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  1. Article ; Online: Combining electromyographic and electrical impedance data sets through machine learning: A study in D2-mdx and wild-type mice.

    Pandeya, Sarbesh / Sanchez, Benjamin / Nagy, Janice A / Rutkove, Seward B

    Muscle & nerve

    2023  Volume 68, Issue 5, Page(s) 781–788

    Abstract: Introduction/aims: Needle impedance-electromyography (iEMG) assesses the active and passive electrical properties of muscles concurrently by using a novel needle with six electrodes, two for EMG and four for electrical impedance myography (EIM). Here, ... ...

    Abstract Introduction/aims: Needle impedance-electromyography (iEMG) assesses the active and passive electrical properties of muscles concurrently by using a novel needle with six electrodes, two for EMG and four for electrical impedance myography (EIM). Here, we assessed an approach for combining multifrequency EMG and EIM data via machine learning (ML) to discriminate D2-mdx muscular dystrophy and wild-type (WT) mouse skeletal muscle.
    Methods: iEMG data were obtained from quadriceps of D2-mdx mice, a muscular dystrophy model, and WT animals. EIM data were collected with the animals under deep anesthesia and EMG data collected under light anesthesia, allowing for limited spontaneous movement. Fourier transformation was performed on the EMG data to provide power spectra that were sampled across the frequency range using three different approaches. Random forest-based, nested ML was applied to the EIM and EMG data sets separately and then together to assess healthy versus disease category classification using a nested cross-validation procedure.
    Results: Data from 20 D2-mdx and 20 WT limbs were analyzed. EIM data fared better than EMG data in differentiating healthy from disease mice with 93.1% versus 75.6% accuracy, respectively. Combining EIM and EMG data sets yielded similar performance as EIM data alone with 92.2% accuracy.
    Discussion: We have demonstrated an ML-based approach for combining EIM and EMG data obtained with an iEMG needle. While EIM-EMG in combination fared no better than EIM alone with this data set, the approach used here demonstrates a novel method of combining the two techniques to characterize the full electrical properties of skeletal muscle.
    Language English
    Publishing date 2023-09-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 438353-9
    ISSN 1097-4598 ; 0148-639X
    ISSN (online) 1097-4598
    ISSN 0148-639X
    DOI 10.1002/mus.27963
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Electrical impedance myography for the early detection of muscle ischemia secondary to compartment syndrome: a study in a rat model.

    Lechtig, Aron / Hanna, Philip / Nagy, Janice A / Wixted, John / Nazarian, Ara / Rutkove, Seward B

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 18252

    Abstract: Acute Compartment Syndrome (ACS) is one of the most devastating orthopedic conditions, affecting any of the body's many compartments, which, if sufficiently severe, may result in disability and amputation. Currently, intra-compartmental pressure ... ...

    Abstract Acute Compartment Syndrome (ACS) is one of the most devastating orthopedic conditions, affecting any of the body's many compartments, which, if sufficiently severe, may result in disability and amputation. Currently, intra-compartmental pressure measurements serve as the gold standard for diagnosing ACS. Diagnosing limbs at risk for ACS before irreversible damage to muscle and nerve is critical. Standard approaches for diagnosing impending compartment syndrome include clinical evaluation of the limb, such as assessment for "tightness" of the overlying skin, reduced pulses distally, and degree of pain, none of which are specific or sensitive. We have proposed a novel method to detect ACS via electrical impedance myography (EIM), where a weak, high-frequency alternating current is passed between one pair of electrodes through a region of tissue, and the resulting surface voltages are measured via a second pair. We evaluated the ability of EIM to detect early muscle ischemia in an established murine model of compression-induced muscle injury, where we collected resistance, reactance, and their dimensionless product, defined as Relative Injury Index (RII) during the study. Our model generated reproducible hypoxia, confirmed by Hypoxyprobe™ staining of endothelial regions within the muscle. Under conditions of ischemia, we demonstrated a reproducible, stable, and significant escalation in resistance, reactance, and RII values, compared to uninjured control limbs. These data make a reasonable argument for additional investigations into using EIM for the early recognition of muscle hypoperfusion and ischemia. However, these findings must be considered preliminary steps, requiring further pre-clinical and clinical validation.
    MeSH term(s) Rats ; Mice ; Animals ; Muscle, Skeletal/physiology ; Electric Impedance ; Myography/methods ; Compartment Syndromes/diagnosis ; Compartment Syndromes/etiology ; Ischemia/diagnosis
    Language English
    Publishing date 2023-10-25
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-45209-w
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  3. Article ; Online: Novel phenotype characterization utilizing electrical impedance myography signatures in murine spinal cord injury neurogenic bladder models.

    Wang, Hsin-Hsiao Scott / Thaker, Hatim / Bigger-Allen, Alex / Nagy, Janice A / Rutkove, Seward B

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 19520

    Abstract: Neurogenic bladder (NB) affects people of all ages. Electric impedance myography (EIM) assesses localized muscle abnormalities. Here, we sought to investigate whether unique detrusor EIM signatures are present in NB due to spinal cord injury (SCI). ... ...

    Abstract Neurogenic bladder (NB) affects people of all ages. Electric impedance myography (EIM) assesses localized muscle abnormalities. Here, we sought to investigate whether unique detrusor EIM signatures are present in NB due to spinal cord injury (SCI). Twenty-eight, 8-10 weeks old, C57BL/6J female mice were studied. Twenty underwent spinal cord transection; 8 served as controls. Cohorts were euthanized at 4 and 6 weeks after spinal cord transection. Each bladder was measured in-situ with EIM with applied frequencies of 1 kHz to 10 MHz, and then processed for molecular and histologic study. SCI mice had greater bladder-to-body weight ratio (p < 0.0001), greater collagen deposition (p = 0.009), and greater smooth-muscle-myosin-heavy-chain isoform A/B ratio (p < 0.0001). Compared with the control group, the SCI group was associated with lower phase, reactance, and resistance values (p < 0.01). Significant correlations (p < 0.001) between bladder-to-body weight ratios and EIM measurements were observed across the entire frequency spectrum. A severely hypertrophied phenotype was characterized by even greater bladder-to-body weight ratios and more depressed EIM values. Our study demonstrated distinct EIM alterations in the detrusor muscle of mice with NB due to SCI. With further refinement, EIM may offer a potential point-of-care tool for the assessment of NB and its response to treatment.
    MeSH term(s) Humans ; Mice ; Female ; Animals ; Muscle, Skeletal/physiology ; Electric Impedance ; Urinary Bladder, Neurogenic/etiology ; Mice, Inbred C57BL ; Myography ; Spinal Cord Injuries ; Phenotype ; Body Weight
    Language English
    Publishing date 2023-11-09
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-46740-6
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  4. Article ; Online: Electrical Impedance Myography Correlates with Functional Measures of Disease Progression in D2-mdx Mice and Boys with Duchenne Muscular Dystrophy.

    Chrzanowski, Stephen Mark / Nagy, Janice A / Pandeya, Sarbesh / Rutkove, Seward B

    Journal of neuromuscular diseases

    2022  

    Abstract: Background: 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 ... ...

    Abstract Background: 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.
    Objective: 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.
    Methods: 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.
    Results: 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.
    Conclusion: 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.
    Language English
    Publishing date 2022-11-25
    Publishing country Netherlands
    Document type Journal Article
    ISSN 2214-3602
    ISSN (online) 2214-3602
    DOI 10.3233/JND-210787
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  5. Article ; Online: Electrical impedance myography for the early detection of muscle ischemia secondary to compartment syndrome

    Aron Lechtig / Philip Hanna / Janice A. Nagy / John Wixted / Ara Nazarian / Seward B. Rutkove

    Scientific Reports, Vol 13, Iss 1, Pp 1-

    a study in a rat model

    2023  Volume 9

    Abstract: Abstract Acute Compartment Syndrome (ACS) is one of the most devastating orthopedic conditions, affecting any of the body’s many compartments, which, if sufficiently severe, may result in disability and amputation. Currently, intra-compartmental pressure ...

    Abstract Abstract Acute Compartment Syndrome (ACS) is one of the most devastating orthopedic conditions, affecting any of the body’s many compartments, which, if sufficiently severe, may result in disability and amputation. Currently, intra-compartmental pressure measurements serve as the gold standard for diagnosing ACS. Diagnosing limbs at risk for ACS before irreversible damage to muscle and nerve is critical. Standard approaches for diagnosing impending compartment syndrome include clinical evaluation of the limb, such as assessment for “tightness” of the overlying skin, reduced pulses distally, and degree of pain, none of which are specific or sensitive. We have proposed a novel method to detect ACS via electrical impedance myography (EIM), where a weak, high-frequency alternating current is passed between one pair of electrodes through a region of tissue, and the resulting surface voltages are measured via a second pair. We evaluated the ability of EIM to detect early muscle ischemia in an established murine model of compression-induced muscle injury, where we collected resistance, reactance, and their dimensionless product, defined as Relative Injury Index (RII) during the study. Our model generated reproducible hypoxia, confirmed by Hypoxyprobe™ staining of endothelial regions within the muscle. Under conditions of ischemia, we demonstrated a reproducible, stable, and significant escalation in resistance, reactance, and RII values, compared to uninjured control limbs. These data make a reasonable argument for additional investigations into using EIM for the early recognition of muscle hypoperfusion and ischemia. However, these findings must be considered preliminary steps, requiring further pre-clinical and clinical validation.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2023-10-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Altered electrical properties in skeletal muscle of mice with glycogen storage disease type II.

    Nagy, Janice A / Semple, Carson / Riveros, Daniela / Sanchez, Benjamin / Rutkove, Seward B

    Scientific reports

    2022  Volume 12, Issue 1, Page(s) 5327

    Abstract: Electrical impedance methods, including electrical impedance myography, are increasingly being used as biomarkers of muscle health since they measure passive electrical properties of muscle that alter in disease. One disorder, Pompe Disease (Glycogen ... ...

    Abstract Electrical impedance methods, including electrical impedance myography, are increasingly being used as biomarkers of muscle health since they measure passive electrical properties of muscle that alter in disease. One disorder, Pompe Disease (Glycogen storage disease type II (GSDII)), remains relatively unstudied. This disease is marked by dramatic accumulation of intracellular myofiber glycogen. Here we assessed the electrical properties of skeletal muscle in a model of GSDII, the Pompe
    MeSH term(s) Animals ; Electric Conductivity ; Electric Impedance ; Female ; Glycogen ; Glycogen Storage Disease Type II/pathology ; Mice ; Muscle, Skeletal/physiology
    Chemical Substances Glycogen (9005-79-2)
    Language English
    Publishing date 2022-03-29
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-022-09328-0
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  7. Article: Surface Electrical Impedance Myography Detects Skeletal Muscle Atrophy in Aged Wildtype Zebrafish and Aged

    Rutkove, Seward B / Chen, Zsu-Zsu / Pandeya, Sarbesh / Callegari, Santiago / Mourey, Tyler / Nagy, Janice A / Nath, Anjali K

    Biomedicines

    2023  Volume 11, Issue 7

    Abstract: Throughout a vertebrate organism's lifespan, skeletal muscle mass and function progressively decline. This age-related condition is termed sarcopenia. In humans, sarcopenia is associated with risk of falling, cardiovascular disease, and all-cause ... ...

    Abstract Throughout a vertebrate organism's lifespan, skeletal muscle mass and function progressively decline. This age-related condition is termed sarcopenia. In humans, sarcopenia is associated with risk of falling, cardiovascular disease, and all-cause mortality. As the world population ages, projected to reach 2 billion older adults worldwide in 2050, the economic burden on the healthcare system is also projected to increase considerably. Currently, there are no pharmacological treatments for sarcopenia, and given the long-term nature of aging studies, high-throughput chemical screens are impractical in mammalian models. Zebrafish is a promising, up-and-coming vertebrate model in the field of sarcopenia that could fill this gap. Here, we developed a surface electrical impedance myography (sEIM) platform to assess skeletal muscle health, quantitatively and noninvasively, in adult zebrafish (young, aged, and genetic mutant animals). In aged zebrafish (~85% lifespan) as compared to young zebrafish (~20% lifespan), sEIM parameters (2 kHz phase angle, 2 kHz reactance, and 2 kHz resistance) robustly detected muscle atrophy (
    Language English
    Publishing date 2023-07-07
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines11071938
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  8. Article ; Online: Design and pilot testing of a 26-gauge impedance-electromyography needle in wild-type and ALS mice.

    Rutkove, Seward B / Le, Mai / Ruehr, Sophie A / Nagy, Janice A / Semple, Carson / Sanchez, Benjamin

    Muscle & nerve

    2022  Volume 65, Issue 6, Page(s) 702–708

    Abstract: Introduction/aims: Needle impedance-electromyography (iEMG) is a diagnostic modality currently under development that combines intramuscular electrical impedance with concentric electromyography (EMG) in a single needle. We designed, manufactured, and ... ...

    Abstract Introduction/aims: Needle impedance-electromyography (iEMG) is a diagnostic modality currently under development that combines intramuscular electrical impedance with concentric electromyography (EMG) in a single needle. We designed, manufactured, and tested a prototype iEMG needle in a cohort of wild-type (WT) and SOD1G93A amyotrophic lateral sclerosis (ALS) mice to assess its ability to record impedance and EMG data.
    Methods: A new six-electrode, 26-gauge, iEMG needle was designed, manufactured and tested. Quantitative impedance and qualitative "gestalt" EMG were performed sequentially on bilateral quadriceps of 16-wk-old SOD1G93A ALS (N = 6) and WT (N = 6) mice by connecting the needle first to an impedance analyzer (with the animal at rest) and then to a standard EMG system (with the animal fully under anesthesia to measure spontaneous activity and briefly during awakening to measure voluntary activity). The needle remained in the muscle throughout the measurement period.
    Results: EMG data were qualitatively similar to that observed with a commercially available concentric EMG needle; fibrillation potentials were observed in 84% of the ALS mice and none of the WT mice; motor unit potentials were also readily identified. Impedance data revealed significant differences in resistance, reactance, and phase values between the two groups, with ALS animals having reduced reactance and resistance values.
    Discussion: This work demonstrates the feasibility of a single iEMG needle conforming to standard dimensions of size and function. Further progress of iEMG technology for enhanced neuromuscular diagnosis and quantification of disease status is currently in development.
    MeSH term(s) Amyotrophic Lateral Sclerosis/diagnosis ; Animals ; Electric Impedance ; Electromyography/methods ; Humans ; Mice ; Muscle, Skeletal ; Muscles ; Needles
    Language English
    Publishing date 2022-04-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 438353-9
    ISSN 1097-4598 ; 0148-639X
    ISSN (online) 1097-4598
    ISSN 0148-639X
    DOI 10.1002/mus.27551
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  9. Article ; Online: Electrical impedance myography detects age-related skeletal muscle atrophy in adult zebrafish.

    Rutkove, Seward B / Callegari, Santiago / Concepcion, Holly / Mourey, Tyler / Widrick, Jeffrey / Nagy, Janice A / Nath, Anjali K

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 7191

    Abstract: 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 ... ...

    Abstract 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.
    MeSH term(s) Humans ; Animals ; Zebrafish ; Sarcopenia ; Electric Impedance ; Reproducibility of Results ; Myography/methods ; Muscle, Skeletal/physiology ; Atrophy
    Language English
    Publishing date 2023-05-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-34119-6
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  10. Article ; Online: Altered electrical properties in skeletal muscle of mice with glycogen storage disease type II

    Janice A. Nagy / Carson Semple / Daniela Riveros / Benjamin Sanchez / Seward B. Rutkove

    Scientific Reports, Vol 12, Iss 1, Pp 1-

    2022  Volume 11

    Abstract: Abstract Electrical impedance methods, including electrical impedance myography, are increasingly being used as biomarkers of muscle health since they measure passive electrical properties of muscle that alter in disease. One disorder, Pompe Disease ( ... ...

    Abstract Abstract Electrical impedance methods, including electrical impedance myography, are increasingly being used as biomarkers of muscle health since they measure passive electrical properties of muscle that alter in disease. One disorder, Pompe Disease (Glycogen storage disease type II (GSDII)), remains relatively unstudied. This disease is marked by dramatic accumulation of intracellular myofiber glycogen. Here we assessed the electrical properties of skeletal muscle in a model of GSDII, the Pompe 6neo/6neo (Pompe) mouse. Ex vivo impedance measurements of gastrocnemius (GA) were obtained using a dielectric measuring cell in 30-week-old female Pompe (N = 10) and WT (N = 10) mice. Longitudinal and transverse conductivity, σ, and the relative permittivity, εr, and Cole–Cole complex resistivity parameters at 0 Hz and infinite frequency, ρo and ρ∞, respectively, and the intracellular resistivity, ρintracellular were determined from the impedance data. Glycogen content (GC) was visualized histologically and quantified biochemically. At frequencies > 1 MHz, Pompe mice demonstrated significantly decreased longitudinal and transverse conductivity, increased Cole–Cole parameters, ρo and ρo-ρ∞, and decreased ρintracellular. Changes in longitudinal conductivity and ρintracellular correlated with increased GC in Pompe animals. Ex vivo high frequency impedance measures are sensitive to alterations in intracellular myofiber features considered characteristic of GSDII, making them potentially useful measures of disease status.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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