Photoacoustic imaging of synovial tissue hypoxia in experimental post-traumatic osteoarthritis.

OBJECTIVES: This pilot study aimed to investigate the feasibility of non-invasively assessing synovial tissue hypoxia in vivo using photoacoustic (PA) imaging in a post-traumatic osteoarthritis model and explore its correlation with OA severity. METHODS: The three-dimensional vasculature structure and oxygenation level of synovial tissues of destabilization of the medial meniscus (DMM)-induced osteoarthritis (OA) mice were longitudinally monitored using PA imaging. Vascular volume/tissue volume (%) and tissue oxygen saturation (sO2) were validated against results obtained by established Power Doppler (PD) imaging and dynamic changes of inhaled O2 concentration respectively. PA changes were correlated with the histological grading of cartilage damages. RESULTS: PA-measurements of vascularity and sO2 demonstrated a strong correlation with localized blood flow detected by PD imaging (r=0.506, p<0.001) and inhaled O2 concentration. DMM knees exhibited much more vascularity in synovial tissue at 4 months after surgery (median 11.3%, IQR: 10.7-15.5%) than the intact knees at time zero (median:5.1%, IQR:3.8-6.8%, p<0.001) as well as the sham-operated knees (median: 4%, IQR: 3.75-5.45%, p=0.017). Paradoxically, synovial tissue sO2 was significantly lower in DDM knees (median: 37.7%, IQR: 36.4-40.6%) than both the intact (47.1%, IQR: 41.9-49.8% p=0.001) and sham-operated knees (45.1% IQR: 45.1-52.4%, p=0.017). The PA-detected synovial tissue hypoxia correlated with the severity of cartilage loss in DMM mice (rho=-0.597, p=0.031). CONCLUSION: Here, we demonstrated PA imaging can be implemented for non-invasive imaging of the synovial tissue. Under PA imaging, synovitis in OA was characterized by increased angiogenesis and synovial tissue hypoxia; the latter was associated with the severity of OA.