Near-Infrared Optical Imaging Noninvasively Detects Acutely Damaged Muscle.

Muscle damage is currently assessed through methods such as muscle biopsy, serum biomarkers, functional testing, and imaging procedures, each with its own inherent limitations, and a pressing need for a safe, repeatable, inexpensive, and noninvasive modality to assess the state of muscle health remains. Our aim was to develop and assess near-infrared (NIR) optical imaging as a novel noninvasive method of detecting and quantifying muscle damage. An immobilization-reambulation model was used for inducing muscle damage and recovery in the lower hindlimbs in mice. Confirmation of muscle damage was obtained using in vivo indocyanine green-enhanced NIR optical imaging, magnetic resonance imaging, and ex vivo tissue analysis. The soleus of the immobilized-reambulated hindlimb was found to have a greater amount of muscle damage compared to that in the contralateral nonimmobilized limb, confirmed by in vivo indocyanine green-enhanced NIR optical imaging (3.86-fold increase in radiant efficiency), magnetic resonance imaging (1.41-fold increase in T2), and an ex vivo spectrophotometric assay of indocyanine green uptake (1.87-fold increase in normalized absorbance). Contrast-enhanced NIR optical imaging provides a sensitive, rapid, and noninvasive screening method that can be used for imaging and quantifying muscle damage and recovery in vivo.

[1]  R. Armstrong,et al.  Eccentric exercise-induced injury to rat skeletal muscle. , 1983, Journal of applied physiology: respiratory, environmental and exercise physiology.

[2]  B. Lomonte,et al.  An overview of lysine-49 phospholipase A2 myotoxins from crotalid snake venoms and their structural determinants of myotoxic action. , 2003, Toxicon : official journal of the International Society on Toxinology.

[3]  J. Tanabe,et al.  Quantitative cerebral perfusion assessment using microscope-integrated analysis of intraoperative indocyanine green fluorescence angiography versus positron emission tomography in superficial temporal artery to middle cerebral artery anastomosis , 2014, Surgical neurology international.

[4]  Ping Gong,et al.  Smart human serum albumin-indocyanine green nanoparticles generated by programmed assembly for dual-modal imaging-guided cancer synergistic phototherapy. , 2014, ACS nano.

[5]  J. C. Kraft,et al.  Interactions of Indocyanine Green and Lipid in Enhancing Near-Infrared Fluorescence Properties: The Basis for Near-Infrared Imaging in Vivo , 2014, Biochemistry.

[6]  J. Frangioni.  In vivo near-infrared fluorescence imaging. , 2003, Current opinion in chemical biology.

[7]  Bahman Anvari,et al.  Biodistribution of encapsulated indocyanine green in healthy mice. , 2009, Molecular pharmaceutics.

[8]  J. Dunn,et al.  Quantitative magnetic resonance imaging of the mdx mouse model of Duchenne muscular dystrophy , 1999, Muscle & nerve.

[9]  Christoph Groden,et al.  Current issues and perspectives in small rodent magnetic resonance imaging using clinical MRI scanners. , 2007, Methods.

[10]  R. Armstrong,et al.  Eccentric contraction-induced injury in normal and hindlimb-suspended mouse soleus and EDL muscles. , 1994, Journal of applied physiology.

[11]  K. Vandenborne,et al.  A model of muscle atrophy using cast immobilization in mice , 2005, Muscle & nerve.

[12]  P. Clarkson,et al.  Muscle Soreness and Serum Creatine Kinase Activity Following Isometric, Eccentric, and Concentric Exercise , 1985, International journal of sports medicine.

[13]  L. Ploutz-Snyder,et al.  Vulnerability to dysfunction and muscle injury after unloading. , 1996, Archives of physical medicine and rehabilitation.

[14]  Hisataka Kobayashi,et al.  Toxicity of Organic Fluorophores Used in Molecular Imaging: Literature Review , 2009, Molecular imaging.

[15]  D. Riley,et al.  Temporal changes in sarcomere lesions of rat adductor longus muscles during hindlimb reloading , 1994, The Anatomical record.

[16]  P. Clarkson,et al.  Exercise-induced muscle damage in humans. , 2002, American journal of physical medicine & rehabilitation.

[17]  Bohumil Bednar,et al.  Dual In Vivo Quantification of Integrin-targeted and Protease-activated Agents in Cancer Using Fluorescence Molecular Tomography (FMT) , 2010, Molecular Imaging and Biology.

[18]  Vasilis Ntziachristos,et al.  Shedding light onto live molecular targets , 2003, Nature Medicine.

[19]  Huabei Jiang,et al.  Diffuse optical tomography guided quantitative fluorescence molecular tomography. , 2008, Applied optics.

[20]  C. Kasper.  Sarcolemmal disruption in reloaded atrophic skeletal muscle. , 1995, Journal of applied physiology.

[21]  D. Thedens,et al.  Sarcolemma-localized nNOS is required to maintain activity after mild exercise , 2008, Nature.

[22]  M. Schweiger,et al.  Three-dimensional in vivo fluorescence diffuse optical tomography of breast cancer in humans. , 2007, Optics express.

[23]  D. Riley,et al.  Sarcomere lesion damage occurs mainly in slow fibers of reloaded rat adductor longus muscles. , 1998, Journal of applied physiology.

[24]  J. Gutiérrez,et al.  A new muscle damaging toxin, myotoxin II, from the venom of the snake Bothrops asper (terciopelo). , 1989, Toxicon : official journal of the International Society on Toxinology.

[25]  B. Lomonte,et al.  Host response to Bothrops asper snake venom. Analysis of edema formation, inflammatory cells, and cytokine release in a mouse model. , 1993, Inflammation.

[26]  F. Trensz,et al.  Regulation of Protein Metabolism in Exercise and Recovery A novel hindlimb immobilization procedure for studying skeletal muscle atrophy and recovery in mouse , 2009 .

[27]  H. Možina,et al.  Near-infrared spectroscopy for evaluation of global and skeletal muscle tissue oxygenation. , 2011, World journal of cardiology.

[28]  E. Hoffman,et al.  Non-invasive Optical Imaging of Muscle Pathology in mdx Mice Using Cathepsin Caged Near-Infrared Imaging , 2010, Molecular Imaging and Biology.

[29]  S. Ohtori,et al.  Longitudinal evaluation of local muscle conditions in a rat model of gastrocnemius muscle injury using an in vivo imaging system , 2015, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[30]  K. Vandenborne,et al.  Noninvasive monitoring of muscle damage during reloading following limb disuse , 2005, Muscle & nerve.

[31]  R. Aspden,et al.  A longitudinal MRI study of muscle atrophy during lower leg immobilization following ankle fracture , 2012, Journal of magnetic resonance imaging : JMRI.

[32]  J. Gutiérrez,et al.  Skeletal muscle degeneration induced by venom phospholipases A2: insights into the mechanisms of local and systemic myotoxicity. , 2003, Toxicon : official journal of the International Society on Toxinology.

[33]  U. Proske,et al.  Muscle damage from eccentric exercise: mechanism, mechanical signs, adaptation and clinical applications , 2001, The Journal of physiology.

[34]  Andreas Raabe,et al.  Near-infrared Indocyanine Green Video Angiography: A New Method for Intraoperative Assessment of Vascular Flow , 2003, Neurosurgery.

[35]  G. Walter,et al.  Noninvasive monitoring of gene correction in dystrophic muscle , 2005, Magnetic resonance in medicine.

[36]  R. Weissleder.  A clearer vision for in vivo imaging , 2001, Nature Biotechnology.

[37]  Krista Vandenborne,et al.  Changes in muscle T2 and tissue damage after downhill running in mdx Mice , 2011, Muscle & nerve.

[38]  S. Forbes,et al.  Age‐related T2 changes in hindlimb muscles of mdx mice , 2016, Muscle & nerve.

[39]  M. Grounds,et al.  Evans Blue Dye as an in vivo marker of myofibre damage: optimising parameters for detecting initial myofibre membrane permeability , 2002, Journal of anatomy.

[40]  Vasilis Ntziachristos,et al.  Looking and listening to light: the evolution of whole-body photonic imaging , 2005, Nature Biotechnology.

[41]  V. Ntziachristos,et al.  Concurrent MRI and diffuse optical tomography of breast after indocyanine green enhancement. , 2000, Proceedings of the National Academy of Sciences of the United States of America.