Meniscus pathology may promote early osteoarthritis. this study assessed human meniscus functionality (i.e. its response to loading) ex vivo based on quantitative T1, T1ρ, and T2 mapping as a function of histological degeneration and loading. Forty-five meniscus samples of variable degeneration were harvested from the lateral meniscus body region of 45 patients during total knee arthroplasties. Samples underwent serial mapping on a 3.0-T MRI scanner (Achieva, Philips) using a force-controlled and torque-inducing compressive loading device. Samples were measured at three loading positions, i.e. unloaded, loaded to 2 bar (compression force 37 N) and 4 bar (69 N). Histology (Pauli classification) and biomechanics (Elastic Modulus) served as references. Based on histology, samples were trichotomized as grossly intact (n = 14), mildly degenerative (n = 16), and moderate-to-severely degenerative (n = 15) and analyzed using appropriate parametric and non-parametric tests. For T1, we found loading-induced decreases in all samples, irrespective of degeneration. For T1ρ, zonal increases in intact (apex) and decreases in degenerative samples (base) were found, while for T2, changes were ambiguous. In conclusion, force-controlled loading and serial MR imaging reveal response-to-loading patterns in meniscus. Zonal T1ρ response-to-loading patterns are most promising in differentiating degeneration, while T1 and T2 aren't clearly related to degeneration.and may provide an imaging-based indication of functional tissue properties. Acute and chronic meniscus pathologies are frequent clinical entities 1. Due to its decisive role in load bearing, load transmission, load dissipation and in providing joint stability, congruity and lubrication 2 , meniscus integrity in form and function is of utmost importance to the knee joint's long-term health 3. Meniscus functionality, which is the tissue's ability to function properly, i.e. to disperse loads and reduce friction, is heavily dependent on its extracellular matrix properties. Collagen fibers, primarily type-I, define the tissue's tensile strength and shock-absorbing properties, while proteoglycans contribute to compressive strength by upholding swelling pressure 2,4,5. Lately, therapeutic efforts have been aimed at preserving and restoring the damaged meniscus secondary to trauma or degeneration 6,7. This is of particular relevance as meniscus and cartilage pathologies are closely interrelated. Consequently, meniscus damage and loss are key features of and risk factors for developing osteoarthritis (OA) 8. The discussion on whether meniscus pathologies are a cause or consequence of knee OA is ongoing 9,10. Yet common consensus prevails that morphological meniscus defects, i.e. surface breakdown and tissue tearing, are the consequence of degenerative changes of the extracellular matrix 11-13 , and contribute to the evolution of OA by altering load distribution and transmission to the adjacent articular cartilage. Hence, detecting such degenerative changes early is necessary in therapeu...