Electrical Impedance Myography Measurements Research Articles

Comparison of Circular and Rectangular-Shaped Electrodes for Electrical Impedance Myography Measurements on Human Upper Arms.

Electrical Impedance Myography (EIM) is a painless, noninvasive approach for assessing muscle conditions through the application of a high-frequency, low-intensity current to the muscle region of interest. However, besides muscle properties, EIM measurements vary significantly with changes in some other anatomical properties such as subcutaneous skin-fat (SF) thickness and muscle girth, as well as non-anatomical factors, such as ambient temperature, electrode shape, inter-electrode distance, etc. This study has been conducted to compare the effects of different electrode shapes in EIM experiments, and to propose an acceptable configuration that is less dependent on factors other than the cellular properties of the muscle. Initially, a finite element model with two different kinds of electrode shapes, namely, rectangular (the conventional shape) and circular (the proposed shape) was designed for a subcutaneous fat thickness ranging from 5 mm to 25 mm. The study concludes, based on the FEM study, that replacing the conventional electrodes with our proposed electrodes can decrease the variation in EIM parameters due to changes in skin-fat thickness by 31.92%. EIM experiments on human subjects with these two kinds of electrode shapes validate our finite element simulation results, and show that circular electrodes can improve EIM effectiveness significantly, irrespective of muscle shape variation.

Electrical impedance myography detects age-related skeletal muscle atrophy in adult zebrafish

Age-related deficits in skeletal muscle function, termed sarcopenia, are due to loss of muscle mass and changes in the intrinsic mechanisms underlying contraction. Sarcopenia is associated with falls, functional decline, and mortality. Electrical impedance myography (EIM)—a minimally invasive, rapid electrophysiological tool—can be applied to animals and humans to monitor muscle health, thereby serving as a biomarker in both preclinical and clinical studies. EIM has been successfully employed in several species; however, the application of EIM to the assessment of zebrafish—a model organism amenable to high-throughput experimentation—has not been reported. Here, we demonstrated differences in EIM measures between the skeletal muscles of young (6 months of age) and aged (33 months of age) zebrafish. For example, EIM phase angle and reactance at 2 kHz showed significantly decreased phase angle (5.3 ± 2.1 versus 10.7 ± 1.5°; p = 0.001) and reactance (89.0 ± 3.9 versus 172.2 ± 54.8 ohms; p = 0.007) in aged versus young animals. Total muscle area, in addition to other morphometric features, was also strongly correlated to EIM 2 kHz phase angle across both groups (r = 0.7133, p = 0.01). Moreover, there was a strong correlation between 2 kHz phase angle and established metrics of zebrafish swimming performance, including turn angle, angular velocity, and lateral motion (r = 0.7253, r = 0.7308, r = 0.7857, respectively, p < 0.01 for all). In addition, the technique was shown to have high reproducibility between repeated measurements with a mean percentage difference of 5.34 ± 1.17% for phase angle. These relationships were also confirmed in a separate replication cohort. Together, these findings establish EIM as a fast, sensitive method for quantifying zebrafish muscle function and quality. Moreover, identifying the abnormalities in the bioelectrical properties of sarcopenic zebrafish provides new opportunities to evaluate potential therapeutics for age-related neuromuscular disorders and to interrogate the disease mechanisms of muscle degeneration.

Electrical impedance myography method of measuring anisotropic tongue tissue

Objective. To date, measurement of the conductivity and relative permittivity properties of anisotropic biological tissues using electrical impedance myography (EIM) has only been possible through an invasive ex vivo biopsy procedure. Here, we present a novel forward and inverse theoretical modeling framework to estimate these properties combining surface and needle EIM measurements. Methods. The framework here presented models the electrical potential distribution within a monodomain, homogeneous, and three-dimensional anisotropic tissue. Finite-element method (FEM) simulations and tongue experimental results verify the validity of our method to reverse-engineer three-dimensional conductivity and relative permittivity properties from EIM measurements. Results. FEM-based simulations confirm the validity of our analytical framework, with relative errors between analytical predictions and simulations smaller than 0.12% and 2.6% in a cuboid and tongue model, respectively. Experimental results confirm qualitative differences in the conductivity and the relative permittivity properties in the x, y, and z directions. Conclusion. Our methodology enables EIM technology to reverse-engineer the anisotropic tongue tissue conductivity and relative permittivity properties, thus unfolding full forward and inverse EIM predictability capabilities. Significance. This new method of evaluating anisotropic tongue tissue will lead to a deeper understanding of the role of biology necessary for the development of new EIM tools and approaches for tongue health measurement and monitoring.

Electrical Impedance Myography Correlates with Functional Measures of Disease Progression in D2-mdx Mice and Boys with Duchenne Muscular Dystrophy.

Sensitive, objective, and longitudinal outcome measures applicable to both pre-clinical and clinical interventions are needed to assess muscle health in Duchenne muscular dystrophy (DMD). Electrical impedance myography (EIM) has the potential to non-invasively measure disease progression in mice and boys with DMD. We sought to evaluate how electrical impedance values (i.e., phase, reactance, and resistance) correlate to established measures of disease in both D2-mdx and wild type (WT) mice and boys with and without DMD. Histological, functional, and EIM data collected from previous studies of WT and D2-mdx mice at 6, 13, 21 and 43 weeks of age were reanalyzed. In parallel, previously collected functional outcome measures and EIM values were reanalyzed from boys with and without DMD at four different age groups from 2 to 14 years old. In mice, disease progression as detected by histological, functional, and EIM measures, was appreciable over this time period and grip strength best correlated to longitudinal phase and reactance impedance values. In boys, disease progression quantified through commonly utilized functional outcome measures was significant and longitudinal phase demonstrated the strongest correlation with functional outcome measures. Similar changes in EIM values, specifically in longitudinal reactance and phase, were found to show significant correlations to functional measures in both mice and boys. Thus, EIM demonstrates applicability in both pre-clinical and clinical settings and can be used as a safe, non-invasive, and longitudinal proxy biomarker to assess muscle health in DMD.

Performing In Vivo and Ex Vivo Electrical Impedance Myography in Rodents.

Electrical impedance myography (EIM) is a convenient technique that can be used in preclinical and clinical studies to assess muscle tissue health and disease. EIM is obtained by applying a low-intensity, directionally focused, electrical current to a muscle of interest across a range of frequencies (i.e., from 1 kHz to 10 MHz) and recording the resulting voltages. From these, several standard impedance components, including the reactance, resistance, and phase, are obtained. When performing ex vivo measurements on excised muscle, the inherent passive electrical properties of the tissue, namely the conductivity and relative permittivity, can also be calculated. EIM has been used extensively in animals and humans to diagnose and track muscle alterations in a variety of diseases, in relation to simple disuse atrophy, or as a measure of therapeutic intervention. Clinically, EIM offers the potential to track disease progression over time and to assess the impact of therapeutic interventions, thus offering the opportunity to shorten the clinical trial duration and reduce sample size requirements. Because it can be performed noninvasively or minimally invasively in living animal models as well as humans, EIM offers the potential to serve as a novel translational tool enabling both preclinical and clinical development. This article provides step-by-step instructions on how to perform in vivo and ex vivo EIM measurements in mice and rats, including approaches to adapt the techniques to specific conditions, such as for use in pups or obese animals.

Modeling and simulation of needle electrical impedance myography in nonhomogeneous isotropic skeletal muscle.

Needle electrical impedance myography (EIM) is a recently developed technique for neuromuscular evaluation. Despite its preliminary successful clinical application, further understanding is needed to aid interpreting EIM outcomes in nonhomogeneous skeletal muscle measurements. The framework presented models needle EIM measurements in a bidomain isotropic model. Finite element method (FEM) simulations verify the validity of our model predictions studying two cases: a spherical volume surrounded by tissue and a two-layered tissue. Our models show that EIM is influenced by the vicinity of tissue with different electrical properties. The apparent resistance, reactance and phase relative errors between our theoretical predictions and FEM simulations in the spherical volume case study are ≤0.2%, ≤1.2% and ≤1.0%, respectively. For the two-layered tissue model case study, the relative errors are ≤2%. We propose a bio-physics driven analytical framework describing needle EIM measurements in a nonhomogeneous bidomain tissue model. Our theoretical predictions may lead to new ways for interpreting needle EIM data in neuromuscular diseases that cause compositional changes in muscle content, e.g. connective tissue deposition within the muscle. These changes will manifest themselves by changing the electric properties of the conductor media and will impact impedance values.

A Finite Element Analysis and Circuit Modelling Methodology for Studying Electrical Impedance Myography of Human Limbs.

Electrical impedance myography (EIM) measures bioimpedance over muscles. This paper proposes a circuit-based modelling methodology originated from finite element analysis (FEA), to emulate tissues and effects from anthropometric variations, and electrode placements, on EIM measurements. The proposed methodology is demonstrated on the upper arms and lower legs. FEA evaluates impedance spectra (Z-parameters), sensitivity, and volume impedance density for variations of subcutaneous fat thickness (t f), muscle thickness (t m), and inter-electrode distance (IED), on limb models over 1Hz-1 MHz frequency range. The limbs' models are based on simplified anatomical data and dielectric properties from published sources. Contributions of tissues to the total impedance are computed from impedance sensitivity and density. FEA Z-parameters are imported into a circuit design environment, and used to develop a three Cole dispersion circuit-based model. FEA and circuit model simulation results are compared with measurements on ten human subjects. Muscle contributions are maximized at 31.25 kHz and 62.5 kHz for the upper arm and lower leg, respectively, at 4 cm IED. The circuit model emulates variations in t f and t m, and simulates up to 89 times faster than FEA. The circuit model matches subjects measurements with RMS errors and , while FEA does with and . We demonstrate that FEA is able to estimate the optimal frequencies and electrode placements, and circuit-based modelling can accurately emulate the limbs' bioimpedance. The proposed methodology facilitates studying the impact of biophysical principles on EIM, enabling the development of future EIM acquisition systems.

Interrater and Intrarater Reliability of Electrical Impedance Myography: A Comparison between Large and Small Handheld Electrode Arrays.

The objective of this study was to evaluate the interrater and intrarater reliability of electrical impedance myography (EIM) using handheld sensors of different sizes. Electrical impedance myography of the biceps brachii muscle of twenty healthy individuals was performed by two raters using both large and small sensors. The procedures were also repeated 5 to 8 days after the first recording session. The repeatability of the resistance, reactance, and phase angle at two different current frequencies (50 and 100 kHz) was assessed by the intraclass correlation coefficient (ICC). The ICCs of the large sensor were higher than those of the small sensor for both the intrarater and interrater reliabilities. High-frequency current tended to improve the ICC for the small sensor. These results indicate reasonable repeatability of the handheld electrode arrays for EIM measurements. The findings suggest that electrode array should be selected appropriately according to the size of the tested muscle.

Relationships between in vivo surface and ex vivo electrical impedance myography measurements in three different neuromuscular disorder mouse models.

Electrical impedance myography (EIM) using surface techniques has shown promise as a means of diagnosing and tracking disorders affecting muscle and assessing treatment efficacy. However, the relationship between such surface-obtained impedance values and pure muscle impedance values has not been established. Here we studied three groups of diseased and wild-type (WT) animals, including a Duchenne muscular dystrophy model (the D2-mdx mouse), an amyotrophic lateral sclerosis (ALS) model (the SOD1 G93A mouse), and a model of fat-related atrophy (the db/db diabetic obese mouse), performing hind limb measurements using a standard surface array and ex vivo measurements on freshly excised gastrocnemius muscle. A total of 101 animals (23 D2-mdx, 43 ALS mice, 12 db/db mice, and corresponding 30 WT mice) were studied with EIM across a frequency range of 8 kHz to 1 MHz. For both D2-mdx and ALS models, moderate strength correlations (Spearman rho values generally ranging from 0.3–0.7, depending on the impedance parameter (i.e., resistance, reactance and phase) were obtained. In these groups of animals, there was an offset in frequency with impedance values obtained at higher surface frequencies correlating more strongly to impedance values obtained at lower ex vivo frequencies. For the db/db model, correlations were comparatively weaker and strongest at very high and very low frequencies. When combining impedance data from all three disease models together, moderate correlations persisted (with maximal Spearman rho values of 0.45). These data support that surface EIM data reflect ex vivo muscle tissue EIM values to a moderate degree across several different diseases, with the highest correlations occurring in the 10–200 kHz frequency range. Understanding these relationships will prove useful for future applications of the technique of EIM in the assessment of neuromuscular disorders.

Invasive electrical impedance myography at different levels of contraction of gastrocnemius muscle of rat.

Electrical impedance myography (EIM) is as an experimental technique that associates muscle impedance with muscular activity. Changes in muscle impedance during contraction occur mainly due to changes in the morphological and physiological characteristics of muscles that lead to different impeditivities in comparison with the resting condition. There is no consensus on the details of muscular impedance during muscle activity. EIM measurements on humans are also influenced by factors such as the electrode-skin interface, layers of skin and fat, and the connective tissue that can generate undesirable effects in the impedance signal. These effects can be avoided if EIM measurements are carried out directly on the muscle by using the models of animals. This study investigates changes in the EIM signal in the gastrocnemius muscles of Wistar rats during different levels of muscular contraction. In vivo experiments were conducted on 19 male rats. The muscle was exposed, fixed on a load cell, and electrically stimulated to evoke different levels of muscle contraction. Signals of the components of impedance were analyzed against the muscular force signal. The results show moderate correlations (p < 0.05) among the impedance-related parameters of resistance (r = -0.76), reactance (r = 0.57), and phase (r = 0.53). In addition to providing an experimental protocol for the invasive collection of data on electrical impedance to minimize problems associated with surface electrodes, this study shows that of the components of impedance, resistance is most affected by the intensity of muscular contractions and that morphological changes influence impedance mainly at low intensities.

Magnetic resonance imaging correlates with electrical impedance myography in facioscapulohumeral muscular dystrophy.

Electrical impedance myography (EIM) has been proposed as a noninvasive biomarker of muscle composition in facioscapulohumeral muscular dystrophy (FSHD). Here we determine the associations of EIM variables with muscle structure measured by MRI. We evaluated 20 patients with FSHD at two centers, comparing EIM measurements (resistance, reactance, and phase at 50, 100, and 211 kHZ) recorded from bilateral vastus lateralis, tibialis anterior, and medial gastrocnemius muscles to MRI skin and subcutaneous fat thickness, MRI T1-based muscle severity score (T1 muscle score), and MRI quantitative intramuscular Dixon fat fraction (FF). While reactance and phase both correlated with FF and T1 muscle score, 50 kHz reactance was most sensitive to muscle structure alterations measured by both T1 score (ρ = -0.71, P < .001) and FF (ρ = -0.74, P < .001). This study establishes the correlation of EIM with structural MRI features in FSHD and supports further evaluation of EIM as a potential biomarker in FSHD clinical trials.

Electrical impedance myography as a biomarker of inclusion body myositis: A cross-sectional study

ObjectiveTo assess the value of electrical impedance myography (EIM) in inclusion body myositis (IBM). MethodsPatients with clinically defined IBM and healthy controls (HC) of similar age group were recruited. Each participant underwent manual muscle testing (MMT), 6-min walk test (6MWT), handgrip dynamometry, and IBM-functional rating scale assessment (IBM-FRS). EIM measurements were obtained from bilateral deltoid, biceps, forearm-flexors, quadriceps, tibialis anterior, and medial gastrocnemius. ResultsFourteen IBM patients and 12 HCs with mean age 68.6 ± 6 and 67.4 ± 5.4 years were included in the final analysis. Averaged phase value at 50 kHz (EIM50) and ratio of phase value at 50 kHz/200 kHz (EIMPR) from six-muscles were significantly lower in IBM patients when compared to HC (5.23 ± 1.34 vs 7.88 ± 1.9, p-value 0.002, and 0.55 ± 0.09 vs. 0.68 ± 0.09, p-value 0.004, respectively). A strong correlation was noted between IBM-FRS, 6MWT, disease-duration and the averaged value of EIM50 and EIMPR in the IBM patients (Spearman |rho|>0.7, p-values < 0.01). ConclusionsEIM can differentiate between IBM patients and HCs and EIM parameters correlate with clinical outcome measures. SignificanceEIM may be a potential objective biomarker for IBM. A longitudinal validation study is warranted.

Electrical impedance myography for the detection of muscle inflammation induced by λ-carrageenan.

Electrical impedance myography (EIM) is a technique for the assessment of muscle health and composition and has been shown to be sensitive to a variety of muscle pathologies including neurogenic atrophy and connective tissue deposition. However, it has been minimally studied in pure inflammation. In this study, we sought to assess EIM sensitivity to experimental inflammation induced by the localized intramuscular injection of λ-carrageenan. A total of 91 mice underwent 1–1000 kHz EIM measurements of gastrocnemius using a needle array, followed by injection of either 0.3% λ-carrageenan in phosphate-buffered saline (PBS) or PBS alone. Animals were then remeasured with EIM at 4, 24, 48, or 72 hours and euthanized and quantitative assessment of muscle histology was performed. Parallel alterations in both 5 and 50 kHz EIM values were identified at 4 and 24 hours, including reductions in phase, reactance, and resistance. In PBS-treated animals these values normalized by 48 hours, whereas substantial reductions in phase and reactance in 5 kHz EIM values persisted at 48 and 72 hours (i.e., values of phase 72 hours post-injection were 6.51 ± 0.40 degrees for λ-carrageenan versus 8.44 ± 0.35 degrees for PBS p<0.001, n = 11 per group). The degree of basophilic area observed in muscle sections by histology correlated to the degree of phase change at these two time points (Rspearman = -0.51, p = 0.0029). Changes in low frequency EIM parameters are sensitive to the presence of inflammatory infiltrates, and have the potential of serving as a simple means of quantifying the presence and extent of muscle inflammation without the need for biopsy.

Exploring the relationship between electrical impedance myography and quantitative ultrasound parameters in Duchenne muscular dystrophy

ObjectivesQuantitative ultrasound (QUS), including grayscale level analysis (GLA) and quantitative backscatter analysis (QBA), and electrical impedance myography (EIM) have been proposed as biomarkers in Duchenne muscular dystrophy (DMD). However, the relationship between these methods has not been assessed. MethodsQUS values (including GLA and QBA) and several EIM measures were recorded from six muscles in 36 DMD and 29 healthy boys between ages 5 and 13 years at baseline, 6-months, and 12-months. ResultsIn the DMD boys, a moderate correlation was noted between QUS and EIM parameters, with the strongest correlations being identified for averaged muscle values. Of the individual muscles, biceps brachii and deltoid showed the strongest correlations. For example, in biceps, the QBA/EIM correlation coefficient (Spearman rho) was ≥0.70 (p < 0.01). Importantly, changes in QUS values over 12 months also correlated moderately with changes in EIM parameters and EIM/QBA rho values mostly varied between −0.53 and −0.70 (p ≤ 0.02). No significant correlations were identified in the healthy boys. ConclusionsA moderate correlation of QUS with EIM in DMD boys suggests that the two technologies provide related data but are sensitive to different pathological features of muscle. SignificanceThe use of both technologies jointly in assessing DMD progression and response to therapy should be considered.

Toward Electrical Impedance Tomography Coupled Ultrasound Imaging for Assessing Muscle Health.

This paper establishes for the first time that a coupled ultrasound (US) and electrical impedance tomography (EIT) system can serve as a non-invasive, spatially localized approach to extract clinically relevant muscle properties. The US/EIT system represents a potential enhancement to electrical impedance myography (EIM), which has shown promise as a non-invasive technology that may have important clinical use in indicating neuromuscular disease status and as a diagnostic tool. A 2.5D EIT algorithm evaluated on simulation, measured phantoms, and measured patient data was studied to evaluate US/EIT's ability to distinguish different aspects of muscle tissue. Simulated and phantom experiments revealed the depths of distinguishability of 3.2 and 4.2 mm in simulation for 10% and 20% changes in muscle properties, respectively, and 3.6 mm in measured phantom experiments assuming a 12% muscle conductivity change. Reconstructions from the patient data established that there were consistent differences 1) between longitudinal (along) and transverse (across) muscle conductivity reconstructions at frequencies of 40 and 80 kHz and 2) side-by-side comparison between healthy and diseased tissue in terms of conductivity, permittivity, and phase at 40 and 80 kHz. Comparisons were made between the EIT reconstructed values and electrical impedance spectroscopy (EIS) measurements (an available surrogate in place of standard EIM measurements) made with the US/EIT system, wherein 1) EIS and EIT show similar sensitivity to longitudinal and transverse differences and 2) EIT showed a more consistent ability to differentiate healthy and diseased tissue. These results suggest that US/EIT appears very promising for non-invasive and spatially localized diagnosis of muscle health.

Separation of Subcutaneous Fat From Muscle in Surface Electrical Impedance Myography Measurements Using Model Component Analysis

Electrical impedance myography (EIM) is a relatively new technique to assess neuromuscular disorders (NMD). Although the application of EIM using surface electrodes (sEIM) has been adopted by the neurology community in recent years to evaluate NMD status, sEIM's sensitivity as a biomarker of skeletal muscle condition is impacted by subcutaneous fat (SF) tissue. Here, we develop a method that is able to remove the contribution of SF from sEIM data. We evaluate independent component analysis (ICA) and principal component analysis (PCA) for this purpose. Then, we introduce the so-called model component analysis (MCA). All methods are validated with numerical simulations using impedivity data from SF and muscle tissues. The methods are then tested with measurements performed in diseased individuals ( n=3). Simulations demonstrate that MCA is the most accurate method at separating the impedivity of SF and muscle tissues with the accuracy being 99.2%, followed by ICA with 51.4%, and finally PCA with 38.5%. Experimental results from sEIM data measured on the triceps brachii of patients are consistent with muscle grayscale level values obtained using ultrasound imaging. MCA can be used to separate the impedivity of SF and muscle tissues from sEIM data, thus increasing the sensitivity to detect changes in the muscle. MCA can make the sEIM technique a better diagnostic tool and biomarker of disease progression and response to therapy by removing the confounding effect of SF tissue in NMD patients with excess subcutaneous fat tissue for any reason.

Electrical impedance myography in facioscapulohumeral muscular dystrophy: A 1‐year follow‐up study

Electrical impedance myography (EIM) is a noninvasive technique for measuring muscle composition and a potential physiological biomarker for facioscapulohumeral muscular dystrophy (FSHD). Thirty-two participants with genetically confirmed and clinically affected FSHD underwent EIM in 7 muscles bilaterally. Correlations between EIM and baseline clinical measures were used to select EIM variables of interest in FSHD, and EIM and clinical measures were followed for 1 year. There were no significant changes in the EIM variables. Although 50-kHZ reactance correlated the strongest with clinical measures at baseline, the 50-211-kHZ phase ratio demonstrated lower within-subject 12-month variability, potentially offering sample size savings for FSHD clinical trial planning. EIM did not identify significant disease progression over 12 months. It is currently unclear whether this is because of limitations of the technology or the slow rate of disease progression in this cohort of FSHD patients over this period of time. Muscle Nerve 58: 213-218, 2018.

An investigation of the accuracy and reliability of body composition assessed with a handheld electrical impedance myography device

The purpose of this study was to compare the body fat per cent (BF%) assessed with a unique handheld electrical impedance myography (EIM) device, along with other popular methods, to dual-energy X-ray absorptiometry (DXA). Participants included 33 males (aged 24.3 ± 4.6 years) and 38 females (aged 25.3 ± 8.9 years) who completed 2 visits separated by 24–72 h. The assessments included DXA, bioelectrical impedance analysis (BIA), skinfold measures (SKF), and three separate EIM measurements. No significant differences in BF% (P > 0.05) were found between all EIM assessments when compared against DXA for both males and females for each visit. All methods showed no significant differences in BF% (P > 0.05) between days within themselves. Across both days, the standard error of the estimate (SEE) for the EIM measurements ranged from 2.66% to 3.15%, the SEE for BIA was 2.80 and 2.85, and for SKF was 2.90 and 2.82. The 95% limits of agreement ranged from ±5.34% to ±6.38% for EIM measurements and were highest for SKF (±7.42% and ±7.47%). The total error for both days was largest for SKF (5.20% and 5.35%) and lowest for the EIM measurements (2.48–3.24%). This investigation supports use of a handheld EIM device as an accurate and reliable method of estimating BF% compared to DXA in young, apparently healthy individuals with BF% in the range of 10–22% for males and 20–32% in females and suggests this EIM device be considered a viable alternative to other established field measurements in this population.

Electrical impedance myography for assessment of Duchenne muscular dystrophy.

Sensitive, objective, and easily applied methods for evaluating disease progression and response to therapy are needed for clinical trials in Duchenne muscular dystrophy (DMD). In this study, we evaluated whether electrical impedance myography (EIM) could serve this purpose. In this nonblinded study, 36 boys with DMD and 29 age-similar healthy boys underwent multifrequency EIM measurements for up to 2 years on 6 muscles unilaterally along with functional assessments. A linear mixed-effects model with random intercept and slope terms was used for the analysis of multifrequency EIM values and functional measures. Seven DMD boys were initiated on corticosteroids; these data were analyzed using a piecewise linear mixed-effects model. In boys > 7.0 years old, a significant difference in the slope of EIM phase ratio trajectories in the upper extremity was observed by 6 months of -0.074/month, p = 0.023, 95% confidence interval (CI) = -0.013, -0.14; at 2 years, this difference was -0.048/month, p < 0.0001, 95% CI = -0.028, -0.068. In boys ≤ 7.0 years old, differences appeared at 6 months in gastrocnemius (EIM phase slope = -0.83 °/kHz/mo, p = 0.007, 95% CI = -0.26, -1.40). EIM outcomes showed significant differences earlier than functional tests. Initiation of corticosteroids significantly improved the slope of EIM phase ratio (0.057/mo, p = 0.00019, 95% CI = 0.028, 0.086) and EIM phase slope (0.14 °/kHz/mo, p = 0.013, 95% CI = 0.028, 0.25), consistent with corticosteroids' known clinical benefit. EIM detects deterioration in muscles of both younger and older boys by 6 months; it also identifies the therapeutic effect of corticosteroid initiation. Because EIM is rapid to apply, painless, and requires minimal operator training, the technique deserves to be further evaluated as a biomarker in DMD clinical therapeutic trials. Ann Neurol 2017;81:622-632.

Electrical impedance myography in individuals with collagen 6 and laminin α-2 congenital muscular dystrophy: a cross-sectional and 2-year analysis.

Electrical impedance myography (EIM) is a noninvasive electrophysiological technique that characterizes muscle properties through bioimpedance. We compared EIM measurements to function, strength, and disease severity in a population with congenital muscular dystrophy (CMD). Forty-one patients with CMD, either collagen 6 related disorders (COL6-RD; n = 21) or laminin α-2-related disorders (LAMA2-RD; n = 20), and 21 healthy pediatric controls underwent 2 yearly EIM exams. In the CMD cohorts, EIM was compared with functional and strength measurements. Both CMD cohorts exhibited change over time and had correlation with disease severity. The 50-kHZ phase correlated well with function and strength in the COL6-RD cohort but not in the LAMA2-RD cohort. EIM is a potentially useful measure in clinical studies with CMD because of its sensitivity to change over a 1-year period and correlation with disease severity. For COL6-RD, there were also functional and strength correlations. Muscle Nerve 57: 54-60, 2018.