Quantitative magnetic resonance imaging (qMRI) is a promising approach to detect early cartilage degeneration. However, there is no consensus on which cartilage component contributes to the tissue's qMRI signal properties. T1, T1ρ, and T2⁎ maps of cartilage samples (n = 8) were generated on a clinical 3.0-T MRI system. All samples underwent histological assessment to ensure structural integrity. For cross-referencing, a discretized numerical model capturing distinct compositional and structural tissue properties, that is, fluid fraction (FF), proteoglycan (PG) and collagen (CO) content and collagen fiber orientation (CFO), was implemented. In a pixel-wise and region-specific manner (central versus peripheral region), qMRI parameter values and modelled tissue parameters were correlated and quantified in terms of Spearman's correlation coefficient ρs. Significant correlations were found between modelled compositional parameters and T1 and T2⁎, in particular in the central region (T1: ρs ≥ 0.7 [FF, CFO], ρs ≤ −0.8 [CO, PG]; T2⁎: ρs ≥ 0.67 [FF, CFO], ρs ≤ −0.71 [CO, PG]). For T1ρ, correlations were considerably weaker and fewer (0.16 ≤ ρs ≤ −0.15). QMRI parameters are characterized in their biophysical properties and their sensitivity and specificity profiles in a basic scientific context. Although none of these is specific towards any particular cartilage constituent, T1 and T2⁎ reflect actual tissue compositional features more closely than T1ρ.

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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.

Serial T1ρ-mapping reveals distinct and complex zonal and regional changes in articular cartilage as a function of loading and unloading. Thereby, longitudinal adaptive processes in hyaline cartilage become evident, which may be used for the tissue's non-invasive functional characterization by T1ρ.

Objective Beyond static assessment, functional techniques are increasingly applied in magnetic resonance imaging (MRI) studies. Stress MRI techniques bring together MRI and mechanical loading to study knee joint and tissue functionality, yet prototypical axial compressive loading devices are bulky and complex to operate. This study aimed to design and validate an MRI-compatible pressure-controlled varus–valgus loading device that applies loading along the joint line. Methods Following the device’s thorough validation, we demonstrated proof of concept by subjecting a structurally intact human cadaveric knee joint to serial imaging in unloaded and loaded configurations, i.e. to varus and valgus loading at 7.5 kPa (= 73.5 N), 15 kPa (= 147.1 N), and 22.5 kPa (= 220.6 N). Following clinical standard (PDw fs) and high-resolution 3D water-selective cartilage (WATSc) sequences, we performed manual segmentations and computations of morphometric cartilage measures. We used CT and radiography (to quantify joint space widths) and histology and biomechanics (to assess tissue quality) as references. Results We found (sub)regional decreases in cartilage volume, thickness, and mean joint space widths reflective of areal pressurization of the medial and lateral femorotibial compartments. Discussion Once substantiated by larger sample sizes, varus–valgus loading may provide a powerful alternative stress MRI technique.

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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.