Dual contrast in computed tomography allows earlier characterization of articular cartilage over single contrast

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.

Effects of human articular cartilage constituents on simultaneous diffusion of cationic and nonionic contrast agents

“…However, at the 72 hour diffusion time point, the gadoteridol partition strongly correlates with the PG concentration, whereas the correlation with collagen (amide I) concentration observed in the 21 hour time point is not present in the mid to deep cartilage sections. High diffusion flux of CA4+ has been suggested to cause drag influencing diffusion of gadoteridol 45,46 . However, current data and experiments are not sufficient to state whether the high uptake of CA4+ in deep cartilage influenced gadoteridol diffusion and decrease in correlation between amide I concentration and gadoteridol partition at 72 hour time point.…”

Molecular Signaling Interactions and Transport at the Osteochondral Interface: A Review

“…It can also provide useful information to design therapeutic molecules and drug delivery systems for these conditions (DiDomenico et al, 2018). Diffusion through the articular surface is the primary route of transport for contrast agents within cartilage (Bashir et al, 1996;Nelson et al, 2018;Bhattarai et al, 2020;Freedman et al, 2020;Meng et al, 2020). A summary of the relevant studies using contrast agent-based diffusion methods for micro-CT is shown in Table 2.…”

Nanotechnology and Osteoarthritis. Part 1: Clinical landscape and opportunities for advanced diagnostics

“…To overcome these shortcomings, Töyräs et al describe the simultaneous use of two or three cartilage permeable and impermeable contrast agents 31,32 . Bismuth oxide nanoparticles, being too large to diffuse into cartilage, accumulate at the cartilage surface and provide a high contrast signal, 31 while tissue‐permeable agents (anionic, neutral, and cationic small molecule iodine, neutral gadolinium) diffuse within cartilage and provide an attenuation reflective of GAG content or porosity 31‐33 . CT's capability to separate X‐ray photon energy spectra allows the interrogation of multiple contrast agents (Figure 3).…”

“…31,32 Bismuth oxide nanoparticles, being too large to diffuse into cartilage, accumulate at the cartilage surface and provide a high contrast signal, 31 while tissue-permeable agents (anionic, neutral, and cationic small molecule iodine, neutral gadolinium) diffuse within cartilage and provide an attenuation reflective of GAG content or porosity. [31][32][33] CT's capability to separate X-ray photon energy spectra allows the interrogation of multiple contrast agents (Figure 3). PA is particularly suited for imaging of peripheral joints such as fingers, hands, elbows, shoulders, knees, and ankles and thus of interest for diagnosing arthritis.…”