Publications by authors named "Ronald Aaron"

8 Publications

  • Page 1 of 1

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

Clin Neurophysiol 2007 Nov 25;118(11):2413-8. Epub 2007 Sep 25.

Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

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 measure's 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.
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November 2007

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

Physiol Meas 2006 Oct 25;27(10):953-9. Epub 2006 Jul 25.

Department of Physics, Northeastern University, Boston, MA 02215, USA.

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.
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October 2006

Assessing neuromuscular disease with multifrequency electrical impedance myography.

Muscle Nerve 2006 Nov;34(5):595-602

Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, TCC-810, Boston, Massachusetts 02215, USA.

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.
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November 2006

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

Clin Neurophysiol 2006 Jun 27;117(6):1244-8. Epub 2006 Apr 27.

Division of Neuromuscular Diseases, Department of Neurology, Harvard Medical School, Beth Israel Deaconess Medical Center, 330 Brookline Ave, TCC 810, Boston, MA 02215, USA.

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.
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June 2006

Electrical impedance myography in the detection of radiculopathy.

Muscle Nerve 2005 Sep;32(3):335-41

Department of Neurology, Division of Neuromuscular Diseases, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.

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 method's 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, theta(avg), were made. In normal subjects, side-to-side differences in theta(avg) averaged 0.64% and were no greater than 15.9% in magnitude. In the 10 patients with radiculopathy, theta(avg)was 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 theta(avg). These findings support the potential utility of EIM in assessment of localized neuromuscular disease.
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September 2005

Electrode position and size in electrical impedance myography.

Clin Neurophysiol 2005 Feb;116(2):290-9

The Department of Neurology, Division of Neuromuscular Diseases, Harvard Medical School, Beth Israel Deaconess Medical Center and the Department of Physics, Northeastern University, Boston, MA 02215, USA.

Objective: Linear-electrical impedance myography (EIM) is a non-invasive technique for the evaluation of muscle, in which high-frequency alternating current is injected into the body via two surface electrodes, and the resulting voltage pattern over a selected muscle is measured using a second, larger set of electrodes. The precise location and size of the electrodes can be critical to the data obtained, and in this study the effects of variation in these factors were evaluated.

Methods: Linear-EIM was performed in 5 subjects while varying the location of the current injecting electrodes and in an additional 8 subjects while varying the position of the voltage electrodes.

Results: The major outcome variable, the 'spatially averaged phase' (theta(avg)), decreased as the ipsilateral current injecting electrode was moved farther from the voltage electrodes, reaching a plateau 15-20 cm distant. As for the voltage electrode array, distal-proximal shifts resulted in the greatest changes, with variation in theta(avg) being as high as 14% per cm; circumferential shifts around the limb had more modest effects.

Conclusions: Linear-EIM results depend systematically on current and voltage electrode positions, but with reasonable care variation can be minimized.

Significance: With proper attention to electrode placement, linear-EIM has sufficient reproducibility to become an important clinical tool in neuromuscular disease evaluation.
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February 2005

Electrical impedance of muscle during isometric contraction.

Physiol Meas 2003 Feb;24(1):213-34

Physics Department, Northeastern University, Boston, MA 02115, USA.

Non-invasive measurements of the 50 kHz impedance of the anterior forearm show that the resistance and reactance increase under voluntary isometric contraction of the finger flexor muscles. The relationship between impedance and force is nonlinear, dependent on the type of test, the history of prior exercise, and the health status of the subject. Nevertheless, useful dynamic response parameters betaR = deltaR/R0deltaF and betax = deltaX/X0deltaF can be defined, typically a few hundredths of a per cent per newton. Evidence is presented for the view that these effects reflect dominantly physiological as opposed to morphological changes in the muscle. In particular, (a) the impedance changes many milliseconds before the force is generated, (b) betaR and betaX change substantially during a series of repetitions of the same exercise, and (c) the impedance does not return to its original value following relaxation of the muscle. Supporting data are presented for six healthy men and women, with ages ranging from 19 to 70 years. A preliminary study of patients with various neuromuscular diseases was also performed, amongst whom marked quantitative and qualitative contrasts with the healthy group were found. Further research aimed at assessing the clinical potential of such measurements is discussed, as are studies to elucidate the underlying mechanisms for the impedance changes. We propose the name 'dynamic electrical impedance myography' for this new technique.
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February 2003

Localized bioimpedance analysis in the evaluation of neuromuscular disease.

Muscle Nerve 2002 Mar;25(3):390-7

Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, TCC-810, Boston, Massachusetts 02215, USA.

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.
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March 2002