Rachel Stewart, Presenter: Nothing to Disclose

Prashant Nareshkumar Bansal MS, Abstract Co-Author: Nothing to Disclose

Mark Grinstaff, Abstract Co-Author: Nothing to Disclose

Brian Snyder, Abstract Co-Author: Nothing to Disclose

To compute the affinity and exclusion of charged contrast agents for imaging glycosaminoglycans (GAGs) of articular cartilage. Three contrast agents, one with four positive charges (CA4+), and two commercially available anionic contrast agents, ioxaglate (Hexabrix) and gadopentetate (Magnevist) were used.

Ten bovine osteochondral plugs were used in this study. Hexabrix and CA4+ were diluted to 16 mgI/mL and Magnevist was used at 0.2M. Sequential transaxial images of the cartilage were acquired using a micro computed tomographic imaging system at an isotropic voxel resolution of 36 µm3. For Contrast Enhanced CT (CECT) imaging, each plug was immersed in contrast solution for 24 h and scanned. Plugs were immersed sequentially in Hexabrix, Magnevist, and CA4+ with saline washes in between. Contrast solutions were also imaged both pre- and post-immersion. GAG content for each plug was determined using the DMMB assay. CECT attenuation was plotted as a function of GAG content for each contrast agent, and each affinity or exclusion factor was computed as a ratio between mean CECT attenuation in the cartilage compared to CT attenuation of the bathing solution.

The electrostatic attraction between CA4+ and anionic GAGs resulted in higher mean CECT attenuation in the tissue, and attenuation correlated more strongly (R2 = 0.83) with GAG content as compared to both anionic contrast agents (R2 = 0.20 and 0.22 for Hexabrix and Magnevist, respectively). Interpreting the slope of the regression line as sensitivity to changes in GAG, CA4+ was 2.7 times more sensitive than Hexabrix and 4.9 times more sensitive than Magnevist. For CA4+, the affinity factor was 2.38 ± 0.26 (Mean ± SD) and the exclusion factor (calculated as the inverse of an affinity factor) was1.69 ± 0.29 for Hexabrix and 2.21 ± 0.18 for Magnevist.

The higher affinity factor combined with the higher sensitivity for CA4+ suggests that the electrostatic attraction between the cationic contrast agent and the GAGs in cartilage tissue will facilitate better quantitative imaging of GAGs. Further, the electrostatic attraction rather than repulsion may provide a better mechanism to image GAGs in articular cartilage.

Multi-charged cationic CT contrast agents may provide better diagnostic information about GAG loss for early OA diagnosis at 10 times lower concentrations than anionic contrast agents.

Stewart, R, Bansal, P, Grinstaff, M, Snyder, B, Affinity and Exclusion of Charged Contrast Agents for Imaging Articular Cartilage.  Radiological Society of North America 2010 Scientific Assembly and Annual Meeting, November 28 - December 3, 2010 ,Chicago IL. http://archive.rsna.org/2010/9009006.html