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.

Due to the adverse effects of de-metallation in past concerning FDA-approved gadolinium-based contrast agents (GBCAs), researchers have been focusing on developing safer and more efficient alternatives that could avoid toxicity caused by free gadolinium ions. Herein, two chiral GBCAs, Gd-LS with sulfonate groups and Gd-T with hydroxyl groups, are reported as potential candidates for magnetic reasonance imaging (MRI). The r₁ relaxivities of TSAP, SAP isomers of Gd-LS and SAP isomer of Gd-T at 1.4 T, 37 °C in water are 7.4 mM⁻¹s⁻¹, 14.5 mM⁻¹s⁻¹ and 5.2 mM⁻¹s⁻¹, respectively. Results show that the hydrophilic functional groups introduced to the chiral macrocyclic scaffold of Gd-T and Gd-LS both give constructive influences on the second-sphere relaxivity and enhance the overall r₁ value. Both cases indicate that the design of GBCAs should also focus on the optimal window in Solomon-Bloembergen-Morgan (SBM) theory and the effects caused by the second-sphere and outer-sphere relaxivity.

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.

The accurate screening of osteoporosis is important for identifying persons at risk. The diagnosis of bone conditions using dual X-ray absorptiometry is limited to extracting areal bone mineral density (BMD) and fails to provide any structural information. Computed tomography (CT) is excellent for morphological imaging but not ideal for material quantification. Advanced photon-counting detector CT (PCD-CT) possesses high spectral sensitivity and material decomposition capabilities to simultaneously determine qualitative and quantitative information. In this study, we explored the diagnostic utility of PCD-CT to provide high-resolution 3-D imaging of bone microarchitecture and composition for the sensitive diagnosis of bone in untreated and ovariectomized rats. PCD-CT accurately decomposed the calcium content within hydroxyapatite phantoms (r = 0.99). MicroCT analysis of tibial bone revealed significant differences in the morphological parameters between the untreated and ovariectomized samples. However, differences in the structural parameters of the mandible between the treatment groups were not observed. BMD determined with microCT and calcium concentration decomposed using PCD-CT differed significantly between the treatment groups in both the tibia and mandible. Quantitative analysis with PCD-CT is sensitive in determining the distribution of calcium and water components in bone and may have utility in the screening and diagnosis of bone conditions such as osteoporosis.