Enhancing timing performance of heterostructures with double-sided readout.

Objective.Heterostructured scintillators offer a promising solution to balance the sensitivity and timing in TOF-PET detectors. These scintillators utilize alternating layers of materials with complementary properties to optimize performance. However, the layering compromises time resolution due to light transport issues. This study explores double-sided readout-enabling improved light collection and Depth-of-Interaction (DOI) information retrieval-to mitigate this effect and enhance the timing capabilities of heterostructures.Approach.The time resolution and DOI performances of 3 × 3 × 20 mm3BGO&EJ232 heterostructures were assessed in a single and double-sided readout (SSR and DSR, respectively) configuration using high-frequency electronics.Main results.Selective analysis of photopeak events yielded a DOI resolution of 6.4 ± 0.04 mm. Notably, the Coincidence Time Resolution (CTR) improved from 262 ± 8 ps (SSR) to 174 ± 6 ps (DSR) when measured in coincidence with a fast reference detector. Additionally, symmetrical configuration of two identical heterostructures in coincidence was tested, yielding in DSR a CTR of 254 ± 8 ps for all photopeak events and 107 ± 5 ps for the fastest events.Significance.By using high-frequency double-sided readout, we could measure DOI resolution and improve the time resolution of heterostructures of up to 40%. The DOI information resulted intrinsically captured in the average between the timestamps of the two SiPMs, without requiring any further correction.

Timing Estimation and Limits in TOF-PET Detectors Producing Prompt Photons.

The production of prompt photons providing high photon time densities is a promising avenue to reach ultrahigh coincidence time resolution (CTR) in time-of-flight PET. Detectors producing prompt photons are receiving high interest experimentally, ignited by past exploratory theoretical studies that have anchored some guiding principles. Here, we aim to consolidate and extend the foundations for the analytical modeling of prompt generating detectors. We extend the current models to a larger range of prompt emission kinetics where more stringent requirements on the prompt photon yield rapidly emerge as a limiting factor. Lower bound and estimator evaluations are investigated with different underlying models, notably by merging or keeping separate the prompt and scintillation photon populations. We further show the potential benefits of knowing the proportion of prompt photons within a detection set to improve the CTR by mitigating the detrimental effect of population (prompt vs scintillation) mixing. Taking into account the fluctuations on the average number of detected prompt photons in the model reveals a limited influence when prompt photons are accompanied by fast scintillation (e.g., LSO:Ce:Ca) but a more significant effect when accompanied by slower scintillation (e.g., BGO). Establishing performance characteristics and limitations of prompt generating detectors is paramount to gauging and targeting the best possible timing capabilities they can offer.

A conformal TOF-DOI Prism-PET prototype scanner for high-resolution quantitative neuroimaging.

BACKGROUND: Positron emission tomography (PET) has had a transformative impact on oncological and neurological applications. However, still much of PET's potential remains untapped with limitations primarily driven by low spatial resolution, which severely hampers accurate quantitative PET imaging via the partial volume effect (PVE). PURPOSE: We present experimental results of a practical and cost-effective ultra-high resolution brain-dedicated PET scanner, using our depth-encoding Prism-PET detectors arranged along a compact and conformal gantry, showing substantial reduction in PVE and accurate radiotracer uptake quantification in small regions. METHODS: The decagon-shaped prototype scanner has a long diameter of 38.5 cm, a short diameter of 29.1 cm, and an axial field-of-view (FOV) of 25.5 mm with a single ring of 40 Prism-PET detector modules. Each module comprises a 16 × 16 array of 1.5 × 1.5 × 20-mm3 lutetium yttrium oxyorthosillicate (LYSO) scintillator crystals coupled 4-to-1 to an 8 × 8 array of silicon photomultiplier (SiPM) pixels on one end and to a prismatoid light guide array on the opposite end. The scanner's performance was evaluated by measuring depth-of-interaction (DOI) resolution, energy resolution, timing resolution, spatial resolution, sensitivity, and image quality of ultra-micro Derenzo and three-dimensional (3D) Hoffman brain phantoms. RESULTS: The full width at half maximum (FWHM) DOI, energy, and timing resolutions of the scanner are 2.85 mm, 12.6%, and 271 ps, respectively. Not considering artifacts due to mechanical misalignment of detector blocks, the intrinsic spatial resolution is 0.89-mm FWHM. Point source images reconstructed with 3D filtered back-projection (FBP) show an average spatial resolution of 1.53-mm FWHM across the entire FOV. The peak absolute sensitivity is 1.2% for an energy window of 400-650 keV. The ultra-micro Derenzo phantom study demonstrates the highest reported spatial resolution performance for a human brain PET scanner with perfect reconstruction of 1.00-mm diameter hot-rods. Reconstructed images of customized Hoffman brain phantoms prove that Prism-PET enables accurate radiotracer uptake quantification in small brain regions (2-3 mm). CONCLUSIONS: Prism-PET will substantially strengthen the utility of quantitative PET in neurology for early diagnosis of neurodegenerative diseases, and in neuro-oncology for improved management of both primary and metastatic brain tumors.

Real-time marker-less tumor tracking with TOF PET:in silicofeasibility study.

Purpose.Although positron emission tomography (PET) can provide a functional image of static tumors for RT guidance, it's conventionally very challenging for PET to track a moving tumor in real-time with a multiple frame/s sampling rate. In this study, we developed a novel method to enable PET based three-dimension (3D) real-time marker-less tumor tracking (RMTT) and demonstrated its feasibility with a simulation study.Methods.For each line-of-response (LOR) acquired, its positron-electron annihilation position is calculated based on the time difference between the two gamma interactions detected by the TOF PET detectors. The accumulation of these annihilation positions from data acquired within a single sampling frame forms a coarsely measured 3D distribution of positron-emitter radiotracer uptakes of the lung tumor and other organs and tissues (background). With clinically relevant tumor size and sufficient differential radiotracer uptake concentrations between the tumor and background, the high-uptake tumor can be differentiated from the surrounding low-uptake background in the measured distribution of radiotracer uptakes. With a volume-of-interest (VOI) that closely encloses the tumor, the count-weighted centroid of the annihilation positions within the VOI can be calculated as the tumor position. All these data processes can be conducted online. The feasibility of the new method was investigated with a simulated cardiac-torso digital phantom and stationary dual-panel TOF PET detectors to track a 28 mm diameter lung tumor with a 4:1 tumor-to-background18FDG activity concentration ratio.Results.The initial study shows TOF PET based RMTT can achieve <2.0 mm tumor tracking accuracy with 5 frame s-1sampling rate under the simulated conditions. In comparison, using reconstructed PET images to track a similar size tumor would require >30 s acquisition time to achieve the same tracking accuracy.Conclusion.With the demonstrated feasibility, the new method may enable TOF PET based RMTT for practical RT applications.

Advances in heterostructured scintillators: toward a new generation of detectors for TOF-PET.

Objective.Time-of-flight-positron emission tomography would highly benefit from a coincidence time resolution (CTR) below 100 ps: improvement in image quality and patient workflow, and reduction of delivered dose are among them. This achievement proved to be quite challenging, and many approaches have been proposed and are being investigated for this scope. One of the most recent consists in combining different materials with complementary properties (e.g. high stopping power for 511 keVγ-ray and fast timing) in a so-calledheterostructure,metascintillatorormetapixel. By exploiting a mechanism of energy sharing between the two materials, it is possible to obtain a fraction of fast events which significantly improves the overall time resolution of the system.Approach.In this work, we present the progress on this innovative technology. After a simulation study using the Geant4 toolkit, aimed at understanding the optimal configuration in terms of energy sharing, we assembled four heterostructures with alternating plates of BGO and EJ232 plastic scintillator. We fabricated heterostructures of two different sizes (3 × 3 × 3 mm3and  3 × 3 × 15 mm3), each made up of plates with two different thicknesses of plastic plates. We compared the timing of these pixels with a standard bulk BGO crystal and a structure made of only BGO plates (layeredBGO).Main results.CTR values of 239 ± 12 ps and 197 ± 10 ps FWHM were obtained for the 15 mm long heterostructures with 100µm and 200µm thick EJ232 plates (both with 100µm thick BGO plates), compared to 271 ± 14 ps and 303 ± 15 ps CTR for bulk and layered BGO, respectively.Significance.Significant improvements in timing compared to standard bulk BGO were obtained for all the configurations tested. Moreover, for the long pixels, depth of interaction (DOI) collimated measurements were also performed, allowing to validate a simple model describing light transport inside the heterostructure.

Low power implementation of high frequency SiPM readout for Cherenkov and scintillation detectors in TOF-PET.

State-of-the-art (SoA) electronic readout for silicon photomultiplier (SiPM)-based scintillation detectors that demonstrate experimental limits in achievable coincidence time resolution (CTR) leverage low noise, high frequency signal processing to facilitate a single photon time response that is near the limit of the SiPMs architecture. This readout strategy can optimally exploit fast luminescence and prompt photon populations, and promising measurements show detector concepts employing this readout can greatly advance PET detector CTR, relative to SoA in clinical systems. However, the technique employs power hungry components which make the electronics chain impractical for channel-dense time-of-flight (TOF)-PET detectors. We have developed and tested a low noise and high frequency readout circuit which is performant at low power and consists of discrete elements with small footprints, making it feasible for integration into TOF-PET detector prototypes. A 3 × 3 mm2Broadcom SiPM with this readout chain exhibited sub-100 ps single photon time resolution at 10 mW of power consumption, with a relatively minor performance degradation to 120 ± 2 ps FWHM at 5 mW. CTR measurements with 3 × 3 × 20 mm3LYSO and fast LGSO scintillators demonstrated 127 ± 3 ps and 113 ± 2 ps FWHM at optimal power operation and 133 ± 2 ps and 121 ± 3 ps CTR at 5 mW. BGO crystals 3 × 3 × 20 mm3in size show 271 ± 5 ps FWHM CTR (1174 ± 14 ps full-width-at-tenth-maximum (FWTM)) at optimal power dissipation and 289 ± 8 ps (1296 ± 33 ps FWTM) at 5 mW. The compact and low power readout topology that achieves this performance thereby offers a platform to greatly advance PET system CTR and also opportunities to provide high performance TOF-PET at reduced material cost.

Study of Annihilation Photon Pair Coincidence Time Resolution Using Prompt Photon Emissions in New Perovskite Bulk Crystals.

Semiconductor-based radiation detectors can typically achieve better energy and spatial resolution when compared to scintillator-based detectors. However, if used for positron emission tomography (PET), semiconductor-based detectors normally cannot achieve excellent coincidence time resolution (CTR), due to the relatively slow charge carrier collection time limited by the carrier drift velocity. If we can collect prompt photons emitted from certain semiconductor materials, there are possibilities that the CTR can be greatly improved, and time-of-flight (ToF) capability can be achieved. In this paper, we studied the prompt photon emission (mainly Cherenkov luminescence) property and fast timing capability of cesium lead chloride (CsPbCl3) and cesium lead bromide (CsPbBr3), which are two new perovskite semiconductor materials. We also compared their performance with thallium bromide (TlBr), another semiconductor material that has already been studied for timing using its Cherenkov emissions. We performed coincidence measurements using silicon photomultipliers (SiPMs), and the full-width-at-half-maximum (FWHM) CTR acquired between a semiconductor sample crystal and a reference lutetium-yttrium oxyorthosilicate (LYSO) crystal (both with dimensions of 3 × 3 × 3 mm3) is 248 ± 8 ps for CsPbCl3, 440 ± 31 ps for CsPbBr3, and 343 ± 16 ps for TlBr. Deconvolving the contribution to CTR from the reference LYSO crystal (around 100 ps) and then multiplying by the square root of 2, the estimated CTR between two of the same semiconductor crystals was calculated as 324 ± 10 ps for CsPbCl3, 606 ± 43 ps for CsPbBr3 and 464 ± 22 ps for TlBr. This ToF capable CTR performance combined with an easily scalable crystal growth process, low cost and toxicity, as well as good energy resolution lead us to the conclusion that new perovskite materials such as CsPbCl3 and CsPbBr3 could be excellent candidates as PET detector materials.

DOI estimation through signal arrival time distribution: a theoretical description including proof of concept measurements.

The challenge to reach 10 ps coincidence time resolution (CTR) in time-of-flight positron emission tomography (TOF-PET) is triggering major efforts worldwide, but timing improvements of scintillation detectors will remain elusive without depth-of-interaction (DOI) correction in long crystals. Nonetheless, this momentum opportunely brings up the prospect of a fully time-based DOI estimation since fast timing signals intrinsically carry DOI information, even with a traditional single-ended readout. Consequently, extracting features of the detected signal time distribution could uncover the spatial origin of the interaction and in return, provide enhancement on the timing precision of detectors. We demonstrate the validity of a time-based DOI estimation concept in two steps. First, experimental measurements were carried out with current LSO:Ce:Ca crystals coupled to FBK NUV-HD SiPMs read out by fast high-frequency electronics to provide new evidence of a distinct DOI effect on CTR not observable before with slower electronics. Using this detector, a DOI discrimination using a double-threshold scheme on the analog timing signal together with the signal intensity information was also developed without any complex readout or detector modification. As a second step, we explored by simulation the anticipated performance requirements of future detectors to efficiently estimate the DOI and we proposed four estimators that exploit either more generic or more precise features of the DOI-dependent timestamp distribution. A simple estimator using the time difference between two timestamps provided enhanced CTR. Additional improvements were achieved with estimators using multiple timestamps (e.g. kernel density estimation and neural network) converging to the Cramér-Rao lower bound developed in this work for a time-based DOI estimation. This two-step study provides insights on current and future possibilities in exploiting the timing signal features for DOI estimation aiming at ultra-fast CTR while maintaining detection efficiency for TOF PET.

A roadmap for sole Cherenkov radiators with SiPMs in TOF-PET.

Time of flight positron emission tomography can strongly benefit from a very accurate time estimator given by Cherenkov radiation, which is produced upon a 511 keV positron-electron annihilation gamma interaction in heavy inorganic scintillators. While time resolution in the order of 30 ps full width at half maximum (FWHM) has been reported using MCP-PMTs and black painted Cherenkov radiators, such solutions have several disadvantages, like high cost and low detection efficiency of nowadays available MCP-PMTs. On the other hand, silicon photomultipliers (SiPMs) are not limited by those obstacles and provide high photon detection efficiency with a decent time response. Timing performance of PbF2crystals of various lengths and surface conditions coupled to SiPMs was evaluated against a reference detector with an optimized test setup using high-frequency readout and novel time walk correction, with special attention on the intrinsic limits for one detected Cherenkov photon only. The average number of detected Cherenkov photons largely depends on the crystal surface state, resulting in a tradeoff between low photon time spread, thus good timing performance, and sensitivity. An intrinsic Cherenkov photon yield of 16.5 ± 3.3 was calculated for 2 × 2 × 3 mm3sized PbF2crystals upon 511 keVγ-deposition. After time walk correction based on the slew rate of the signal, assuming two identical detector arms in coincidence, and using all events, a time resolution of 215 ps FWHM (142 ps FWHM) was obtained for 2 × 2 × 20 mm3(2 × 2 × 3 mm3) sized PbF2crystals, compared to 261 ps (190 ps) without correction. Selecting on one detected photon only, a single photon coincidence time resolution of 113 ps FWHM for black painted and 166 ps for Teflon wrapped crystals was measured for 3 mm length, compared to 145 ps (black) and 263 ps (Teflon) for 20 mm length.

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.

A Quantitative Evaluation of Joint Activity and Attenuation Reconstruction in TOF PET/MR Brain Imaging.

Time-of-flight (TOF) PET data provide an effective means for attenuation correction (AC) when no (or incomplete or inaccurate) attenuation information is available. Since MR scanners provide little information on photon attenuation of different tissue types, AC in hybrid PET/MR scanners has always been challenging. In this contribution, we aim at validating the activity reconstructions of the maximum-likelihood ordered-subsets activity and attenuation (OSAA) reconstruction algorithm on a patient brain data set. We present a quantitative comparison of joint reconstructions with the current clinical gold standard-ordered-subsets expectation maximization-using CT-based AC in PET/CT, as well as the current state of the art in PET/MR, that is, zero time echo (ZTE)-based AC. Methods: The TOF PET emission data were initially used in a preprocessing stage to estimate crystal maps of efficiencies, timing offsets, and timing resolutions. Applying these additional corrections during reconstructions, OSAA, ZTE-based, and the vendor-provided atlas-based AC techniques were analyzed and compared with CT-based AC. In our initial study, we used the CT-based estimate of the expected scatter and later used the ZTE-based and OSAA attenuation estimates to compute the expected scatter contribution of the data during reconstructions. In all reconstructions, a maximum-likelihood scaling of the single-scatter simulation estimate to the emission data was used for scatter correction. The reconstruction results were analyzed in the 86 segmented regions of interest of the Hammers atlas. Results: Our quantitative analysis showed that, in practice, a tracer activity difference of +0.5% (±2.1%) and +0.1% (±2.3%) could be expected for the state-of-the-art ZTE-based and OSAA AC methods, respectively, in PET/MR compared with the clinical gold standard in PET/CT. Conclusion: Joint activity and attenuation estimation methods can provide an effective solution to the challenging AC problem for brain studies in hybrid TOF PET/MR scanners. With an accurate TOF-based (timing offsets and timing resolutions) calibration, and similar to the results of the state-of-the-art method in PET/MR, regional errors of joint TOF PET reconstructions are within a few percentage points.

Feasibility study of a point-of-care positron emission tomography system with interactive imaging capability.

PURPOSE: We investigated the feasibility of a novel positron emission tomography (PET) system that provides near real-time feedback to an operator who can interactively scan a patient to optimize image quality. The system should be compact and mobile to support point-of-care (POC) molecular imaging applications. In this study, we present the key technologies required and discuss the potential benefits of such new capability. METHODS: The core of this novel PET technology includes trackable PET detectors and a fully three-dimensional, fast image reconstruction engine implemented on multiple graphics processing units (GPUs) to support dynamically changing geometry by calculating the system matrix on-the-fly using a tube-of-response approach. With near real-time image reconstruction capability, a POC-PET system may comprise a maneuverable front PET detector and a second detector panel which can be stationary or moved synchronously with the front detector such that both panels face the region-of-interest (ROI) with the detector trajectory contoured around a patient's body. We built a proof-of-concept prototype using two planar detectors each consisting of a photomultiplier tube (PMT) optically coupled to an array of 48 × 48 lutetium-yttrium oxyorthosilicate (LYSO) crystals (1.0 × 1.0 × 10.0 mm3 each). Only 38 × 38 crystals in each arrays can be clearly re-solved and used for coincidence detection. One detector was mounted to a robotic arm which can position it at arbitrary locations, and the other detector was mounted on a rotational stage. A cylindrical phantom (102 mm in diameter, 150 mm long) with nine spherical lesions (8:1 tumor-to-background activity concentration ratio) was imaged from 27 sampling angles. List-mode events were reconstructed to form images without or with time-of-flight (TOF) information. We conducted two Monte Carlo simulations using two POC-PET systems. The first one uses the same phantom and detector setup as our experiment, with the detector coincidence re-solving time (CRT) ranging from 100 to 700 ps full-width-at-half-maximum (FWHM). The second study simulates a body-size phantom (316 × 228 × 160 mm3 ) imaged by a larger POC-PET system that has 4 × 6 modules (32 × 32 LYSO crystals/module, four in axial and six in transaxial directions) in the front panel and 3 × 8 modules (16 × 16 LYSO crystals/module, three in axial and eight in transaxial directions) in the back panel. We also evaluated an interactive scanning strategy by progressively increasing the number of data sets used for image reconstruction. The updated images were analyzed based on the number of data sets and the detector CRT. RESULTS: The proof-of-concept prototype re-solves most of the spherical lesions despite a limited number of coincidence events and incomplete sampling. TOF information reduces artifacts in the reconstructed images. Systems with better timing resolution exhibit improved image quality and reduced artifacts. We observed a reconstruction speed of 0.96 × 106 events/s/iteration for 600 × 600 × 224 voxel rectilinear space using four GPUs. A POC-PET system with significantly higher sensitivity can interactively image a body-size object from four angles in less than 7 min. CONCLUSIONS: We have developed GPU-based fast image reconstruction capability to support a PET system with arbitrary and dynamically changing geometry. Using TOF PET detectors, we demonstrated the feasibility of a PET system that can provide timely visual feedback to an operator who can scan a patient interactively to support POC imaging applications.

Performance characteristics of silicon photomultiplier based 15-cm AFOV TOF PET/CT.

BACKGROUND: This paper describes the National Electrical Manufacturers Association (NEMA) system performance of the Discovery MI 3-ring PET/CT (GE Healthcare) installed in Bruges, Belgium. This time-of-flight (TOF) PET camera is based on silicon photomultipliers instead of photomultiplier tubes. METHODS: The NEMA NU2-2012 standard was used to evaluate spatial resolution, sensitivity, image quality (IQ) and count rate curves of the system. Timing and energy resolution were determined. RESULTS: Full width at half maximum (FWHM) of spatial resolution in radial, tangential and axial direction was 4.69, 4.08 and 4.68 mm at 1 cm; 5.58, 4.64 and 5.83 mm at 10 cm; and 7.53, 5.08 and 5.47 mm at 20 cm from the centre of the field of view (FOV) for the filtered backprojection reconstruction. For non-TOF ordered subset expectation maximization (OSEM) reconstruction without point spread function (PSF) correction, FWHM was 3.87, 3.69 and 4.15 mm at 1 cm; 4.80, 3.81 and 4.87 mm at 10 cm; and 7.38, 4.16 and 3.98 mm at 20 cm. Sensitivity was 7.258 cps/kBq at the centre of the FOV and 7.117 cps/kBq at 10-cm radial offset. Contrast recovery (CR) using the IQ phantom for the TOF OSEM reconstruction without PSF correction was 47.4, 59.3, 67.0 and 77.0% for the 10-, 13-, 17- and 22-mm radioactive spheres and 82.5 and 85.1% for the 28- and 37-mm non-radioactive spheres. Background variability (BV) was 16.4, 12.1, 9.1, 6.6, 5.1 and 3.8% for the 10-, 13-, 17-, 22-, 28- and 37-mm spheres. Lung error was 8.5%. Peak noise equivalent count rate (NECR) was 102.3 kcps at 23.0 kBq/ml with a scatter fraction of 41.2%. Maximum accuracy error was 3.88%. Coincidence timing resolution was 375.6 ps FWHM. Energy resolution was 9.3% FWHM. Q.Clear reconstruction significantly improved CR and reduced BV compared with OSEM. CONCLUSION: System sensitivity and NECR are lower and IQ phantom's BV is higher compared with larger axial FOV (AFOV) scanners like the 4-ring discovery MI, as expected from the smaller solid angle of the 3-ring system. The other NEMA performance parameters are all comparable with those of the larger AFOV scanners.

Joint Reconstruction of Activity and Attenuation in Time-of-Flight PET: A Quantitative Analysis.

Methods for joint activity reconstruction and attenuation reconstruction of time-of-flight (TOF) PET data provide an effective solution to attenuation correction when no (or incomplete or inaccurate) information on attenuation is available. One of the main barriers limiting use of these methods in clinical practice is their lack of validation in a relatively large patient database. In this contribution, we aim to validate reconstruction performed with maximum-likelihood activity reconstruction and attenuation registration (MLRR) in a whole-body patient dataset. Furthermore, a partial validation (because the scale problem of the algorithm is avoided for now) of reconstruction performed with maximum-likelihood activity and attenuation (MLAA) is also provided. We present a quantitative comparison between these 2 methods of joint reconstruction and the current clinical gold standard, maximum-likelihood expectation maximization (MLEM) with CT-based attenuation correction. Methods: The whole-body TOF PET emission data of each patient dataset were processed as a whole to reconstruct an activity volume covering all the acquired bed positions, helping reduce the problem of a scale per bed position in MLAA to a global scale for the entire activity volume. Three reconstruction algorithms were used: MLEM, MLRR, and MLAA. A maximum-likelihood scaling of the single-scatter simulation estimate to the emission data was used for scatter correction. The reconstruction results for various regions of interest were then analyzed. Results: The joint reconstructions of the whole-body patient dataset provided better quantification than the gold standard in cases of PET and CT misalignment caused by patient or organ motion. Our quantitative analysis showed a difference of -4.2% ± 2.3% between MLRR and MLEM and a difference of -7.5% ± 4.6% between MLAA and MLEM, averaged over all regions of interest. Conclusion: Joint reconstruction of activity and attenuation provides a useful means to estimate tracer distribution when CT-based-attenuation images are subject to misalignment or are not available. With an accurate estimate of the scatter contribution in the emission measurements, the joint reconstructions of TOF PET data are within clinically acceptable accuracy.

Performance evaluation of a new high-sensitivity time-of-flight clinical PET/CT system.

BACKGROUND: PoleStar m660 is a newly developed clinical PET/CT system with time-of-flight (TOF) capability. The aim of this study is to characterize the performance of the new system. Spatial resolution, sensitivity, scatter fraction, and noise equivalent count rate (NECR) were measured on the scanner according to the NEMA NU 2-2012 protocol. The timing resolution was measured using a rotating line source that orbited around the center of field of view (CFOV) at a radius of 20 cm. The image quality phantom was also imaged to quantify the percent contrast, percent background variability, and residual error. The impacts of data acquisition time and bed overlap on the PET image quality were also evaluated using phantom and patient studies. RESULTS: The transverse (axial) spatial resolutions were 3.59 mm (3.67), 4.08 mm (4.65), and 5.32 mm (6.48) full width at half maximum (FWHM) at 1 cm, 10 cm, and 20 cm, respectively, off the CFOV. The measured sensitivity was 10.7 cps/kBq at the CFOV and 10.4 cps/kBq at 10 cm off the CFOV. The peak NECR was 216.7 kcps at an activity concentration of 29.1 kBq/ml, and the scatter fraction was 38.2%. An average of 435 ps FWHM timing resolution was measured. For the image quality phantom, the contrast recovery ratios ranged from 33.9 to 76.4%, while the background variability ranged from 4.7 to 2.0%. In the preliminary clinical study, no noticeable difference in the image quality was observed when the scan time for the whole body and brain was reduced to 1 min/bed and 3 min, respectively. The tested 21% bed overlap showed no significant difference in the image quality compared with the default 38% bed overlap setting. CONCLUSIONS: The physical performances of the PoleStar m660 PET/CT system showed good sensitivity, count rate performance, and timing resolution. The improved performance could help to reduce the acquisition time and bed overlap in the clinical application without detectable compromise in the image quality.

Proof-of-concept prototype time-of-flight PET system based on high-quantum-efficiency multianode PMTs.

PURPOSE: Time-of-flight (TOF) information in positron emission tomography (PET) scanners enhances the diagnostic power of PET scans owing to the increased signal-to-noise ratio of reconstructed images. There are numerous additional benefits of TOF reconstruction, including the simultaneous estimation of activity and attenuation distributions from emission data only. Exploring further TOF gains by using TOF PET scanners is important because it can broaden the applications of PET scans and expand our understanding of TOF techniques. Herein, we present a prototype TOF PET scanner with fine-time performance that can experimentally demonstrate the benefits of TOF information. METHODS: A single-ring PET system with a coincidence resolving time of 360 ps and a spatial resolution of 3.1/2.2 mm (filtered backprojection/ordered-subset expectation maximization) was developed. The scanner was based on advanced high-quantum-efficiency (high-QE) multianode photomultiplier tubes (PMTs). The impact of its fine-time performance was demonstrated by evaluating body phantom images reconstructed with and without TOF information. Moreover, the feasibility of the scanner as an experimental validator of TOF gains was verified by investigating the improvement of images under various conditions, such as the use of joint estimation algorithms of activity and attenuation, erroneous data correction factors (e.g., without normalization correction), and incompletely sampled data. RESULTS: The prototype scanner showed excellent performance, producing improved phantom images, when TOF information was employed in the reconstruction process. In addition, investigation of the TOF benefits using the phantom data in different conditions verified the usefulness of the developed system for demonstrating the practical effects of TOF reconstruction. CONCLUSIONS: We developed a prototype TOF PET scanner with good performance and a fine-timing resolution based on advanced high-QE multianode PMTs and demonstrated its feasibility as an experimental validator of TOF gains, suggesting its usefulness for investigating new applications of PET scans and clarifying TOF techniques in detail.

Principles of Simultaneous PET/MR Imaging.

Combined PET/MR imaging scanners capable of acquiring simultaneously the complementary information provided by the 2 imaging modalities are now available for human use. After addressing the hardware challenges for integrating the 2 imaging modalities, most of the efforts in the field have focused on developing MR-based attenuation correction methods for neurologic and whole-body applications, implementing approaches for improving one modality by using the data provided by the other and exploring research and clinical applications that could benefit from the synergistic use of the multimodal data.

Advances in time-of-flight PET.

This paper provides a review and an update on time-of-flight PET imaging with a focus on PET instrumentation, ranging from hardware design to software algorithms. We first present a short introduction to PET, followed by a description of TOF PET imaging and its history from the early days. Next, we introduce the current state-of-art in TOF PET technology and briefly summarize the benefits of TOF PET imaging. This is followed by a discussion of the various technological advancements in hardware (scintillators, photo-sensors, electronics) and software (image reconstruction) that have led to the current widespread use of TOF PET technology, and future developments that have the potential for further improvements in the TOF imaging performance. We conclude with a discussion of some new research areas that have opened up in PET imaging as a result of having good system timing resolution, ranging from new algorithms for attenuation correction, through efficient system calibration techniques, to potential for new PET system designs.

Update on time-of-flight PET imaging.

Time-of-flight (TOF) PET was initially introduced in the early days of PET. The TOF PET scanners developed in the 1980s had limited sensitivity and spatial resolution, were operated in 2-dimensional mode with septa, and used analytic image reconstruction methods. The current generation of TOF PET scanners has the highest sensitivity and spatial resolution ever achieved in commercial whole-body PET, is operated in fully-3-dimensional mode, and uses iterative reconstruction with full system modeling. Previously, it was shown that TOF provides a gain in image signal-to-noise ratio that is proportional to the square root of the object size divided by the system timing resolution. With oncologic studies being the primary application of PET, more recent work has shown that in modern TOF PET scanners there is an improved tradeoff between lesion contrast, image noise, and total imaging time, leading to a combination of improved lesion detectability, reduced scan time or injected dose, and more accurate and precise lesion uptake measurement. Because the benefit of TOF PET is also higher for heavier patients, clinical performance is more uniform over all patient sizes.

Determination of accuracy and precision of lesion uptake measurements in human subjects with time-of-flight PET.

UNLABELLED: Inclusion of time-of-flight (TOF) information in PET reconstructions has been demonstrated to improve image quality through better signal-to-noise ratios, faster convergence, better lesion detectability, and better image uniformity. The goal of this work was to assess the impact of TOF information on the accuracy and precision of quantitative measurements of activity uptake in small lesions in clinical studies. METHODS: Data from small (10-mm diameter) spheres were merged with list-mode data from 6 healthy volunteers after injection of (18)F-FDG. Six spheres having known activity uptake with respect to the average whole-body uptake were embedded in both the liver and the lung of the subject's data. Images were reconstructed with TOF information and without TOF information (non-TOF reconstruction). The measured uptake was compared with the known activity; variability was measured across 60 bootstrapped replicates of the merged data, across the 6 spheres within a given organ, and across all spheres in all subjects. RESULTS: The average uptake across all spheres and subjects was approximately 50% higher in the lung and 20% higher in the liver with TOF reconstruction than with non-TOF reconstruction at comparable noise levels. The variabilities across replicates, across spheres within an organ, and across all spheres and subjects were 20%-30% lower with TOF reconstruction than with non-TOF reconstruction in the lung; in the liver, the variabilities were 10%-20% lower with TOF reconstruction than with non-TOF reconstruction. CONCLUSION: TOF reconstruction leads to more accurate and precise measurements, both within a subject and across subjects, of the activity in small lesions under clinical conditions.