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.

https://jnm.snmjournals.org/content/jnumed/early/2017/09/21/jnumed.116.184028.full.pdf

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

There have been major advances in PET technology that cumulatively have helped improve image quality, increased the range of applications for PET, and contributed to the more widespread use of PET. Examples of these technologic advances include whole-body imaging, 3-dimensional imaging, new scintillator materials, iterative reconstruction algorithms, combined PET/CT, and preclinical PET. New advances on the immediate horizon include the reintroduction of time-of-flight PET, which takes advantage of the favorable timing properties of newer scintillators; the integration of PET and MRI scanners into a dual-modality imaging system; and the possibility of further significant improvements in spatial resolution in preclinical PET systems. Sensitivity remains a limiting factor in many PET studies. Although, conceptually, huge gains in sensitivity are still possible, realizing these gains is thwarted largely by economic rather than scientific concerns. Predicting the future is fraught with difficulty; nonetheless, it is apparent that ample opportunities remain for new development and innovation in PET technology that will be driven by the demands of molecular medicine, notably sensitive and specific molecular diagnostic tools and the ability to quantitatively monitor therapeutic entities that include small molecules, peptides, antibodies, nanoparticles, DNA/RNA, and cells.

https://jnm.snmjournals.org/content/jnumed/47/11/1735.full.pdf

The 2006 Henry N. Wagner Lecture: Of Mice and Men (and Positrons)—Advances in PET Imaging Technology

The long patient port of a PET scanner tends to put stress on patients, especially patients with claustrophobia. It also prevents doctors and technicians from taking care of patients during scanning. In this paper, we proposed an 'open PET' geometry, which consists of two axially separated detector rings. A long and continuous field-of-view (FOV) including a 360° opened gap between two detector rings can be imaged enabling a fully 3D image reconstruction of all the possible lines-of-response. The open PET will become practical if iterative image reconstruction methods are applied even though image reconstruction of the open PET is analytically an incomplete problem. First we implemented a 'masked' 3D ordered subset expectation maximization (OS-EM) in which the system matrix was obtained from a long 'gapless' scanner by applying a mask to detectors corresponding to the open space. Next, in order to evaluate imaging performance of the proposed open PET geometry, we simulated a dual HR+ scanner (ring diameter of D = 827 mm, axial length of W = 154 mm × 2) separated by a variable gap. The gap W was the maximum limit to have axially continuous FOV of 3W though the maximum diameter of FOV at the central slice was limited to D/2. Artifacts, observed on both sides of the open space when the gap exceeded W, were effectively reduced by inserting detectors partially into unnecessary open spaces. We also tested the open PET geometry using experimental data obtained by the jPET-D4. The jPET-D4 is a prototype brain scanner, which has 5 rings of 24 detector blocks. We simulated the open jPET-D4 with a gap of 66 mm by eliminating 1 block-ring from experimental data. Although some artifacts were seen at both ends of the opened gap, very similar images were obtained with and without the gap. The proposed open PET geometry is expected to lead to realization of in-beam PET, which is a method for an in situ monitoring of charged particle therapy, by letting the beams pass through the gap. The proposed open PET geometry will also allow simultaneous PET/CT measurements of the same PET FOV as the CT FOV, in contrast to the conventional PET/CT where each FOV is separated by several tens of centimeters.

http://iopscience.iop.org/article/10.1088/0031-9155/53/3/015/pdf

A proposal of an open PET geometry.

The world's first total-body PET scanner with an axial field of view (AFOV) of 194 cm is now in clinical and research use at our institution. The uEXPLORER PET/CT system is the first commercially available total-body PET scanner. Here we present a detailed physical characterization of this scanner based on National Electrical Manufacturers Association (NEMA) NU 2-2018 along with a new set of measurements devised to appropriately characterize the total-body AFOV. Methods: Sensitivity, count-rate performance, time-of-flight resolution, spatial resolution, and image quality were evaluated following the NEMA NU 2-2018 protocol. Additional measurements of sensitivity and count-rate capabilities more representative of total-body imaging were performed using extended-geometry phantoms based on the world-average human height (∼165 cm). Lastly, image quality throughout the long AFOV was assessed with the NEMA image quality (IQ) phantom imaged at 5 axial positions and over a range of expected total-body PET imaging conditions (low dose, delayed imaging, short scan duration). Results: Our performance evaluation demonstrated that the scanner provides a very high sensitivity of 174 kcps/MBq, a count-rate performance with a peak noise-equivalent count rate of approximately 2 Mcps for total-body imaging, and good spatial resolution capabilities for human imaging (≤3.0 mm in full width at half maximum near the center of the AFOV). Excellent IQ, excellent contrast recovery, and low noise properties were illustrated across the AFOV in both NEMA IQ phantom evaluations and human imaging examples. Conclusion: In addition to standard NEMA NU 2-2018 characterization, a new set of measurements based on extending NEMA NU 2-2018 phantoms and experiments was devised to characterize the physical performance of the first total-body PET system. The rationale for these extended measurements was evident from differences in sensitivity, count-rate-activity relationships, and noise-equivalent count-rate limits imposed by differences in dead time and randoms fraction between the NEMA NU 2 70-cm phantoms and the more representative total-body imaging phantoms. Overall, the uEXPLORER PET system provides ultra-high sensitivity that supports excellent spatial resolution and IQ throughout the field of view in both phantom and human imaging.

https://jnm.snmjournals.org/content/jnumed/early/2020/10/23/jnumed.120.250597.full.pdf

Performance Evaluation of the uEXPLORER Total-Body PET/CT Scanner Based on NEMA NU 2-2018 with Additional Tests to Characterize PET Scanners with a Long Axial Field of View.

The axial field of view (AFOV) of the current generation of clinical whole-body PET scanners range from 15–22 cm, which limits sensitivity and renders applications such as whole-body dynamic imaging or imaging of very low activities in whole-body cellular tracking studies, almost impossible. Generally, extending the AFOV significantly increases the sensitivity and count-rate performance. However, extending the AFOV while maintaining detector thickness has significant cost implications. In addition, random coincidences, detector dead time, and object attenuation may reduce scanner performance as the AFOV increases. In this paper, we use Monte Carlo simulations to find the optimal scanner geometry (i.e. AFOV, detector thickness and acceptance angle) based on count-rate performance for a range of scintillator volumes ranging from 10 to 93 l with detector thickness varying from 5 to 20 mm. We compare the results to the performance of a scanner based on the current Siemens Biograph mCT geometry and electronics. Our simulation models were developed based on individual components of the Siemens Biograph mCT and were validated against experimental data using the NEMA NU-2 2007 count-rate protocol. In the study, noise-equivalent count rate (NECR) was computed as a function of maximum ring difference (i.e. acceptance angle) and activity concentration using a 27 cm diameter, 200 cm uniformly filled cylindrical phantom for each scanner configuration. To reduce the effect of random coincidences, we implemented a variable coincidence time window based on the length of the lines of response, which increased NECR performance up to 10% compared to using a static coincidence time window for scanners with a large maximum ring difference values. For a given scintillator volume, the optimal configuration results in modest count-rate performance gains of up to 16% compared to the shortest AFOV scanner with the thickest detectors. However, the longest AFOV of approximately 2 m with 20 mm thick detectors resulted in performance gains of 25–31 times higher NECR relative to the current Siemens Biograph mCT scanner configuration.

/pdf/optimal-whole-body-pet-scanner-configurations-for-different-4suv102z77.pdf

Optimal whole-body PET scanner configurations for different volumes of LSO scintillator: a simulation study

A new positron emission tomography (PET) scanner for whole-body studies has been developed. The scanner has 720 block detectors, each of which consists of a flat panel position-sensitive photomultiplier and a 16/spl times/8 BGO crystal array. The detector system is composed of 12 layers of block detector rings stacked axially, and each ring consists of a circular array of 60 block detectors. Since each block detector ring contains eight crystal rings, the total number of detector rings is 96 and the axial field of view (FOV) is 685 mm, which is sufficient to measure a whole-body with two steps of scan. The detector ring diameter is 1 020 mm and the transaxial FOV is 600 mm in diameter. Coarse slice septa are placed between the block detector rings, which are effective to reduce scattered coincidence events while keeping a high detection sensitivity. Parallel 16 personal computers are used for the data acquisition and processing to deal with a large amount of event data. The acquired data in 3-D manner are converted to 2-D data set with Fourier rebinning algorithm and reconstructed with a fast iterative algorithm "DRAMA". The reconstructed images for the whole body are obtained within 5 min after the scan. By using the coarse septa, the scatter fraction measured with NEMA NU2-2001 standard was 31.4% whose value was significantly lower than that of 3-D PET without septa. The system sensitivity was 9.72 cps/kBq, and the peak counts of the noise equivalent count rate used with direct random-subtraction was 113.6 kcps at 10.5 kBq/ml.

A high-throughput whole-body PET scanner using flat panel PS-PMTs

A small animal PET scanner using 256-channel PS-PMTs has been designed, constructed, and evaluated. The scanner has twelve detector modules, each of which consists of a double-layer array of LYSO crystals and three PS-PMTs (Hama- matsu R8400-00-M256). In the LYSO crystal block, 32 times 53 crystal elements are optically coupled to 32 times 54 crystal elements with a shift of half the element pitch in the axial direction. The dimension of each crystal element is 1.275 times 2.675 mm2 in cross section and 7 mm in depth. The twelve detector modules are positioned on a 182 mm diameter ring to form 107 detector rings with 1.4 mm pitch. The transaxial FOV is 100 mm in diameter and the axial FOV is 151 mm, which is sufficient to cover the whole body of a mouse. In order to compensate for non-uniform outputs from the multi-anodes of the PS-PMTs, ASICs having 64-channel variable gain amplifiers and summing amplifiers are used in the front-end circuits. The preliminary experimental results are the transaxial resolution of 2.0 mm FWHM in the CFOV, and the axial resolution of 2.8 mm FWHM on the axis of the ring. The absolute coincidence sensitivity is 8.1% for a point source at the CFOV with setting an energy window of 350-750 keV and a timing window of 10 ns. The applicable imaging capability of the scanner was demonstrated by animal studies with a rat.

A. Katabe

Papers

A high-throughput whole-body PET scanner using flat panel PS-PMTs

Development of a Small Animal PET Scanner Using DOI Detectors