Project Summary Clinical time-of-flight positron emission tomography (TOF-PET) systems capable of excellent coincidence time resolution (CTR) promise to drastically enhance effective 511 keV photon sensitivity. The ability to more precisely localize annihilation origins along system response lines constrains event data, providing improved signal-to- noise ratio (SNR) and reconstructed image quality by associating 511 keV photons more closely to their true origin. This SNR enhancement increases as CTR is improved, and a major goal of ongoing PET instrumentation research and development is to push system CTR ≤100 ps full-width-at-half-maximum (FWHM). At this level of performance, events are constrained ≤1.5 cm, providing more than a five-fold increase in SNR relative to a system with no TOF capability. Advanced systems capable of ≤100 ps FWHM CTR would effectively more than double or quadruple the effective 511 keV system sensitivity, in comparison to state-of-the-art, clinical TOF-PET systems (250-400 ps FWHM CTR). Thus, advancing CTR is also a pathway for greatly improved system sensitivity without increasing detection volume and system cost. Standard PET detectors comprising segmented arrays of high-aspect-ratio scintillation crystal elements cannot achieve this level of performance and are ultimately limited by poor light collection efficiency and depth-dependent scintillation photon transit time jitter seen by the photodetector. To address this, we propose to develop a new detector readout concept which allows scintillation photons to be counted and a unique timestamp to be assigned for the first arriving photon at each photosensor pixel. We will leverage this new advancement in scalable PET detector readout and produce PET detector modules capable of high resolution, three-dimensional positioning capabilities and 100 ps FWHM CTR in a design that also makes no sacrifices on 511 keV photon detection efficiency. The new detector design will be integrated into large area detector modules that span the full axial extent (>20 cm) of a clinical PET system, including front-end signal and back-end data processing. We will construct a prototype tomographic imaging setup and quantify relevant system performance metrics and the imaging performance of future clinical systems made from this new detector. The proposed PET detector technologies can have a significant impact on quantitative PET imaging. The image SNR enabled by the significant boost in effective sensitivity can be employed to substantially reduce tracer dose and shorten scan time/increase patient throughput, or to better visualize and quantify smaller lesions/features in the presence of significant background, which are important features that can make PET more practical and accurate, as well as help to expand its roles in patient management.

Project Narrative We propose to develop and demonstrate the clinical imaging performance of high resolution, clinical time-of- flight positron emission tomography detectors that achieve 100 ps FWHM coincidence time resolution. This detector technology can facilitate PET systems with substantially enhanced reconstructed image signal-to-noise ratio and contrast-to-noise ratio, which can be exploited to improve lesion detection and quantification, or greatly reduce injected radiation dose or scan duration, making PET more accurate, safe, and practical across a wide variety of imaging studies.