Analysis of diffusion kinetics of anionic and cationic iodinated contrast agents using in-vivo CT imaging of rabbit knee cartilage

INTRODUCTION: Contrast Enhanced CT imaging of articular cartilage (CECT) is predicated on the use of positively or negatively charged contrast agents that function as mobile ionic probes that partition themselves in direct or indirect proportion to the glycosaminoglycan (GAG) content of the cartilage matrix according to Donnan equilibrium. Ex-vivo studies have shown that CECT imaging of cartilage using anionic, iodinated contrast agents can be used to monitor changes in the GAG content and biomechanical properties of cartilage. For CECT to be successful clinically, after the contrast agent is injected intra-articularly, it must diffuse into and equilibrate within the cartilage extracellular matrix (ECM) before the concentration gradient of the contrast agent significantly decreases in the synovial joint space. This quasi-steady state equilibrium must last long enough to allow CT imaging to be performed. To facilitate the segmentation of the cartilage from the contrast agent in the joint space, the x-ray attenuation profile of the contrast agent in the joint should be sufficiently different from the xray attenuation profile of the contrast agent diffused into the cartilage. Cationic contrast agents achieve this steady-state equilibrium better than anionic contrast agents. In an ex-vivo study of articular cartilage lining the femoral condyles of rabbit knees, we demonstrated that cationic contrast agents are able to map the inhomogeneous distribution of GAGs along the cartilage surface at 10-20x lower concentration than anionic contrast agent and are able to quantify changes in GAG content of bovine cartilage at similarly low concentrations. As a next step towards demonstrating the clinical potential for CECT imaging of cartilage invivo, the specific aims of this study were to compare the diffusion kinetics of an FDA approved, anionic (-1 charge) iodinated contrast agent (HexabrixTM, Mallindcrockdt, MO, USA, 80 mgI/mL) to a cationic iodinated contrast agent that we developed (CA4+, 12 mgI/mL) by performing CECT imaging of cartilage in-vivo using a New Zealand White rabbit knee model.