Semiquantitative Evaluation of Muscle Repair by Diffusion Tensor Imaging in Mice

Muscle injury is one of the most common traumas in orthopedic and sports medicine. However, there are only a few treatment options with marginal clinical benefits for this condition. Muscle repair after injury involves multiple and complex processes, such as the inflammation phase, regeneration phase, and remodeling phase. To develop a treatment modality and to examine the efficacy of novel interventions and agents for patients with muscle injuries, it is essential to establish a reliable and sensitive method to monitor the changes in muscle structure and status during muscle repair. Diffusion‐weighted magnetic resonance imaging has been widely used to assess the diffusivity of water molecules in tissue. When it is used in combination with diffusion tensor imaging (DTI), the microstructure of muscle tissue can be indirectly depicted. In the present study, we evaluated the time‐course changes in the diffusivity and anisotropy in muscles by DTI and histology after injury in mice. We found that the diffusivity and anisotropy exhibit distinct kinetics during muscle repair and that these kinetics were significantly altered in mutant mice with a defect in muscle regeneration. Our data show that muscle repair processes can be readily evaluated and monitored by DTI technique and suggest that DTI can be clinically applied for assessing muscle injury and repair in humans. © 2018 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

[1]  P. Saftig,et al.  Ectodomain shedding and ADAMs in development , 2012, Development.

[2]  T. Yankeelov,et al.  Multi‐parametric MRI characterization of inflammation in murine skeletal muscle , 2014, NMR in biomedicine.

[3]  H Kalimo,et al.  Muscle strain injuries. , 2000, Current opinion in rheumatology.

[4]  K. Horiuchi,et al.  Dual functions of cell-autonomous and non-cell-autonomous ADAM10 activity in granulopoiesis. , 2011, Blood.

[5]  Susumu Mori,et al.  Structural insights into the rodent CNS via diffusion tensor imaging , 2012, Trends in Neurosciences.

[6]  M. Kushmerick,et al.  Multiparameter MRI analysis of the time course of induced muscle damage and regeneration , 2014, Journal of magnetic resonance imaging : JMRI.

[7]  Christoph Lepper,et al.  Inducible lineage tracing of Pax7‐descendant cells reveals embryonic origin of adult satellite cells , 2010, Genesis.

[8]  Victor Alves,et al.  A hitchhiker's guide to diffusion tensor imaging , 2012, Front. Neurosci..

[9]  H. Okano,et al.  Application of q-Space Diffusion MRI for the Visualization of White Matter , 2016, The Journal of Neuroscience.

[10]  C. Pierpaoli,et al.  Diffusion MRI and the detection of alterations following traumatic brain injury , 2017, Journal of neuroscience research.

[11]  W. Pear,et al.  Brief Report: Blockade of Notch Signaling in Muscle Stem Cells Causes Muscular Dystrophic Phenotype and Impaired Muscle Regeneration , 2013, Stem cells.

[12]  A. Palmisano,et al.  Magnetic Resonance Imaging at 7T Reveals Common Events in Age-Related Sarcopenia and in the Homeostatic Response to Muscle Sterile Injury , 2013, PloS one.

[13]  H. Okano,et al.  In Vivo Tracing of Neural Tracts in the Intact and Injured Spinal Cord of Marmosets by Diffusion Tensor Tractography , 2007, The Journal of Neuroscience.

[14]  M. Chou,et al.  Principles and Limitations of Computational Algorithms in Clinical Diffusion Tensor MR Tractography , 2010, American Journal of Neuroradiology.

[15]  D. Le Bihan,et al.  Diffusion tensor imaging: Concepts and applications , 2001, Journal of magnetic resonance imaging : JMRI.

[16]  P. Basser,et al.  MR diffusion tensor spectroscopy and imaging. , 1994, Biophysical journal.

[17]  S. Eustace,et al.  MR imaging of muscle injury. , 2009, Magnetic resonance imaging clinics of North America.

[18]  Martijn Froeling,et al.  Techniques and applications of skeletal muscle diffusion tensor imaging: A review , 2016, Journal of magnetic resonance imaging : JMRI.

[19]  G. Duda,et al.  Time course of skeletal muscle regeneration after severe trauma , 2011, Acta orthopaedica.

[20]  Tom H. Cheung,et al.  Notch Signaling Is Necessary to Maintain Quiescence in Adult Muscle Stem Cells , 2012, Stem cells.

[21]  Dinesh Kumbhare,et al.  Diffusion tensor imaging in evaluation of human skeletal muscle injury , 2006, Journal of magnetic resonance imaging : JMRI.

[22]  J A Maldjian,et al.  Traumatic brain injury: diffusion-weighted MR imaging findings. , 1999, AJNR. American journal of neuroradiology.

[23]  A. Uezumi,et al.  Hesr1 and Hesr3 are essential to generate undifferentiated quiescent satellite cells and to maintain satellite cell numbers , 2011, Development.

[24]  K. Horiuchi,et al.  A Disintegrin and Metalloprotease 10 (ADAM10) Is Indispensable for Maintenance of the Muscle Satellite Cell Pool* , 2015, The Journal of Biological Chemistry.

[25]  F. Schick,et al.  Diffusion characteristics of large molecules assessed by proton MRS on a whole-body MR system. , 2004, Magnetic resonance imaging.

[26]  Pratik Mukherjee,et al.  Visualizing white matter pathways in the living human brain: diffusion tensor imaging and beyond. , 2007, Neuroimaging clinics of North America.

[27]  J. E. Tanner Use of the Stimulated Echo in NMR Diffusion Studies , 1970 .

[28]  Tomokazu Numano,et al.  Characteristics of diffusion-weighted stimulated echo pulse sequence in human skeletal muscle , 2012, Radiological Physics and Technology.

[29]  D. Robertson,et al.  Sports-related muscle injury in the lower extremity. , 2006, Clinics in sports medicine.

[30]  Y. Assaf,et al.  Diffusion Tensor Imaging (DTI)-based White Matter Mapping in Brain Research: A Review , 2007, Journal of Molecular Neuroscience.

[31]  Martijn Froeling,et al.  Skeletal muscle diffusion tensor‐MRI fiber tracking: rationale, data acquisition and analysis methods, applications and future directions , 2017, NMR in biomedicine.

[32]  Federico Ambrogi,et al.  Magnetic Resonance Imaging Allows the Evaluation of Tissue Damage and Regeneration in a Mouse Model of Critical Limb Ischemia , 2015, PloS one.