Non-invasive detection of local microstructural damage in tendonvia Diffusion Tensor MRI

Tendon is critical for musculoskeletal function as it transfers forces generated by muscle to bone and stores energy during movement. Impaired mechanical function in tendon limits mobility and results from fatigue-induced damage progression that outpaces the restorative processes maintaning tissue health, a phenomenom we term mechanopathology. Early and non-invasive detection of tendon mechanopathologies is vital to prevent further damage, but is lacking in the clinical space. Here, we evaluate the ability of diffusion tensor magnetic resonance imaging (DT-MRI) to detect mechanical fatigue damage in tendon, and validate our findings using histologic assessments of collagen fiber microstructure and molecular structure. We found that fatigue-induced changes in DT-MRI metrics of tendon are spatially heterogeneous, and correspond to regions with damaged collagen fiber microstructure. While secondary structures of collagen molecules were damaged by fatigue loading, they do not spatially correspond to fatigue-induced changes in DT-MRI metrics. Fatigueinduced changes in DT-MRI metrics can be partially explained by quantitative metrics of post-fatigue collagen fiber microstructure, estimating the limit of detection of DT-MRI metrics to fatigue-induced damage in tendon. Our findings indicate that DT-MRI metrics are sensitive to fatigue-induced local damage in tendon, supporting the potential of DT-MRI as a non-invasive and translatable tool to clinically detect mechanopathologies in tendon.