Ronald Aaron

Localized bioimpedance analysis in the evaluation of neuromuscular disease

Localized bioimpedance analysis is a novel, noninvasive technique with potential application to neuromuscular disease. In this procedure, high‐frequency alternating current is passed through muscle, and parameters related to the consequent voltage pattern are evaluated. Currents flowing perpendicular to muscle fibers encounter many more cell membranes than do currents flowing parallel to them, producing surface voltage patterns that are altered by disease. Using this technique, 45 normal subjects and 25 patients with various neuromuscular diseases were studied, including 4 with amyotrophic lateral sclerosis, 4 with inflammatory myopathy, and 11 with inclusion‐body myositis. Two parameters, the spatially averaged phase and the effective longitudinal resistivity, were altered in patients with neuromuscular disease. Reductions in phase correlated to disease progression, whereas normalization of phase correlated with disease remission. In patients with inclusion‐body myositis, a unique pattern of reduced phase and elevated resistivity was identified. These findings suggest that localized bioimpedance analysis has the potential of playing a substantial role in the diagnostic and therapeutic evaluation of neuromuscular disease.

Electrical impedance myography to assess outcome in amyotrophic lateral sclerosis clinical trials

OBJECTIVE Standard outcome measures used for amyotrophic lateral sclerosis (ALS) clinical trials, including the ALS functional rating scale-revised (ALSFRS-R), maximal voluntary isometric contraction testing (MVICT), and manual muscle testing (MMT), are limited in their ability to detect subtle disease progression. Electrical impedance myography (EIM) is a new non-invasive technique that provides quantitative data on muscle health by measuring localized tissue impedance. This study investigates whether EIM could provide a new outcome measure for use in ALS clinical trials work. METHODS Fifteen ALS patients underwent repeated EIM measurements of one or more muscles over a period of up to 18 months and the primary outcome variable, theta(z-max), measured. The theta(z-max) megascore was then calculated using the same approach as has been applied in the past for MVICT. This and the MMT data were then used to assess each measures statistical power to detect a given effect on disease progression in a hypothetical planned clinical therapeutic trial. RESULTS theta(z-max) showed a mean decline of about 21% for the test period, averaged across all patients and all tested muscles. The theta(z-max) megascore had a power of 73% to detect a 10% treatment effect in our planned hypothetical trial, as compared to a 28% power for MMT. These results also compared favorably to historical data for ALSFRS-R and MVICT arm megascore from the trial of celecoxib in ALS, where both measures had only a 23% power to detect the same 10% treatment effect. CONCLUSIONS The theta(z-max) megascore may provide a powerful new outcome measure for ALS clinical trials. SIGNIFICANCE The application of EIM to future ALS trials may allow for smaller, faster studies with an improved ability to detect subtle progression of the disease and treatment effects.

Assessing neuromuscular disease with multifrequency electrical impedance myography

Electrical impedance myography (EIM) is a noninvasive technique for neuromuscular assessment in which low‐intensity alternating current is applied to a muscle and the consequent surface voltage patterns are evaluated. Previous work using a single frequency of 50 kHZ has demonstrated quantitative correlation of EIM parameters with disease status. In this investigation we examined the use of multifrequency EIM, studying a prototypical neurogenic disease (amyotrophic lateral sclerosis, ALS) and myopathic disorder (inflammatory myopathy, IM). Eleven ALS patients, 7 IM patients, and 46 normal subjects participated in the study. Although disease‐specific patterns were not identified such that IM could be differentiated from ALS, impedance vs. frequency patterns for diseased subjects differed substantially from those of the age‐matched normal subjects, with the greatest alterations occurring in the most severe cases. Multifrequency EIM may be well‐suited to serve as an easily applied technique to assess disease severity in a variety of neuromuscular conditions. Muscle Nerve, 2006

Evaluation of boundary element methods for the EEG forward problem: effect of linear interpolation

The authors implement the approach for solving the boundary integral equation for the electroencephalography (EEG) forward problem proposed by de Munck (1992), in which the electric potential varies linearly across each plane triangle of the mesh. Previous solutions have assumed the potential is constant across an element. The authors calculate the electric potential and systematically investigate the effect of different mesh choices and dipole locations by using a three concentric sphere head model for which there is an analytic solution. Implementing the linear interpolation approximation results in errors that are approximately half those of the same mesh when the potential is assumed to be constant, and provides a reliable method for solving the problem.<<ETX>>

Electrical impedance myography in the bedside assessment of inflammatory myopathy

Electrical impedance myography (EIM) is a new technique with potential for the noninvasive bedside assessment of myopathy. EIM was performed on the quadriceps of 10 patients with inflammatory myopathy and 10 normal subjects. The major EIM parameter, the spatially averaged phase, was 35% lower in the myositis patients and correlated with whole-body (r = 0.765, p = 0.01) and quadriceps (r = 0.673, p = 0.03) strength.

Electrical impedance myography in the detection of radiculopathy

Electrical impedance myography (EIM) is a new bioimpedance‐based technique for neuromuscular disease assessment. Past work has focused on EIM in the evaluation of diffuse diseases (such as myopathy). In this study, the methods most basic form, linear‐EIM, was used for the assessment of restricted radiculopathic disease. Ten normal subjects and 10 patients with unilateral cervical or lumbosacral radiculopathy, diagnosed by electromyography and clinical criteria, were enrolled. Linear‐EIM was performed bilaterally on all individuals, and comparisons with the major outcome variable, θavg, were made. In normal subjects, side‐to‐side differences in θavg averaged 0.64% and were no greater than 15.9% in magnitude. In the 10 patients with radiculopathy, θavgwas consistently lower in the affected extremity, with a mean side‐to‐side difference of 15.3%, but ranging as low as 72.3%; there was a tendency for muscles with more prominent chronic neurogenic change to show greater relative reductions in θavg. These findings support the potential utility of EIM in assessment of localized neuromuscular disease. Muscle Nerve, 2005

Effects of age on muscle as measured by electrical impedance myography.

Electrical impedance myography (EIM) is a painless and non-invasive technique for the assessment of muscle which we apply here to the effects of normal aging. The paper presents a cross-sectional analysis of EIM data from the quadriceps and tibialis anterior of 100 healthy subjects (44 men, 56 women, ages 18-90 years). The principal EIM parameter, the spatially averaged phase theta(avg), shows a roughly quadratic reduction with increasing age, declining more steeply beyond 60 years. The correlation was stronger in men (quadriceps: r2 = 0.68 for men, 0.52 for women; tibialis anterior: r2 = 0.74 for men, 0.38 for women; p < 0.001 throughout). Additionally, four subjects (age greater than 75 years) were asked to return for repeat testing several years after their initial assessment. These longitudinal results qualitatively confirm the cross-sectional data, though with greater reductions in theta(avg) at high age. The findings of this study support the potential use of EIM as a simple and effort-independent test of muscle health in the elderly.

Test–retest reproducibility of 50 kHz linear-electrical impedance myography

OBJECTIVE Electrical impedance myography (EIM) is a method for evaluating muscle in which high-frequency, low-intensity alternating current is applied to a body region and the resulting surface voltage pattern over a muscle of interest is measured. In this study, the reproducibility for the simplest of these techniques, 50 kHz linear-EIM, was assessed for three muscles. METHODS Fifty kilohertz linear-EIM was performed on the biceps, quadriceps, and tibialis anterior of 30 normal subjects ranging in age from 21 to 90 years, and the major outcome variable, the spatially averaged phase (thetaavg), measured. The measurements were repeated within 250 days and comparisons between the two data sets made. RESULTS Reproducibility, as measured by the intraclass correlation coefficients for all three muscles, was very high at 0.970, 0.971, and 0.938 for biceps, quadriceps, and tibialis anterior, respectively. Variability between measurements was on average 4.2% for all muscle combined, with an upper limit of 16.8%. CONCLUSIONS Fifty kilohertz linear-EIM demonstrates excellent test-retest reproducibility. SIGNIFICANCE These results support the view that 50 kHz linear-EIM has the potential to be used as a simple, fast, and non-invasive measurement for the assessment of disease status, either as part of individual patient care or as a surrogate outcome measure in clinical trials work.

Multifrequency Electrical Impedance Myography In Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a devastating neuromuscular disease characterized by muscle wasting, generalized weakness, respiratory failure, and eventually death, and there is great need for objective, quantitative methods of assessment of disease progression to assist in the evaluation of potential new treatments. Electrical impedance myography (EIM) is a tetrapolar impedance-based technique that evaluates muscle tissue health through the surface application and measurement of low-intensity, highfrequency current. The simplest form of EIM, measurement of the phase (θ) at 50 kHz, has shown sensitivity to the progression of the disease. Investigation has now been extended to multifrequency measurements covering the 10 to 300 kHz range, via a pilot study involving 10 ALS patients followed for periods up to 2 years. We find that the normal frequency dependences of θ gradually change as the disease progresses: in general θ decreases with increasing disease severity at all frequencies. Notably, the maximum normally observed in the 40-70 kHz range disappear entirely and, in the most advanced cases the slopes of phase curves become positive at the highest frequencies.

Frequency Dependence of Forearm Muscle Impedance During Isometric Gripping Contractions

Earlier Electrical Impedance Myography (EIM) measurements at 50 kHz have shown that muscle resistance (R) and reactance (X) both increase when generating force via isometric contraction. Measurements have now been extended to the 3 to 100 kHz range, allowing interpretation in terms of circuit models for the muscle. R and X data were obtained using a tetrapolar lock-in amplifier system, together with a very low compliance dynamometer to measure gripping force generated by the finger flexors. Six male subjects were asked to generate 10 kg force pulses lasting 8 to 10 seconds, and analysis in terms of a 5-element resistor-capacitor model showed that the extracellular fluid resistance increased by 3.9±1.4%, while the membrane capacitance increased by 5.6±2%. To study time dependences, five were asked to generate 100 second long, 5 to 17.5 kg pulses. R and X were found to drift monotonically at frequency dependent rates, and similar analysis showed that this was attributable almost entirely to cell membrane and intracellular effects, the extracellular fluid playing virtually no role. Fractional rates of change for the remaining circuit parameters were roughly proportional to pulse strength and roughly same for all five subjects.