Molecular photoacoustic imaging for early diagnosis and treatment monitoring of rheumatoid arthritis in a mouse model.

Rheumatoid arthritis (RA) is a progressive inflammatory joint disease. Early diagnosis is critical for timely therapeutic intervention. However, it lacks effective diagnostic methods capable of detecting disease progression in its early stage and evaluating treatment efficacy in clinics. Photoacoustic (PA) molecular imaging is a novel imaging modality that can detect in the early stage of disease and continuously monitor its progression. In this study, Evans blue (EB) was used as a PA contrast agent to detect the angiogenesis and microcirculation dysfunction in RA joint. In collagen-induced arthritis (CIA) mouse model, a distinct increase of PA signal was detected early at 2 weeks, with significant higher PA signal intensities from the RA joints compared to the normal joints. More importantly, we detected an increasing trend of PA signal intensity week by week post CIA induction, demonstrating the potential of EB-enhanced PA imaging in monitoring the development of RA. However, joint damage was silent in the X-ray at 2 weeks post CIA induction, which suggested the superiority of PA imaging in RA early detection. In addition, striking decrease of PA signal intensities in the RA joints was observed after administration with etanercept compared with the untreated RA joints. The signal changes exhibited by PA imaging were confirmed by clinical observation and histological examinations. This study demonstrated the promising use of EB-enhanced PA imaging for the early diagnosis and its feasibility for RA treatment monitoring.