Imaging of proteoglycan and water contents in human articular cartilage with full‐body CT using dual contrast technique

Abstract

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.

Synchrotron MicroCT Reveals the Potential of the Dual Contrast Technique for Quantitative Assessment of Human Articular Cartilage Composition

“…D) as gadoteridol should diffuse into cartilage according to cartilage water content (which is around 80%). Moreover, the CA4+ partitions were slightly higher than those reported earlier even though the sample preparation and experimental conditions were similar. Beam hardening cannot explain the high gadoteridol partitions as a monochromatic beam was used.…”

“…The concentrations in the contrast agent mixture phantoms and the contrast agent partitions within cartilage were solved using Beer–Lambert law and Bragg's additive rule for mixtures, as were done in our earlier studies: where α is the total X‐ray attenuation of the contrast agent mixture within phantom or cartilage with energy E , µ is the mass attenuation coefficient, and C is the concentration of iodine (I) or gadolinium (Gd) in the mixture. The contrast agent concentrations in the mixtures and within cartilage are solved using Equation based on the radiation intensities of two different X‐ray energies applied (in this study 32 and 34 keV) as follows: …”

“…The diffusion of non‐ionic contrast agent reflects the water content and permeability when the contrast agent partition is determined prior to diffusion equilibrium. Further, by normalizing the cationic contrast agent distribution with that of non‐ionic agent distribution, the PG content within cartilage is estimated more accurately . This technique is based on exploiting two X‐ray energies that enable simultaneous determination of the distributions of the contrast agents within cartilage.…”

“…Further, by normalizing the cationic contrast agent distribution with that of non-ionic agent distribution, the PG content within cartilage is estimated more accurately. 19,22 This technique is based on exploiting two X-ray energies that enable simultaneous determination of the distributions of the contrast agents within cartilage. To achieve this, X-ray energies must be chosen carefully based on the applied contrast agents and their element-specific kedges (i.e., photoelectric absorption edges).…”

dGEMRIC and CECT Comparison of Cationic and Anionic Contrast Agents in Cadaveric Human Metacarpal Cartilage

“…Contrast agents were given 24 h to reach equilibrium within the tissue, and we recognize that this time span is not practical for clinical use and alternative strategies are being investigated. One potential approach to overcome this limitation is the dual‐contrast method whereby a second nonionic contrast agent is used to adjust for the contributions of water content and permeability at early time diffusion time points to afford improved correlations with GAG content . As we compared the performance of Gd4+ and CA4+ to the state‐of‐the‐art commercial agents, there is a difference in charge between the cationic and anionic agents, and this is another limitation of the study.…”