Project Summary/Abstract A major advantage of coincidence detection of annihilation photons from positron-emitting radiotracers is the availability of time-of-flight (TOF) information, and the ability to measure TOF differences to better localize the positron emitter. Normally for positron emission tomography (PET), TOF information is used as a weighting kernel during image reconstruction and results in an effective sensitivity gain that can be used to reduce radiation dose, improve signal-to-noise ratio, or reduce scan duration. The magnitude of these benefits depend on the TOF resolution, which is governed by the timing performance of the detectors. Current state of the art for PET scanners is ~220 ps which corresponds to a localization of ~3.3 cm. A transformational change would occur, however, if a TOF resolution of <30 ps could be achieved. This would localize events within 4.5 mm, allowing images to be directly generated without a reconstruction algorithm at a spatial resolution that matches what is achieved in clinical PET scanners today. We refer to this as direct positron emission imaging (PEI). With this superb TOF resolution and reconstruction-free imaging, we enter a new regime where we expect major increases in image signal-to-noise, both due to the additional TOF information, and the removal of noise amplification inherent in reconstructing noisy data with noisy corrections from projection data. We propose to develop a first proof-of-concept imaging system that uses ultra-fast detectors to directly produces cross-sectional images without reconstruction and to quantify the performance of PEI both through simulations and experimentally. Since direct PEI does not have the same sampling constraints for data collection as PET, it creates opportunities for portable, and flexible imaging devices, with implications for patient-tailored or task-specific imaging applications (i.e. cardiac or breast imaging), as well as open designs for general purpose applications. To achieve the unprecedented TOF capabilities needed for direct PEI, we will exploit promptly emitted Cerenkov radiation that is generated with <10 ps in certain materials, including scintillators, in response to a 511 keV photon interaction. Our proposed novel detector design integrates a Cerenkov radiator directly into the entrance window of an ultra-fast microchannel plate photomultiplier tube, which is the fastest photon detector currently available with a response time of 25 ps. This approach eliminates all optical reflections between the point of light generation and the photocathode, preserving the prompt timing nature of Cerenkov photons. We then combine the integrated Cerenkov radiator detector with auxiliary photodetector read-out for robust coincidence detection, and complement this with advanced signal processing algorithms we have pioneered using convolutional neural networks to extract all possible timing information from the digitized detector waveforms and ultimately to perform reconstruction-free imaging using only the digitized waveforms as input. In summary, we aim to prove that direct PEI is possible, to characterize its properties and to provide the technological and algorithmic foundations for eventual translation for human imaging.

Narrative Positron emission tomography (PET) imaging with radiotracers is used in hospitals around the world for several applications, including cancer staging and response to treatment assessment, and also is an important tool in biomedical research for investigating a wide range of health and disorders. The raw data collected by a PET scanner does not immediately produce an image and is instead reconstructed from a series of angular views using a tomographic reconstruction algorithm, but theoretically, the physics does allow for directly producing an image provided the detectors are sufficiently fast to determine the detection time difference of the photons with resolution of less than 25 picoseconds. In this proposal we aim to develop ultra-fast instrumentation and supporting computational algorithms leading to the first demonstration of a reconstruction-free imaging system for cross-sectional imaging of radiotracers.