Contrast enhanced computed tomographic imaging of articular cartilage: Interrelationships with biochemical and biomechanical properties

Articular Cartilage (AC) is comprised of glycosaminoglycans (GAGs), collagen and water that determine its mechanical properties and function. Osteoarthritis (OA) is a degenerative joint disease that affects cartilage mechanical properties and impairs its function. Loss of GAGs is one of the key indicators of early OA. Hence, a sensitive imaging technique that can monitor early changes in GAG content may afford opportunities for treatment and prevention of OA. Cartilage does not attenuate x-rays very well; therefore CT along with an anionic iodinated contrast agent has been used to measure changes in GAG content. Furthermore, since the compressive properties of AC are highly correlated with its GAG content and it's permeability to water, these agents can also be used to monitor the compressive properties of AC. The motivation behind this work was to explore the use of anionic and cationic contrast agents for Contrast Enhanced CT (CECT) of AC and demonstrate the feasibility of CECT as a diagnostic tool to quantitatively monitor the GAG content and compressive properties of AC.;Initially, it was demonstrated that anionic CECT can predict changes in GAG content and compressive properties of AC whose GAG content was depleted using chondroitinase-ABC. Next, we demonstrated that CECT could be used to quantitatively evaluate GAG content of intact joint surface cartilage and that the mass transfer of the contrast agent into the cartilage could be boosted by thirty minutes of mechanical convection comparable to 24 hours of passive diffusion. These results provide evidence of the clinical feasibility of this technique.;Further, novel cationic contrast agents were shown to generate stronger correlations and were 5 times more sensitive than anionic contrast agents in predicting changes in GAG content of normal and degraded AC. Finally, an in vivo rabbit knee model for imaging AC with anionic and cationic contrast agents was developed to quantify early changes in GAG content. Cationic CECT afforded improved visualization and statistically significant correlations with GAG content at 7 times lower concentration than the anionic CECI. We anticipate that cationic CECI will lead to improved quantification of cartilage GAG content for early OA diagnosis.;In summary, CECI has the potential to be a quantitative diagnostic tool for basic research and clinical practice.