Role of the Extracellular Matrix in Loss of Muscle Force With Age and Unloading Using Magnetic Resonance Imaging, Biochemical Analysis, and Computational Models

Usha Sinha; Vadim Malis; Jiun-Shyan Chen; Robert Csapo; Ryuta Kinugasa; Marco Vincenzo Narici; Shantanu Sinha

doi:10.3389/fphys.2020.00626

Role of the Extracellular Matrix in Loss of Muscle Force With Age and Unloading Using Magnetic Resonance Imaging, Biochemical Analysis, and Computational Models

Front Physiol. 2020 Jun 18:11:626. doi: 10.3389/fphys.2020.00626. eCollection 2020.

Authors

Usha Sinha¹, Vadim Malis², Jiun-Shyan Chen³, Robert Csapo⁴, Ryuta Kinugasa^{5

6}, Marco Vincenzo Narici⁷, Shantanu Sinha⁸

Affiliations

¹ Department of Physics, San Diego State University, San Diego, CA, United States.
² Department of Physics, University of California, San Diego, San Diego, CA, United States.
³ Department of Structural Engineering, University of California, San Diego, San Diego, CA, United States.
⁴ Research Unit for Orthopaediic Sports Medicine and Injury Prevention, ISAG, Private University for Health Sciences, Medical Informatics and Technology, Hall in Tirol, Austria.
⁵ Department of Human Sciences, Kanagawa University, Yokohama, Japan.
⁶ Computational Engineering Applications Unit, Advanced Center for Computing and Communication, RIKEN, Saitama, Japan.
⁷ Institute of Physiology, Department of Biomedical Sciences, University of Padua, Padua, Italy.
⁸ Department of Radiology, University of California, San Diego, San Diego, CA, United States.

Abstract

The focus of this review is the application of advanced MRI to study the effect of aging and disuse related remodeling of the extracellular matrix (ECM) on force transmission in the human musculoskeletal system. Structural MRI includes (i) ultra-low echo times (UTE) maps to visualize and quantify the connective tissue, (ii) diffusion tensor imaging (DTI) modeling to estimate changes in muscle and ECM microstructure, and (iii) magnetization transfer contrast imaging to quantify the macromolecular fraction in muscle. Functional MRI includes dynamic acquisitions during contraction cycles enabling computation of the strain tensor to monitor muscle deformation. Further, shear strain extracted from the strain tensor may be a potential surrogate marker of lateral transmission of force. Biochemical and histological analysis of muscle biopsy samples can provide "gold-standard" validation of some of the MR findings. The review summarizes biochemical studies of ECM adaptations with age and with disuse. A brief summary of animal models is included as they provide experimental confirmation of longitudinal and lateral force transmission pathways. Computational muscle models enable exploration of force generation and force pathways and elucidate the link between structural adaptations and functional consequences. MR image findings integrated in a computational model can explain and predict subject specific functional changes to structural adaptations. Future work includes development and validation of MRI biomarkers using biochemical analysis of muscle tissue as a reference standard and potential translation of the imaging markers to the clinic to noninvasively monitor musculoskeletal disease conditions and changes consequent to rehabilitative interventions.

Keywords: age and disuse related muscle force loss; extracellular matrix; lateral transmission of force; strain imaging; structural muscle MRI.

Publication types

Review

Grants and funding

R01 AG056999/AG/NIA NIH HHS/United States