Triple Contrast Computed Tomography Reveals Site-Specific Differences In Human Knee Joint Biomechanical Properties

Purpose: Conventional computed tomography (CT) cannot separate articular cartilage from surrounding soft tissues or detect degenerative changes in cartilage. Contrast agents can be used to enhance the cartilage-synovial fluid contrast. Depending on their properties, contrast agents can stay in the synovial fluid or diffuse into cartilage, enabling tissue condition characterization. We hypothesize utilization of a triple contrast agent in clinical CT enables comprehensive evaluation of the cartilage condition within the knee joint. In this study, for the first time, we harnessed a triple contrast agent and a clinical CT to scan cadaveric knee joints. The aim is to study the feasibility of this method for cartilage segmentation and condition evaluation. The triple contrast agent consists of cationic, iodinated CA4+, non-ionic, gadolinium-based gadoteridol, and bismuth nanoparticles (BiNPs). BiNPs remain in synovial fluid due to their large size, thus, allowing to distinguish the cartilage morphology, while CA4+ and gadoteridol diffuse into cartilage. The diffusion of CA4+ is driven by the negatively charged proteoglycans in cartilage, and gadoteridol diffusion reflects the water content and permeability of cartilage. Dual-energy scanning is used to separate the dual contrast agent concentrations inside the tissue.