Optical imaging tools are in high demand by the biomedical research and clinical communities for applications that greatly impact the life sciences.The invention of fluorescent molecular tomography (FMT) a decade ago can be considered a breakthrough in optical imaging, as it allows for unprecedented, in-vivo, non-invasive and quantitative 3D imaging of fluorescent probes. However, it has been recently shown than its performance can be greatly improved using a priori information for the tomographic algorithm regarding the distribution of optical parameters in tissue.Multispectral Optoacoustic Tomography (MSOT) is a new non-invasive medical imaging modality that is able to retrieve the 3D distribution of light energy deposition in small animals in vivo, and not invasively. Its high resolution has revolutionized the field of optical imaging, having many important applications in preclinical research and clinical diagnosis.By combining MSOT and FMT in a hybrid system, a unique synergy is established, since MSOT can potentially provide the input needed by FMT to achieve a radical improvement in its imaging performance, not to mention that the simple combination of the molecular information yielded by FMT with the functional and anatomical information yielded by MSOT is certainly useful for biomedical researchers and clinics. Furthermore a FMT/MSOT system will be capable of serving as a cheap diagnostic tool for rheumatoid arthritis (RA), shifting the expensive MRI diagnosis paradigm, and for the first time rendering economically viable the frequent monitoring of this aging-related disease, which is a major cause of mortality in Europe.The objective of this project is to develop the first hybrid FMT/MSOT system, engineering the optimal tomographic approaches for exploiting the system’s synergies to achieve unprecedented FMT performance. The system’s capacity as a tool for the diagnosis of RA will be tested at the clinic.