Oxygenation-driven multimodal photoacoustic/ultrasonic imaging enhances evaluation of enthesitis disease activity in psoriatic arthritis

Conventional ultrasound (US) evaluation of enthesitis in psoriatic arthritis (PsA) is limited by its inability to quantify metabolic alterations such as hypoxia, a key driver of disease activity. We introduce an oxygenation-integrated multimodal photoacoustic/ultrasound (PA/US) imaging framework designed to quantify entheseal oxygen saturation (SO2) for assessing entheseal disease activity in PsA. In this cross-sectional study, 25 PsA patients underwent bilateral PA/US imaging of 12 entheses, where ultrasound lesions were scored using the Outcome Measures in Rheumatology scoring system, and PA-derived SO2 levels, quantified via dual-wavelength PA imaging, were classified into hyperoxia or hypoxia groups using k-means clustering. This approach provides metabolic insights complementary to conventional ultrasonic assessment. A composite score integrating hypoxia with US parameters was validated against clinical disease activity indices (Disease Activity Score 28-C-reactive protein, DAS28-CRP; Disease Activity Index for Psoriatic Arthritis, DAPSA). Among 300 entheses, 103 (34.3%) exhibited PA positivity, with 40 (38.8%) classified as hypoxia. Hypoxia scores independently predicted DAS28-CRP ([Formula: see text] = 0.618, p = 0.001) and DAPSA ([Formula: see text] = 0.612, [Formula: see text]). The hypoxia-optimized PAUS score demonstrated superior correlation with disease activity indices compared to conventional US (DAS28-CRP: r = 0.615, p = 0.001 versus r = 0.474, p = 0.017; DAPSA: r = 0.743, [Formula: see text] versus r = 0.567, p = 0.003), alongside superior diagnostic accuracy for minimal disease activity (area under the curve, AUC 0.776 versus 0.614, p = 0.008) and low disease activity (AUC 0.853 versus 0.772, p = 0.009). This multimodal scoring system enhances the stratification of PsA disease activity by providing unique metabolic insights, offering a potential tool for therapeutic monitoring and guiding treat-to-target strategies.