Effects of Human Articular Cartilage Constituents on Simultaneous Diffusion of Cationic and Non-ionic Contrast Agents

Abhisek Bhattarai, Janne T A Mäkelä, Behdad Pouran, Heikki Kröger, Harrie Weinans, Mark W Grinstaff, Juha Töyräs, Mikael J Turunen
Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society 2020 August 7
Contrast-enhanced computed tomography is an emerging diagnostic technique for osteoarthritis. However, the effects of increased water content, as well as decreased collagen and proteoglycan concentrations due to cartilage degeneration, on the diffusion of cationic and non-ionic agents, are not fully understood. We hypothesize that for a cationic agent, these variations increase the diffusion rate while decreasing partition, whereas, for a non-ionic agent, these changes increase both the rate of diffusion and partition. Thus, we examine the diffusion of cationic and non-ionic contrast agents within degraded tissue in time- and depth-dependent manners. Osteochondral plugs (N=15, d=8mm) were extracted from human cadaver knee joints, immersed in a mixture of cationic CA4+ and non-ionic gadoteridol contrast agents, and imaged at multiple time-points, using the dual contrast method. Water content, and, collagen and proteoglycan concentrations were determined using lyophilization, infrared spectroscopy, and digital densitometry, respectively. Superficial to mid (0-60% depth) cartilage CA4+ partitions correlated with water content (R<-0.521, p<0.05), whereas in deeper (40-100%) cartilage, CA4+ correlated only with proteoglycans (R>0.671, p<0.01). Gadoteridol partition correlated inversely with collagen concentration (0-100%, R<-0.514, p<0.05). Cartilage degeneration substantially increased the time for CA4+ compared to healthy tissue (248±171 vs 175±95 min) to reach the bone-cartilage interface, whereas for gadoteridol the time (111±63 vs 179±163 min) decreased. The work clarifies the diffusion mechanisms of two different contrast agents and presents depth and time-dependent effects resulting from articular cartilage constituents. The results will inform the development of new contrast agents and optimal timing between agent administration and joint imaging. This article is protected by copyright. All rights reserved.

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