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

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. The accuracy of thickness measurements was assessed by comparison with micro-computed tomography (micro-CT) measurements. It also investigated whether the local grey level (median HU value of the articular cartilage layer) correlates with tissue mechanical competence. The latter was evaluated in terms of instantaneous and equilibrium responses by indenting the cartilage layer with a spherical indenter up to 15% of its thickness, a value representative of the in vivo level of tissue deformation.

Three different grey-level gradients were distinguishable within the articular cartilage in contrast-enhanced HR-pQCT. Additionally, contrast-enhanced imaging enabled the accurate quantification of articular cartilage thickness. Significant relationships, assessed using Spearman’s rank correlation coefficient (ρ), were found between the morphology or grey level of the articular cartilage and its mechanical competence. Tissue thickness showed a strong negative relationship with the instantaneous elastic response (ρ = -0.85 ), whereas local grey level proteoglycans content showed a moderate positive relationship with the tissue elastic response at equilibrium (ρ = 0.39).

The results support extending the proposed approach to human articular cartilage, with the potential to discriminate early-degenerated tissue and to detect local variation in mechanical behaviour across the articular surface.

In this data set we made available:

a) The  elastic – i.e., instantaneous elastic modulus, E0 (MPa) –, viscous – i.e., relaxation time, τ (s), and stretching parameter, β (-) –, and equilibrium – equilibrium modulus, Eeq (MPa) –  mechanical properties describing the response of the articular cartilage to indentation. Furthermore, the exponent of the stretched exponential function – (1/τ)β –, and the ratio between E0 and Eeq – E0 /Eeq – are also provided. The values of the properties related to the three indentations peculiar of each investigated sample are reported. Full details regarding the indentation protocol applied to investigate the articular cartilage response, and the computation of these parameters can be found in previous publications (https://doi.org/10.3390/ma15186425; https://doi.org/10.3390/ma18132943).

b) The results of the analysis, reported as CT number (HU), of the images acquired using a High Resolution-peripheral Quantitative Computed Tomography (HR-pQCT) system. More in detail, for each investigated sample, the CT number of the articular cartilage, the exhausted CA4+ solution, and the difference between them, is provided.  

c) The thickness of the articular cartilage (mm), computed by evaluating the images acquired by a High Resolution-peripheral Quantitative Computed Tomography system and by a Micro Computed Tomography.

This research was founded by Fondazione del Monte di Bologna e Ravenna (grant number 2024.0065).