In vivo human knee varus-valgus loading apparatus for analysis of MRI-based intratissue strain and relaxometry

The diagnosis of early-stage osteoarthritis remains as an unmet challenge in medicine and a roadblock to evaluating the efficacy of disease-modifying treatments. Recent studies demonstrate that unique patterns of intratissue cartilage deformation under cyclic loading can serve as potential biomarkers to detect early disease pathogenesis. However, a workflow to obtain deformation, strain maps, and quantitative MRI metrics due to the loading of articular cartilage in vivo has not been fully developed. In this study, we characterize and demonstrate an apparatus that is capable of applying a varus-valgus load to the human knee in vivo within an MRI environment to enable the measurement of cartilage structure and mechanical function. The apparatus was first tested in a lab environment, then the functionality and utility of the apparatus were examined during varus loading in a clinical 3T MRI system for human imaging. We found that the device enables quantitative MRI metrics for biomechanics and relaxometry data acquisition during joint loading leading to compression of the medial knee compartment. Integration with spiral DENSE MRI during cyclic loading provided time-dependent displacement and strain maps within the tibiofemoral cartilage. The results from these procedures demonstrate that the performance of this loading apparatus meets the design criteria and enables a simple and practical workflow for future studies of clinical cohorts, and the identification and validation of imaging-based biomechanical biomarkers.