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Joel S Karp

Publications and source records attributed to Joel S Karp.

17 recordsLinked to original sources

Positron emission tomography.

The developments in positron emission tomography (PET) are reviewed with an emphasis on instrumentation for clinical PET imaging. After a brief summary of positron imaging before the advent of computed tomography, various improvements are highlighted including the move from PET scanners with septa to fully 3D scanners, changes in the preferred scintillators, efforts to improve the energy discrimination, and improvements in attenuation correction. Time-of-flight PET imaging is given special attention due to the recent revival of this technique, which promises significant improvement. Besides technical instrumentation efforts, other factors which influenced the acceptance of clinical PET are also discussed.

Animals↗

PET energy-based scatter estimation and image reconstruction with energy-dependent corrections.

In this paper we propose a comprehensive energy-based scatter correction approach for positron emission tomography (PET). We take advantage of the marked difference between the energy spectra of the unscattered and scattered photons, and use the detailed energy information that comes with the list-mode data for the estimation of the scattered events distribution in the data space. Also, inside the maximum-likelihood expectation maximization (ML-EM) image reconstruction algorithm, we introduce energy-dependent factors that individualize the correction terms for each event, given its position and energy information. The central piece of our approach is the two-dimensional detector energy response model represented as a linear combination of four components, each one representing a particular state a PET event can be found in: both photons unscattered, the second scattered while the first not, the first photon scattered while the second not and both photons scattered. For a set of events collected in the vicinity of a point in the projection space, the coefficient of each component is determined by applying a statistical estimator. As a result we obtain the number of scattered events that are in the given set. The model also gives us the variation of scatter fraction with the photon pair energies for that particular position in the data space. A simulation study that demonstrates the proposed methods is presented.

Algorithms↗

Fast reconstruction of 3D time-of-flight PET data by axial rebinning and transverse mashing.

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.

Algorithms↗

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.

Algorithms↗

Concurrent CBF and CMRGlc changes during human brain activation by combined fMRI-PET scanning.

A novel approach for concurrent measurement of regional cerebral blood flow (CBF) and regional cerebral metabolic rate for glucose consumption (CMRGlc) in humans is proposed and validated in normal subjects during visual stimulation. 18F-labeled fluorodeoxyglucose was administered during the measurement of CBF by continuous arterial spin labeled magnetic resonance imaging (MRI). Subsequent positron emission tomographic (PET) scanning demonstrated the distribution of labeled deoxyglucose during the MRI acquisition. An excellent concordance between regional CBF and regional CMRGlc during visual stimulation was found, consistent with previously published PET findings. Although initially validated using a brief, non-quantitative protocol, this approach can provide quantitative CBF and CMRGlc, with a broad range of potential applications in functional physiology and pathophysiology.

Algorithms↗

Evidence of myocardial hibernation in the septic heart.

OBJECTIVE: Myocardial hibernation is an adaptive response to ischemia and hypoxia. Hibernating cardiomyocytes are reversibly hypocontractile and demonstrate characteristic metabolic and ultrastructural changes. These include a switch in primary substrate utilization from fatty acids to glucose, up-regulation of the myocardial specific glucose transporters (GLUT1 and GLUT4), and glycogen deposition within and between cardiomyocytes. We hypothesized that myocardial hibernation may underlie sepsis-associated myocardial depression. DESIGN: Prospective observational study aimed at identifying the characteristic changes of hibernation in the septic heart. SETTING: University hospital-based laboratory. SUBJECTS: Forty-three C57Bl6 male mice. INTERVENTIONS: Mice underwent cecal ligation and double puncture, sham operation, or no operation and were evaluated 48 hrs after the procedure. MEASUREMENTS AND MAIN RESULTS: Using novel, clinically relevant technology such as magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography imaging, we found septic mice to have diminished cardiac performance, increased myocardial glucose uptake, increased steady-state levels of myocardial GLUT4, and increased deposits of glycogen, recapitulating the changes during hibernation. Importantly, these changes occurred in the setting of preserved arterial oxygen tension and myocardial perfusion. CONCLUSIONS: Sepsis-associated cardiac dysfunction may reflect hibernation. Furthermore, such down-regulation of cellular function may underlie sepsis-induced dysfunction in other organ systems.

Animals↗

Imaging performance of A-PET: a small animal PET camera.

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 x 2 x 10 mm3 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.

Animals↗

Optimization of a fully 3D single scatter simulation algorithm for 3D PET.

We describe a new implementation of a single scatter simulation (SSS) algorithm for the prediction and correction of scatter in 3D PET. In this implementation, out of field of view (FoV) scatter and activity, side shields and oblique tilts are explicitly modelled. Comparison of SSS predictions with Monte Carlo simulations and experimental data from uniform, line and cold-bar phantoms showed that the code is accurate for uniform as well as asymmetric objects and can model different energy resolution crystals and low level discriminator (LLD) settings. Absolute quantitation studies show that for most applications, the code provides a better scatter estimate than the tail-fitting scatter correction method currently in use at our institution. Several parameters such as the density of scatter points, the number of scatter distribution sampling points and the axial extent of the FoV were optimized to minimize execution time, with particular emphasis on patient studies. Development and optimization were carried out in the case of GSO-based scanners, which enjoy relatively good energy resolution. SSS estimates for scanners with lower energy resolution may result in different agreement, especially because of a higher fraction of multiple scatter events. The algorithm was applied to a brain phantom as well as to clinical whole-body studies. It proved robust in the case of large patients, where the scatter fraction increases. The execution time, inclusive of interpolation, is typically under 5 min for a whole-body study (axial FoV: 81 cm) of a 100 kg patient.

Algorithms↗

PET/CT scanner instrumentation, challenges, and solutions.

PET/CT scanners offer a hardware solution for aligning and viewing functional and anatomic images that is immune to many of the errors in strictly software registration techniques. Moreover, PET attenuation-corrected emission scans benefit from the use of the onboard CT for fast, low-noise attenuation correction. Along with the significant improved localization and reduced acquisition time, PET/CT scanners also introduce new instrumentation challenges ranging from patient movement to quantitative attenuation correction. This article provides an overview of current PET/CT scanner technology, a discussion of challenges faced by these systems, and pending solutions.

Humans↗

PET instrumentation.

PET is a nuclear medicine imaging modality and belongs to the family of emission CT, which also includes single-photon emission CT. PET measures the physiologic function inside the human body by measuring the concentration of a radioactively-labeled compound that is taken up by and accumulated in the body's organs. This article discusses the instrumentation used in PET.

Humans↗

Clinical validation of fully 3-D versus 2.5-D RAMLA reconstruction on the Philips-ADAC CPET PET scanner.

INTRODUCTION: Fully three-dimensional (3-D) reconstruction algorithms have the potential to better utilize PET data acquired in true 3-D acquisition modes, as compared to 2-D approaches involving data reduction through rebinning procedures followed by a 2-D or 2.5-D reconstruction. Our previous studies, involving simulated and real phantom data from PET scanners working purely in 3-D acquisition mode, showed that the fully 3-D reconstruction approaches bring appreciable improvement on physical measures and visual image quality as well. Reconstruction procedures utilized in those studies were based upon the row action maximum likelihood algorithm (RAMLA) implemented on our clinical scanners. The purpose of this study was to investigate if the fully 3-D RAMLA reconstruction software brings an appreciable improvement in clinical image quality and reader confidence. MATERIALS AND METHODS: Ninety patient scans acquired on the Philips CPET scanner at our institution were reconstructed using 2.5-D RAMLA and 3-D RAMLA with differing reconstruction parameters. These scans were blindly presented to four experienced PET scan readers who graded various aspects of image quality. RESULTS: Our study concluded that 3-D RAMLA on the CPET scanner reduces artifacts and image noise and improves clinical confidence in interpreting PET images. CONCLUSION: This study led to the routine use of 3-D RAMLA reconstruction on the CPET scanner at our institution.

Algorithms↗

Imaging characteristics of a 3-dimensional GSO whole-body PET camera.

UNLABELLED: A whole-body 3-dimensional PET scanner using gadolinium oxyorthosilicate (GSO) crystals has been designed to achieve high sensitivity and reduced patient scanning time. This scanner has a diameter of 82.0 cm and an axial field of view of 18 cm without interplane septa. The detector comprises of 4 x 6 x 20 mm(3) GSO crystals coupled via an optically continuous light guide to an array of 420 photomultiplier tubes (39-mm diameter) in a hexagonal arrangement. The patient port diameter is 56 cm, and 2.86-cm (1.125 in.) thick lead shielding is used to fill in the region up to the detector ring. METHODS: Performance measurements on the scanner were made using the National Electrical Manufactures Association (NEMA) NU 2-2001 procedures. Additional counting rate measurements with a large phantom were performed to evaluate imaging characteristics for heavier patients. The image-quality torso phantom with hot or cold spheres was also measured as a function of counting rate to evaluate different techniques for randoms and scatter subtraction as well as to determine an optimum imaging time. RESULTS: The transverse and axial resolutions near the center are 5.5 and 5.6 mm, respectively. The absolute sensitivity of this scanner measured with a 70-cm-long line source is 4.36 cps/kBq, whereas the scatter fraction is 40% with a 20 x 70 cm line source cylinder. For the same cylinder, the peak noise equivalent count (NEC) rate of 30 kcps at an activity concentration of 9.25 kBq/mL (0.25 micro Ci/mL) leads to a 7% increase in the peak NEC value. A significant reduction in the peak NEC is observed with a larger 35 x 70 cm line source cylinder. Image-quality measurements show that the small 10-mm sphere in the NEMA NU 2-2001 image-quality phantom is clearly visible in a scan time of 3 min, and there is no noticeable degradation in image contrast at high activity levels. CONCLUSION: This whole-body scanner represents a new generation of 3D, high-sensitivity, and high-performance PET cameras capable of producing high-quality images in <30 min for a full patient scan. The use of a pixelated GSO Anger-logic detector leads to a high-sensitivity scanner design with good counting rate capability due to the reduced light spread in the detector and fast decay time of GSO. The light collection over the detector is fairly uniform, leading to a good energy resolution and, thus, reduced scatter in the collected data due to a tight energy gate.

Equipment Design↗

Developments in instrumentation for emission computed tomography.

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.

Equipment Design↗

Performance of a brain PET camera based on anger-logic gadolinium oxyorthosilicate detectors.

UNLABELLED: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Brain↗

N,N-dimethyl-2-(2-amino-4-(18)F-fluorophenylthio)-benzylamine (4-(18)F-ADAM): an improved PET radioligand for serotonin transporters.

UNLABELLED: There has been considerable interest in the development of PET radioligands that are useful for imaging serotonin transporter (SERT) in the living human brain. For the last decade, (11)C-(+)McN5652 has been the most promising PET agent for studying SERT in humans. However, this agent has some limitations. Recently, a new promising SERT PET radioligand, 3-(11)C-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile, has been reported. We recently reported the synthesis of a new (18)F-labeled SERT PET radioligand, N,N-dimethyl-2-(2-amino-4-(18)F-fluorophenylthio)benzylamine (4-(18)F-ADAM), which may have advantages over (11)C-labeled radioligands. The purpose of this study was to evaluate this newly developed (18)F-labeled PET radioligand as a promising agent for studying SERT in the living human brain. METHODS: This agent was evaluated by studying its in vitro binding to different monoamine transporters, its in vivo biodistributions in rats, its integrity and pharmacologic profiles in rat brain, and its distribution in a female baboon brain. RESULTS: In vitro binding assays showed that 4-F-ADAM displayed high affinity to SERT sites (inhibition constant = 0.081 nmol/L, using membrane preparations of LLC-PK1 cells expressing the specific transporter) and showed more than 1,000- and 28,000-fold selectivity for SERT over norepinephrine transporter and dopamine transporter, respectively. Biodistribution of 4-(18)F-ADAM in rats showed a high initial uptake and slow clearance in the brain (2.13%, 1.90%, and 0.95% injected dose per organ at 2, 30, and 60 min after intravenous injection, respectively), with the specific binding peaking at 2 h after injection (hypothalamus/cerebellum = 12.49). The uptake in blood, muscle, lung, kidney, and liver was also initially high but cleared rapidly. The radioactivity in the femur increases with time for 4-(18)F-ADAM, indicating that in vivo defluorination may occur. In vivo metabolism studies in rats showed that 4-(18)F-ADAM was not metabolized in rat brain (>96% of radioactivity was recovered as parent compound at 1 h after injection). However, it metabolized rapidly in the blood. Less than 7% of the radioactivity recovered from plasma was the parent compound, with the majority of radioactivity in the plasma not extractable by ethyl acetate. Blocking studies showed significant decreases in the uptake of 4-(18)F-ADAM in the brain regions (hypothalamus, hippocampus, and striatum) where SERT concentrations are high when rats were pretreated with (+)McN5652 (2 mg/kg 5 min before intravenous injection of 4-(18)F-ADAM). However, changes in the uptake of 4-(18)F-ADAM in these brain regions were less significant when rats were pretreated with either methylphenidate or nisoxetine. The baboon study showed that uptake of 4-(18)F-ADAM in the midbrain peaked at approximately 1 h after injection and then declined slowly. The ratios of the radioactivity in the midbrain to that in the cerebellum (where the concentration of SERT is low) at 2 and 3 h after injection were 3.2 and 4.2, respectively. CONCLUSION: 4-(18)F-ADAM is suitable as a PET radioligand for studying SERT in the living brain. Further characterization of this new radioligand in humans is warranted.

Animals↗

PET performance measurements using the NEMA NU 2-2001 standard.

UNLABELLED: The NU 2-1994 standard document for PET performance measurements has recently been updated. The updated document, NU 2-2001, includes revised measurements for spatial resolution, intrinsic scatter fraction, sensitivity, counting rate performance, and accuracy of count loss and randoms corrections. The revised measurements are designed to allow testing of dedicated PET systems in both 2-dimensional and 3-dimensional modes as well as coincidence gamma cameras, conditions not considered in the original NU 2-1994 standard. In addition, the updated measurements strive toward being more representative of clinical studies, in particular, whole-body imaging. METHODS: Performance measurements following the NU 2-1994 and NU 2-2001 standards were performed on several different PET scanners. Differences between the procedures and resulting performance characteristics, as well as the rationale for these changes, were noted. RESULTS: Spatial resolution is measured with a point source in all 3 directions, rather than a line source, as specified previously. For the measurements of intrinsic scatter fraction, sensitivity, and counting rate performance, a 70-cm line source is now specified, instead of a 19-cm-long cylindric phantom. The longer configuration permits measurement of these performance characteristics over the entire axial field of view of all current PET scanners and incorporates the effects of activity outside the scanner. A measurement of image quality has been added in an effort to measure overall image quality under clinically realistic conditions. This measurement replaces the individual measurements of uniformity and of the accuracy of corrections for attenuation and scatter. CONCLUSION: The changes from the NU 2-1994 standard to the NU 2-2001 standard strive toward establishing relevance with clinical studies. The tests in the updated standard also are, in general, simpler and less time-consuming to perform than those in the NU 2-1994 standard.

Gamma Cameras↗