No abstract

The response to loading of human articular cartilage as assessed by magnetic resonance imaging (MRI) remains to be defined in relation to histology and biomechanics. Therefore, an MRI-compatible whole-knee joint loading device for the functional in situ assessment of cartilage was developed and validated in this study. A formalin-fixed human knee was scanned by computed tomography in its native configuration and digitally processed to create femoral and tibial bone models. The bone models were covered by artificial femoral and tibial articular cartilage layers in their native configuration using cartilage-mimicking polyvinyl siloxane. A standardized defect of 8 mm diameter was created within the artificial cartilage layer at the central medial femoral condyle, into which native cartilage samples of similar dimensions were placed. After describing its design and specifications, the comprehensive validation of the device was performed using a hydraulic force gauge and digital electronic pressure-sensitive sensors. Displacement-controlled quasi-static uniaxial loading to 2.5 mm [Formula: see text] and 5.0 mm [Formula: see text] of the mobile tibia versus the immobile femur resulted in forces of [Formula: see text] N [Formula: see text] and [Formula: see text] N [Formula: see text] (on the entire joint) and local pressures of [Formula: see text] MPa [Formula: see text] and [Formula: see text] MPa [Formula: see text] (at the site of the cartilage sample). Upon confirming the MRI compatibility of the set-up, the response to loading of macroscopically intact human articular cartilage samples ([Formula: see text]) was assessed on a clinical 3.0-T MR imaging system using clinical standard proton-density turbo-spin echo sequences and T2-weighted multi-spin echo sequences. Serial imaging was performed at the unloaded state [Formula: see text] and at consecutive loading positions (i.e. at [Formula: see text] and [Formula: see text]. Biomechanical unconfined compression testing (Young's modulus) and histological assessment (Mankin score) served as the standards of reference. All samples were histologically intact (Mankin score, [Formula: see text]) and biomechanically reasonably homogeneous (Young's modulus, [Formula: see text] MPa). They could be visualized in their entirety by MRI and significant decreases in sample height [[Formula: see text]: [Formula: see text] mm; [Formula: see text]: [Formula: see text] mm; [Formula: see text]: [Formula: see text] mm; [Formula: see text] (repeated-measures ANOVA)] as well as pronounced T2 signal decay indicative of tissue pressurization were found as a function of compressive loading. In conclusion, our compression device has been validated for the noninvasive response-to-loading assessment of human articular cartilage by MRI in a close-to-physiological experimental setting. Thus, in a basic research context cartilage may be functionally evaluated beyond mere static analysis and in reference to histology and biomechanics.

To assess human articular cartilage tissue functionality by serial multiparametric quantitative MRI (qMRI) mapping as a function of histological degeneration. Forty-nine cartilage samples obtained during total knee replacement surgeries were placed in a standardized artificial knee joint within an MRI-compatible compressive loading device and imaged in situ and at three loading positions, i.e. unloaded, at 2.5 mm displacement (20% body weight [BW]) and at 5 mm displacement (110% BW). Using a clinical 3.0 T MRI system (Achieva, Philips), serial T1, T1ρ, T2 and T2* maps were generated for each sample and loading position. Histology (Mankin scoring) and biomechanics (Young’s modulus) served as references. Samples were dichotomized as intact ( int , n = 27) or early degenerative ( deg , n = 22) based on histology and analyzed using repeated-measures ANOVA and unpaired Student’s t-tests after log-transformation. For T1ρ, T2 and T2*, significant loading-induced differences were found in deg (in contrast to int ) samples, while for T1 significant decreases in all zones were observed, irrespective of degeneration. In conclusion, cartilage functionality may be visualized using serial qMRI parameter mapping and the response-to-loading patterns are associated with histological degeneration. Hence, loading-induced changes in qMRI parameter maps provide promising surrogate parameters of tissue functionality and status in health and disease.

Water, collagen, and proteoglycans determine articular cartilage functionality. If altered, susceptibility to premature degeneration is increased. This study investigated the effects of enzymatic proteoglycan depletion on cartilage functionality as assessed by advanced Magnetic Resonance Imaging (MRI) techniques under standardized loading. Lateral femoral condylar cartilage-bone samples from patients undergoing knee replacement (n = 29) were serially imaged by Proton Density-weighted and T1, T1ρ, T2, and T2* mapping sequences on a clinical 3.0 T MRI scanner (Achieva, Philips). Using pressure-controlled indentation loading, samples were imaged unloaded and quasi-statically loaded to 15.1 N and 28.6 N, and both before and after exposure to low-concentrated (LT, 0.1 mg/mL, n = 10) or high-concentrated trypsin (HT, 1.0 mg/mL, n = 10). Controls were not treated (n = 9). Responses to loading were assessed for the entire sample and regionally, i.e. sub- and peri-pistonally, and zonally, i.e. upper and lower sample halves. Trypsin effects were quantified as relative changes (Δ), analysed using appropriate statistical tests, and referenced histologically. Histological proteoglycan depletion was reflected by significant sub-pistonal decreases in T1 (p = 0.003) and T2 (p = 0.008) after HT exposure. Loading-induced changes in T1ρ and T2* were not related. In conclusion, proteoglycan depletion alters cartilage functionality and may be assessed using serial T1 and T2 mapping under loading.

Objective: To investigate changes in response to sequential pressure-controlled loading and unloading in human articular cartilage of variable histological degeneration using serial T1r mapping. Method: We obtained 42 cartilage samples of variable degeneration from the medial femoral condyles of 42 patients undergoing total knee replacement. Samples were placed in a standardized artificial knee joint within an MRI-compatible whole knee-joint compressive loading device and imaged before (d 0), during (d ld1 , d ld2 , d ld3 , d ld4 , d ld5) and after (d rl1 , d rl2 , d rl3 , d rl4 , d rl5) pressure-controlled loading to 0.663 ± 0.021 kN (94% body weight) using serial T1r mapping (spin-lock multigradient echo sequence; 3.0T MRI system [Achieva, Philips]). Reference assessment included histology (Mankin scoring) and conventional biomechanics (Tangent stiffness). We dichotomized sample into intact (n ¼ 21) and degenerative (n ¼ 21) based on histology and analyzed data using Mann Whitney, Kruskal Wallis, oneway ANOVA tests and Spearman's correlation, respectively. Results: At d 0 , we found no significant differences between intact and degenerative samples, while the response-to-loading patterns were distinctly different. In intact samples, T1r increases were consistent and non-significant, while in degenerative samples, T1r increases were significantly higher (P ¼ 0.004, d0 vs dld1, d0 vs dld3), yet undulating and variable. With unloading, T1r increases subsided, yet were persistently elevated beyond d0. Conclusion: Cartilage mechanosensitivity is related to histological degeneration and assessable by serial T1r mapping. Unloaded, T1r characteristics are not significantly different in intact vs degenerative cartilage, while load bearing is organized in intact cartilage and disorganized in degenerative cartilage.