The chapter focuses on positron emission tomography (PET), a medical imaging technique that combines high speed with high complexity data processing. In PET, optical sensors detect gamma events generated by the annihilation of an electron and a positron, by measuring hundreds of individual photon times-ofarrival. These measurements are carefully analyzed, every 6.4 ls, by ultra-fast networks and distributed reconstruction algorithms, all running in parallel at several gigabit-per-second. In this context, we present an array of 4 × 4 digital silicon photomultipliers (MD-SiPMs) integrated in standard CMOS, capable of capturing and digitizing up to 32 million individual photon times-of-arrival per second, for up to 0.6 million gamma events per second. For each gamma event the equivalent energy is also computed to help the reconstruction algorithms screen out noise. The sensor is the core of the world’s first endoscopic digital PET, a tool with unprecedented levels of contrast and detail for early and accurate cancer diagnostics.