Effect of collagen cross-linking on quantitative MRI parameters of articular cartilage.

OBJECTIVE: To investigate the sensitivity of quantitative magnetic resonance imaging (MRI) parameters to increase of collagen cross-linking in articular cartilage, a factor possibly contributing to the aging-related development of osteoarthritis (OA). The issue has not been widely studied although collagen cross-links may significantly affect the evaluation of cartilage imaging outcome. DESIGN: Osteochondral samples (n = 14) were prepared from seven bovine patellae. To induce cross-linking, seven samples were incubated in threose while the other seven served as non-treated controls. The specimens were scanned at 9.4 T for T1, T1Gd (dGEMRIC), T2, adiabatic and continuous wave (CW) T1ρ, adiabatic T2ρ and T1sat relaxation times. Specimens from adjacent tissue were identically treated and used for reference to determine biomechanical properties, collagen, proteoglycan and cross-link contents, fixed charge density (FCD), collagen fibril anisotropy and water concentration of cartilage. RESULTS: In the threose-treated sample group, cross-links (pentosidine, lysyl pyridinoline (LP)), FCD and equilibrium modulus were significantly (P < 0.05) higher as compared to the non-treated group. Threose treatment resulted in significantly greater T1Gd relaxation time constant (+26%, P < 0.05), although proteoglycan content was not altered. Adiabatic and CW-T1ρ were also significantly increased (+16%, +28%, P < 0.05) while pre-contrast T1 was significantly decreased (-10%, P < 0.05) in the threose group. T2, T2ρ and T1sat did not change significantly. CONCLUSION: Threose treatment induced collagen cross-linking and changes in the properties of articular cartilage, which were detected by T1, T1Gd and T1ρ relaxation time constants. Cross-linking should be considered especially when interpreting the outcome of contrast-enhanced MRI in aging populations.

Diffusion of Gd-DTPA²â» into articular cartilage.

OBJECTIVES: The delayed Gadolinium-Enhanced MRI of Cartilage (dGEMRIC) technique is a method proposed for non-invasive measurement of cartilage glycosaminoglycan (GAG) content. In this method, gadopentetate (Gd-DTPA²â») is assumed to distribute in cartilage in inverse relation to the GAG distribution, thus allowing quantification of the GAG content. For accurate GAG quantification, the kinetics of Gd-DTPA²â» in articular cartilage is of critical importance. However, the diffusion of Gd-DTPA²â» has not been systematically studied over long time periods using MRI-feasible gadopentetate concentrations. Thus, the present study aims to investigate the diffusion of gadopentetate into cartilage in vitro in intact and enzymatically degraded cartilage. METHODS: The diffusion of gadopentetate into bovine articular cartilage was investigated at 9.4 T over 18-h time period using repeated T(1) measurements in two models, (1) comparing intact and trypsin-treated tissue and (2) assessing the effect of penetration direction. The diffusion process was further assessed by determining the gadopentetate flux and diffusivity. The results were compared with histological and biochemical reference methods. RESULTS AND CONCLUSIONS: The results revealed that passive diffusion of Gd-DTPA²â» was significantly slower than previously assumed, leading to overestimation of the GAG content at equilibrating times of few hours. Moreover, Gd-DTPA²â» distribution was found to depend not only on GAG content, but also on collagen content and diffusion direction. Interestingly, the dGEMRIC technique was found to be most sensitive to cartilage degradation in the early stages of diffusion process, suggesting that full equilibrium between gadopentetate and cartilage may not be required in order to detect cartilage degeneration.