Performance evaluation of the PennPET explorer with expanded axial coverage.

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

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

Total body (TB) positron emission tomography (PET) instruments have dramatically changed the paradigm of PET clinical and research studies due to their very high sensitivity and capability to image dynamic radiopharmaceutical distributions in the major organs of the body simultaneously. In this manuscript, we review the design of these systems and discuss general challenges and trade-offs to maximize the performance gains of current TB-PET systems. We then describe new concepts and technology that may impact future TB-PET systems. The manuscript summarizes what has been learned from the initial sites with TB-PET and explores potential research and clinical applications of TB-PET. The current generation of TB-PET systems range in axial field-of-view (AFOV) from 1 to 2 m and serve to illustrate the benefits and opportunities of a longer AFOV for various applications in PET. In only a few years of use these new TB-PET systems have shown that they will play an important role in expanding the field of molecular imaging and benefiting clinical practice.

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

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

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

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

Performance Characteristics of Long Axial Field-of-View PET Scanners with Axial Gaps.

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 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 non-uniform axial noise profile. Axial resolution shows small (<0.5 mm) loss from the edge of the AFOV to the center, even for a 143-cm AFOV scanner with an unrestricted acceptance angle. The presence of large axial gaps increases the variability in axial resolution and contrast recovery across the AFOV compared to a system without gaps. More modest axial gaps show less variable behavior. The results suggest that designs where the gap is no larger than one-half of the width of a detector ring may be preferred, although the optimal choice of scanner design with the trade-offs of performance and AFOV will depend on its intended usage.

Scanner Design Considerations for Long Axial Field-of-View PET Systems.

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.

Quantifying bias and precision of kinetic parameter estimation on the PennPET Explorer, a long axial field-of-view scanner.

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 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 (k4 ≠ 0) for the FLT study and both a two-tissue-compartment model (k4 = 0) and Patlak graphical analysis for the FDG study to estimate flux (Ki) and delivery (K1) parameters. Quantification of flux and K1 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.

Biodistribution, dosimetry, and temporal signal-to-noise ratio analyses of normal and cancer uptake of [68Ga]Ga-P15-041, a gallium-68 labeled bisphosphonate, from first-in-human studies.

INTRODUCTION: [68Ga]Ga-P15-041 ([68Ga]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 h; normal organ dosimetry was calculated using OLINDA/EXM. Dynamic imaging included a 60 min 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 [68Ga]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 min than at 180 min post-injection. CONCLUSIONS: Dosimetry estimates are acceptable and [68Ga]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 [68Ga]Ga-P15-041 would not require cyclotron infrastructure for manufacturing and distribution, allowing for improved patient access to a promising PET bone imaging agent.

Benefit of Improved Performance with State-of-the Art Digital PET/CT for Lesion Detection in Oncology.

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.

PennPET Explorer: Design and Preliminary Performance of a Whole-Body Imager.

We report on the development of the PennPET Explorer whole-body imager. Methods: The PennPET Explorer is a multiring system designed with a long axial field of view. The imager is scalable and comprises multiple 22.9-cm-long ring segments, each with 18 detector modules based on a commercial digital silicon photomultiplier. A prototype 3-segment imager has been completed and tested with an active 64-cm axial field of view. Results: The instrument design is described, and its physical performance measurements are presented. These include sensitivity of 55 kcps/MBq, spatial resolution of 4.0 mm, energy resolution of 12%, timing resolution of 256 ps, and a noise-equivalent count rate above 1,000 kcps beyond 30 kBq/mL. After an evaluation of lesion torso phantoms to characterize quantitative accuracy, human studies were performed on healthy volunteers. Conclusion: The physical performance measurements validated the system design and led to high-quality human studies.

PennPET Explorer: Human Imaging on a Whole-Body Imager.

The PennPET Explorer, a prototype whole-body imager currently operating with a 64-cm axial field of view, can image the major body organs simultaneously with higher sensitivity than that of commercial devices. We report here the initial human imaging studies on the PennPET Explorer, with each study designed to test specific capabilities of the device. Methods: Healthy subjects were imaged with FDG on the PennPET Explorer. Subsequently, clinical subjects with disease were imaged with 18F-FDG and 68Ga-DOTATATE, and research subjects were imaged with experimental radiotracers. Results: We demonstrated the ability to scan for a shorter duration or, alternatively, with less activity, without a compromise in image quality. Delayed images, up to 10 half-lives with 18F-FDG, revealed biologic insight and supported the ability to track biologic processes over time. In a clinical subject, the PennPET Explorer better delineated the extent of 18F-FDG-avid disease. In a second clinical study with 68Ga-DOTATATE, we demonstrated comparable diagnostic image quality between the PennPET scan and the clinical scan, but with one fifth the activity. Dynamic imaging studies captured relatively noise-free input functions for kinetic modeling approaches. Additional studies with experimental research radiotracers illustrated the benefits from the combination of large axial coverage and high sensitivity. Conclusion: These studies provided a proof of concept for many proposed applications for a PET scanner with a long axial field of view.

Numerical observer study of lesion detectability for a long axial field-of-view whole-body PET imager using the PennPET Explorer.

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.

Validation of phantom-based harmonization for patient harmonization.

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 [18 F]-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. Postreconstruction filtering (resolution recovery and Gaussian smoothing) was applied to determine if the effect on the phantom images translates equivalently to subject images. Three postfiltering 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 postfilters 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 three sphere sizes was significantly reduced in the subjects using postfiltering strategies chosen to harmonize CRCmean or CRCmax based on phantom measurements: RMSpd of the CRCmean values in subjects was reduced from 36% to < 8% after harmonizing CRCmean , while RMSpd for CRCmax was reduced from ~33% to < 6% after harmonizing CRCmax with a different strategy. However, with this strategy designed to harmonize CRCmax , the RMSpd for CRCmean only improved to ~14% in subjects. CONCLUSIONS: The consistency of the CRC measurements between the phantom and subject data demonstrates that harmonization strategies defined with phantom studies track well to patient images. However, quantitative agreement between different scanners as represented by the RMSpd depends on the metric chosen for harmonization.

Analytic TOF PET reconstruction algorithm within DIRECT data partitioning framework.

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.

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.

Comparison of list-mode and DIRECT approaches for time-of-flight PET reconstruction.

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.

Impact of time-of-flight PET on whole-body oncologic studies: a human observer lesion detection and localization study.

UNLABELLED: 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.

Efficient 3-D TOF PET reconstruction using view-grouped histo-images: DIRECT-direct image reconstruction for TOF.

For modern time-of-flight (TOF) positron emission tomography (PET) systems, in which the number of possible lines of response and TOF bins is much larger than the number of acquired events, the most appropriate reconstruction approaches are considered to be list-mode methods. However, their shortcomings are relatively high computational costs for reconstruction and for sensitivity matrix calculation. Efficient treatment of TOF data within the proposed DIRECT approach is obtained by 1) angular (azimuthal and co-polar) grouping of TOF events to a set of views as given by the angular sampling requirements for the TOF resolution, and 2) deposition (weighted-histogramming) of these grouped events, and correction data, into a set of "histo-images," one histo-image per view. The histo-images have the same geometry (voxel grid, size and orientation) as the reconstructed image. The concept is similar to the approach involving binning of the TOF data into angularly subsampled histo-projections-projections expanded in the TOF directions. However, unlike binning into histo-projections, the deposition of TOF events directly into the image voxels eliminates the need for tracing and/or interpolation operations during the reconstruction. Together with the performance of reconstruction operations directly in image space, this leads to a very efficient implementation of TOF reconstruction algorithms. Furthermore, the resolution properties are not compromised either, since events are placed into the image elements of the desired size from the beginning. Concepts and efficiency of the proposed data partitioning scheme are demonstrated in this work by using the DIRECT approach in conjunction with the row-action maximum-likelihood (RAMLA) algorithm.

Benefit of time-of-flight in PET: experimental and clinical results.

UNLABELLED: 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 approximately 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 single-scatter 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 10 to 37 mm. To assess the benefit of TOF PET for clinical imaging, 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.

Investigation of time-of-flight benefit for fully 3-D PET.

The purpose of this paper is to determine the benefit that can be achieved in image quality for a time-of-flight (TOF) fully three-dimensional (3-D) whole-body positron emission tomography (PET) scanner. We simulate a 3-D whole-body time-of-flight PET scanner with a complete modeling of spatial and energy resolutions. The scanner is based on LaBr3 Anger-logic detectors with which 300ps timing resolution has been achieved. Multiple simulations were performed for 70-cm long uniform cylinders with 27-cm and 35-cm diameters, containing hot spheres (22, 17, 13, and 10-mm diameter) in a central slice and 10-mm diameter hot spheres in a slice at 1/4 axial FOV. Image reconstruction was performed with a list-mode iterative TOF algorithm and data were analyzed after attenuation and scatter corrections for timing resolutions of 300, 600, 1000 ps and non-TOF for varying count levels. The results show that contrast recovery improves slightly with TOF (NEMA NU2-2001 analysis), and improved timing resolution leads to a faster convergence to the maximum contrast value. Detectability for 10-mm diameter hot spheres estimated using a nonprewhitening matched filter (NPW SNR) also improves nonlinearly with TOF. The gain in image quality using contrast and noise measures is proportional to the object diameter and inversely proportional to the timing resolution of the scanner. The gains in NPW SNR are smaller, but they also increase with increasing object diameter and improved timing resolution. The results show that scan times can be reduced in a TOF scanner to achieve images similar to those from a non-TOF scanner, or improved image quality achieved for same scan times.