PET is widely considered the most sensitive technique available for noninvasively studying physiology, metabolism, and molecular pathways in the living human being. However, the utility of PET, being a photon-deficient modality, remains constrained by factors including low signal-to-noise ratio, long imaging times, and concerns about radiation dose. Two developments offer the potential to dramatically increase the effective sensitivity of PET. First by increasing the geometric coverage to encompass the entire body, sensitivity can be increased by a factor of about 40 for total-body imaging or a factor of about 4-5 for imaging a single organ such as the brain or heart. The world's first total-body PET/CT scanner is currently under construction to demonstrate how this step change in sensitivity affects the way PET is used both in clinical research and in patient care. Second, there is the future prospect of significant improvements in timing resolution that could lead to further effective sensitivity gains. When combined with total-body PET, this could produce overall sensitivity gains of more than 2 orders of magnitude compared with existing state-of-the-art systems. In this article, we discuss the benefits of increasing body coverage, describe our efforts to develop a first-generation total-body PET/CT scanner, discuss selected application areas for total-body PET, and project the impact of further improvements in time-of-flight PET.Key Words: instrumentation; molecular imaging; PET/CT; instrumentation; PET; total-body imaging J Nucl Med 2018; 59:3-12 DOI: 10.2967/jnumed.116.184028Al l nuclear medicine studies in humans are limited by the trade-offs between the number of detected decay events, imaging time, and absorbed dose. The number of detected events determines the signal-to-noise ratio (SNR) in the final image, but constraints on administered activity, as well as high random event rates and dead time that occur at high activities, currently prevent acquisition of high-SNR images in short times. This in turn limits the ability to perform high-resolution, dynamic imaging studies with tracer kinetic modeling, because short-time-frame datasets are always noisy. A further limitation is that although the tracer injection is systemic and radiotracer is present in the entire body, current imaging systems contain only a small portion of the body within the field of view (FOV). For applications in which the distribution of radiotracer in the entire body or multiple organ systems is of interest, this limitation leads to further inefficiencies and makes it difficult to acquire dynamic data from all the tissues of interest. If one takes whole-body PET scanning with 18 F-FDG as an example, the total efficiency with which pairs of coincidence photons that escape the body are detected is well under 1% even on today's best scanners. Simplistically, this number can be derived by considering that the average geometric sensitivity within the FOV of a typical clinical PET scanner is under 5% and that with an axial coverage of ...

The fundamental limits of spatial resolution in positron emission tomography (PET) have been understood for many years. The physical size of the detector element usually plays the dominant role in determining resolution, but the combined contributions from acollinearity, positron range, penetration into the detector ring, and decoding errors in the detector modules often combine to be of similar size. In addition, the sampling geometry and statistical noise further degrade the effective resolution. This paper describes quantitatively describes these effects, discusses potential methods for reducing the magnitude of these effects, and computes the ultimately achievable spatial resolution for clinical and pre-clinical PET cameras.

PET scanners based on LSO have the potential for significantly better coincidence timing resolution than the 6 ns FWHM typically achieved with BGO. This study analyzes the performance enhancements made possible by improved timing as a function of the coincidence time resolution. If 500 ps FWHM coincidence timing resolution can be achieved in a complete PET camera, the following four benefits can be realized for whole-body FDG imaging: 1) the random event rate can be reduced by using a narrower coincidence timing window, increasing the peak NECR by 50%; 2) using time-of-flight (TOF) in the reconstruction algorithm will reduce the noise variance by a factor of 5; 3) emission and transmission data can be acquired simultaneously, reducing the total scan time; and 4) axial blurring can be reduced by using TOF to determine the correct axial plane of origin for each event. While TOF was extensively studied in the 1980s, practical factors limited its effectiveness at that time and little attention has been paid to timing in PET since then. As these potential improvements are substantial and the advent of LSO PET cameras gives us the means to obtain them without other sacrifices, efforts to improve PET timing should resume after their long dormancy.

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