While the first time-of-flight (TOF)-positron emission tomography (PET) systems were already built in the early 1980s, limited clinical studies were acquired on these scanners. PET was still a research tool, and the available TOF-PET systems were experimental. Due to a combination of low stopping power and limited spatial resolution (caused by limited light output of the scintillators), these systems could not compete with bismuth germanate (BGO)-based PET scanners. Developments on TOF system were limited for about a decade but started again around 2000. The combination of fast photomultipliers, scintillators with high density, modern electronics, and faster computing power for image reconstruction have made it possible to introduce this principle in clinical TOF-PET systems. This paper reviews recent developments in system design, image reconstruction, corrections, and the potential in new applications for TOF-PET. After explaining the basic principles of time-of-flight, the difficulties in detector technology and electronics to obtain a good and stable timing resolution are shortly explained. The available clinical systems and prototypes under development are described in detail. The development of this type of PET scanner also requires modified image reconstruction with accurate modeling and correction methods. The additional dimension introduced by the time difference motivates a shift from sinogram- to listmode-based reconstruction. This reconstruction is however rather slow and therefore rebinning techniques specific for TOF data have been proposed. The main motivation for TOF-PET remains the large potential for image quality improvement and more accurate quantification for a given number of counts. The gain is related to the ratio of object size and spatial extent of the TOF kernel and is therefore particularly relevant for heavy patients, where image quality degrades significantly due to increased attenuation (low counts) and high scatter fractions. The original calculations for the gain were based on analytical methods. Recent publications for iterative reconstruction have shown that it is difficult to quantify TOF gain into one factor. The gain depends on the measured distribution, the location within the object, and the count rate. In a clinical situation, the gain can be used to either increase the standardized uptake value (SUV) or reduce the image acquisition time or administered dose. The localized nature of the TOF kernel makes it possible to utilize local tomography reconstruction or to separate emission from transmission data. The introduction of TOF also improves the joint estimation of transmission and emission images from emission data only. TOF is also interesting for new applications of PET-like isotopes with low branching ratio for positron fraction. The local nature also reduces the need for fine angular sampling, which makes TOF interesting for limited angle situations like breast PET and online dose imaging in proton or hadron therapy. The aim of this review is to introduce the reader i...

The goal of this simulation study is the performance evaluation and comparison of six potential designs for a time-of-flight PET scanner for pediatric patients of up to about 12 years of age. It is designed to have a high sensitivity and provide high-contrast and high-resolution images. The simulated pediatric PET is a full ring scanner, consisting of 32  ×  32 mm monolithic LYSO:Ce crystals coupled to digital silicon photomultiplier arrays. The six considered designs differ in axial lengths (27.2 cm, 54.4 cm and 102 cm) and crystal thicknesses (22 mm and 11 mm). The simulations are based on measured detector response data. We study two possible detector arrangements: 22 mm-thick crystals with dual-sided readout and 11 mm-thick crystals with back-sided readout. The six designs are simulated by means of the GEANT4 application for tomographic emission software, using the measured spatial, energy and time response of the monolithic scintillator detectors as input. The performance of the six designs is compared on the basis of four studies: (1) spatial resolution; (2) NEMA NU2-2012 sensitivity and scatter fraction (SF) tests; (3) non-prewhitening signal-to-noise ratio observer study; and (4) receiver operating characteristics analysis. Based on the results, two designs are identified as cost-effective solutions for fast and efficient imaging of children: one with 54.4 cm axial field-of-view (FOV) and 22 mm-thick crystals, and another one with 102 cm axial FOV and 11 cm-thick crystals. The first one has a higher center point sensitivity than the second one, but requires dual-sided readout. The second design has the advantage of allowing a whole-body scan in a single bed position acquisition. Both designs have the potential to provide an excellent spatial resolution (∼2 mm) and an ultra-high sensitivity (>100 cps [Formula: see text]).