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To assess the utility of longitudinal ultrasound (US) to quantify volumetric changes in joint soft tissues during the progression of posttraumatic osteoarthritis (PTOA) in mice, and validate the US results with histological findings. A longitudinal cohort of 3-month-old wild-type C57BL/6 male mice received the Hulth-Telhag surgical procedure on right knee to induce PTOA, and sham surgery on their left knee as control. US scans were performed on both knees before, 2, 4, 6, and 8 weeks post-surgery. Joint space volume and Power-Doppler (PD) volume were obtained from US images via Amira software. A parallel cross-sectional cohort of mice was killed at each US time point, and knee joints were subjected to histological analysis to obtain synovial soft-tissue area and OARSI scores. The correlation between US joint space volume and histological synovial soft-tissue area or OARSI score was assessed via linear regression analysis. US images indicated increased joint space volume in PTOA joints over time, which was associated with synovial inflammation and cartilage damage by histology. These changes started from 2 weeks post-surgery and gradually became more severe. No change was detected in sham joints. Increased joint space volume was significantly correlated with increased synovial soft-tissue area and the OARSI score ( P <0.001). PD signal was detected in the joint space of PTOA joints at 6 weeks post-surgery, which was consistent with the location of blood vessels that stained positively for CD31 and alpha-smooth muscle actin in the synovium. This study indicates that US is a cost-effective longitudinal outcome measure of volumetric and vascular changes in joint soft tissues during PTOA progression in mice, which positively correlates with synovial inflammation and cartilage damage.

Utilization of longitudinal ultrasound to quantify joint soft-tissue changes in a mouse model of posttraumatic osteoarthritis