Non-invasive detection of local microstructural damage in tendon using 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 maintaining tissue health, a phenomenon 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. Fatigue-induced 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 use of DT-MRI as a non-invasive tool to detect tendon mechanopathologies and motivating future work toward clinical translation. STATEMENT OF SIGNIFICANCE: Non-invasive imaging techniques capable of detecting fatigue-induced damage in tendon are lacking in the clinical practice. Diffusion Tensor MRI (DT-MRI) is a non-invasive imaging technique that is sensitive to tissue microstructure, but its sensitivity to detect fatigue-induced damage in tendon - and other connective soft tissues - has not been evaluated. Here, we show that DT-MRI can identify local damage to the collagen fiber microstructure of tendon and establish the detection limits of 9.4 tesla DT-MRI metrics to such damage. Collectively, our findings support DT-MRI as a noninvasive tool for detecting fatigue-induced damage in tendon, and potentially other soft connective tissues, warranting further development to facilitate clinical translation.