Electrical impedance myography: MRI‐like data without the need for MRI

Assessing disease progression and the therapeutic efficacy of potential interventions in primary muscle disease has been undergoing a slow transformation over the past 20 years. Whereas clinical measures, such as the 6-minute walk test or quantitative muscle strength testing, remain important outcomes, there has been increased interest in identifying tools or biomarkers that can provide quantitative assessment of muscle condition and that do not rely on a patient's level of motivation or effort. Such measures may also have the potential of identifying changes presymptomatically and may be sensitive to smaller but meaningful treatment effects. Several modalities may be of value, including dual-energy X-ray absorptiometry, quantitative ultrasound techniques, and computerized tomography. However, magnetic resonance imaging (MRI) has evolved to be the measure of greatest interest. MRI's noninvasive nature, remarkably detailed images of muscle, the absence of ionizing radiation, and its generally wide availability have led to its use in a variety of muscle diseases, including muscular dystrophies, congenital myopathies, and myositis. Changes in T1 values and fat fraction, using the Dixon technique, show great promise, being sensitive to even modest progression over time. MRI's potential value in the assessment of facioscapulohumeral muscular dystrophy (FSHD) is no exception. In fact, given the variability of affected muscles across individuals in this disease, having a tool that can quantify the condition of a specific, tailored group of muscles in any one person over time may be especially helpful when evaluating for potential therapeutic effects. MRI does have challenges, however. It usually entails the patient being studied at a radiology suite separate from where clinical care is provided, requires the subject to lie flat (not always possible in some diseases due to spinal deformity or associated pulmonary dysfunction), necessitates complex imaging processing, and ultimately demands detailed image analysis that can be time-consuming and subject to bias and error. One simpler and possibly more efficient technology that could provide analogous information on muscle composition with application in FSHD is electrical impedance myography (EIM). In EIM, a weak high multifrequency electrical current is passed between an outer pair of surface electrodes and resulting voltages are measured with a second inner pair of electrodes. From these voltages, three parameters, the reactance, resistance, and phase angle, are obtained. Alterations in the underlying composition and structure of the underlying muscle caused by progressive disease impact the resulting surface voltages. Resistance, a measure of the difficulty of passing an electrical current through a tissue, provides a simple measure of water content, with fatty replacement leading to higher values. Reactance, a measure of the capacitive nature of the myofibers, decreases in value with worsening disease severity. The phase angle (a proportion of these two values) will generally decrease with worsening disease status. Previous work in other muscle disorders has demonstrated significant differences in these values between healthy and diseased muscles and also the potential for sensitivity to progression and drug effect (most notably corticosteroids in Duchenne muscular dystrophy). Indeed, strong relationships have been identified in animals between muscle composition and EIM values, including the degree of fibrosis in dystrophin-deficient mouse muscle. EIM has also been correlated with MRI T2 abnormalities in the mdx mouse. Thus, both MRI and EIM are sensitive to compositional and structure changes in chronic muscle disease—namely loss of myofibers and fatty and fibrotic replacement. Yet, until now, the nature of EIM's alteration in disease has not been compared with MRI in humans. In this issue, Hamel et al performed a small study, which included 20 patients with genetically confirmed FSHD1 and compared the T1 and fat fraction (FF) values in bilateral vastus lateralis, tibialis anterior, and gastrocnemius with EIM data also obtained from these muscles. The authors were also interested in evaluating the degree to which the subcutaneous fat overlying the muscles influenced the data, as this is expected to impact EIM values to some extent. Their results are promising and consistent with other investigations that have sought to better understand the nature of EIM change in neuromuscular disease. They found that the 50-kHz reactance is sensitive to muscle composition, with correlation coefficients of −0.71 and − 0.74 for T1 signal and FF, respectively (P < .001 for both) and that the values are not significantly impacted by subcutaneous fat thickness (eg, R = 0.23, P = 0.33). Reactance and phase values correlated inconsistently with FF, T1 signal, as well as functional measures (only 100-kHz phase). Resistance values, in contrast, were strongly associated with subcutaneous fat thickness. Ultimately, the authors concluded that EIM reactance data may be a meaningful biomarker for future clinical trials in FSHD and that EIM deserves further attention and study. Their study was completed in a rigorous manner, with correction for multiple comparisons to ensure that significant findings were not overstated. Moreover, the results are generally consistent with Received: 1 February 2020 Revised: 3 February 2020 Accepted: 9 February 2020