Abstract. Charged contrast agents have been used both in vitro and in vivo for estimation of the fixed charge density (FCD) in articular cartilage. In the present study, the effects of molecular size and charge on the diffusion and equilibrium distribution of several magnetic resonance imaging (MRI) and computed tomography (CT) contrast agents were investigated. Full thickness cartilage disks (Ø = 4.0 mm, n = 64) were prepared from fresh bovine patellae. Contrast agent (gadopentetate: Magnevist®, gadodiamide: Omniscan™, ioxaglate: Hexabrix™ or sodium iodide: NaI) diffusion was allowed either through the articular surface or through the deep cartilage. CT imaging of the samples was conducted before contrast agent administration and after 1, 5, 9, 16, 25 and 29 h (and with three samples after 2, 3, 4 and 5 days) diffusion using a clinical peripheral quantitative computed tomography (pQCT) instrument. With all contrast agents, the diffusion through the deep cartilage was slower when compared to the diffusion through the articular surface. With ioxaglate, gadopentetate and gadodiamide it took over 29 h for diffusion to reach the near-equilibrium state. The slow diffusion of the contrast agents raise concerns regarding the validity of techniques for FCD estimation, as these contrast agents may not reach the equilibrium state that is assumed. However, since cartilage composition, i.e. deep versus superficial, had a significant effect on diffusion, imaging of the nonequilibrium diffusion process might enable more accurate assessment of cartilage integrity.

General scientific summary. Contrast enhanced cartilage tomography (CECT) was applied to investigate the effect of molecular size and charge on the diffusion of MRI and CT contrast agents in vitro. Full thickness cartilage discs were detached from visually intact bovine patellae. The discs were exposed to contrast agents in a sample holder which allowed contrast agent penetration only through the articular surface or through the deep cartilage, mimicking the in vivo situation. The samples were imaged with a clinical peripheral quantitative tomographic (pQCT) instrument. For all contrast agents, contrast agent diffusion through deep cartilage was slower than through the articular surface. Furthermore, equilibration times of over 29 h suggest that diffusion equilibrium, which is the basic assumption in dGEMRIC, may not be reached within clinically feasible diffusion times. However, since cartilage composition has an effect on diffusion, imaging of the nonequilibrium diffusion process might enable more accurate assessment of cartilage integrity.

Print publication: Issue 22 (21 November 2009)
Received 13 July 2009, in final form 18 September 2009
Published 28 October 2009