Contrast agent electrostatic attraction rather than repulsion to glycosaminoglycans affords a greater contrast uptake ratio and improved quantitative CT imaging in cartilage.

The purpose of this study is to evaluate the effect of contrast agent charge on the contrast agent uptake ratio (CUR) in cartilage and to image the naturally occurring variations in glycosaminoglycan (GAG) content present in bovine articular cartilage. In an ex vivo bovine osteochondral plug model, we utilized three charged contrast agents (Gadopentetate/Magnevist [-2], Ioxaglate/Hexabrix [-1], and CA4+ [+4]) and μCT to image cartilage. The X-ray attenuation of the cartilage tissue after equilibration in each contrast agent was also related to the initial X-ray attenuation of each contrast agent in solution to compute the uptake of the respective contrast agent (i.e., the CUR). Use of the cationic contrast agent resulted in significantly higher equilibrium X-ray attenuations in cartilage ECM than either of the anionic contrast agents (Gadopentetate [-2] and Ioxaglate [-1]). The CUR (Mean±SD) as computed in this study was 2.38 (±0.26) for the cationic contrast agent indicating a 2.38 fold increase in computed tomography (CT) attenuation of the cartilage. For the anionic contrast agents, the CUR was 0.62 (±0.26) for Ioxaglate [-1] and 0.52 (±0.17) for Gadopentetate [-2], indicating exclusion of 38% Ioxaglate and 48% Gadopentetate from the cartilage extracellular matrix. The cationic contrast agent exhibited significant correlations between CT attenuation and GAG content whereas Ioxaglate and Gadopentetate did not (R(2)=0.83 for CA4+, R(2)=0.20 for Ioxaglate, and R(2)=0.22 for Gadopentetate). Electrostatic attraction of CA4+ allowed effective imaging of the GAG components of articular cartilage at 50% lower molar concentration than Ioxaglate and 20-fold lower molar concentration than Gadopentetate. The CA4+ contrast agent exhibited a significant correlation between CT attenuation and GAG content in ex vivo bovine osteochondral plugs.