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.

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.

Advances in Breast PET Instrumentation.

Dedicated breast PET scanners currently have a spatial resolution in the 1.5 to 2 mm range, and the ability to provide tomographic images and quantitative data. They are also commercially available from a few vendors. A review of past and recent advances in the development and performance of dedicated breast PET scanners is summarized.

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.

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.

Impact of Tomosynthesis Acquisition on 3D Segmentations of Breast Outline and Adipose/Dense Tissue with AI: A Simulation-Based Study.

Digital breast tomosynthesis (DBT) reconstructions introduce out-of-plane artifacts and false-tissue boundaries impacting the dense/adipose and breast outline (convex hull) segmentations. A virtual clinical trial method was proposed to segment both the breast tissues and the breast outline in DBT reconstructions. The DBT images of a representative population were simulated using three acquisition geometries: a left-right scan (conventional, I), a two-directional scan in the shape of a "T" (II), and an extra-wide range (XWR, III) left-right scan at a six-times higher dose than I. The nnU-Net was modified including two losses for segmentation: (1) tissues and (2) breast outline. The impact of loss (1) and the combination of loss (1) and (2) was evaluated using models trained with data simulating geometry I. The impact of the geometry was evaluated using the combined loss (1&2). The loss (1&2) improved the convex hull estimates, resolving 22.2% of the false classification of air voxels. Geometry II was superior to I and III, resolving 99.1% and 96.8% of the false classification of air voxels. Geometry III (Dice = (0.98, 0.94)) was superior to I (0.92, 0.78) and II (0.93, 0.74) for the tissue segmentation (adipose, dense, respectively). Thus, the loss (1&2) provided better segmentation, and geometries T and XWR improved the dense/adipose and breast outline segmentations relative to the conventional scan.

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.

A personalized deep learning denoising strategy for low-count PET images.

Objective. Deep learning denoising networks are typically trained with images that are representative of the testing data. Due to the large variability of the noise levels in positron emission tomography (PET) images, it is challenging to develop a proper training set for general clinical use. Our work aims to develop a personalized denoising strategy for the low-count PET images at various noise levels.Approach.We first investigated the impact of the noise level in the training images on the model performance. Five 3D U-Net models were trained on five groups of images at different noise levels, and a one-size-fits-all model was trained on images covering a wider range of noise levels. We then developed a personalized weighting method by linearly blending the results from two models trained on 20%-count level images and 60%-count level images to balance the trade-off between noise reduction and spatial blurring. By adjusting the weighting factor, denoising can be conducted in a personalized and task-dependent way.Main results.The evaluation results of the six models showed that models trained on noisier images had better performance in denoising but introduced more spatial blurriness, and the one-size-fits-all model did not generalize well when deployed for testing images with a wide range of noise levels. The personalized denoising results showed that noisier images require higher weights on noise reduction to maximize the structural similarity and mean squared error. And model trained on 20%-count level images can produce the best liver lesion detectability.Significance.Our study demonstrated that in deep learning-based low dose PET denoising, noise levels in the training input images have a substantial impact on the model performance. The proposed personalized denoising strategy utilized two training sets to overcome the drawbacks introduced by each individual network and provided a series of denoised results for clinical reading.

Application of a generalized scan statistic model to evaluate TOF PET images.

Noise equivalent counts (NEC) have been used as a measure or proxy of PET image quality for many years. It has been shown to be a useful metric, for example to determine clinical patient dosage. However, NEC should be used cautiously in evaluating image quality since it is a global data quality measure that does not take into account localized effects due to spatial resolution and image reconstruction, as well as the effect of time-of-flight (TOF) imaging on resultant images. In this work, we study the use of a numerical observer that uses a generalized scan-statistic model to estimate lesion detectability with localization in a uniform background phantom, for varying activity levels and scan times. Data were acquired on a clinical whole-body TOF PET scanner. Data show that ALROC increases as a function of NEC but at high activity levels it approaches a peak value earlier than the NEC peak. Also, the ALROC for images acquired with the same NEC, but at two different activity levels and scan times, is similar. Our results show that with TOF information we can either achieve improved clinical performance for heavy patients, or reduce the scan time or injected activity while maintaining similar ALROC value as in a Non-TOF image.

Reconstruction-free positron emission imaging.

Measurement of the arrival times of annihilation photons in a detector with greater precision is opening the way to new direct forms of tomographic positon emission imaging that do not require back-projection based reconstruction techniques.

Time of Flight in Perspective: Instrumental and Computational Aspects of Time Resolution in Positron Emission Tomography.

The first time-of-flight positron emission tomography (TOF-PET) scanners were developed as early as in the 1980s. However, the poor light output and low detection efficiency of TOF-capable detectors available at the time limited any gain in image quality achieved with these TOF-PET scanners over the traditional non-TOF PET scanners. The discovery of LSO and other Lu-based scintillators revived interest in TOF-PET and led to the development of a second generation of scanners with high sensitivity and spatial resolution in the mid-2000s. The introduction of the silicon photomultiplier (SiPM) has recently yielded a third generation of TOF-PET systems with unprecedented imaging performance. Parallel to these instrumentation developments, much progress has been made in the development of image reconstruction algorithms that better utilize the additional information provided by TOF. Overall, the benefits range from a reduction in image variance (SNR increase), through allowing joint estimation of activity and attenuation, to better reconstructing data from limited angle systems. In this work, we review these developments, focusing on three broad areas: 1) timing theory and factors affecting the time resolution of a TOF-PET system; 2) utilization of TOF information for improved image reconstruction; and 3) quantification of the benefits of TOF compared to non-TOF PET. Finally, we offer a brief outlook on the TOF-PET developments anticipated in the short and longer term. Throughout this work, we aim to maintain a clinically driven perspective, treating TOF as one of multiple (and sometimes competitive) factors that can aid in the optimization of PET imaging performance.

A proof-of-concept study of an in-situ partial-ring time-of-flight PET scanner for proton beam verification.

Development of a PET system capable of in-situ imaging requires a design that can accommodate the proton treatment beam nozzle. Among the several PET instrumentation approaches developed thus far, the dual-panel PET scanner is often used as it is simpler to develop and integrate within the proton therapy gantry. Partial-angle coverage of these systems can however lead to limited-angle artefacts in the reconstructed PET image. We have previously demonstrated via simulations that time-of-flight (TOF) reconstruction reduces the artifacts accompanying limited-angle data, and permits proton range measurement with 1-2 mm accuracy and precision. In this work we show measured results from a small proof-of-concept dual-panel PET system that uses TOF information to reconstruct PET data acquired after proton irradiation. The PET scanner comprises of two detector modules, each comprised of an array of 4×4×30 mm3 lanthanum bromide scintillator. Measurements are performed with an oxygen-rich gel-water, an adipose tissue equivalent material, and in vitro tissue phantoms. For each phantom measurement, 2 Gy dose was deposited using 54 - 100 MeV proton beams. For each phantom, a Monte Carlo simulation generating the expected distribution of PET isotope from the corresponding proton irradiation was also performed. Proton range was calculated by drawing multiple depth-profiles over a central region encompassing the proton dose deposition. For each profile, proton range was calculated using two techniques (a) 50% pick-off from the distal edge of the profile, and (b) comparing the measured and Monte Carlo profile to minimize the absolute sum of differences over the entire profile. A 10 min PET acquisition acquired with minimal delay post proton-irradiation is compared with a 10 min PET scan acquired after a 20 min delay. Measurements show that PET acquisition with minimal delay is necessary to collect 15O signal, and maximize 11C signal collection with a short PET acquisition. In comparison with the 50% pick-off technique, the shift technique is more robust and offers better precision in measuring the proton range for the different phantoms. Range measurements from PET images acquired with minimal delay, and the shift technique demonstrate the ability to achieve <1.5 mm accuracy and precision in estimating proton range.

Investigating Low-Dose Image Quality in Whole-Body Pediatric 18F-FDG Scans Using Time-of-Flight PET/MRI.

In this study, we investigated the diagnostic performance of whole-body 18F-FDG imaging using a PET/MRI scanner with time-of-flight capability for low-dose clinical imaging of pediatric patients. In addition to clinically acquired image data using a dosing regimen of 3.7 MBq/kg, images from simulated low-dose regimens (1.9-0.41 MBq/kg) were evaluated using several metrics: SUV quantitation, qualitative image quality, and lesion detectability. Methods: Low-dose images were generated by truncating the list-mode PET data to reduce the count statistics. Changes in PET quantitation for low-dose images were assessed using volume-of-interest analysis of healthy tissue and suspected lesions. Three pediatric radiologists reviewed the image volumes without knowing the dose level. Qualitative image quality was assessed on the basis of Likert scoring. Radiologists were also asked to identify suspected lesions within the liver for PET-only and PET/MR images. Lesion detectability was measured using a receiver-operating-characteristic study and quantified using a free-response receiving-operating-characteristic (FROC) methodology to assess changes in performance for low-dose images. Results: Our analysis of volume-of-interest quantitation showed that SUVs remain stable down to ⅓ dose (1.2 MBq/kg). Likert scoring of PET/MR images showed no noticeable trend with dose level; however, scores of PET-only images were lower for low-dose scans, with a 12% reduction for ⅓-dose images compared with full-dose images. There was minimal change in total lesion count for different dose levels; however, all 3 readers had an increase in false-negatives for ⅓-dose images compared with full-dose images. Using the FROC methodology to quantify lesion-detection performance for human observers, no significant differences were observed for the 3 dosing levels when using the averaged reader data (all P values > 0.103). For all readers, the FROC performance was higher for PET/MRI than for PET alone. Conclusion: Reductions to the lowest recommended pediatric dosing regimens are possible when using PET/MRI. The data suggest that the administered dose can be decreased to 2.46 MBq/kg, a 33% reduction in PET activity, with no degradation in image quality, leading to a corresponding reduction in absorbed dose.

Quantitative PET in the 2020s: a roadmap.

Positron emission tomography (PET) plays an increasingly important role in research and clinical applications, catalysed by remarkable technical advances and a growing appreciation of the need for reliable, sensitive biomarkers of human function in health and disease. Over the last 30 years, a large amount of the physics and engineering effort in PET has been motivated by the dominant clinical application during that period, oncology. This has led to important developments such as PET/CT, whole-body PET, 3D PET, accelerated statistical image reconstruction, and time-of-flight PET. Despite impressive improvements in image quality as a result of these advances, the emphasis on static, semi-quantitative 'hot spot' imaging for oncologic applications has meant that the capability of PET to quantify biologically relevant parameters based on tracer kinetics has not been fully exploited. More recent advances, such as PET/MR and total-body PET, have opened up the ability to address a vast range of new research questions, from which a future expansion of applications and radiotracers appears highly likely. Many of these new applications and tracers will, at least initially, require quantitative analyses that more fully exploit the exquisite sensitivity of PET and the tracer principle on which it is based. It is also expected that they will require more sophisticated quantitative analysis methods than those that are currently available. At the same time, artificial intelligence is revolutionizing data analysis and impacting the relationship between the statistical quality of the acquired data and the information we can extract from the data. In this roadmap, leaders of the key sub-disciplines of the field identify the challenges and opportunities to be addressed over the next ten years that will enable PET to realise its full quantitative potential, initially in research laboratories and, ultimately, in clinical practice.

Imaging studies for evaluating impact of position sampling techniques in PET scanners.

Previously we have evaluated two crystal calibration techniques that can be applied to pixelated detector designs to improve system spatial resolution without detector motion. The inter-crystal positioning technique utilizes sub-sampling in the crystal flood map to better sample the Compton scatter events in the detector. The Compton scatter rejection technique, on the other hand, rejects those events that are located further from individual crystal centers in the flood map. Here we performed imaging studies with a Mini Deluxe hot rod phantom and a hot sphere phantom (sphere diameters of 4.95 and 7.86-mm with 6:1 uptake relative to background) using the standard crystal calibration technique, as well as the inter-crystal and Compton rejection calibration techniques. Our results show improved separation of 1.6-mm diameter hot rods with the two new crystal calibration techniques that is consistent with improved spatial resolution. For the hot sphere phantom the contrast recovery is improved with both the inter-crystal and Compton rejection calibration techniques over the standard calibration technique. The only drawback of the inter-crystal calibration technique is the increase in the number of possible lines-of-response (LORs) (factor of 16) that may slow image reconstruction. With the Compton rejection calibration technique, loss of counts leads to increased noise in the images.

Update on latest advances in time-of-flight PET.

This paper provides an update on time-of-flight (TOF) PET with a focus on latest hardware developments leading to current commercial PET/CT instruments. We describe advances in scintillator development, new photosensors and associated electronics readout, and detector designs for utilization in complete systems. Next, we introduce the latest commercial PET/CT scanners based on the aforementioned technologies, and discuss the detector design choices made that are relevant to differences in the system performance. Finally, we end with a discussion of the latest performance benchmarks for improved timing in PET detectors, challenges in scaling this performance to a complete system, and the outlook towards achieving a sub-50 ps coincidence timing resolution (CTR) in a PET detector.