Walk-through flat panel total-body PET: a patient-centered design for high throughput imaging at lower cost using DOI-capable high-resolution monolithic detectors.

PURPOSE: Long axial field-of-view (LAFOV) systems have a much higher sensitivity than standard axial field-of-view (SAFOV) PET systems for imaging the torso or full body, which allows faster and/or lower dose imaging. Despite its very high sensitivity, current total-body PET (TB-PET) throughput is limited by patient handling (positioning on the bed) and often a shortage of available personnel. This factor, combined with high system costs, makes it hard to justify the implementation of these systems for many academic and nearly all routine nuclear medicine departments. We, therefore, propose a novel, cost-effective, dual flat panel TB-PET system for patients in upright standing positions to avoid the time-consuming positioning on a PET-CT table; the walk-through (WT) TB-PET. We describe a patient-centered, flat panel PET design that offers very efficient patient throughput and uses monolithic detectors (with BGO or LYSO) with depth-of-interaction (DOI) capabilities and high intrinsic spatial resolution. We compare system sensitivity, component costs, and patient throughput of the proposed WT-TB-PET to a SAFOV (= 26 cm) and a LAFOV (= 106 cm) LSO PET systems. METHODS: Patient width, height (= top head to start of thighs) and depth (= distance from the bed to front of patient) were derived from 40 randomly selected PET-CT scans to define the design dimensions of the WT-TB-PET. We compare this new PET system to the commercially available Siemens Biograph Vision 600 (SAFOV) and Siemens Quadra (LAFOV) PET-CT in terms of component costs, system sensitivity, and patient throughput. System cost comparison was based on estimating the cost of the two main components in the PET system (Silicon Photomultipliers (SiPMs) and scintillators). Sensitivity values were determined using Gate Monte Carlo simulations. Patient throughput times (including CT and scout scan, patient positioning on bed and transfer) were recorded for 1 day on a Siemens Vision 600 PET. These timing values were then used to estimate the expected patient throughput (assuming an equal patient radiotracer injected activity to patients and considering differences in system sensitivity and time-of-flight information) for WT-TB-PET, SAFOV and LAFOV PET. RESULTS: The WT-TB-PET is composed of two flat panels; each is 70 cm wide and 106 cm high, with a 50-cm gap between both panels. These design dimensions were justified by the patient sizes measured from the 40 random PET-CT scans. Each panel consists of 14 × 20 monolithic BGO detector blocks that are 50 × 50 × 16 mm in size and are coupled to a readout with 6 × 6 mm SiPMs arrays. For the WT-TB-PET, the detector surface is reduced by a factor of 1.9 and the scintillator volume by a factor of 2.2 compared to LAFOV PET systems, while demonstrating comparable sensitivity and much better uniform spatial resolution (< 2 mm in all directions over the FOV). The estimated component cost for the WT-TB-PET is 3.3 × lower than that of a 106 cm LAFOV system and only 20% higher than the PET component costs of a SAFOV. The estimated maximum number of patients scanned on a standard 8-h working day increases from 28 (for SAFOV) to 53-60 (for LAFOV in limited/full acceptance) to 87 (for the WT-TB-PET). By scanning faster (more patients), the amount of ordered activity per patient can be reduced drastically: the WT-TB-PET requires 66% less ordered activity per patient than a SAFOV. CONCLUSIONS: We propose a monolithic BGO or LYSO-based WT-TB-PET system with DOI measurements that departs from the classical patient positioning on a table and allows patients to stand upright between two flat panels. The WT-TB-PET system provides a solution to achieve a much lower cost TB-PET approaching the cost of a SAFOV system. High patient throughput is increased by fast patient positioning between two vertical flat panel detectors of high sensitivity. High spatial resolution (< 2 mm) uniform over the FOV is obtained by using DOI-capable monolithic scintillators.

The potential of a medium-cost long axial FOV PET system for nuclear medicine departments.

PURPOSE: Total body positron emission tomography (TB-PET) has recently been introduced in nuclear medicine departments. There is a large interest in these systems, but for many centers, the high acquisition cost makes it very difficult to justify their current operational budget. Here, we propose medium-cost long axial FOV scanners as an alternative. METHODS: Several medium-cost long axial FOV designs are described with their advantages and drawbacks. We describe their potential for higher throughput, more cost-effective scanning, a larger group of indications, and novel research opportunities. The wider spread of TB-PET can also lead to the fast introduction of new tracers (at a low dose), new methodologies, and optimized workflows. CONCLUSIONS: A medium-cost TB-PET would be positioned between the current standard PET-CT and the full TB-PET systems in investment but recapitulate most advantages of full TB-PET. These systems could be more easily justified financially in a standard academic or large private nuclear medicine department and still have ample research options.

Abbreviated scan protocols to capture 18F-FDG kinetics for long axial FOV PET scanners.

PURPOSE: Kinetic parameters from dynamic 18F-fluorodeoxyglucose (FDG) imaging offer complementary insights to the study of disease compared to static clinical imaging. However, dynamic imaging protocols are cumbersome due to the long acquisition time. Long axial field-of-view (LAFOV) PET scanners (> 70 cm) have two advantages for dynamic imaging over clinical PET scanners with a standard axial field-of-view (SAFOV; 16-30 cm). The large axial coverage enables multi-organ dynamic imaging in a single bed position, and the high sensitivity may enable clinically routine abbreviated dynamic imaging protocols. METHODS: In this work, we studied two abbreviated protocols using data from a 65-min dynamic 18F-FDG scan: (A) dynamic imaging immediately post-injection (p.i.) for variable durations, and (B) dynamic imaging immediately p.i. for variable durations plus a 1-h p.i. (5-min-long) datapoint. Nine cancer patients were imaged on the Biograph Vision Quadra (Siemens Healthineers). Time-activity curves over the lesions (N = 39) were fitted using the Patlak graphical analysis and a 2-tissue-compartment (2C, k4 = 0) model for variable scan durations (5-60 min). Kinetic parameters from the complete dataset served as the reference. Lesions from all cancers were grouped into low, medium, and high flux groups, and bias and precision of Ki (Patlak) and Ki, K1, k2, and k3 (2C) were calculated for each group. RESULTS: Using only early dynamic data with the 2C (or Patlak) model, accurate quantification of Ki required at least 50 (or 55) min of dynamic data for low flux lesions, at least 30 (or 40) min for medium flux lesions, and at least 15 (or 20) min for high flux lesions to achieve both 10% bias and precision. The addition of the final (5-min) datapoint allowed for accurate quantification of Ki with a bias and precision of 10% using only 10-15 min of early dynamic data for either model. CONCLUSION: Dynamic imaging for 10-15 min immediately p.i. followed by a 5-min scan at 1-h p.i can accurately and precisely quantify 18F-FDG on a long axial FOV scanner, potentially allowing for more widespread use of dynamic 18F-FDG imaging.

An algorithm for automated ROI definition in water or epoxy-filled NEMA NU-2 image quality phantoms.

Drawing regions of interest (ROIs) in positron emission tomography/computed tomography (PET/CT) scans of the National Electrical Manufacturers Association (NEMA) NU-2 Image Quality (IQ) phantom is a time-consuming process that allows for interuser variability in the measurements. In order to reduce operator effort and allow batch processing of IQ phantom images, we propose a fast, robust, automated algorithm for performing IQ phantom sphere localization and analysis. The algorithm is easily altered to accommodate different configurations of the IQ phantom. The proposed algorithm uses information from both the PET and CT image volumes in order to overcome the challenges of detecting the smallest spheres in the PET volume. This algorithm has been released as an open-source plug-in to the Osirix medical image viewing software package. We test the algorithm under various noise conditions, positions within the scanner, air bubbles in the phantom spheres, and scanner misalignment conditions. The proposed algorithm shows run-times between 3 and 4 min and has proven to be robust under all tested conditions, with expected sphere localization deviations of less than 0.2 mm and variations of PET ROI mean and maximum values on the order of 0.5% and 2%, respectively, over multiple PET acquisitions. We conclude that the proposed algorithm is stable when challenged with a variety of physical and imaging anomalies, and that the algorithm can be a valuable tool for those who use the NEMA NU-2 IQ phantom for PET/CT scanner acceptance testing and QA/QC.

Image-based Modeling of PSF Deformation with Application to Limited Angle PET Data.

The point-spread-functions (PSFs) of reconstructed images can be deformed due to detector effects such as resolution blurring and parallax error, data acquisition geometry such as insufficient sampling or limited angular coverage in dual-panel PET systems, or reconstruction imperfections/simplifications. PSF deformation decreases quantitative accuracy and its spatial variation lowers consistency of lesion uptake measurement across the imaging field-of-view (FOV). This can be a significant problem with dual panel PET systems even when using TOF data and image reconstruction models of the detector and data acquisition process. To correct for the spatially variant reconstructed PSF distortions we propose to use an image-based resolution model (IRM) that includes such image PSF deformation effects. Originally the IRM was mostly used for approximating data resolution effects of standard PET systems with full angular coverage in a computationally efficient way, but recently it was also used to mitigate effects of simplified geometric projectors. Our work goes beyond this by including into the IRM reconstruction imperfections caused by combination of the limited angle, parallax errors, and any other (residual) deformation effects and testing it for challenging dual panel data with strongly asymmetric and variable PSF deformations. We applied and tested these concepts using simulated data based on our design for a dedicated breast imaging geometry (B-PET) consisting of dual-panel, time-of-flight (TOF) detectors. We compared two image-based resolution models; i) a simple spatially invariant approximation to PSF deformation, which captures only the general PSF shape through an elongated 3D Gaussian function, and ii) a spatially variant model using a Gaussian mixture model (GMM) to more accurately capture the asymmetric PSF shape in images reconstructed from data acquired with the B-PET scanner geometry. Results demonstrate that while both IRMs decrease the overall uptake bias in the reconstructed image, the second one with the spatially variant and accurate PSF shape model is also able to ameliorate the spatially variant deformation effects to provide consistent uptake results independent of the lesion location within the FOV.

Design and performance of a high spatial resolution, time-of-flight PET detector.

This paper describes the design and performance of a high spatial resolution PET detector with time-of-flight capabilities. With an emphasis on high spatial resolution and sensitivity, we initially evaluated the performance of several 1.5 × 1.5 and 2.0 × 2.0 mm2 and 12-15 mm long LYSO crystals read out by several appropriately sized PMTs. Experiments to evaluate the impact of reflector on detector performance were performed and the final detector consisted of a 32 × 32 array of 1.5 × 1.5 × 15 mm3 LYSO crystals packed with a diffuse reflector and read out by a single Hamamatsu 64 channel multi-anode PMT. Such a design made it compact, modular and offered a cost-effective solution to obtaining excellent energy and timing resolution. To minimize the number of readout signals, a compact front-end readout electronics that summed anode signals along each of the orthogonal directions was also developed. Experimental evaluation of detector performance demonstrates clear discrimination of the crystals within the detector. An average energy resolution (FWHM) of 12.7 ± 2.6% and average coincidence timing resolution (FWHM) of 348 ps was measured, demonstrating suitability for use in the development of a high spatial resolution time-of-flight scanner for dedicated breast PET imaging.

Timing and Energy Resolution of new near-UV SiPMs coupled to LaBr3:Ce for TOF-PET.

The high light output and fast decay time of LaBr3:Ce scintillation detectors leads to excellent timing performance. To realize the potential of timing resolution with LaBr3:Ce we have investigated the performance with SiPMs, which enable 1-to-1 coupling to individual crystals, and which have been optimized for the near-ultraviolet (NUV) scintillation light emission of LaBr3:Ce. Coincidence timing resolution (CTR) of 100 ps was measured for a 4×4×5 mm3 LaBr3:30%Ce crystal directly coupled to a large-area 4×4 mm2 NUV-SiPM. Results show very little dependence on temperature, in the range of -20° to 20°C, and bias voltage, from 2 V to 5 V over breakdown. Optimal performance was achieved at an over-voltage (OV) range of 3 V - 5 V, at which high gain and high photon detection efficiency are achieved. Though saturation was evident at 511 keV, an energy resolution of 6.8% was measured after correcting for non-linearity. We also measured a CTR of 110 ps for a 4×4×5mm3 LaBr3:5%Ce crystal and 245 ps for a 4×4×30 mm3 LaBr3:5%Ce crystal using the NUV-SIPM. The poorer timing measurement for the 30-mm long crystal is due mainly to a systematic shift in the time pick-off as a function of the depth-of-interaction. The excellent temperature stability, fast rise time, high gain, and low noise of the NUV-SiPM make it a practical and highly appealing photodetector for the readout of a LaBr3:Ce TOF-PET detector.

Energy-based scatter estimation in clinical PET.

BACKGROUND: Scatter correction (SC) is essential in PET for accurate quantitative imaging. The state-of-the-art SC method is single-scatter simulation (SSS). Although this method is usually robust and accurate, it can fail in some situations, for example when there is motion between the CT and PET scans in PET/CT. Therefore, it is of interest to consider other SC methods. PURPOSE: In this work, an energy-based scatter estimation (EBS) method is described in detail, tested in phantoms and patients, and compared to SSS. METHODS: This version of EBS was developed for list-mode data from Biograph Vision-600 PET/CT scanner. EBS is based on digitized 2D energy histograms in each bin of a coarsely sampled PET sinogram, either with or without time of flight (TOF). The histograms are modeled as a noisy realization of a linear combination of nine basis functions whose parameters were derived from a measurement of the 511-keV photopeak spectrum as well as Monte-Carlo simulations of the scattering process. EBS uses an iterative expectation maximization approach to determine the coefficients in the linear combination, and from this estimates the scatter. The investigation was restricted to 18 F-based PET data in which the acquired number of counts was similar to the levels seen in oncological whole-body PET/CT scans. To evaluate the performance, phantom scans were used that involved the NEMA NU2-2018 protocol, a slab phantom, an NU 2-1994 phantom, a cardiac phantom in an anthropomorphic chest phantom, and a uniformly-filled torso phantom with a bladder phantom slightly outside the axial field of view. Contrast recovery (CR) and other parameters were evaluated in images reconstructed with SSS and EBS. Furthermore, FDG PET scans of seven lung cancer patients were used in the evaluation. Standardized uptake values (SUV) based on SSS and EBS were compared in 27 lesions. RESULTS: EBS and SSS images were visually similar in all cases except the torso + bladder phantom, where the EBS was much closer to the expected uniform image. The NU2-2018 analysis indicated a 2% scatter residual in EBS images compared to 3% with SSS, and 10% higher background variability, which is a surrogate for image noise. The cardiac phantom scan showed that CR was 98.2% with EBS and 99.6% with SSS, and that the SSS sinogram had values greater than the net-true emission sinogram, indicating a slight overcorrection in the case of SSS. In the lesion SUV comparison in patient scans, EBS correlated strongly (R2  = 0.9973) with SSS, and SUV based on EBS were systematically 0.1 SUV lower. In the case of the torso + bladder phantom portion, the SSS image of the torso + bladder phantom was 299% times hotter than expected in one area, due to scatter estimation error, compared to 16% colder with EBS. CONCLUSIONS: In evaluating clinically relevant parameters such as SUV in focal lesions, EBS and SSS give almost the same results. In phantoms, some scatter figures of merit were slightly improved by use of EBS, though an image variability figure of merit was slightly degraded. In typical oncological whole-body PET/CT, EBS may be a suitable replacement for SSS, especially when SSS fails due to technical problems during the scan.

Recovery of the spatially-variant deformations in dual-panel PET reconstructions using deep-learning.

Dual panel PET systems, such as Breast-PET (B-PET) scanner, exhibit strong asymmetric and anisotropic spatially-variant deformations in the reconstructed images due to the limited-angle data and strong depth of interaction effects for the oblique LORs inherent in such systems. In our previous work, we studied time-of-flight (TOF) effects and image-based spatially-variant PSF resolution models within dual-panel PET reconstruction to reduce these deformations. The application of PSF based models led to better and more uniform quantification of small lesions across the field of view (FOV). However, the ability of such a model to correct for PSF deformation is limited to small objects. On the other hand, large object deformations caused by the limited-angle reconstruction cannot be corrected with the PSF modeling alone. In this work, we investigate the ability of deep-learning (DL) networks to recover such strong spatially-variant image deformations using first simulated PSF deformations in image space of a generic dual panel PET system and then using simulated and acquired phantom reconstructions from dual panel B-PET system developed in our lab at University of Pennsylvania. For the studies using real B-PET data, the network was trained on the simulated synthetic data sets providing ground truth for objects resembling experimentally acquired phantoms on which the network deformation corrections were then tested. The synthetic and acquired limited-angle B-PET data were reconstructed using DIRECT-RAMLA reconstructions, which were then used as the network inputs. Our results demonstrate that DL approaches can significantly eliminate deformations of limited angle systems and improve their quantitative performance.

Image Denoising of Low-Dose PET Mouse Scans with Deep Learning: Validation Study for Preclinical Imaging Applicability.

PURPOSE: Positron emission tomography (PET) image quality can be improved by higher injected activity and/or longer acquisition time, but both may often not be practical in preclinical imaging. Common preclinical radioactive doses (10 MBq) have been shown to cause deterministic changes in biological pathways. Reducing the injected tracer activity and/or shortening the scan time inevitably results in low-count acquisitions which poses a challenge because of the inherent noise introduction. We present an image-based deep learning (DL) framework for denoising lower count micro-PET images. PROCEDURES: For 36 mice, a 15-min [18F]FDG (8.15 ± 1.34 MBq) PET scan was acquired at 40 min post-injection on the Molecubes ß-CUBE (in list mode). The 15-min acquisition (high-count) was parsed into smaller time fractions of 7.50, 3.75, 1.50, and 0.75 min to emulate images reconstructed at 50, 25, 10, and 5% of the full counts, respectively. A 2D U-Net was trained with mean-squared-error loss on 28 high-low count image pairs. RESULTS: The DL algorithms were visually and quantitatively compared to spatial and edge-preserving denoising filters; the DL-based methods effectively removed image noise and recovered image details much better while keeping quantitative (SUV) accuracy. The largest improvement in image quality was seen in the images reconstructed with 10 and 5% of the counts (equivalent to sub-1 MBq or sub-1 min mouse imaging). The DL-based denoising framework was also successfully applied on the NEMA-NU4 phantom and different tracer studies ([18F]PSMA, [18F]FAPI, and [68 Ga]FAPI). CONCLUSION: Visual and quantitative results support the superior performance and robustness in image denoising of the implemented DL models for low statistics micro-PET. This offers much more flexibility in optimizing preclinical, longitudinal imaging protocols with reduced tracer doses or shorter durations.

Synthesis of 18F-labeled phenolphthalein and naphtholphthalein.

The fluorination of phenolphthalein and naphtholphthalein was performed with diluted fluorine gas under acidic conditions. For both compounds we observed an electrophilic fluorination into ortho position to the hydroxyl group. Through the use of this reaction we synthesized and characterized mono-and difluorinated derivatives of phenolphthalein and naphtholphthalein. The compounds were also prepared in the 18F labeled form, which are usable as a new type of probe for in vivo pH measurement in biological objects using Cerenkov imaging or combination of light absorption and PET.

Resolution Enhancement in PET Reconstruction Using Collimation.

Collimation can improve both the spatial resolution and sampling properties compared to the same scanner without collimation. Spatial resolution improves because each original crystal can be conceptually split into two (i.e., doubling the number of in-plane crystals) by masking half the crystal with a high-density attenuator (e.g., tungsten); this reduces coincidence efficiency by 4× since both crystals comprising the line of response (LOR) are masked, but yields 4× as many resolution-enhanced (RE) LORs. All the new RE LORs can be measured by scanning with the collimator in different configurations. In this simulation study, the collimator was assumed to be ideal, neither allowing gamma penetration nor truncating the field of view. Comparisons were made in 2D between an uncollimated small-animal system with 2-mm crystals that were assumed to be perfectly absorbing and the same system with collimation that narrowed the effective crystal size to 1 mm. Digital phantoms included a hot-rod and a single-hot-spot, both in a uniform background with activity ratio of 4:1. In addition to the collimated and uncollimated configurations, angular and spatial wobbling acquisitions of the 2-mm case were also simulated. Similarly, configurations with different combinations of the RE LORs were considered including (i) all LORs, (ii) only those parallel to the 2-mm LORs; and (iii) only cross pairs that are not parallel to the 2-mm LORs. Lastly, quantitative studies were conducted for collimated and uncollimated data using contrast recovery coefficient and mean-squared error (MSE) as metrics. The reconstructions show that for most noise levels there is a substantial improvement in image quality (i.e., visual quality, resolution, and a reduction in artifacts) by using collimation even when there are 4× fewer counts or - in some cases - comparing with the noiseless uncollimated reconstruction. By comparing various configurations of sampling, the results show that it is the matched combination of both improved spatial resolution of each LOR and the increase in the number of LORs that yields improved reconstructions. Further, the quantitative studies show that for low-count scans, the collimated data give better MSE for small lesions and the uncollimated data give better MSE for larger lesions; for high-count studies, the collimated data yield better quantitative values for the entire range of lesion sizes that were evaluated.

Design Study of a Whole-Body PET Scanner with Improved Spatial and Timing Resolution.

Current state-of-art whole-body PET scanners achieve a system spatial resolution of 4-5 mm with limited sensitivity. Since the reconstructed spatial resolution and image quality are limited by the count statistics, there has not been a significant push for developing higher resolution whole-body PET scanners. Our goal in this study is to investigate the impact of improved spatial resolution together with time-of-flight (TOF) capability on lesion uptake estimation and lesion detectability, two important tasks in whole-body oncologic studies. The broader goal of this project is the development of a new state-of-art TOF PET scanner operating within an MRI while pushing the technology in PET system design. We performed Monte Carlo simulations to test the effects of crystal size (4 mm and 2.6 mm wide crystals), TOF timing resolution (300ps and 600ps), and 2-level depth-of-interaction (DOI) capability. Spatial resolution was calculated by simulating point sources in air at multiple positions. Results show that smaller crystals produced improved resolution, while degradation of resolution due to parallax error could be reduced with a 2-level DOI detector. Lesion phantoms were simulated to measure the contrast recovery coefficient (CRC) and area under the LROC curve (ALROC) for 0.5 cm diameter lesions with 6:1 activity uptake relative to the background. Smaller crystals produce higher CRC, leading to increased ALROC values or a reduction in scan time. Improved timing resolution provides faster CRC convergence and once again leads to an increase in ALROC value or reduced scan time. Based on our choice of timing resolution and crystal size, improved timing resolution (300ps) with larger crystals (4 mm wide) has similar ALROC as smaller crystals (2.6 mm wide) with 600ps timing resolution. A 2-level DOI measurement provides some CRC and ALROC improvement for lesions further away from the center, leading to a more uniform performance within the imaging field-of-view (FOV). Given a choice between having either an improved spatial resolution, improved timing resolution, or DOI capability, improved spatial or timing resolution provide an overall higher ALROC relative to a 2-level DOI detector.

Design Optimization of a TOF, Breast PET Scanner.

A dedicated breast positron emission tomography (PET) scanner with limited angle geometry can provide flexibility in detector placement around the patient as well as the ability to combine it with other imaging modalities. A primary challenge of a stationary limited angle scanner is the reduced image quality due to artifacts present in the reconstructed image leading to a loss in quantitative information. Previously it has been shown that using time-of-flight (TOF) information in image reconstruction can help reduce these image artifacts arising due to missing angular projections. Our goal in this work is to optimize the TOF, breast scanner design by performing studies for estimating image uniformity and lesion activity uptake as a function of system timing resolution, scanner angular coverage and shape. Our results show that (i) 1.5 × 1.5 × 15 mm3 lutetium oxy-orthosilicate (LSO) crystals provide a high spatial resolution and system sensitivity relative to clinical scanners, (ii) 2/3 angular coverage scanner design with TOF timing resolution less than 600 ps is appropriate for providing a tomographic image with fewer artifacts and good lesion uptake estimation relative to other partial ring designs studied in this work, (iii) a flat scanner design with 2/3 angular coverage is affected more by larger parallax error than a curved scanner geometry with the same angular coverage, but provides more uniform lesion contrast estimate over the imaging field-of-view (FOV), (iv) 2/3 angular coverage, flat, 300 ps TOF scanner design (for short, practical scan times of ≤ 5 mins per breast) provides similar precision of contrast recovery coefficient (CRC) values to a full curved, non-TOF scanner, and (v) employing depth-of-interaction (DOI) measuring detector and/or implementing resolution modeling (RM) in image reconstruction lead to improved and more uniform spatial resolution and lesion contrast over the whole FOV.

Evaluation of cost-effective system designs for long axial field-of-view PET scanners.

Objective. Current commercial positron emission tomography (PET) scanners have excellent performance and diagnostic image quality primarily due to improvements in scanner sensitivity and time-of-flight (TOF) resolution. Recent years have seen the development of total-body PET scanners with longer axial field-of-view (AFOV) that increase sensitivity for single organ imaging, and also image more of the patient in a single bed position thereby enabling multi-organ dynamic imaging. While studies have shown significant capabilities of these systems, cost will be a major factor in their widespread adoption in the clinic. Here we evaluate alternative designs that achieve many advantages of long AFOV PET while utilizing cost-effective detector hardware.Approach. We utilize Monte Carlo simulations and clinically relevant lesion detectability metric to study the impact of scintillator type lutetium oxyorthosilicate or bismuth germanate (LSO or BGO), scintillator thickness (10-20 mm), and TOF resolution on resultant image quality in a 72 cm long scanner. Detector TOF resolution was varied based on current scanner performance, as well as expected future performance from detector designs that currently hold most promise for scaling into a scanner.Main results. Results indicate that BGO is competitive with LSO (both 20 mm thick) if we assume that it uses TOF (e.g. Cerenkov timing with 450 ps fwhm and Lorentzian distribution) and the LSO scanner has TOF resolution similar to the latest PMT-based scanners (∼500-650 ps). Alternatively, a system using 10 mm thick LSO with 150 ps TOF resolution can also provide similar performance. Both these alternative systems can provide cost savings (25%-33%) relative to a scanner using 20 mm LSO with ∼50% of effective sensitivity, but still 500%-700% higher than a conventional AFOV scanner.Significance. Our results have relevance to the development of long AFOV PET, where reduced cost of these alternative designs can provide wider accessibility for use in situations requiring imaging of multiple organs simultaneously.

Performance evaluation of the PennPET explorer with expanded axial coverage.

Objective.This work evaluated the updated PennPET Explorer total-body (TB) PET scanner, which was extended to 6 rings with updated readout firmware to achieve a 142 cm axial field of view (AFOV) without 7.6 cm inter-ring axial gaps.Approach.National Electrical Manufacturers Association (NEMA) NU 2-2018 measurements were performed with modifications including longer phantoms for sensitivity and count-rate measurements and additional positions for spatial resolution and image quality. A long uniform phantom and the clinical trials network (CTN) phantom were also used.Main results.The total sensitivity increased to 140 kcps MBq-1for a 70 cm line, a gain of 1.8x compared to the same system with axial gaps; an additional 47% increase in total counts was observed with a 142 cm line at the same activity per cm. The noise equivalent count rate (NECR) increased by 1.8x without axial gaps. The peak NECR is 1550 kcps at 25 kBq cc-1for a 140 cm phantom; due to increased randoms, the NECR is lower than with a 70 cm phantom, for which NECR is 2156 kcps cc-1at 25 kBq cc-1and continues increasing. The time-of-flight resolution is 250 ps, increasing by <10 ps at the highest activity. The axial spatial resolution degrades by 0.6 mm near the center of the AFOV, compared to 4 mm resolution near the end. The NEMA image quality phantom showed consistent contrast recovery throughout the AFOV. A long uniform phantom demonstrated axial uniformity of uptake and noise, and the CTN phantom demonstrated quantitative accuracy for both18F and89Zr.Significance. The performance evaluation of the updated PennPET Explorer demonstrates significant gains compared to conventional scanners and shows where the current NEMA standard needs to be updated for TB-PET systems. The comparisons of systems with and without inter-ring gaps demonstrate the performance trade-offs of a more cost-effective TB-PET system with incomplete detector coverage.

Data-driven, energy-based method for estimation of scattered events in positron emission tomography.

Objective.Scattered events add bias in the reconstructed positron emission tomography (PET) images. Our objective is the accurate estimation of the scatter distribution, required for an effective scatter correction.Approach.In this paper, we propose a practical energy-based (EB) scatter estimation method that uses the marked difference between the energy distribution of the non-scattered and scattered events in the presence of randoms. In contrast to previous EB methods, we model the unscattered events using data obtained from measured point sources.Main results.We demonstrate feasibility using Monte Carlo simulated as well as experimental data acquired on the long axial field-of-view (FOV) PennPET EXPLORER scanner. Simulations show that the EB scatter estimated sinograms, for all phantoms, are in excellent agreement with the ground truth scatter distribution, known from the simulated data. Using the standard NEMA image quality (IQ) phantom we find that both the EB and single scatter simulation (SSS) provide good contrast recovery values. However, the EB correction gives better lung residuals.Significance.Application of the EB method on measured data showed, that the proposed method can be successfully translated to real-world PET scanners. When applied to a 20 cm diameter ×20 cm long cylindrical phantom the EB and SSS algorithms demonstrated very similar performance. However, on a larger 35 cm × 30 cm long cylinder the EB can better account for increased multiple scattering and out-of-FOV activity, providing more uniform images with 12%-36% reduced background variability. In typical PET ring sizes, the EB estimation can be performed in a matter of a few seconds compared to the several minutes needed for SSS, leading to efficiency advantages over the SSS implementation. as well.

Total-body PET: a new paradigm for molecular imaging.

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.

Preliminary Evaluation of 68Ga-P16-093, a PET Radiotracer Targeting Prostate-Specific Membrane Antigen in Prostate Cancer.

PURPOSE: Prostate-specific membrane antigen (PSMA) is a promising molecular target for imaging of prostate adenocarcinoma. 68Ga-P16-093, a small molecule PSMA ligand, previously showed equivalent diagnostic performance compared to 68Ga-PSMA-11 PET/CT in a pilot study of prostate cancer patients with biochemical recurrence (BCR). We performed a pilot study for further characterization of 68Ga-P16-093 including comparison to conventional imaging. PROCEDURES: Patients were enrolled into two cohorts. The biodistribution cohort included 8 treated prostate cancer patients without recurrence, who underwent 6 whole body PET/CT scans with urine sampling for dosimetry using OLINDA/EXM. The dynamic cohort included 15 patients with BCR and 2 patients with primary prostate cancer. Two patients with renal cell carcinoma were also enrolled for exploratory use. A dynamic PET/CT was followed by 2 whole body scans for imaging protocol optimization based on bootstrapped replicates. 68Ga-P16-093 PET/CT was compared for diagnostic performance against available 18F-fluciclovine PET/CT, 99mTc-MDP scintigraphy, diagnostic CT, and MRI. RESULTS: 68Ga-P16-093 deposited similar effective dose (0.024 mSv/MBq) and lower urinary bladder dose (0.064 mSv/MBq) compared to 68Ga-PSMA-11. The kidneys were the critical organ (0.290 mSv/MBq). While higher injected activities were preferable, lower injected activities at 74-111 MBq (2-3 mCi) yielded 80% retention in signal-to-noise ratio. The optimal injection-to-scan interval was 60 min, with acceptable delay up to 90 min. 68Ga-P16-093 PET/CT showed superior diagnostic performance over conventional imaging with overall patient-level lesion detection rate of 71%, leading to a change in management in 42% of the patients. CONCLUSIONS: Based on its favorable imaging characteristics and diagnostic performance in prostate cancer, 68Ga-P16-093 PET/CT merits further investigation in larger clinical studies.

PET Imaging of Leg Arteries for Determining the Input Function in PET/MRI Brain Studies Using a Compact, MRI-compatible PET System.

In this study, we used a compact, high-resolution, and MRI-compatible PET camera (VersaPET) to assess the feasibility of measuring the image-derived input function (IDIF) from arteries in the leg with the ultimate goal of enabling fully quantitative PET brain imaging without blood sampling. We used this approach in five 18F-FDG PET/MRI brain studies in which the input function was also acquired using the gold standard of serial arterial blood sampling. After accounting for partial volume, dispersion, and calibration effects, we compared the metabolic rates of glucose (MRglu) quantified from VersaPET IDIFs in 80 brain regions to those using the gold standard and achieved a bias and variability of <5% which is within the range of reported test-retest values for this type of study. We also achieved a strong linear relationship (R2 >0.97) against the gold standard across regions. The results of this preliminary study are promising and support further studies to optimize methods, validate in a larger cohort, and extend to the modeling of other radiotracers.