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Assessment of cartilage composition via tomographic imaging is critical after cartilage injury to prevent post‐traumatic osteoarthritis. Diffusion of cationic contrast agents in cartilage is affected by proteoglycan loss and elevated water content. These changes have opposite effects on diffusion and, thereby, reduce the diagnostic accuracy of cationic agents. Here, we apply, for the first time, a clinical full‐body CT for dual contrast imaging of articular cartilage. We hypothesize that full‐body CT can simultaneously determine the diffusion and partitioning of cationic and non‐ionic contrast agents and that normalization of the cationic agent partition with that of the non‐ionic agent minimizes the effect of water content and tissue permeability, especially at early diffusion time points. Cylindrical (d = 8 mm) human osteochondral samples (n = 45; four cadavers) of a variable degenerative state were immersed in a mixture of cationic iodinated CA4+ and non‐charged gadoteridol contrast agents and imaged with a full‐body CT scanner at various time points. Determination of contrast agents’ distributions within cartilage was possible at all phases of diffusion. At early time points, gadoteridol, and CA4+ distributed throughout cartilage with lower concentrations in the deep cartilage. At ≥24 h, the gadoteridol concentration remained nearly constant, while the CA4+ concentration increased toward deep cartilage. Normalization of the CA4+ partition with that of gadoteridol significantly (p < 0.05) enhanced correlation with proteoglycan content and Mankin score at the early time points. To conclude, the dual contrast technique was found advantageous over single contrast imaging enabling more sensitive diagnosis of cartilage degeneration. © 2019 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. J Orthop Res 9999:1–12, 2019.

Impact injuries of cartilage may initiate post-traumatic degeneration, making early detection of injury imperative for timely surgical or pharmaceutical interventions. Cationic (positively-charged) CT contrast agents detect loss of cartilage proteoglycans (PGs) more sensitively than anionic (negatively-charged) or non-ionic (non-charged, i.e., electrically neutral) agents. However, degeneration related loss of PGs and increase in water content have opposite effects on the diffusion of the cationic agent, lowering its sensitivity. In contrast to cationic agents, diffusion of non-ionic agents is governed only by steric hindrance and water content of cartilage. We hypothesize that sensitivity of an iodine(I)-based cationic agent may be enhanced by simultaneous use of a non-ionic gadolinium(Gd)-based agent. We introduce a quantitative dual energy CT technique (QDECT) for simultaneous quantification of two contrast agents in cartilage. We employ this technique to improve the sensitivity of cationic CA4+ (q =+4) by normalizing its partition in cartilage with that of non-ionic gadoteridol. The technique was evaluated with measurements of contrast agent mixtures of known composition and human osteochondral samples (n = 57) after immersion (72 h) in mixture of CA4+ and gadoteridol. Samples were arthroscopically graded and biomechanically tested prior to QDECT (50/100 kV). QDECT determined contrast agent mixture compositions correlated with the true compositions (R= 0.99, average error = 2.27%). Normalizing CA4+ partition in cartilage with that of gadoteridol improved correlation with equilibrium modulus (from ρ = 0.701 to 0.795). To conclude, QDECT enables simultaneous quantification of I and Gd contrast agents improving diagnosis of cartilage integrity and biomechanical status.