Energy-based scatter estimation in clinical PET.

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

Advances in Breast PET Instrumentation.

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

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

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

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

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

Quantitative PET in the 2020s: a roadmap.

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

Evaluating attenuation correction strategies in a dedicated, single-gantry breast PET-tomosynthesis scanner.

We are developing a dedicated, combined breast positron emission tomography (PET)-tomosynthesis scanner. Both the PET and digital breast tomosynthesis (DBT) scanners are integrated in a single gantry to provide spatially co-registered 3D PET-tomosynthesis images. The DBT image will be used to identify the breast boundary and breast density to improve the quantitative accuracy of the PET image. This paper explores PET attenuation correction (AC) strategies that can be performed with the combined breast PET-DBT scanner to obtain more accurate, quantitative high-resolution 3D PET images. The PET detector is comprised of a 32 × 32 array of 1.5 × 1.5 × 15 mm3 LYSO crystals. The PET scanner utilizes two detector heads separated by either 9 or 11 cm, with each detector head having a 4 × 2 arrangement of PET detectors. GEANT4 Application for Tomographic Emission simulations were performed using an anthropomorphic breast phantom with heterogeneous attenuation under clinical DBT-compression. FDG-avid lesions, each 5 mm in diameter with 8:1 uptake, were simulated at four locations within the breast. Simulations were performed with a scan time of 2 min. PET AC was performed using the actual breast simulation model as well as DBT reconstructed volumetric images to derive the breast outline. In addition to using the known breast density as defined by the breast model, we also modeled it as uniform patient-independent soft-tissue, and as a uniform patient-specific material derived from breast tissue composition. Measured absolute lesion uptake was used to evaluate the quantitative accuracy of performing AC using the various strategies. This study demonstrates that AC is necessary to obtain a closer estimate of the true lesion uptake and background activity in the breast. The DBT image dataset assists in measuring lesion uptake with low bias by facilitating accurate breast delineation as well as providing accurate information related to the breast tissue composition. While both the uniform soft-tissue and patient-specific material approaches provides a close estimate to the ground truth, <5% bias can be achieved by using a uniform patient-specific material to define the attenuation map.

Roadmap toward the 10 ps time-of-flight PET challenge.

Since the seventies, positron emission tomography (PET) has become an invaluable medical molecular imaging modality with an unprecedented sensitivity at the picomolar level, especially for cancer diagnosis and the monitoring of its response to therapy. More recently, its combination with x-ray computed tomography (CT) or magnetic resonance (MR) has added high precision anatomic information in fused PET/CT and PET/MR images, thus compensating for the modest intrinsic spatial resolution of PET. Nevertheless, a number of medical challenges call for further improvements in PET sensitivity. These concern in particular new treatment opportunities in the context personalized (also called precision) medicine, such as the need to dynamically track a small number of cells in cancer immunotherapy or stem cells for tissue repair procedures. A better signal-to-noise ratio (SNR) in the image would allow detecting smaller size tumours together with a better staging of the patients, thus increasing the chances of putting cancer in complete remission. Moreover, there is an increasing demand for reducing the radioactive doses injected to the patients without impairing image quality. There are three ways to improve PET scanner sensitivity: improving detector efficiency, increasing geometrical acceptance of the imaging device and pushing the timing performance of the detectors. Currently, some pre-localization of the electron-positron annihilation along a line-of-response (LOR) given by the detection of a pair of annihilation photons is provided by the detection of the time difference between the two photons, also known as the time-of-flight (TOF) difference of the photons, whose accuracy is given by the coincidence time resolution (CTR). A CTR of about 10 picoseconds FWHM will ultimately allow to obtain a direct 3D volume representation of the activity distribution of a positron emitting radiopharmaceutical, at the millimetre level, thus introducing a quantum leap in PET imaging and quantification and fostering more frequent use of 11C radiopharmaceuticals. The present roadmap article toward the advent of 10 ps TOF-PET addresses the status and current/future challenges along the development of TOF-PET with the objective to reach this mythic 10 ps frontier that will open the door to real-time volume imaging virtually without tomographic inversion. The medical impact and prospects to achieve this technological revolution from the detection and image reconstruction point-of-views, together with a few perspectives beyond the TOF-PET application are discussed.

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.

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.

Spatially-variant image-based modeling of PSF deformations with application to a limited angle geometry from a dual-panel breast-PET imager.

Dual-panel PET system configuration can lead to spatially variable point-spread functions (PSF) of considerable deformations due to depth-of-interaction effects and limited angular coverage. If not modelled properly, these effects result in decreased and inconsistent recovery of lesion activity across the field-of-view (FOV), as well as mispositioning of lesions in the reconstructed image caused by strong PSF asymmetries. We implemented and evaluated models of such PSF deformations with spatially-variant image-based resolution modeling (IRM) within reconstruction (varRM) using the Direct Image REConstruction for Time-of-flight (DIRECT) method and within post-reconstruction deconvolution methods. In addition, DIRECT reconstruction was performed with a spatially-invariant IRM (invRM) and without resolution modeling (noRM) for comparison. The methods were evaluated using simulated data for a realistic breast model with a set of 5 mm lesions located throughout the FOV of a dual-panel Breast-PET scanner. We simulated high-count data to focus on the ability of each method to correctly recover the PSF deformations, and a clinically realistic count level to assess the impact of low count data on the quantitative performance of the evaluated techniques. Performance of the methods evaluated herein was assessed by comparing lesion activity recovery (%BIAS), consistency (%SD) across the FOV, overall error (%RMSE), and recovery of each lesion location. As expected, all techniques using IRM provide considerable improvement over the noRM reconstruction. For the high-count cases, the overall quantitative performance of all IRM techniques, whether within reconstruction or within post-reconstruction, is similar if the lesion location misplacements are ignored. However, invRM provides less consistent performance on activity across lesions and is not able to recover accurate lesion locations. For a clinically realistic count level, varRM reconstruction consistently outperforms all compared approaches, while the post-reconstruction IRM approaches exhibit higher %SD and %RMSE values due to being more affected by the data noise than the within-reconstruction IRM approaches.

Advances in time-of-flight PET.

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

Update on time-of-flight PET imaging.

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

Radionuclide methods and instrumentation for breast cancer detection and diagnosis.

Breast cancer mammography is a well-acknowledged technique for patient screening due to its high sensitivity. However, in addition to its low specificity the sensitivity of mammography is limited when imaging patients with dense breasts. Radionuclide imaging techniques, such as coincidence photon-based positron emission tomography and single photon emission computed tomography or scintimammography, can play a role in assisting screening of such patients. Radionuclide techniques can also be useful in assessing treatment response of patients with breast cancer to therapy, and staging of patients to diagnose the disease extent. However, the performance of these imaging modalities is generally limited because of the poor spatial resolution and sensitivity of the commercially available multipurpose imaging systems. Here, we describe some of the dedicated imaging systems (positron emission mammography [PEM] and breast-specific gamma imaging [BSGI]) that have been developed both commercially and in research laboratories for radionuclide imaging of breast cancer. Clinical studies with dedicated PEM scanners show improved sensitivity to detecting cancer in patients when using PEM in conjunction with additional imaging modalities, such as magnetic resonance imaging or mammography or both, as well as improved disease staging that can have an effect on surgical planning. High-resolution BSGI systems are more widely available commercially and several clinical studies have shown very high sensitivity and specificity in detecting cancer in high-risk patients. Further development of dedicated PEM and BSGI systems is ongoing, promising further expansion of radionuclide imaging techniques in the realm of breast cancer detection and treatment.

Fundamentals of PET and PET/CT imaging.

In this review, the fundamental principles of fluorodeoxyglucose (FDG) positron emission tomography (PET) and FDG PET/computed tomography (CT) imaging have been described. The basic physics of PET instrumentation, radiotracer chemistry, and the artifacts, as well as normal physiological or benign pathological variants, have been described and presented to the readers in a lucid manner to enable them an easy grasp of the fundamentals of the subject. Finally, we have outlined the current developments in quantitative PET imaging, including dual time point and delayed PET imaging, time-of-flight technology in PET imaging and partial volume correction, and global disease assessment with their potential of being incorporated into the assessment of benign and malignant disorders.

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.

Improvement in lesion detection with whole-body oncologic time-of-flight PET.

UNLABELLED: Time-of-flight (TOF) PET has great potential in whole-body oncologic applications, and recent work has demonstrated qualitatively in patient studies the improvement that can be achieved in lesion visibility. The aim of this work was to objectively quantify the improvement in lesion detectability that can be achieved in lung and liver lesions with whole-body (18)F-FDG TOF PET in a cohort of 100 patients as a function of body mass index, lesion location and contrast, and scanning time. METHODS: One hundred patients with BMIs ranging from 16 to 45 were included in this study. Artificial 1-cm spheric lesions were imaged separately in air at variable locations of each patient's lung and liver, appropriately attenuated, and incorporated in the patient list-mode data with 4 different lesion-to-background contrast ranges. The fused studies with artificial lesion present or absent were reconstructed using a list-mode unrelaxed ordered-subsets expectation maximization with chronologically ordered subsets and a gaussian TOF kernel for TOF reconstruction. Conditions were compared on the basis of performance of a 3-channel Hotelling observer signal-to-noise ratio in detecting the presence of a sphere of unknown size on an anatomic background while modeling observer noise. RESULTS: TOF PET yielded an improvement in lesion detection performance (3-channel Hotelling observer signal-to-noise ratio) over non-TOF PET of 8.3% in the liver and 15.1% in the lungs. The improvement in all lesions was 20.3%, 12.0%, 9.2%, and 7.5% for mean contrast values of 2.0:1, 3.2:1, 4.4:1, and 5.7:1, respectively. Furthermore, this improvement was 9.8% in patients with a BMI of less than 30 and 11.1% in patients with a BMI of 30 or more. Performance plateaued faster as a function of number of iterations with TOF than non-TOF. CONCLUSION: Over all contrasts and body mass indexes, oncologic TOF PET yielded a significant improvement in lesion detection that was greater for lower lesion contrasts. This improvement was achieved without compromising other aspects of PET imaging.

Death and proliferation time course of stem cells transplanted in the myocardium.

PURPOSE: Noninvasive positron emission tomography (PET) imaging of reporter gene is combined with quantitative real-time polymerase reverse transcription (RT-PCR) method to study the time course of death and proliferation of stem cells transplanted in the myocardium. METHODS: Male murine embryonic stem cells (ESCs) were stably transfected with a mutant version of herpes simplex virus type 1 thymidine kinase (HSV1-sr39tk) reporter gene; 5 x 10(6) such cells were injected into the myocardium of female athymic rats. While the transplanted cells was monitored by in vivo 9-(4-[F-18]fluoro-3-hydroxymethylbutyl)guanine ([F-18]FHBG) PET imaging of the heart, their absolute number was estimated by RT-PCR from hearts harvested at 3-5 h, 24 h, days 4, 7, and 14 after transplantation. RESULTS: (1) Forty percent of injected cells were retained in the heart while majority of injected cells were lost within a few hours after injection. Cell death was peaked at 24 h when 18% of donor cells retained in the heart were dead. (2) The substantial cell loss was reversed by significant proliferation of ESCs. This led to the recovery of cell number to 3.4 million (70% of injected dose) at day 4 and first visual observation of in vivo [F-18] signal in the heart. (3) A robust correlation (R (2) = 0.9) between percent of injected dose per gram of tissue derived from in vivo PET signal and the number of donor cells estimated by RT-PCR was revealed. CONCLUSIONS: The time course of transplanted stem cells surviving in the heart reveals a process of substantial cell loss within 24 h of injection and subsequent recovery of cell number through proliferation. Such proliferation can be noninvasively monitored by reporter gene imaging.

A recovery coefficient method for partial volume correction of PET images.

OBJECTIVES: Correction of the "partial volume effect" has been an area of great interest in the recent times in quantitative PET imaging and has been mainly studied with count recovery models based upon phantoms that incorporate hot spheres in a cold background. The goal of this research study was to establish a similar model that is closer to a biological imaging environment, namely hot spheres/lesions in a warm background and to apply this model in a small cohort of patients. METHODS: A NEMA phantom with six spheres (diameters 1-3.7 cm) was filled with (18)FDG to give sphere:background activity ratios of 8:1, 6:1, and 4:1 for three different acquisitions on a Philips Allegro scanner. The hot sphere SUVmax and the background average SUV were measured for calculation of recovery coefficients (RCs). Using the RCs, the lesion diameters, and the lesion:background ratio, the SUVmax of 64 lesions from 17 patients with biopsy proven lung cancer were corrected. RESULTS: The RCs versus sphere diameters produced characteristic logarithmic curves for each phantom (RCs ranged from 80% to 11%). From a cohort of 17 patients with biopsy proven lung cancer, 64 lesions combined had a mean SUVmax of 7.0 and size of 2.5 cm. After partial volume correction of the SUVmax of each lesion, the average SUVmax increased to 15.5. CONCLUSIONS: Hot spheres in a warm background more closely resemble the actual imaging situation in a living subject when compared to hot spheres in a cold background. This method could facilitate generation of equipment specific recovery coefficients for partial volume correction. The clinical implications for the increased accuracy in SUV determination are certainly of potential value in oncologic imaging.

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.