Time of Flight in Perspective: Instrumental and Computational Aspects of Time Resolution in Positron Emission...

The first time-of-flight positron emission tomography (TOF-PET) scanners were developed as early as in the 1980s. However, the poor light output and low detection efficiency of TOF-capable detectors available at the time limited any gain in image quality achieved with these TOF-PET scanners over the traditional non-TOF PET scanners. The discovery of LSO and other Lu-based scintillators revived interest in TOF-PET and led to the development of a second generation of scanners with high sensitivity and spatial resolution in the mid-2000s. The introduction of the silicon photomultiplier (SiPM) has recently yielded a third generation of TOF-PET systems with unprecedented imaging performance. Parallel to these instrumentation developments, much progress has been made in the development of image reconstruction algorithms that better utilize the additional information provided by TOF. Overall, the benefits range from a reduction in image variance (SNR increase), through allowing joint estimation of activity and attenuation, to better reconstructing data from limited angle systems. In this work, we review these developments, focusing on three broad areas: 1) timing theory and factors affecting the time resolution of a TOF-PET system; 2) utilization of TOF information for improved image reconstruction; and 3) quantification of the benefits of TOF compared to non-TOF PET. Finally, we offer a brief outlook on the TOF-PET developments anticipated in the short and longer term. Throughout this work, we aim to maintain a clinically driven perspective, treating TOF as one of multiple (and sometimes competitive) factors that can aid in the optimization of PET imaging performance.