Osteoarthritis (OA) is a chronic joint disease that causes disability and pain. The osteochondral interface is a gradient tissue region that plays a significant role in maintaining joint health. It has been shown that during OA, increased neoangiogenesis creates porous channels at the osteochondral interface allowing the transport of molecules related to OA. Importantly, the connection between these porous channels and the early stages of OA development is still not fully understood. Microcomputed tomography (microCT) offers the ability to image the porous channels at the osteochondral interface, however, a contrast agent is necessary to delineate the different X-ray attenuations of the tissues. In this study BaYbF₅-SiO₂ nanoparticles are synthesized and optimized as a microCT contrast agent to obtain an appropriate contrast attenuation for subsequent segmentation of structures of interest, that is, porous channels, and mouse subchondral bone. For this purpose, BaYbF₅ nanoparticles were synthesized and coated with a biocompatible silica shell (SiO₂). The optimized BaYbF₅-SiO₂ 27 nm nanoparticles exhibited the highest average microCT attenuation among the biocompatible nanoparticles tested. The BaYbF₅-SiO₂ 27 nm nanoparticles increased the mean X-ray attenuation of structures of interest, for example, porous channel models and mouse subchondral bone. The BaYbF₅-SiO₂ contrast attenuation was steady after diffusion into mouse subchondral bone. In this study, we obtained for the first time, the average microCT attenuation of the BaYbF₅-SiO₂ nanoparticles into porous channel models and mouse subchondral bone. In conclusion, BaYbF₅-SiO₂ nanoparticles are a potential contrast agent for imaging porous channels at the osteochondral interface using microCT.