Abstract
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 nonionic agents, are not fully understood. We hypothesize that for a cationic agent, these variations increase the diffusion rate while decreasing partition, whereas, for a nonionic agent, these changes increase both the rate of diffusion and partition. Thus, we examine the diffusion of cationic and nonionic contrast agents within degraded tissue in time‐ and depth‐dependent manners. Osteochondral plugs (N = 15, d = 8 mm) were extracted from human cadaver knee joints, immersed in a mixture of cationic CA4+ and nonionic 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 < .05), whereas in deeper (40%‐100%) cartilage, CA4+ correlated only with proteoglycans (R > 0.671, P < .01). Gadoteridol partition correlated inversely with collagen concentration (0%‐100%, R < −0.514, P < .05). Cartilage degeneration substantially increased the time for CA4+ compared with healthy tissue (248 ± 171 vs 175 ± 95 minute) to reach the bone‐cartilage interface, whereas for gadoteridol the time (111 ± 63 vs 179 ± 163 minute) 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.
Highlights
Articular cartilage is avascular, and its metabolic function is regulated via diffusion and convection of charged and uncharged solutes between the synovial fluid and the constituents of the cartilage extracellular matrix (ECM).[1]
Superficial to mid (0%‐60% depth) cartilage CA4+ partitions correlated with water content (R < −0.521, P < .05), whereas in deeper (40%‐100%) cartilage, CA4+ correlated only with proteoglycans (R > 0.671, P < .01)
We evaluated the composition of the human articular cartilage samples via microscopy and spectroscopy and measured the diffusion of the contrast agents by dual‐contrast contrast‐ enhanced computed tomography (CECT)
Summary
Its metabolic function is regulated via diffusion and convection of charged and uncharged solutes between the synovial fluid and the constituents of the cartilage extracellular matrix (ECM).[1] Cartilage ECM is a heterogeneous structure, mainly consisting of interstitial water (60%‐85%), collagen fibrils (50%‐80% of dry content), and negatively charged proteoglycans (PGs; 20%‐30% of dry content).[2,3] Changes in the tissue composition alter the interstitial fluid flow 2,4 and mechanical properties.[5,6,7] The diffusion of a contrast agent inside the tissue, followed by subsequent contrast‐enhanced imaging, provides information on the health status of the cartilage tissue.[8,9,10,11,12] For example, contrast‐ enhanced computed tomography (CECT) is used to evaluate osteoarthritis (OA)‐related degeneration of cartilage and the associated alterations in the composition and morphology.[13,14,15,16]. Anionic agents suffer from low sensitivity, as they diffuse against the fixed negative charge that prevails inside healthy articular cartilage. Cationic contrast agents molecules are attracted into the tissue through electrostatic attraction and are used to directly quantify cartilage PG concentration.[12,14,18]
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