Optoacoustic (OA) imaging is a promising modality for quantifying blood oxygen saturation (sO2) in various biomedical applications - in diagnosis, monitoring of organ function, or even tumor treatment planning. We present an accurate and practically feasible real-time capable method for quantitative imaging of sO2 based on combining multispectral (MS) and multiple illumination (MI) OA imaging with learned spectral decoloring (LSD). For this purpose we developed a hybrid real-time MI MS OA imaging setup with ultrasound (US) imaging capability; we trained gradient boosting machines on MI spectrally colored absorbed energy spectra generated by generic Monte Carlo simulations and used the trained models to estimate sO2 on real OA measurements. We validated MI-LSD in silico and on in vivo image sequences of radial arteries and accompanying veins of five healthy human volunteers. We compared the performance of the method to prior LSD work and conventional linear unmixing. MI-LSD provided highly accurate results in silico and consistently plausible results in vivo. This preliminary study shows a potentially high applicability of quantitative OA oximetry imaging, using our method
