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 (sO ₂) were validated against results obtained by established Power Doppler (PD) imaging and dynamic changes of inhaled O ₂ concentration respectively. PA changes were correlated with the histological grading of cartilage damages. Results: PA-measurements of vascularity and sO ₂ demonstrated a strong correlation with localized blood flow detected by PD imaging (r = 0.506, p < 0.001) and inhaled O ₂ 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 sO ₂ 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.