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Magnetic resonance imaging (MRI) under mechanical loading, commonly referred to as stress MRI, allows the evaluation of functional properties of intra- and periarticular tissues non-invasively beyond static assessment. Quantitative MRI can identify physiological and pathological responses to loading as indication of, potentially treatable, early degeneration and load transmission failure. Therefore, we have developed and validated an MRI-compatible pressure-controlled axial loading device to compress human knee specimens under variable loading intensity and axis deviation. Ten structurally intact human knee specimens (mean age 83.2 years) were studied on a 3.0T scanner (Achieva, Philips). Proton density-weighted fat-saturated turbo spin-echo and high-resolution 3D water selective 3D gradient-echo MRI scans were acquired sequentially at 10° joint flexion in seven configurations: unloaded and then at approximately half and full body weight loading in neutral, 10° varus and 10° valgus alignment, respectively. Following manual segmentation in both femorotibial compartments, cartilage thickness (ThC) was determined as well as meniscus extrusion (ExM). These measures were compared to computed tomography scans, histological grading (Mankin and Pauli scores), and biomechanical properties (Instantaneous Young's Modulus). Compartmental, regional and subregional changes in ThC and ExM were reflective of loading intensity and joint alignment, with the greatest changes observed in the medial compartment during varus and in the lateral compartment during valgus loading. These were not significantly associated with the histological tissue status or biomechanical properties. In conclusion, this study explores the physiological in-situ response of knee cartilage and meniscus, based on stress MRI, and as a function of loading intensity, joint alignment, histological tissue status, and biomechanical properties, as another step towards clinical implementation.

Biomechanical Magnetic Resonance Imaging (MRI) of articular cartilage, i.e. its imaging under loading, is a promising diagnostic tool to assess the tissue's functionality in health and disease. This study aimed to assess the response to static and dynamic loading of histologically intact cartilage samples by functional MRI and pressure-controlled in-situ loading. To this end, 47 cartilage samples were obtained from the medial femoral condyles of total knee arthroplasties (from 24 patients), prepared to standard thickness, and placed in a standard knee joint in a pressure-controlled whole knee-joint compressive loading device. Cartilage samples' responses to static (i.e. constant), dynamic (i.e. alternating), and no loading, i.e. free-swelling conditions, were assessed before (δ0), and after 30 min (δ1) and 60 min (δ2) of loading using serial T1ρ maps acquired on a 3.0T clinical MRI scanner (Achieva, Philips). Alongside texture features, relative changes in T1ρ (Δ1, Δ2) were determined for the upper and lower sample halves and the entire sample, analyzed using appropriate statistical tests, and referenced to histological (Mankin scoring) and biomechanical reference measures (tangent stiffness). Histological, biomechanical, and T1ρ sample characteristics at δ0 were relatively homogenous in all samples. In response to loading, relative increases in T1ρ were strong and significant after dynamic loading (Δ1 = 10.3 ± 17.0%, Δ2 = 21.6 ± 21.8%, p = 0.002), while relative increases in T1ρ after static loading and in controls were moderate and not significant. Generally, texture features did not demonstrate clear loading-related associations underlying the spatial relationships of T1ρ. When realizing the clinical translation, this in-situ study suggests that serial T1ρ mapping is best combined with dynamic loading to assess cartilage functionality in humans based on advanced MRI techniques.