of Disease Etiology

“…Electrical impedance myography is another method for measuring intrinsic muscle properties and has been utilized as a pre-clinical and clinical non-invasive biomarker in numerous settings of muscle disease. Hakim et al (2017) showed that EIM was able to measure significant difference in EIM parameters in DMD canines that significantly correlated with fibrotic build-up in the measured muscles. EIM has also been utilized in multiple clinical settings in FSHD (Rutkove et al, 2007;Mul et al, 2018), ALS (Rutkove et al, 2007, and DMD where it was also shown to be responsive to intervention with corticosteroids.…”

Electrical Impedance Methods in Neuromuscular Assessment: An Overview

“…EIM has also been applied in various animal studies as models of human disease; mice (Li et al 2012), rats (Ahad and Rutkove 2009), and dogs (Hakim et al 2017) have been measured using adhesive electrodes, surface metal electrodes, and needle electrodes. The specifics of which electrode is used depends on the size of the animal, the presence of fur, and the specific questions of interest.…”

Estimating myofiber cross‐sectional area and connective tissue deposition with electrical impedance myography: A study in D2‐mdx mice

“…Previous studies have also investigated relationships between impedance values and cell size and connective tissue deposition. In preclinical studies of the mdx mouse model, 25,46–48 as well as in a canine model of DMD, 49 we demonstrated a significant correlation between EIM values and HP tissue content. However, impedance values have not been used previously to predict morphological features of dystrophic muscle, such as myofiber size or fibrosis.…”