PROJECT SUMMARY Nalu Scientific LLC (NSL) proposes to develop and optimize the design of a silicon photomultiplier (SiPM) based, low-power, high channel density, waveform-digitizing readout microchip for TOF-PET that will increase image quality and provide more accurate and precise quantization, with the potential to significantly improve early diagnosis or lower exposure while also allowing greater flexibility in the development of personalized patient imaging strategies. The key idea behind the project is that of using the information of the full waveform acquired from the sensors that can provide information to overcome the limitations of traditional approaches, like the very fine accuracy in the threshold definition, dependence on low and high frequency noise, necessity of ad-hoc corrections for waveform amplitude (“time-walk”) and shape variation, and imprecise energy information, as well as no information about depth of interaction. NSL’s patented waveform-digitizing “System on Chip” readout ASIC technology has the potential to substantially improve TOF-PET imaging from its current state. During Phase I, we developed analytic modeling of light production and transport in scintillating crystals, along with realistic simulations of sensor and readout electronics in order to derive baseline technical specifications for a WFD readout chip. We then implemented a machine learning model to harvest and demonstrate the benefits of WFD. In phase II, we will complete the design, fabricate and test a SiPM-based, low-power, high channel density, waveform-digitizing readout microchip for TOF-PET, and validate the concept by developing and testing a PET subsystem as a demonstrator. We will collaborate with Dr. Hamid Sabet (Harvard) in improving the modeling of phase I, defining the advantages and limitations of the use of waveform information in a full PET system setting, and implementing a flat-panel PET detector demonstrator. The project specific aims are 1: Design and Fabricate Waveform digitizer chip for PET applications. 2: Design and Fabricate a DAQ system for PET incorporating the WFD readout chip. 3: WFD-based Detector Assembly Integration and characterization. In Phase II, in order to reach the specific aims, we will complete the design of the prototype chip following the specifications derived in phase I, using state of the art tools to confirm the functionality and performance of the chip before fabrication and verifying it with thorough testing. We then will fabricate a DAQ system capable of synchronizing multiple copies of the readout chip and handling expected data rates from realistic TOF-PET detector environments, and finally evaluate them in a realistic condition using phantom testing. The successful completion of the work is expected to result in the definition of a novel readout device and system that could prove transformative for the field of next generation PET scanners.