Long Axial Field-of-View PET Systems

Total body (TB) positron emission tomography (PET) instruments have dramatically changed the paradigm of PET clinical and research studies due to their very high sensitivity and capability to image dynamic radiopharmaceutical distributions in the major organs of the body simultaneously. In this manuscript, we review the design of these systems and discuss general challenges and trade-offs to maximize the performance gains of current TB-PET systems. We then describe new concepts and technology that may impact future TB-PET systems. The manuscript summarizes what has been learned from the initial sites with TB-PET and explores potential research and clinical applications of TB-PET. The current generation of TB-PET systems range in axial field-of-view (AFOV) from 1 to 2 m and serve to illustrate the benefits and opportunities of a longer AFOV for various applications in PET. In only a few years of use these new TB-PET systems have shown that they will play an important role in expanding the field of molecular imaging and benefiting clinical practice.

This article describes aspects of PET scanner design for long axial field-of-view systems and how these choices have an impact on scanner performance.

PET instruments are now available with a long axial field-of-view (LAFOV) to enable imaging the total-body, or at least head and torso, simultaneously and without bed translation. This has two major benefits, a dramatic increase in system sensitivity and the ability to measure kinetics with wider axial coverage so as to include multiple organs. This article presents a review of the technology leading up to the introduction of these new instruments, and explains the benefits of an LAFOV PET-CT instrument. To date there are two platforms developed for total-body PET (TB-PET), an outcome of the EXPLORER Consortium of the University of California at Davis (UC Davis) and the University of Pennsylvania (Penn). The uEXPLORER at UC Davis has an AFOV of 194 cm and was developed by United Imaging Healthcare. The PennPET EXPLORER was developed at Penn and is based on the digital detector from Philips Healthcare. This multiring system is scalable and has been tested with 3 rings but is now being expanded to 6 rings for 140 cm. Initial human studies with both EXPLORER systems have demonstrated the successful implementation and benefits of LAFOV scanners for both clinical and research applications. Examples of such studies are described in this article.

This work uses lesion detectability to characterize the performance of long axial field of view (AFOV) PET scanners which have increased sensitivity compared to clinical scanners. Studies were performed using the PennPET Explorer, a 70-cm long AFOV scanner built at the University of Pennsylvania, for small lesions distributed in a uniform water-filled cylinder (simulations and measurements), an anthropomorphic torso phantom (measurement), and a human subject (measurement). The lesion localization and detection task was quantified numerically using a generalized scan statistics methodology. Detectability was studied as a function of background activity distribution, scan duration for a single bed position, and axial location of the lesions. For the cylindrical phantom, the areas under the localization receiver operating curve (ALROCs) of lesions placed at various axial locations in the scanner were greater than 0.8 – a value considered to be clinically acceptable (i.e., 80% probability of detecting lesion) – for scan times of 60 s or longer for standard-of-care (SoC) clinical dose levels. 10-mm diameter lesions placed in the anthropomorphic phantom and human subject resulted in ALROCs of 0.8 or greater for scan times longer than 30 s in the lung region and 60 s in the liver region, also for SoC doses. ALROC results from all three activity distributions show similar trends as a function of counts detected per axial location. These results will be used to guide decisions on imaging parameters, such as scan time and patient dose, when imaging patients in a single bed position on long AFOV systems and can also be applied to clinical scanners with consideration of the sensitivity differences.

The PennPET Explorer, a prototype whole-body imager currently operating with a 64-cm axial field-of-view (FOV), can image the major body organs simultaneously with higher sensitivity than that of commercial devices. We report here the initial human imaging studies on the PennPET Explorer with each study designed to test specific capabilities of the device. We demonstrate the ability to scan for shorter duration, or, alternatively with less activity, without a compromise in image quality. Delayed images, up to 10 half-lives with FDG, reveal biological insight and support the ability to track biologic processes over time. In one clinical patient, the PennPET Explorer better delineates extent of ¹⁸F-fluorodeoxyglucose (FDG)-avid disease. In a second clinical study with ⁶⁸Ga-DOTATATE we demonstrate comparable diagnostic image quality on the PennPET compared to the clinical scan, but with one-fifth the activity. Dynamic imaging studies capture relatively noise-free input functions for kinetic modeling approaches. Additional studies with experimental research radiotracers illustrate the benefits from the combination of large axial coverage and high sensitivity. These studies provide proof-of-concept for many proposed applications for a long axial FOV PET scanner.

We report on the development of the PennPET Explorer whole-body imager. Methods: The PennPET Explorer is a multi-ring system designed with a long axial field-of-view (AFOV). The imager is scalable and comprises multiple 22.9-cm long ring-segments, each with 18 detector modules based on the digital Philips Digital Photon Counting (PDPC) silicon photomultiplier. A prototype three-segment imager has been completed and tested with an active 64-cm AFOV. Results: The instrument design is described, and its physical performance measurements are presented. These include sensitivity of 55 kcps/MBq, spatial resolution of 4.0 mm, energy resolution of 12%, timing resolution of 250 ps, and a noise equivalent count rate above 1000 kcps beyond 30 kBq/cc. Following an evaluation of lesion torso phantoms to characterize the imager’s quantitative accuracy, human studies were performed on normal volunteers. Conclusion: The physical performance measurements validate the system design and lead to the high quality human studies. A more detailed examination of human imaging with this whole-body imager is presented in a companion paper.

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.

The first total-body positron emission tomography (TB-PET) scanner represents a radical change for experimental medicine and diagnostic health care.

PET imaging is a key diagnostic tool used clinically to follow and treat disease. While static FDG scans are routine in the clinic, dynamic imaging of disease-specific tracers is important to provide a more precise measure of treatment response. Commercial scanners have limited axial field-of-view and, therefore, we are building a 70 cm long axial FOV TOF PET/CT scanner to enable whole-body dynamic imaging with very high sensitivity. Our scanner is based on detectors with digital SiPMs to provide 300 ps, or better, timing resolution. In this paper, we describe the design and expected performance of this system that will be used for clinical and translational research at the University of Pennsylvania.

There is a growing interest in the design and construction of a PET scanner with a very long axial extent. One critical design challenge is the impact of the long axial extent on the scanner spatial resolution properties. In this work, we characterize the effect of parallax error in PET system designs having an axial field-of-view (FOV) of 198 cm (total-body PET scanner) using fully-3D Monte Carlo simulations. Two different scintillation materials were studied: LSO and LaBr₃. The crystal size in both cases was 4  ×  4  ×  20 mm³. Several different depth-of-interaction (DOI) encoding techniques were investigated to characterize the improvement in spatial resolution when using a DOI capable detector. To measure spatial resolution we simulated point sources in a warm background in the center of the imaging FOV, where the effects of axial parallax are largest, and at several positions radially offset from the center. Using a line-of-response based ordered-subset expectation maximization reconstruction algorithm we found that the axial resolution in an LSO scanner degrades from 4.8 mm to 5.7 mm (full width at half max) at the center of the imaging FOV when extending the axial acceptance angle (α) from  ±12° (corresponding to an axial FOV of 18 cm) to the maximum of  ±67°—a similar result was obtained with LaBr₃, in which the axial resolution degraded from 5.3 mm to 6.1 mm. For comparison we also measured the degradation due to radial parallax error in the transverse imaging FOV; the transverse resolution, averaging radial and tangential directions, of an LSO scanner was degraded from 4.9 mm to 7.7 mm, for a measurement at the center of the scanner compared to a measurement with a radial offset of 23 cm. Simulations of a DOI detector design improved the spatial resolution in all dimensions. The axial resolution in the LSO-based scanner, with α  =  ± 67°, was improved from 5.7 mm to 5.0 mm by incorporating a two-layer DOI detector. These results characterize the maximum axial blurring for a fully open 2 m long PET scanner and demonstrate that large sensitivity gains are possible with a modest reduction in resolution when using current clinical detector technology with no DOI capability.

Current generation of commercial time-of-flight (TOF) PET scanners utilize 20–25 mm thick LSO or LYSO crystals and have an axial FOV (AFOV) in the range of 16–22 mm. Longer AFOV scanners would provide increased intrinsic sensitivity and require fewer bed positions for whole-body imaging. Recent simulation work has investigated the sensitivity gains that can be achieved with these long AFOV scanners, and has motivated new areas of investigation such as imaging with a very low dose of injected activity as well as providing whole-body dynamic imaging capability in one bed position. In this simulation work we model a 72 cm long scanner and prioritize the detector design choices in terms of timing resolution, crystal size (spatial resolution), crystal thickness (detector sensitivity), and depth-of-interaction (DOI) measurement capability. The generated list data are reconstructed with a list-mode OSEM algorithm using a Gaussian TOF kernel that depends on the timing resolution and blob basis functions for regularization. We use lesion phantoms and clinically relevant metrics for lesion detectability and contrast measurement. The scan time was fixed at 10 min for imaging a 100 cm long object assuming a 50% overlap between adjacent bed positions. Results show that a 72 cm long scanner can provide a factor of ten reduction in injected activity compared to an identical 18 cm long scanner to get equivalent lesion detectability. While improved timing resolution leads to further gains, using 3 mm (as opposed to 4 mm) wide crystals does not show any significant benefits for lesion detectability. A detector providing 2-level DOI information with equal crystal thickness also does not show significant gains. Finally, a 15 mm thick crystal leads to lower lesion detectability than a 20 mm thick crystal when keeping all other detector parameters (crystal width, timing resolution, and DOI capability) the same. However, improved timing performance with 15 mm thick crystals can provide similar or better performance than that achieved by a detector using 20 mm thick crystals.