Assessment of morphology, radiopacity gradient and mechanical properties of articular cartilage with contrast-enhanced high-resolution peripheral quantitative computed tomography

Introduction: Degenerative alterations in proteoglycans content and collagen structure compromise the mechanical integrity of articular cartilage and, therefore, its viscoelastic properties. Early detection of these subtle alterations is a prerequisite for enabling intervention with promising treatments under development. Although magnetic resonance imaging provides valuable compositional information, its limited spatial resolution restricts its effectiveness in evaluating thin, soft tissues such as articular cartilage. Contrast-enhanced high-resolution peripheral quantitative computed tomography (HR-pQCT) offers an optimal compromise between spatial resolution and radiation exposure, enabling high-resolution evaluation of the cartilage layer and potentially overcoming this limitation. This study investigated the feasibility of using HR-pQCT enhanced with the cationic contrast agent CA4+ to determine the proteoglycan gradient and thickness of articular cartilage from bovine stifle joints. Methods: The accuracy of thickness measurements was assessed by comparison with micro-computed tomography (μCT) measurements. It also investigated whether the local CT number (mean HU value of the articular cartilage, either uncorrected or corrected to the HU value of CA4+ bath) correlates with tissue mechanical competence. The latter was evaluated in terms of instantaneous, stress-relaxation and equilibrium responses by indenting the cartilage layer with a spherical indenter up to 15%, a value representative of the level of tissue deformation occurring in vivo. Results and discussion: A depth-wise gradient of CT number was distinguishable within the articular cartilage in contrast-enhanced HR-pQCT, allowing in post-processing the subdivision of cartilage into its three main layers. Additionally, contrast-enhanced imaging enabled the accurate quantification of articular cartilage thickness. Significant relationships of varying strength, assessed using Spearman's rank correlation coefficient (ρ), were found between thickness and instantaneous elastic response (ρ = -0.85), stress-relaxation behaviour (ρ = -0.61), and equilibrium elastic response (ρ = -0.38) of articular cartilage. The same relationship with CT number showed comparable strength. These results, achieved through investigation of healthy bovine articular cartilage, support extending the proposed approach to human articular cartilage. The proposed approach, based on high-resolution X-ray scanner imaging enhanced with a cationic contrast agent, may have the potential to discriminate early-degenerated tissue by capturing subtle local alterations in thickness or CT number gradients. This could reveal changes in the relative thicknesses of the superficial, middle, and deep layers, across the articular surface, while also providing an indication of local alterations to the mechanical competence of the articular cartilage.