Dataset Information

Estimating Myofiber Size With Electrical Impedance Myography: a Study In Amyotrophic Lateral Sclerosis MICE.

ABSTRACT:

Introduction

A method for quantifying myofiber size noninvasively would find wide use, including primary diagnosis and evaluating response to therapy.

Methods

Using prediction algorithms, including the least absolute shrinkage and selection operator, we applied multifrequency electrical impedance myography (EIM) to amyotrophic lateral sclerosis superoxide dismutase 1 G93A mice of different ages and assessed myofiber size histologically.

Results

Multifrequency EIM data provided highly accurate predictions of myofiber size, with a root mean squared error (RMSE) of only 14% in mean myofiber area (corresponding to ± 207 µm² for a mean area of 1,488 µm² ) and an RMSE of only 8.8% in predicting the coefficient of variation in fiber size distribution.

Discussion

This impedance-based approach provides predictive variables to assess myofiber size and distribution with good accuracy, particularly in diseases in which myofiber atrophy is the predominant histological feature, without the requirement for biopsy or burdensome quantification. Muscle Nerve 58: 713-717, 2018.

SUBMITTER: Kapur K

PROVIDER: S-EPMC6246784 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

Estimating Myofiber Size With Electrical Impedance Myography: a Study In Amyotrophic Lateral Sclerosis MICE.

Kapur Kush K Nagy Janice A JA Taylor Rebecca S RS Sanchez Benjamin B Rutkove Seward B SB

Muscle & nerve 20180902 5

<h4>Introduction</h4>A method for quantifying myofiber size noninvasively would find wide use, including primary diagnosis and evaluating response to therapy.<h4>Methods</h4>Using prediction algorithms, including the least absolute shrinkage and selection operator, we applied multifrequency electrical impedance myography (EIM) to amyotrophic lateral sclerosis superoxide dismutase 1 G93A mice of different ages and assessed myofiber size histologically.<h4>Results</h4>Multifrequency EIM data provi ...[more]

PMID: 30175407

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Project description:Loss of muscle mass and strength represents one of the most significant contributors to impaired function in older adults. Convenient and non-invasive biomarkers are needed that can readily identify and track age-related muscle change. Previous data has suggested electrical impedance myography (EIM) has the potential to serve in this capacity. In this study we investigated how changes in EIM compared with other standard measures of muscle structure and function in aged compared with young mice. A total of 19 male mice aged approximately 25 months and 19 male mice aged 3 months underwent surface multifrequency EIM of the right gastrocnemius muscle using standard methods. Fore and hind limb grip strength, sciatic compound muscle action potential amplitude, and in-situ force of the gastrocnemius were also measured; after sacrifice, gastrocnemius myofiber size was assessed using standard histology. Spearman correlation coefficients were calculated to investigate the association between EIM and muscle characteristics. EIM in aged animals demonstrated significantly lower 50 kHz impedance phase (p<0.001) and reactance (p<0.01) values as well as reduced multifrequency parameters. In contrast, absolute gastrocnemius muscle mass was no different between young and aged mice (p = 0.58) but was reduced in aged mice after normalization to body mass (p<0.001). Median myofiber size in the aged mice was not different from that of young mice (p = 0.72). Aged mice showed reduced muscle function on the basis of normalized fore limb (p<0.001) and normalized hind limb (p<0.001) grip strength, as well as normalized gastrocnemius twitch (p<0.001) and normalized maximal isometric force (p<0.001). Sciatic compound muscle action potential amplitude was reduced in aged mice (p<0.05). EIM parameters showed good correlation with reduced standard physiological and electrophysiological measures of muscle health. Our study suggests that EIM is sensitive to aged-related muscle change and may represent a convenient and valuable method of quantifying loss of muscle health.

Project description:BackgroundThe lack of functional dystrophin protein in Duchenne muscular dystrophy (DMD) causes chronic skeletal muscle inflammation and degeneration. Therefore, the restoration of functional dystrophin levels is a fundamental approach for DMD therapy. Electrical impedance myography (EIM) is an emerging tool that provides noninvasive monitoring of muscle conditions and has been suggested as a treatment response biomarker in diverse indications. Although magnetic resonance imaging (MRI) of skeletal muscles has become a standard measurement in clinical trials for DMD, EIM offers distinct advantages, such as portability, user-friendliness, and reduced cost, allowing for remote monitoring of disease progression or response to therapy. To investigate the potential of EIM as a biomarker for DMD, we compared longitudinal EIM data with MRI/histopathological data from an X-linked muscular dystrophy (mdx) mouse model of DMD. In addition, we investigated whether EIM could detect dystrophin-related changes in muscles using antisense-mediated exon skipping in mdx mice.MethodsThe MRI data for muscle T2, the magnetic resonance spectroscopy (MRS) data for fat fraction, and three EIM parameters with histopathology were longitudinally obtained from the hindlimb muscles of wild-type (WT) and mdx mice. In the EIM study, a cell-penetrating peptide (Pip9b2) conjugated antisense phosphorodiamidate morpholino oligomer (PPMO), designed to induce exon-skipping and restore functional dystrophin production, was administered intravenously to mdx mice.ResultsMRI imaging in mdx mice showed higher T2 intensity at 6 weeks of age in hindlimb muscles compared to WT mice, which decreased at ≥ 9 weeks of age. In contrast, EIM reactance began to decline at 12 weeks of age, with peak reduction at 18 weeks of age in mdx mice. This decline was associated with myofiber atrophy and connective tissue infiltration in the skeletal muscles. Repeated dosing of PPMO (10 mg/kg, 4 times every 2 weeks) in mdx mice led to an increase in muscular dystrophin protein and reversed the decrease in EIM reactance.ConclusionsThese findings suggest that muscle T2 MRI is sensitive to the early inflammatory response associated with dystrophin deficiency, whereas EIM provides a valuable biomarker for the noninvasive monitoring of subsequent changes in skeletal muscle composition. Furthermore, EIM reactance has the potential to monitor dystrophin-deficient muscle abnormalities and their recovery in response to antisense-mediated exon skipping.

Dataset Information

Estimating Myofiber Size With Electrical Impedance Myography: a Study In Amyotrophic Lateral Sclerosis MICE.

Introduction

Methods

Results

Discussion

Publications

Estimating Myofiber Size With Electrical Impedance Myography: a Study In Amyotrophic Lateral Sclerosis MICE.

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