Circuit modeling of the electrical impedance: I. Neuromuscular disease.

Multifrequency electrical impedance myography (MFEIM) in the 3-300 kHz range was applied to 68 subjects representing 19 different neuromuscular diseases, and the impedances analyzed using the 5-element circuit model. Depending on severity, the 'cellular' parameters r(2), r(3), 1/c(1) and 1/c(2) were found to be as much as 10- to 20-fold larger than for normal subjects (taking age and girth into account), but in almost every case the extracellular fluid parameter r(1) was at most only marginally affected. Strong correlations are found between r(2) and 1/c(1,) but in the case of ALS that breaks down when c(1) (representing the muscle fiber membrane capacitance) falls below half the normal value. Also, c(2) (tentatively associated with intracellular organelle membranes) was found to be the most sensitive to disease progress in ALS, about three times more so than the 50 kHz phase, already suggested for use in clinical drug testing. We conclude that following parameters obtained using the combined MFEIM/5-element circuit analysis scheme offer a reliable, non-invasive and objective way of characterizing muscle in neuromuscular disease or during clinical drug testing.