Abstract
Cationic computed tomography contrast agents are more sensitive for detecting cartilage degeneration than anionic or non-ionic agents. However, osteoarthritis-related loss of proteoglycans and increase in water content contrarily affect the diffusion of cationic contrast agents, limiting their sensitivity. The quantitative dual-energy computed tomography technique allows the simultaneous determination of the partitions of iodine-based cationic (CA4+) and gadolinium-based non-ionic (gadoteridol) agents in cartilage at diffusion equilibrium. Normalizing the cationic agent partition at diffusion equilibrium with that of the non-ionic agent improves diagnostic sensitivity. We hypothesize that this sensitivity improvement is also prominent during early diffusion time points and that the technique is applicable during contrast agent diffusion. To investigate the validity of this hypothesis, osteochondral plugs (d = 8 mm, N = 33), extracted from human cadaver (n = 4) knee joints, were immersed in a contrast agent bath (a mixture of CA4+ and gadoteridol) and imaged using the technique at multiple time points until diffusion equilibrium. Biomechanical testing and histological analysis were conducted for reference. Quantitative dual-energy computed tomography technique enabled earlier determination of cartilage proteoglycan content over single contrast. The correlation coefficient between human articular cartilage proteoglycan content and CA4+ partition increased with the contrast agent diffusion time. Gadoteridol normalized CA4+ partition correlated significantly (P < .05) with Mankin score at all time points and with proteoglycan content after 4 hours. The technique is applicable during diffusion, and normalization with gadoteridol partition improves the sensitivity of the CA4+ contrast agent.
Highlights
As a consequence of instantaneous impact, articular cartilage can become injured, leading to the development of post‐traumatic osteoarthritis (PTOA).[1]
The correlation coefficients between the Mankin score and CA+ partition of the full‐thickness cartilage increased at all the diffusion time points after normalizing with the partition of the non‐ionic gadoteridol (Figure 3)
The correlation coefficient between Optical density (OD) and CA4+ partition increased with the contrast agent diffusion time (Figure 4A)
Summary
As a consequence of instantaneous impact (eg, related to sports accident), articular cartilage can become injured, leading to the development of post‐traumatic osteoarthritis (PTOA).[1]. The uptake of a cationic agent depends both on the electrostatic attraction between the positively charged molecule and the negative fixed charge in cartilage, and the passive diffusion controlled by cartilage water content and permeability.[21] in degenerated cartilage, the uptake of the cationic agent is simultaneously reduced due to the decrease of negatively charged PGs, and enhanced due to the increase in permeability and water content These opposite effects limit the diagnostic effectiveness of the cationic agents, especially in the first hours of diffusion, which is vital for the clinical feasibility of the agent. Improvement in the sensitivity of the cationic agent would enable early detection of minor injuries and lesions, allowing timely selection of treatment, reducing the risk for PTOA This quantitative technique is based on the simultaneous diffusion of two contrast agents (iodine‐based CA4+ and gadolinium‐ based gadoteridol) into cartilage. We quantify the error in the partition of the contrast agents arising from the ongoing diffusion in the cartilage when the imaging is performed separately with two X‐ray tube voltages
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