Discriminating neurogenic from myopathic disease via measurement of muscle anisotropy.

Electrical impedance myography (EIM) is a non-invasive method of muscle evaluation that relies on application of high-frequency, low-intensity alternating electrical current to a limb and measurement of the consequent surface voltages over a muscle or muscle group of interest.10,13 Abnormalities in muscle fiber structure and muscle membrane health are reflected in the impedance changes measured in this way.5,10,15 The major parameters measured include resistance (R) and reactance (X), and, from these, the phase (θ) of the tissue can be calculated. Although R and X are both potentially valuable variables in their own right, the phase tends to help account for size and shape effects and has thus been the focus of much of our EIM work to date. Indeed, phase declines in both localized and generalized neuromuscular disorders and has the potential to serve as a new approach for assessing disease severity. 5,10,11,15 EIM measurements are influenced by two distinct aspects of electrical conduction of muscle: (1) the properties of individual fibers, in particular via the capacitance of their membranes; and (2) the high degree of columnar order in the arrangement of the fibers. Indeed, the tightly bundled fiber structure of muscle confers an important additional feature accessible to EIM: the characteristic that the ease of electrical current flow varies according to its angle relative to the muscle fibers.1,2,4,8 This directional dependence of the impedance to current flow, termed anisotropy, impacts the three major EIM variables, X, R, and θ. Whereas the electrical anisotropy of muscle has been appreciated for decades, to our knowledge its potential measurement in the assessment of neuromuscular disorders has only recently been considered.3 Both muscle and nerve disorders might be expected to produce substantially different effects. The columnar structure is more disrupted in myopathic states, in contrast to a relative preservation of structure in neurogenic states. In principal then, direct measurement of anisotropy has the potential to become a new tool for assessment of neuromuscular disease. We recently studied the anisotropy of the tibialis anterior muscle in a group of normal subjects and demonstrated that, for current flow parallel and perpendicular to the major muscle fiber direction, clear anisotropy could be identified at a variety of frequencies. Certain electrode sizes and ratios were most sensitive to this parameter.3 However, in order to make the technique more powerful and accurate for clinical use, it will likely be necessary to assess a variety of intermediate angles, because small inconsistencies in electrode position with muscle fiber alignment may lead to inaccuracies in the measured anisotropy. Thus, here we examine the anisotropic characteristics of the biceps brachii and tibialis anterior muscles in 15 normal subjects, at multiple angles relative to the major muscle fiber direction. In addition, 12 individuals with established neuro-muscular disease, 6 with amyotrophic lateral sclerosis (ALS) and 6 with myopathy, were also studied to assess the potential for anisotropy measurements to provide diagnostic information.