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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.

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−1 for 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−1 for 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−1 at 25 kBq cc−1 and continues increasing. The time-of-flight resolution is 250 ps, increasing by 18F and 89Zr. 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.

Long axial field-of-view (AFOV) PET scanners allow for full-body dynamic imaging in a single bed-position at very high sensitivity. However, the benefits for kinetic parameter estimation have yet to be studied. This work uses 1) a dynamic Geant4 Application for Tomographic Emission (GATE) simulation of [18F]-fluorothymidine (FLT) in a modified NEMA IQ phantom and 2) a lesion embedding study of spheres in a dynamic [18F]-fluorodeoxyglucose (FDG) human subject imaged on the PennPET Explorer. Both studies were designed using published kinetic data of lung and liver cancers and modeled using two tissue compartments. Data were reconstructed at various emulated doses. Sphere time-activity curves (TACs) were measured on resulting dynamic images, and TACs were fit using a two-tissue-compartment model ( $k_{4}\neq 0$ ) for the FLT study and both a two-tissue-compartment model ( $k_{4}=0$ ) and Patlak graphical analysis for the FDG study to estimate flux ( $K_{i}$ ) and delivery ( $K_{1}$ ) parameters. Quantification of flux and $K_{1}$ shows lower bias and better precision for both radiotracers on the long AFOV scanner, especially at low doses. Dynamic imaging on a long AFOV system can be achieved for a greater range of injected doses, as low as 0.5–2 mCi depending on the sphere size and flux, compared to a standard AFOV scanner, while maintaining good kinetic parameter estimation.

INTRODUCTION: [(68)Ga]Ga-P15-041 ([(68)Ga]Ga-HBED-CC-BP) is a novel bone-seeking PET radiotracer that can be generator-produced. We undertook a Phase 0/I clinical trial to assess its potential for imaging bone metastases in prostate cancer including assessment of radiotracer biodistribution and dosimetry. METHODS: Subjects with prostate cancer and known or suspected osseous metastatic disease were enrolled into one of two arms: dosimetry or dynamic. Dosimetry was performed with 6 whole body PET acquisitions and urine collection spanning 3 hours; normal organ dosimetry was calculated using OLINDA/EXM. Dynamic imaging included a 60-minute acquisition over a site of known or suspected disease followed by two whole body scans. Bootstrapping and subsampling of the acquired list-mode data were conducted to recommend image acquisition parameters for future clinical trials. RESULTS: Up to 233 MBq (6.3 mCi) of [(68)Ga]Ga-P15-041 was injected into 12 enrolled volunteers, 8 in dosimetry and 4 in dynamic cohorts. Radiotracer accumulated in known bone lesions and cleared rapidly from blood and soft tissue. The highest individual organ dose was 0.135 mSv/MBq in the urinary bladder wall. The average effective dose was 0.0173 ± 0.0036 mSv/MBq. An average injected activity of 166.5 MBq (4.5 mCi) resulted in absorbed dose estimates of 22.5 mSv to the urinary bladder wall, 8.2 mSv to the kidneys, and an effective dose of 2.9 mSv. Lesion signal to noise ratios on images generated from subsampled data were significantly higher for injected activities above 74 MBq (2 mCi) and were also significantly higher for imaging at 90 minutes than at 180 minutes post-injection. CONCLUSIONS: Dosimetry estimates are acceptable and [(68)Ga]Ga-P15-041 uptake characteristics in patients with confirmed bone metastases support its continued development. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: Use of [(68)Ga]Ga-P15-041 would not require cyclotron infrastructure for manufacturing and distribution, allowing for improved patient access to a promising PET bone imaging agent.

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.

Kinetic parameters from dynamicIn this work, we studied two abbreviated protocols using data from a 65-min dynamicUsing only early dynamic data with the 2C (or Patlak) model, accurate quantification of KDynamic imaging for 10-15 min immediately p.i. followed by a 5-min scan at 1-h p.i can accurately and precisely quantify

Prostate-specific membrane antigen (PSMA) is a promising molecular target for imaging of prostate adenocarcinoma.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.Based on its favorable imaging characteristics and diagnostic performance in prostate cancer

The introduction of long (>60 cm) axial field-of-view (LAFOV) PET systems has shown their potential for clinical and research applications. LAFOV scanners are expensive, so there is interest in designing systems with longer axial coverage while mitigating cost by introducing detector gaps. We used measurements on the PennPET Explorer (64-cm axial field-of-view (AFOV) prototype) and simulations of scanners up to 143-cm long to assess scanner performance with axial gaps introduced by varying the number of detector rows in each ring. Removing detectors reduces the total sensitivity and results in a nonuniform axial noise profile. Axial resolution shows small (

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

Long axial field-of-view (AFOV) PET scanners have valuable benefits for both clinical and research applications. Thus far, two of these scanners are currently operational in the US: the 194-cm uExplorer at UC Davis and the PennPET Explorer at the University of Pennsylvania. We had previously reported performance metrics and human imaging studies on the 64-cm PennPET Explorer and have recently completed extending the AFOV of the scanner to a 5-ring, 112-cm system. We extended the NEMA metrics to scanners longer than 65-cm and performed sensitivity, count rate, spatial resolution, and contrast recovery measurements on the 5-ring system. The sensitivity of the system was 104 kcps/MBq; the peak NEC measured with a 20×70 cm count rate phantom was 1.6 Mcps @ 39 kBq/cc; the axial spatial resolution degraded slightly for the 62° acceptance angle; and the contrast recovery did not degrade as a function of increased axial acceptance angle. Therefore, extending the axial length of the PennPET Explorer from 64 cm to 112 cm, while expanding the acceptance angle, resulted in gains in sensitivity and count rate with minimal degradations in spatial resolution and no degradation of contrast recovery.

Due to limited counts in voxel-wise time activity curves, the indirect methods that generate kinetic parametric image from dynamic PET reconstructions often have poor image quality. The TOF PET data can be naturally and efficiently stored in histoimage, and 4D tracer distribution can be efficiently reconstructed using the DIRECT (Direct Image REConstruction for Tof) approaches. We aim to develop efficient dynamic/parametric reconstruction with improved quantitative quality from time-of-flight PET data by taking advantage of its intrinsic kinetic models in our DIRECT frameworks. We have implemented volume of interest (VOI) based and voxel-wise parametric fitting using the linearized Patlak model. We further modified DIRECT reconstructions to support 4D nested reconstruction approach with interleaving tomographic reconstruction and parametric fitting at each iteration. To evaluate proposed dynamic reconstruction approaches, we generate 4D dynamic data sets using the synthetic lesion embedding technique. First, a human subject injected with FDG was scanned on the PennPET Explorer scanner configured with 70 cm axial FOV. Then lung and liver lesions were synthetically embedded using pre-scanned sphere data sets with predetermined time-activity curves. We showed that VOI based method can accurately estimate the Patlak parameters from the frame based reconstructions after corrections. The 4D nested DIRECT reconstruction with Patlak fitting can substantially reduce noise in the reconstructed image frames and provide efficient and feasible tool for direct reconstruction of kinetic parametric image.

The latest digital whole-body PET scanners provide a combination of higher sensitivity and improved spatial and timing resolution. We performed a lesion detectability study on two generations of Biograph PET/CT scanners, the mCT Flow and the Vision, to study the impact of improved physical performance on clinical performance. Our hypothesis was that the improved performance of the Vision would result in improved lesion detectability, allowing shorter imaging times or, equivalently, a lower injected dose. Methods: Data were acquired with the Society of Nuclear Medicine and Molecular Imaging Clinical Trials Network torso phantom combined with a 20-cm-diameter cylindrical phantom. Spherical lesions were emulated by acquiring sphere-in-air data and combining them with the phantom data to generate combined datasets with embedded lesions of known contrast. Two sphere sizes and uptakes were used: 9.89-mm-diameter spheres with 6:1 (lung) and 3:1 (cylinder) local activity concentration uptakes and 4.95-mm-diameter spheres with 9.6:1 (lung) and 4.5:1 (cylinder) local activity concentration uptakes. Standard image reconstruction was performed: an ordinary Poisson ordered-subsets expectation maximization algorithm with point-spread function and time-of-flight modeling and postreconstruction smoothing with a 5-mm gaussian filter. The Vision images were also generated without any postreconstruction smoothing. Generalized scan statistics methodology was used to estimate the area under the localized receiver-operating-characteristic curve (ALROC). Results: The higher sensitivity and improved time-of-flight performance of the Vision leads to reduced contrast in the background noise nodule distribution. Measured lesion contrast is also higher on the Vision because of its improved spatial resolution. Hence, the ALROC is noticeably higher for the Vision than for the mCT Flow. Conclusion: Improved overall performance of the Vision provides a factor of 4-6 reduction in imaging time (or injected dose) over the mCT Flow when using the ALROC metric for lesions at least 9.89 mm in diameter. Smaller lesions are barely detected in the mCT Flow, leading to even higher ALROC gains with the Vision. The improved spatial resolution of the Vision also leads to a higher measured contrast that is closer to the real uptake, implying improved quantification. Postreconstruction smoothing, however, reduces this improvement in measured contrast, thereby reducing the ALROC for small, high-uptake lesions.

Purpose To improve the precision of multicenter clinical trials, several efforts are underway to determine scanner-specific parameters for harmonization using standardized phantom measurements. The goal of this study was to test the correspondence between quantification in phantom and patient images and validate the use of phantoms for harmonization of patient images. Methods The National Electrical Manufacturers’ Association image quality phantom with hot spheres was scanned on two time-of-flight PET scanners. Whole-body [18F]-fluorodeoxyglucose (FDG)-PET scans were acquired of subjects on the same systems. List-mode events from spheres (diam.: 10-28 mm) measured in air on each scanner were embedded into the phantom and subject list-mode data from each scanner to create lesions with known uptake with respect to the local background in the phantom and each subject's liver and lung regions, as a proxy to characterize true lesion quantification. Images were analyzed using the contrast recovery coefficient (CRC) typically used in phantom studies and serving as a surrogate for the standardized uptake value used clinically. Post-reconstruction filtering (resolution recovery and Gaussian smoothing) was applied to determine if the effect on the phantom images translates equivalently to subject images. Three post-filtering strategies were selected to harmonize the CRCmean or CRCmax values between the two scanners based on the phantom measurements and then applied to the subject images. Results Both the average CRCmean and CRCmax values for lesions embedded in the lung and liver in four subjects (BMI range 25-38) agreed to within 5% with the CRC values for lesions embedded in the phantom for all lesion sizes. In addition, the relative changes in CRCmean and CRCmax resulting from the application of the post-filters on the subject and phantom images were consistent within measurement uncertainty. Further, the root mean squared percent difference (RMSpd) between CRC values on the two scanners calculated over the 3 sphere sizes was significantly reduced in the subjects using post-filtering strategies chosen to harmonize CRCmean or CRCmax based on phantom measurements: RMSpd of the CRCmean values in subjects was reduced from 36% to

The purpose of this work is to compare the performance of our prototype listmode OSEM reconstruction implementation with that of mashed sinogram-based OSEM reconstruction that we currently employ in our clinical software. Na-22 point source measurements were used to compare resolution at different points along transverse FOV. A Data Spectrum torso phantom with micro-hollow spheres and hollow sphere was used to compare contrast recovery. A mini-Derenzo phantom scan was performed to see if finer structures are better visualized using listmode reconstruction. One brain dataset and a whole body clinical dataset were also reconstructed and compared. Both average transverse and axial FWHM improved in point source data reconstructed with listmode reconstruction. Contrast recovery improvements with listmode reconstruction in sphere of inner diameters 4.95mm, 7.86 mm, 9.89 mm, 12.43 mm, 15.43mm and 19.79 mm are respectively 13.0%, 10.7%, 5.0%, 5.5%, 4.3% and 4.1%. 2.4 mm rods in the mini-Derenzo phantom are better visualized with listmode reconstruction. In brain data finer structures are better visualized and recovery of multiple small update locations, including physiologically important regions like putamen, is higher. In patient data listmode reconstruction helps visualize multiple small lesions which are difficult to see in images reconstructed with sinogram OSEM algorithm. All images reconstructed using listmode reconstruction are sharper with better contrast.

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

Clinically, PET/CT is widely used in oncology and cardiology. In the realm of research, dynamic PET imaging provides valuable information about ongoing biologic processes in the body. Currently, all commercial PET scanners have an axial field of view (AFOV) less than 25 cm, and whole-body scans are taken in multiple static, step-and-shoot bed positions. We are currently building a scanner with a larger AFOV, called the PennPET Explorer. The increased sensitivity from extending the AFOV beyond 25 cm will allow for lower dose imaging, improved count statistics, and simultaneous whole-body static and dynamic imaging. To quantify the effect of extending the AFOV of a PET scanner, we have created GATE simulations of the 16.4-cm AFOV Philips Vereos PET/CT scanner, and extended this to 23cm (E23) and 70-cm (E70) AFOV PET scanners. The simulation model is based on the 1:1 coupled digital detectors used in the Vereos scanner that has a timing resolution of 320 ps. NEMA NU2–2012 sensitivity, spatial resolution, count rate, and image quality standards were run on each of the three simulated scanners and corroborated with measured data from the Vereos. Additionally, low-dose studies were emulated using the image quality simulations from the E23 and E70 scanners. While there was little variation in contrast recovery coefficient (CRC) values across the three geometries, there were notable differences in sensitivity, spatial resolution, and count rate performance. Sensitivity increased from 5.5 kcps/MBq on the Vereos to 10.8 kcps/MBq on the E23 and 90.5 kcps/MBq on the E70. Transaxial spatial resolution at the scanner center (FWHM: 4.0 mm) did not degrade with increased AFOV, while the axial resolution at the center degraded slightly from 3.8 mm (Vereos) to 4.5 mm (E70) due to increased axial parallax errors. At 55 kBq/cc - the activity concentration at peak noise equivalent count rate (NECR) (155 kcps) measured on the Vereos scanner - the NECR were 550 kcps and 4440 kcps for the E23 and E70 scanners, respectively. Lowdose studies showed equivalent CRC measurement precision between the full dose E23 scanner and ${\textstyle \frac {1}{2}}- {\textstyle \frac {1}{4}}$ dose on the E70 scanner. Moving forward, these simulated scanners, along with scanners with even longer AFOVs, will assist in planning both static and dynamic patient studies on the PennPET Explorer when operational.

The benefit of time-of-flight (TOF) in PET reconstruction has been established for clinical imaging, and the signal-to-noise benefit with TOF has been demonstrated to increase with higher randoms fractions. TOF information mitigates and reduces image artifacts arising from errors in the corrections, but it may not account for all changes with count rate. Standard performance measures of image quality are carried out at low or clinical count rates for whole-body scanning, but the dependence of TOF quantitative performance on count rate has not been well-studied. All scanners with detector modules that employ photosensor-sharing experience pile-up of detected events with increasing count rate. We investigated the quantitative accuracy of TOF PET using cardiac and uniform phantoms imaged over a range of activities. At very high count rates the cardiac phantom showed significantly degraded image quality and quantification errors without TOF; TOF reconstruction was more stable to image artifacts and biases at high activities. For the uniform phantom, however, when the same number of prompt-delay events (trues+scatters) was reconstructed at different activities, a systematic negative bias in a large region was observed with increasing activity for TOF reconstructions. This bias was significantly larger than that for non-TOF reconstructions. This finding correlates with a cool center seen in the TOF images and suggests an overcorrection for scatter. At high count rates, object scatter modeled by the TOF-modified single scatter simulation (SSS) does not change, but detector pile-up leads to an increase in detected events with higher energies and long TOF tails than at low activities, neither of which is modeled by TOF-SSS. Deadtime correction factors implicitly include these sources of bias but depend on the algorithm (TOF vs. non-TOF) and likely the activity distribution as well through the inaccurate scatter estimate.

Iterative reconstruction algorithms are routinely used for clinical practice; however, analytic algorithms are relevant candidates for quantitative research studies due to their linear behavior. While iterative algorithms also benefit from the inclusion of accurate data and noise models the widespread use of time-of-flight (TOF) scanners with less sensitivity to noise and data imperfections make analytic algorithms even more promising. In our previous work we have developed a novel iterative reconstruction approach (DIRECT: direct image reconstruction for TOF) providing convenient TOF data partitioning framework and leading to very efficient reconstructions. In this work we have expanded DIRECT to include an analytic TOF algorithm with confidence weighting incorporating models of both TOF and spatial resolution kernels. Feasibility studies using simulated and measured data demonstrate that analytic-DIRECT with appropriate resolution and regularization filters is able to provide matched bias versus variance performance to iterative TOF reconstruction with a matched resolution model.

Early clinical results with time-of-flight (TOF) positron emission tomography (PET) systems have demonstrated the advantages of TOF information in PET reconstruction. Reconstruction approaches in TOF-PET systems include list-mode and binned iterative algorithms as well as confidence-weighted analytic methods. List-mode iterative TOF reconstruction retains the resolutions of the data in the spatial and temporal domains without any binning approximations but is computationally intensive. We have developed an approach [DIRECT (direct image reconstruction for TOF)] to speed up TOF-PET reconstruction that takes advantage of the reduced angular sampling requirement of TOF data by grouping list-mode data into a small number of azimuthal views and co-polar tilts and depositing the grouped events into histo-images, arrays with the sampling and geometry of the final image. All physical effects are included in the system model and deposited in the same histo-image structure. Using histo-images allows efficient computation during reconstruction without ray-tracing or interpolation operations. The DIRECT approach was compared with 3-D list-mode TOF ordered subsets expectation maximization (OSEM) reconstruction for phantom and patient data taken on the University of Pennsylvania research LaBr (3) TOF-PET scanner. The total processing and reconstruction time for these studies with DIRECT without attention to code optimization is approximately 25%-30% that of list-mode TOF-OSEM to achieve comparable image quality. Furthermore, the reconstruction time for DIRECT is independent of the number of events and/or sizes of the spatial and TOF kernels, while the time for list-mode TOF-OSEM increases with more events or larger kernels. The DIRECT approach is able to reproduce the image quality of list-mode iterative TOF reconstruction both qualitatively and quantitatively in measured data with a reduced time.

Phantom studies have shown improved lesion detection performance with time-of-flight (TOF) PET. In this study, we evaluate the benefit of fully 3-dimensional, TOF PET in clinical whole-body oncology using human observers to localize and detect lesions in realistic patient anatomic backgrounds. Our hypothesis is that with TOF imaging we achieve improved lesion detection and localization for clinically challenging tasks, with a bigger impact in large patients. Methods: One hundred patient studies with normal 18 F-FDG uptake were chosen. Spheres (diameter, 10 mm) were imaged in air at variable locations in the scanner field of view corresponding to lung and liver locations within each patient. Sphere data were corrected for attenuation and merged with patient data to produce fused list-mode data files with lesions added to normal-uptake scans. All list files were reconstructed with full corrections and with or without the TOF kernel using a list-mode iterative algorithm. The images were presented to readers to localize and report the presence or absence of a lesion and their confidence level. The interpretation results were then analyzed to calculate the probability of correct localization and detection, and the area under the localized receiver operating characteristic (LROC) curve. The results were analyzed as a function of scan time per bed position, patient body mass index (BMI , 26 and BMI $ 26), and type of imaging (TOF and non-TOF). Results: Our results showed that longer scan times led to an improved area under the LROC curve for all patient sizes. With TOF imaging, there was a bigger increase in the area under the LROC curve for larger patients (BMI $ 26). Finally, we saw smaller differences in the area under the LROC curve for large and small patients when longer scan times were combined with TOF imaging. Conclusion: A combination of longer scan time (3 min in this study) and TOF imaging provides the best performance for imaging large patients or a low-uptake lesion in small or large patients. This imaging protocol also provides similar performance for all patient sizes for lesions in the same organ type with similar relative uptake, indicating an ability to provide a uniform clinical diagnosis in most oncologic lesion detection tasks.

Proton beam therapy can deliver a high radiation dose to a tumor without significant damage to surrounding healthy tissue or organs. One way of verifying the delivered dose distribution is to image the short-lived positron emitters produced by the proton beam as it travels through the patient. A potential solution to the limitations of PET imaging in proton beam therapy is the development of a high sensitivity, in situ PET scanner that starts PET imaging almost immediately after patient irradiation while the patient is still lying on the treatment bed. A partial ring PET design is needed for this application in order to avoid interference between the PET detectors and the proton beam, as well as restrictions on patient positioning on the couch. A partial ring also allows us to optimize the detector separation (and hence the sensitivity) for different patient sizes. Our goal in this investigation is to evaluate an in situ PET scanner design for use in proton therapy that provides tomographic imaging in a partial ring scanner design using time-of-flight (TOF) information and an iterative reconstruction algorithm. GEANT4 simulation of an incident proton beam was used to produce a positron emitter distribution, which was parameterized and then used as the source distribution inside a water-filled cylinder for EGS4 simulations of a PET system. Design optimization studies were performed as a function of crystal type and size, system timing resolution, scanner angular coverage and number of positron emitter decays. Data analysis was performed to measure the accuracy of the reconstructed positron emitter distribution as well as the range of the positron emitter distribution. We simulated scanners with varying crystal sizes (2-4 mm) and type (LYSO and LaBr(3)) and our results indicate that 4 mm wide LYSO or LaBr(3) crystals (resulting in 4-5 mm spatial resolution) are adequate; for a full-ring, non-TOF scanner we predict a low bias (

A prototype time-of-flight (TOF) PET scanner based on cerium-doped lanthanum bromide [LaBr(3) (5% Ce)] has been developed. LaBr(3) has a high light output, excellent energy resolution and fast timing properties that have been predicted to lead to good image quality. Intrinsic performance measurements of spatial resolution, sensitivity and scatter fraction demonstrate good conventional PET performance; the results agree with previous simulation studies. Phantom measurements show the excellent image quality achievable with the prototype system. Phantom measurements and corresponding simulations show a faster and more uniform convergence rate, as well as more uniform quantification, for TOF reconstruction of the data, which have 375 ps intrinsic timing resolution, compared to non-TOF images. Measurements and simulations of a hot and cold sphere phantom show that the 7% energy resolution helps to mitigate residual errors in the scatter estimate because a high energy threshold (480 keV) can be used to restrict the amount of scatter accepted without a loss of true events. Preliminary results with incorporation of a model of detector blurring in the iterative reconstruction algorithm not only show improved contrast recovery but also point out the importance of an accurate resolution model of the tails of LaBr(3)'s point spread function. The LaBr(3) TOF-PET scanner demonstrated the impact of superior timing and energy resolutions on image quality.

Significant improvements have made it possible to add the technology of time-of-flight (TOF) to improve PET, particularly for oncology applications. The goals of this work were to investigate the benefits of TOF in experimental phantoms and to determine how these benefits translate into improved performance for patient imaging. Methods: In this study we used a fully 3-dimensional scanner with the scintillator lutetium-yttrium oxyorthosilicate and a system timing resolution of ;600 ps. The data are acquired in list-mode and reconstructed with a maximum-likelihood expectation maximization algorithm; the system model includes the TOF kernel and corrections for attenuation, detector normalization, randoms, and scatter. The scatter correction is an extension of the model-based singlescatter simulation to include the time domain. Phantom measurements to study the benefit of TOF include 27-cm- and 35-cm-diameter distributions with spheres ranging in size from 10to37mm.ToassessthebenefitofTOFPETforclinicalimaging, patient studies are quantitatively analyzed. Results: The lesion phantom studies demonstrate the improved contrast of the smallest spheres with TOF compared with non-TOF and also confirm the faster convergence of contrast with TOF. These gains are evident from visual inspection of the images as well as a quantitative evaluation of contrast recovery of the spheres and noise in the background. The gains with TOF are higher for larger objects. These results correlate with patient studies in which lesions are seen more clearly and with higher uptake at comparable noise for TOF than with non-TOF. Conclusion: TOF leads to a better contrast-versus-noise trade-off than non-TOF but one that is difficult to quantify in terms of a simple sensitivity gain improvement: A single gain factor for TOF improvement does not include the increased rate of convergence with TOF nor does it consider that TOF may converge to a different contrast than non-TOF. The experimental phantom results agree with those of prior simulations and help explain the improved image quality with TOF for patient oncology studies.

Scanners with different performance characteristics and reconstruction protocols can produce images that show large variations in uptake in small lesions. There have been a number of studies aimed at reducing this variability for clinical trials using phantom data to optimize the acquisition and/or reconstruction protocols. The underlying assumption is that the protocols that harmonize the phantom images will also result in reduced variability in patient images among scanners/sites. The goal of this study was to use patient data with embedded lesions of known uptake to test this assumption. The NEMA image quality (IQ) phantom with hot spheres (diam.: 10–37 mm) was scanned on two time-of-flight (TOF) PET scanners and reconstructed using a list-mode TOF ordered subsets expectation maximization (OSEM) algorithm. Patient FDG data were also acquired on these scanners and the data stored in list-mode format. List-mode events from spheres measured in air on these systems were embedded into the phantom and patient list-mode data to insert 5–6 spheres in the phantom background region and the patient liver and lung regions with a known (9.7:1) uptake with respect to the local uptake. The impact of applying post-reconstruction filtering (both resolution recovery and Gaussian smoothing) on the phantom and patient images was also studied to determine if changes measured with the phantom images using these post-filters would be the same as those measured with patient images. Contrast recovery coefficient (CRC) values measured from lesion embedding studies on the phantoms and patients agree with one another, although CRC max showed greater variability. Additionally, relative changes in CRC brought about by application of the reconstruction post-filters to the patient images were consistent with those observed for the phantom images. This study illustrates, therefore, that these methods may be used to harmonize patient studies by first optimizing (and harmonizing) the reconstruction approach with the NEMA IQ phantom.

Purpose : A 18 fluorine-labeled derivative of vasoactive intestinal peptide [ 18 F- Arg 15 ,Arg 21 VIP( 18 F-dVIP)] was evaluated as a potential imaging agent for breast cancer by comparison with 2-deoxy-2-[ 18 F]fluoro-D-glucose (FDG) using standard ex vivo determinations and small animal position emission tomography (PET) imaging. Procedures : Human breast carcinomas, T-47D and MDA-MB231, tumor-bearing nude mice were injected intravenously with 18 F-dVIP or FDG for imaging and/or biodistribution ( ex vivo ) determined by gamma counting. Results : FDG had two- to three-fold greater tumor accumulation and target-to-non target contrast relative to 18 F-dVIP. VIP receptors were detected in both tumor types but in low concentrations ( 18 F-dVIP cleared into the kidneys. Conclusions : 18 F-dVIP uptake in mice T-47D tumors and kidneys determined by imaging correlated with values determined by ex vivo counting suggesting that tumor and other tissue uptakes can be quantified by in vivo positron projection imaging. (Mol Imag Biol 2002;4:369–379)

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 18F-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.

Three-dimensional (3D) reconstructions from fully 3D positron emission tomography (PET) data can yield high-quality images but at a high computational cost. The 3D row action maximum likelihood algorithm (3D RAMLA) with spherically-symmetric basis functions (blobs) has recently been modified to reconstruct multi-slice 2D PET data after Fourier rebinning (FORE) but still using 3D basis functions (2.5D RAMLA. In this study 2.5D RAMLA and 3D RAMLA were applied to several patient and phantom PET datasets to assess their clinical performance. RAMLA performance was compared to that for the reconstruction techniques in routine clinical use on the authors' PET scanners. Torso phantom and whole-body patient scans acquired on the C-PET scanner were reconstructed after FORE with filtered back-projection (FORE+FBP), the ordered subsets expectation maximization algorithm (FORE+OSEM), and FORE+2.5D RAMLA for various reconstruction parameters. The 3D Hoffman brain phantom scanned on the HEAD Penn-PET scanner was reconstructed with the 3D reprojection algorithm (3DRP) and 3D RAMLA, as well, as FORE+FBP, FORE+OSEM, and FORE+2.5D RAMLA. The authors' results demonstrate improvement of 3D and 2.5D RAMLA with blob basis functions, compared to the reconstruction methods currently in clinical use, in terms of contrast recovery and noise, especially in regions of limited statistics.

We investigated the effects of varying the injected dose, speed of injection, and scan duration to maximize the sensitivity of noninvasive activation studies with 15O-water and three-dimensional positron emission tomography. A covert word generation task was used in four subjects with bolus injections of 2.5 to 3D mCi of 15O-water. The noise equivalent counts (NEC) for the whole brain peaked at an injected dose of 12 to 15 mCi. This was lower than expected from phantom studies, presumably because of the effect of radioactivity outside of the brain. A 10 mCi injection gave an NEC of 92.4 +/- 2.2% of the peak value. As the scan duration increased from 60 to 90 to 120 seconds, the areas of activation decreased in size or were no longer detected. Therefore, we selected a 1 minute scan using 10 mCi for bolus injections. We then performed simulation studies to evaluate, for a given CBF change, the effect on signal-to-noise ratio (S/N) of longer scan duration with slow tracer infusions. Using a measured arterial input function from a bolus injection, new input functions for longer duration injections and the corresponding tissue data were simulated. Combining information about image noise derived from Hoffman brain phantom studies with the simulated tissue data allowed calculation of the S/N for a given CBF change. The simulation shows that a slow infusion permits longer scan acquisitions with only a small loss in S/N. This allows the investigator to choose the injection duration, and thus the time period during which scan values are sensitive to regional CBF.

The finite spatial resolution of PET scanners leads to a loss of quantitative accuracy in the measurement of activity in small structures. We sought to study the impact of resolution modeling on the accuracy and precision of contrast measurements in whole-body imaging. Resolution models of differing degrees of accuracy were incorporated into the system model of a 3D iterative time-of-flight PET reconstruction algorithm. Phantom and patient data with 10-mm hot spheres at multiple locations were used to measure the accuracy and variability of contrast recovery coefficient (CRC) measurements. In both phantom and patient studies, the accuracy of CRC values in small structures at clinically reasonable noise levels increased significantly (40–70%, depending on the activity distribution) when a simple, spatially invariant resolution model was included in the reconstruction, compared with the CRC values without resolution modeling (∼0.3); more accurate models led to a modest (≤10%) further improvement in the quantitative accuracy. In simulated trues-only phantom data, the variability of CRC values with resolution modeling was comparable to or reduced from that without resolution modeling. In the measured phantom and patient studies, the precision of CRC values was generally not significantly affected by the inclusion of resolution modeling in the reconstruction algorithm. For whole-body imaging, a simple resolution model provides a marked increase in contrast recovery without a concurrent increase in the variability of the contrast measurement.

Time-of-flight (TOF) PET imaging provides several benefits including faster, more uniform convergence, higher contrast at a given noise level, and improved lesion detectability [1–5]. Previous phantom studies have suggested that there may be an additional benefit of TOF, namely a reduction in the variability of the lesion uptake [6]. In this work we investigated the variability in lesion uptake in human data with a complex distribution of activity and attenuation. We studied this effect as a function of the location within the body, the number of collected counts, and the timing resolution.

There has recently been renewed interest in time-of-flight (TOF) PET due to the availability of fast scintillators that also have high light output and high stopping power, as well as cost-effective fast photomultiplier tubes and stable electronics. Early results with these TOF-PET systems have shown both an improved contrast/noise trade-off and faster convergence compared with reconstructions without TOF information. Simulations have predicted further improvement in imaging performance with better timing resolution. A prototype whole-body PET scanner incorporating Ce-doped LaBr 3 crystals and specialized timing circuitry to take advantage of the scintillator’s fast timing characteristics has recently been completed. The intrinsic performance of the scanner has been measured. The average energy resolution over all crystals is 6.5%, and the system timing resolution is 375 ps. The scatter fraction for 20-, 27-, and 35-cm diameter cylinders is 21, 27, and 32%, respectively, for a 485-keV lower energy threshold. The average spatial resolution is 5.8 mm at 1 cm and 6.5 mm at 10 cm. Resolution modeling has been incorporated into the list-mode TOF iterative algorithm. Simulation studies were carried out to measure the relative impact of timing resolution, energy resolution and lower energy threshold, and spatial resolution modeling on TOF-PET imaging performance as characterized by the contrast/noise trade-off. It was found that improved timing resolution leads to faster, more uniform convergence with less variability in quantification as a function of either radial position or local activity environment. Better energy resolution allows for the use of a tighter energy window, which leads to fewer accepted scatter events and improved quantitative accuracy. Resolution modeling improves contrast recovery at the cost of slower convergence; further work is needed to define an accurate model of the point spread function for the LaBr 3 system. The superior timing and energy resolutions appear to mitigate the loss of spatial resolution that arises from the lower stopping power of the crystal.

TOF resolution is known to degrade with increasing count rate. During TOF-PET reconstruction the timing resolution of the data is used as an input for the reconstruction algorithm. The effect of the kernel width on the reconstruction was investigated in this paper. We looked at contrast recovery and background uniformity. Noise free simulation data were used together with high count measured TOF-PET data. The results clearly indicate that only the correct kernel should be used to reconstruct the data. Other kernels result in wrong contrast and less uniform background regions. Therefore it would be very useful to be able to estimate the TOF kernel from the data themselves. It is first shown that the likelihood reaches a maximum at the correct timing resolution. Then a method to estimate the kernel from both a non-TOF reconstruction and the measured TOF data is described. The determination of the timing resolution is performed with an iterative method using the non-TOF MLEM reconstruction and Richardson-Lucy deconvolution.

The next generation human PET scanners will possess the capability to measure the time-of-flight (TOF) information due to the availability of faster scintillators like LaBr3 and LSO. These systems will be able to measure timing resolutions well below 1 ns. The shorter point spread function (compared to conventional PET) allows reconstruction from fewer angles. We show that with improved TOF-resolution, the number of angles needed to obtain artifact free reconstruction decreases with improving TOF resolution. In a ring scanner this property can be exploited by mashing the data from adjacent angles using the TOF information. Based on the angular sampling criterion for PET we propose an angular sampling criterion for TOF-PET. Simulated data of 2D TOF-PET systems were reconstructed from a varying number of angles with iterative reconstruction. The comparison with the listmode reconstruction confirmed the predicted relationship. Simulated 3D TOF-PET data were rebinned into a 2D data. The relationship between the number of angles and the TOF resolution also determines the maximum axial acceptance angle where rebinning can be done without contrast loss. The angular sampling criterion for TOF-PET can will be useful to determine the number of mashing angles and axial tilts for a certain timing resolution

Rebinning is used in PET to reduce three-dimensional (3D) data to a set of stacked two-dimensional (2D) slices that can be reconstructed using a conventional 2D algorithm. Rebinning is an attractive alternative to 3D reconstruction for time-of-flight PET data because the errors made by rebinning are much smaller while the data size is much larger than for conventional 3D PET. For rebinning algorithms that require consistent projection data, attenuation correction is performed prior to rebinning. However, statistical reconstruction algorithms assume Poisson-distributed data with uncorrected data as the input and incorporate attenuation effects in the system model. The usual assumption with rebinned data is that the attenuation factor for direct 2D lines of response (LORs) is close to that for the oblique LORs that contribute to the 2D LOR during rebinning. This approximation breaks down for objects with non-uniform attenuation distributions and sharp axial attenuation discontinuities, especially for large axial acceptance angles. Average 2D attenuation factors, calculated as the weighted average of attenuation factors for LORs contributing to each rebinned LOR, is a more accurate representation of attenuation effects seen by rebinned data. The weighted attenuation factors are easily determined from the ratio of rebinned data with and without prior attenuation correction. Using the weighted attenuation factors leads to a modest reduction in image noise near attenuation discontinuities.

A proto-type time-of-flight (TOF) 3D PET scanner based on lanthanum bromide detectors has been developed. The LaBr/sub 3/(5%Ce) Anger-logic detectors in this new scanner use 4/spl times/4/spl times/30 mm pixels and continuous light-guide coupled to a hexagonal array of 50-mm PMTs. The scanner consists of 24 modules with a 93-cm detector diameter and 25-cm axial field-of-view. Initial characterization of scanner performance has been performed, including energy and timing performance. We currently measure an overall system energy resolution of 7.5% and a system timing resolution is 460 ps, although we expect these results to improve eventually when the electronics are fully optimized. Since there are not yet standard tests to quantify the benefit of TOF, we designed two phantoms with hot and cold spheres in 27-cm and 35-cm diameter vessels to evaluate the TOF performance as a function of body size. The data from this scanner are reconstructed with a fully 3D list-mode iterative TOF algorithm with all data corrections incorporated into the system model. We find that TOF reconstruction reduces the noise and background variability, especially for the larger phantom representing a large patient. In addition, TOF improves detail and contrast of the spheres (lesions), especially the smallest 10-mm sphere. The TOF reconstruction reaches convergence faster than the non-TOF reconstruction, and the rate of convergence is seen to be more insensitive to object size. These results indicate that TOF will help improve image quality and potentially reduce scan time with clinical patients.

Faster scintillators like LaBr(3) and LSO have sparked renewed interest in PET scanners with time-of-flight (TOF) information. The TOF information adds another dimension to the data set compared to conventional three-dimensional (3D) PET with the size of the projection data being multiplied by the number of TOF bins. Here we show by simulations and analytical reconstruction that angular sampling for two-dimensional (2D) TOF PET can be reduced significantly compared to what is required for conventional 2D PET. Fully 3D TOF PET data, however, have a wide range of oblique and transverse angles. To make use of the smaller necessary angular sampling we reduce the 3D data to a set of 2D histoprojections. This is done by rebinning the 3D data to 2D data and by mashing these 2D data into a limited number of angles. Both methods are based on the most likely point given by the TOF measurement. It is shown that the axial resolution loss associated with rebinning reduces with improved timing resolution and becomes less than 1 mm for a TOF resolution below 300 ps. The amount of angular mashing that can be applied without tangential resolution loss increases with improved TOF resolution. Even quite coarse angular mashing (18 angles out of 324 measured angles for 424 ps) does not significantly reduce image quality in terms of the contrast or noise. The advantages of the proposed methods are threefold. Data storage is reduced to a limited number of 2D histoprojections with TOF information. Compared to listmode format we have the advantage of a predetermined storage space and faster reconstruction. The method does not require the normalization of projections prior to rebinning and can be applied directly to measured listmode data.

In the reconstruction of data from time-of-flight (TOF) PET systems, the timing resolution is assumed to be known accurately; in iterative reconstruction, it is included in the system model, typically as a Gaussian function. The width of the reconstruction TOF kernel is taken to be equal to the measured coincidence timing resolution (tau). If tau changes (e.g., as a function of count rate), the TOF kernel used in reconstruction will not accurately model the measured data. The goal of this work was to assess the effect of using an inaccurate value of tau in the reconstruction TOF kernel. The Alderson phantom with 10-mm hot spheres was imaged on the Philips Gemini TF PET/CT system (585-ps intrinsic timing resolution). Distributions of hot spheres in 27- and 35-cm diameter warm cylinders were also simulated (trues only) for 300- and 600-ps timing resolutions. The data were reconstructed using up to 20 iterations of TOF-OSEM with 20 chronological subsets. For simulated data, reconstruction with a TOF kernel 10-25% narrower than tau led to a 3-12% decrease in contrast for all sphere sizes at the same background noise level because sphere events were misplaced due to the finite timing accuracy. Using a reconstruction TOF kernel 10-25% wider than tau resulted in a 3-7% increase in contrast. Even wider reconstruction kernels led to still higher contrasts for kernel widths up to 2-3 times tau, although at the cost of increased reconstruction time and slower convergence rates. For kernel widths greater than 3tau, the performance decreased, as the reconstruction approached the non-TOF algorithm. These trends were also observed with the measured data, although much less pronounced. The results indicate that contrast/noise performance is fairly insensitive to inaccuracies in the reconstruction TOF kernel, provided that it is not narrower than the actual timing resolution of the data.

For modern time-of-flight (TOF) positron emission tomography (PET) systems, in which the number of possible lines of response (LOR) and TOF bins is much larger than the number of acquired events, the most appropriate reconstruction approaches are considered to be the list-mode ones, where the processing of the acquired data is done event by event. However, their shortcomings are relatively high computational costs for reconstruction and sensitivity matrix calculation. Furthermore, new sensitivity matrix has to be calculated for each (attenuation) object, and all possible LORs have to be considered for its calculation, not only those which coincide with the actually detected events. Efficient treatment of the TOF data within the proposed DIRECT - Direct Image Reconstruction for TOF - approach is allowed by 1) proper angular (polar and co-polar) grouping of the TOF events to a set of views as given by angular sampling requirements for TOF resolution - each view having a common TOF kernel, and 2) placement/deposit of the grouped events, and all correction data, into the "histo-images" (one histo-image per view), having the same geometry (voxel grid and orientation) as the reconstructed image. Unlike binning, proper storing operation does not compromise resolution of the data since events are directly stored into the histo-image elements at desired image (voxel) resolution. The reconstruction operations do not negatively affect the resolution neither since no tracing or interpolation operations are needed - all data and operations are directly in the image space. Very efficient reconstruction operations and calculation of correction coefficients can be designed utilizing the image equivalent format and grouping, as demonstrated in this work using DIRECT approach with iterative row-action maximum-likelihood (RAMLA) algorithm.

A model of deadtime for emission and transmission scans in positron emission tomography (PET) scanners with two-dimensional detectors has been developed. The model takes into account coincidence losses due to singles losses and multiple events, as well as mispositioning errors at higher count rates caused by pulse pile-up, within a detector block. The model is applicable to emission distributions and to spatially varying singles distributions seen with a rotating pin transmission source. An automatic procedure to determine the parameters of this model based on decaying emission studies has also been developed. Different singles dead time factors are required for emission and blank distributions due to differences in their energy spectra. The model was tested on emission and pin transmission data taken on the Scanditronix PC2048-15B scanner. >

The purpose of this work is to determine the benefit which can be achieved in image quality for a time-of-flight (TOF) capable 3D whole-body PET scanner. We simulate a 3D whole-body time-of-flight PET scanner with a complete modeling of spatial and energy resolutions. The simulated scanner has a diameter of 84-cm, an axial FOV of 25-cm, and uses a 4times4times30-mm3 pixelated LaBr3 Anger-logic detector. Multiple simulations were performed for a 27-cm diameter and 70-cm long uniform cylinder with hot spheres (22,17,13, and 10-m diameter) in central slice, and 10-mm diameter hot spheres in a slice at 1/4 axial FOV (8:1 activity uptake ratio with respect to background). Image reconstruction was performed with a list-mode iterative TOF algorithm and data were currently analyzed for true coincidences after attenuation correction for timing resolutions of 300,600,1000-ps and non-TOF. Our results show that contrast recovery improves with TOF (NEMA NU2-2001 analysis). Detectability for 10-mm diameter hot spheres estimated using a non-prewhitening matched filter (NPW SNR) also improves with TOF and best results are obtained for timing resolution les300 ps

The evolution of positron emission tomography (PET) imaging for small animals has led to the development of dedicated PET scanner designs with high resolution and sensitivity. The animal PET scanner achieves these goals for imaging small animals such as mice and rats. The scanner uses a pixelated Anger-logic detector for discriminating 2 /spl times/ 2 /spl times/ 10 mm/sup 3/ crystals with 19-mm-diameter photomultiplier tubes. With a 19.7-cm ring diameter, the scanner has an axial length of 11.9 cm and operates exclusively in three-dimensional imaging mode, leading to very high sensitivity. Measurements show that the scanner design achieves a spatial resolution of 1.9 mm at the center of the field-of-view. Initially designed with gadolinium orthosilicate but changed to lutetium-yttrium orthosilicate, the scanner now achieves a sensitivity of 3.6% for a point source at the center of the field-of-view with an energy window of 250-665 keV. Iterative image reconstruction, together with accurate data corrections for scatter, random, and attenuation, are incorporated to achieve high-quality images and quantitative data. These results are demonstrated through our contrast recovery measurements as well as sample animal studies.

Transmission scans using a single-photon point source on a positron emission tomography (PET) scanner are inherently acquired in a cone-beam geometry. Traditionally, these data are binned into radially parallel oblique projections and then rebinned using single-slice rebinning (SSRB) into a set of two-dimensional parallel sinograms. For axially oblique lines of response (LORs), the SSRB approximation results in axial and tangential blurring of the transmission image, especially at large radial distances. For the animal PET scanner recently completed at the University of Pennsylvania, there is interest in placing the transmission source outside the scanner in order to maximize the transverse field of view (FOV). For this extremely asymmetric configuration, however, the LORs are very oblique (axial angle=19-42 deg). We compared three methods of processing transmission data, SSRB or FORE followed by two-dimensional (2D) reconstruction and an iterative algorithm for transmission data that uses the cone-beam LORs directly (TR-OSEM-CB). All three algorithms produce acceptable transmission images when the source is inside the scanner. For the case when the transmission source is outside the scanner, TR-OSEM-CB produces images with only minor artifacts near the ends of the axial FOV. SSRB and FORE images have significant axial blurring, although the central region of the FORE image is artifact-free and potentially useful for generating attenuation correction factors. Moving the source closer to the detector ring reduces the residual artifacts seen with TR-OSEM-CB.

A high-sensitivity, high-resolution brain PET scanner ("G-PET") has been developed. This scanner is similar in geometry to a previous brain scanner developed at the University of Pennsylvania, the HEAD Penn-PET, but the detector technology and electronics have been improved to achieve enhanced performance.This scanner has a detector ring diameter of 42.0 cm with a patient aperture of 30.0 cm and an axial field of view of 25.6 cm. It comprises a continuous light-guide that couples 18,560 (320 x 58 array) 4 x 4 x 10 mm(3) gadolinium oxyorthosilicate (GSO) crystals to 288 (36 x 8 array) 39-mm photomultiplier tubes in a hexagonal arrangement. The scanner operates only in 3-dimensional (3D) mode because there are no interplane septa. Performance measurements on the G-PET scanner were made following National Electrical Manufacturers Association NU 2-2001 procedures for most measurements, although NU 2-1994 procedures were used when these were considered more appropriate for a brain scanner (e.g., scatter fraction and counting-rate performance measurements).The transverse and axial resolutions near the center are 4.0 and 5.0 mm, respectively. At a radial offset of 10 cm, these numbers deteriorate by approximately 0.5 mm. The absolute sensitivity of this scanner measured with a 70-cm long line source is 4.79 counts per second (cps)/kBq. The scatter fraction measured with a line source in a 20-cm-diameter x 19-cm-long cylinder is 39% (for a lower energy threshold of 410 keV). For the same cylinder, the peak noise equivalent counting rate is 60 kcps at an activity concentration of 7.4 kBq/mL (0.20 micro Ci/mL), whereas the peak true coincidence rate is 132 kcps at an activity concentration of 14 kBq/mL (0.38 micro Ci/mL). Images from the Hoffman brain phantom as well as (18)F-FDG patient scans illustrate the high quality of images acquired on the G-PET scanner.The G-PET scanner attains the goal of high performance for brain imaging through the use of an Anger-logic GSO detector design with continuous optical coupling. This detector design leads to good energy resolution, which is needed in 3D imaging to minimize scatter and random coincidences.

Instrumentation for emission computed tomography continues to evolve, taking advantage of developments in detector technology, data processing and correction methods, and reconstruction algorithms. This article reviews the basic principles and latest developments in emission computed tomography instrumentation, for both positron emission tomography and single-photon emission computed tomography applications.

True 3D reconstructions from fully 3D PET data can yield high-quality images but at a high computational cost. The 3D row action maximum likelihood algorithm (3D RAMLA) with 3D spherically-symmetric basis functions (blobs) has recently been modified to reconstruct multi-slice 2D PET data after Fourier rebinning (FORE) but still using 3D basis functions (2.5 D RAMLA). In this study both 2.5 D RAMLA and 3D RAMLA were applied to different patient and phantom PET data to assess their clinical performance. Whole-body scans acquired on the C-PET scanner were reconstructed with FORE+FBP, FORE+OSEM, and FORE+2.5 D RAMLA for various reconstruction parameters (blob radius and shape, relaxation parameter). The 3D Hoffman brain phantom scanned on the HEAD Penn-PET scanner was reconstructed with 3DRP and 3D RAMLA, as well as FORE+OSEM. The authors' results demonstrate improvement of the RAMLA compared to the popular reconstruction methods in terms of contrast recovery and noise, especially in regions of limited statistics.

True three-dimensional (3D) reconstructions from fully 3D positron emission tomography (PET) data yield high-quality images but at a high computational cost. Image representation using three-dimensional spherically-symmetric basis functions on a body-centered cubic (BCC) grid, as opposed to a simple cubic (SC) grid, can reduce the computational demands of a 3D approach without compromising image quality by reducing the number of image elements to be reconstructed. The goal of this study was to determine if the image quality improvements predicted for the 3D row action maximum likelihood algorithm (RAMLA) over 2.5D RAMLA after Fourier rebinning (FORE) would be seen with clinical PET data. Torso phantom, whole-body patient, and brain patient studies were used in this analysis. Data were corrected for detector efficiency, scatter, and randoms prior to reconstruction. Attenuation effects were either incorporated into the system model or pre-corrected prior to reconstruction. Higher contrast at comparable noise levels (or lower noise for comparable contrast) are seen with 3D RAMLA (SC or BCC grid) for both phantom and patient data. The brain patient data show improved axial resolution with 3D RAMLA, where the degradation in resolution with FORE is eliminated. Application of a fully 3D reconstruction algorithm is possible in clinically reasonable times.