Electrical impedance myography captures features of muscle structure measured by MRI and transcriptomic analysis in facioscapulohumeral muscular dystrophy.

Background: Electrical impedance myography (EIM) has been proposed as an efficient, non-invasive biomarker of muscle composition in facioscapulohumeral muscular dystrophy (FSHD).

Objective: We investigate whether EIM parameters are associated with muscle structure measured by magnetic resonance imaging (MRI), muscle histology, and transcriptomic analysis as well as strength at the individual leg muscle level.

Methods: We performed a multi-center cross-sectional study enrolling 33 patients with FSHD. EIM measurements were recorded from bilateral vastus lateralis, tibialis anterior (TA), and medial gastrocnemius muscles and compared to quantitative muscle volume measures by MRI as well as knee extension and ankle dorsiflexion strength by quantitative muscle testing. EIM measurements of the bilateral TA were further compared to histology and transcriptomic analysis (RNAseq) of muscle and fat content.

Results: EIM phase at multiple frequencies was positively associated to the amount of muscle measured by MRI (ρ = 0.48 to 0.70, p $\le$ 0.001) and negatively associated to the amount of fat replacement of muscle (ρ = -0.53 to -0.73, p $\le$ 0.001). EIM phase of the vastus lateralis and TA was positively associated with knee extension and ankle dorsiflexion strength normalized to age and sex (ρ = 0.45 to 0.60, p < 0.0001). The bilateral TA muscles were analyzed at the histopathological and molecular (transcriptomic) levels and showed that EIM phase was positively associated with amount of muscle (ρ = 0.33 to 0.35, p < .01) and negatively associated with amount of fat (ρ = -0.36 to -0.56, p < .001) by transcriptomic analysis.

Conclusions: This study supports the hypothesis that the amount and quality of muscle tissue as assessed by EIM is associated with the amount and quality of muscle tissues as assessed by MRI and muscle biopsy, with all measures ultimately being strongly associated with muscle strength. These data provide further convergent validity for the use of EIM as a potential non-invasive biomarker to assess muscle health in FSHD.