Mean Cartilage Attenuation Measured In Situ in an Osteoarthritis Mouse Model Using Contrast-Enhanced Micro-Computed Tomography is Indicative of Cartilage Degeneration.

Abstract

ObjectiveTo develop and validate an in vivo image acquisition protocol for assessment of cartilage degeneration in an osteoarthritis (OA) mouse model using contrast-enhanced micro-computed tomography (CECT).DesignThree-, four-, seven-, and 10-month-old male STR/ort OA (n = 8) and healthy control CBA/1 (n = 8) mice were imaged using synchrotron-radiation micro-computed tomography. Mean attenuation of cartilage and mean attenuation difference between cartilage and contrast agent (mean Δ attenuation), to control for flux, were calculated and correlated to previously published cartilage parameters measured in the same mice. In a second experiment, C57Bl/6 mice underwent destabilization of medial meniscus (DMM) surgery or sham surgery. At 0 (n = 8 DMM), and 4 weeks (n = 10 DMM, n = 6 sham) post-surgery, mice were imaged using CECT. Mean attenuation and Osteoarthritis Research Society International (OARSI) score of cartilage were calculated, and mean attenuation and OARSI score were correlated.ResultsMean Δ attenuation of medial cartilage was lower in STR/ort OA mice compared to healthy control CBA/1 at 3-, 4-, 7-, and 10-months of age. Medial mean Δ attenuation was positively correlated to cartilage volume and thickness and negatively correlated with surface-to-volume ratio and Collins score. The mean attenuation and OARSI score of cartilage in DMM OA mice was higher than in sham controls in the medial tibia. Mean attenuation was positively correlated with OARSI score in the medial tibia.ConclusionsAn in vivo CECT imaging method was developed and validated. Mean attenuation is sensitive to cartilage degeneration in OA mouse models when imaged against a contrast agent as a background and using in vivo compatible image acquisition parameters.