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Cartilage functionality is determined by tissue structure and composition. If altered, cartilage is predisposed to premature degeneration. This pathomimetical study of early osteoarthritis evaluated the dose-dependant effects of collagenase-induced collagen disintegration and proteoglycan depletion on cartilage functionality as assessed by serial T1, T1ρ, T2, and T2* mapping under loading. 30 human femoral osteochondral samples underwent imaging on a clinical 3.0 T MRI scanner (Achieva, Philips) in the unloaded reference configuration (δ 0) and under pressure-controlled quasi-static indentation loading to 15.1 N (δ 1) and to 28.6 N (δ 2). Imaging was performed before and after exposure to low (LC, 0.5 mg/mL; n = 10) or high concentration (HC, 1.5 mg/mL; n = 10) of collagenase. Untreated samples served as controls (n = 10). Loading responses were determined for the entire sample and the directly loaded (i.e. sub-pistonal) and bilaterally adjacent (i.e. peri‑pistonal) regions, referenced histologically, quantified as relative changes, and analysed using adequate parametric and non-parametric statistical tests. Dose-dependant surface disintegration and tissue loss were reflected by distinctly different pre- and post-exposure response-to-loading patterns. While T1 generally decreased with loading, regardless of collagenase exposure, T1ρ increased significantly after HC exposure (p = 0.008). Loading-induced decreases in T2 were significant after LC exposure (p = 0.006), while changes in T2* were ambiguous. In conclusion, aberrant loading-induced changes in T2 and T1ρ reflect moderate and severe matrix changes, respectively, and indicate the close interrelatedness of matrix changes and functionality in cartilage. Image, graphical abstract [ABSTRACT FROM AUTHOR]

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 (δ 0), and after 30 min (δ 1) and 60 min (δ 2) of loading using serial T1ρ maps acquired on a 3.0T clinical MRI scanner (Achieva, Philips). Alongside texture features, relative changes in T1ρ (Δ 1 , Δ 2) 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 δ 0 were relatively homogenous in all samples. In response to loading, relative increases in T1ρ were strong and significant after dynamic loading (Δ 1 = 10.3 ± 17.0%, Δ 2 = 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. [Display omitted] • In vivo , human cartilage is subjected to a range of different loading conditions. • The imaging correspondence of these remains largely unknown. • This study investigated the effects of static, dynamic and no loading on cartilage. • Serial T1ρ maps were quantified as imaging markers of functionality. • Dynamic loading conditions are most promising for perspective in-vivo studies. [ABSTRACT FROM AUTHOR]

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. Image 1 • Stress MRI techniques allow functional assessment of knee joint structures. • A dedicated device for in-situ loading of human cadaveric knee joints was developed. • Imaging biomarkers, e.g. cartilage thickness, are related to loading parameters. • Loading intensity and alignment affect cartilage and meniscus responses to loading. • Histological and biomechanical measures are unrelated to responses to loading. [ABSTRACT FROM AUTHOR]