Total-Body PET: Maximizing Sensitivity to Create New Opportunities for Clinical Research and Patient Care

Abstract

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 ...

Hybrid Imaging: Instrumentation and Data Processing

“…Following the introduction of this concept and after several simulation studies, the EXPLORER (Extreme Performance Long Research scanner) consortium was set up with the task of building the world's first total-body PET/CT system-the EXPLORER PET/CT [109,110]. The EXPLORER has a 200 cm aFOV based on mainstream PET detector technology.…”

Oxygen and brain death; back from the brink

“…(c) Summary of the bioenergetic demands of the human brain, highlighting its limited energy reserves, in the form of O 2 , glucose and ATP, combined with high rates of metabolism. Note the almost exclusive cerebral uptake of glucose, as illustrated by the (first) whole‐body three‐dimensional positron emission tomography/computed tomography image using 18 F‐fluorodeoxyglucose (Cherry et al., ) and extraordinarily high rates of neuronal metabolism (numbers reflect average energy consumption/turnover based on an average brain mass of 1508.91 g and 86.06 × 10 9 neurons documented by Herculano‐Houzel, ). Indeed, the cerebral rate of ATP turnover at rest alone is so high that it is roughly equivalent to that documented in human skeletal (leg) muscle during the extreme physical demands of a marathon (Hochachka, ).…”

“…(); Bailey (); Cherry et al. (); Engl & Attwell (); Herculano‐Houzel (); Kety (); Martins et al. (); and Waldrop ().…”

Maximum likelihood activity and attenuation estimation using both emission and transmission data with application to utilization of Lu‐176 background radiation in TOF PET

“…shows that only 1k‐10k counts in the blank scan are needed to eliminate the unknown scale problem and realize the benefit of MLAA‐TX. Such count rate is achievable by using LSO/LYSO background radiation, especially in the long axial field of view EXPLORER scanners . This will be very useful for low‐dose PET imaging where using a CT scan to obtain attenuation image is undesirable due to the additional radiation dose.…”