Simultaneous Quantitation of Cationic and Non-ionic Contrast Agents in Articular Cartilage Using Synchrotron MicroCT Imaging

Abstract

Early diagnosis of acute cartilage injuries enables monitoring of disease progression and improved treatment option planning to prevent post-traumatic osteoarthritis. In contrast-enhanced computed tomography (CECT), the changes in cationic agent diffusion within the tissue reflect cartilage degeneration. The diffusion in degenerated cartilage depends on proteoglycan (PG) content and water content, but each having an opposite effect on diffusion, thus compromising the diagnostic sensitivity. To overcome this limitation, we propose the simultaneous imaging of cationic (sensitive to PG and water contents) and non-ionic (sensitive to water content) agents. In this study, quantitative dual-energy CT (QDECT) imaging of two agents is reported for the first time at clinically feasible imaging time points. Furthermore, this is the first time synchrotron microCT with monochromatic X-rays is employed in cartilage CECT. Imaging was conducted at 1 and 2 h post contrast agent immersion. Intact, PG-depleted, and mechanically injured + PG-depleted cartilage samples ( n = 33) were imaged in a mixture of cationic (iodine-based CA4+) and non-ionic (gadolinium-based gadoteridol) agents. Concurrent evaluation of CA4+ and gadoteridol partitions in cartilage is accomplished using QDECT. Subsequent normalization of the CA4+ partition with that of the gadoteridol affords CA4+ attenuations that significantly correlate with PG content – a key marker of OA.

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

“…CA4+ distributions within cartilage were as expected (at 2 h decreasing and at 72 h increasing trends toward cartilage–bone interface) and in line with the previous studies at both diffusion time points measured in human and bovine articular cartilage . For gadoteridol, the shapes of the distribution profiles were similar to those reported earlier at both diffusion time points . However, the gadoteridol partitions (over 100%) at the diffusion equilibrium were unexpectedly high (Fig.…”

“…This correlation along with minor error between the true and measured concentrations, reflects that the determination of the concentrations is accurate and linear within whole range of concentrations with the present dual contrast technique. A similar correlation between measured and true concentrations in the mixture phantoms was observed in our recent synchrotron microCT study with different X‐ray energies (25 and 37 keV) . In the present study, we took advantage of the narrow X‐ray beam energy bandwidth and used the image acquisition energies (32 and 34 keV) very close to iodine k ‐edge (33.2 keV) to minimize the time difference between the measurements due to energy change and to maximize the image contrast.…”

“…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, 33 as were done in our earlier studies 19,22,34 :…”

“…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: …”

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.…”