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.
Highlights
INTRODUCTIONThe loss of muscle mass with aging and with unloading (e.g., disuse) has been studied extensively
The loss of muscle mass with aging and with unloading has been studied extensively
Scanning electron microscopy (SEM) images of the connective tissue reveal that the endomysium is a highly ordered network that surrounds individual muscle fibers (Purslow and Trotter, 1994) while the perimysium includes extended cables organized as bundles of collagen fibers that terminates on muscle cells (Gillies and Lieber, 2011)
Summary
The loss of muscle mass with aging and with unloading (e.g., disuse) has been studied extensively. Transcriptional profiling studies performed in rat soleus muscles have shown that a large proportion of genes exerting a biological role in the ECM and cell adhesion is decreased in older muscles (Pattison et al, 2003) This observation suggests that the age-associated fibrogenic processes are driven by a decreased degradation capacity, rather than by increased formation of collagenous structures. It is important to note that aging and disuse may induce changes in the structure and biochemical composition of the ECM, which are expected to be associated with impaired transmission of contractile force through lateral pathways [i.e., through shearing between adjacent muscle fibers across costameres and the network of intramuscular connective tissue (IMCT)] (Csapo et al, 2020). It should be noted that the proposed MR indices are novel and validation with biopsy analysis, animal models, or computational models are either ongoing or need to be performed in future studies
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