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J S Karp

Publications and source records attributed to J S Karp.

At least 19 recordsLinked to original sources
PubMed2005

A count-rate model for PET scanners using pixelated Anger-logic detectors with different scintillators.

A high count-rate simulation (HCRSim) model has been developed so that all results are derived from fundamental physics principles. Originally developed to study the behaviour of continuous sodium iodide (NaI(Tl)) detectors, this model is now applied to PET scanners based on pixelated Anger-logic detectors using lanthanum bromide (LaBr(3)), gadolinium orthosilicate (GSO) and lutetium orthosilicate (LSO) scintillators. This simulation has been used to study the effect on scanner deadtime and pulse pileup at high activity levels due to the scintillator stopping power (mu), decay time (tau) and energy resolution. Simulations were performed for a uniform 20 cm diameter x 70 cm long cylinder (NEMA NU2-2001 standard) in a whole-body scanner with an 85 cm ring diameter and a 25 cm axial field-of-view. Our results for these whole-body scanners demonstrate the potential of a pixelated Anger-logic detector and the relationship of its performance with the scanner NEC rate. Faster signal decay and short coincidence timing window lead to a reduction in deadtime and randoms fraction in the LaBr(3) and LSO scanners compared to GSO. The excellent energy resolution of LaBr(3) leads to the lowest scatter fraction for all scanners and helps compensate for reduced sensitivity compared to the GSO and LSO scanners, leading to the highest NEC values at high activity concentrations. The LSO scanner has the highest sensitivity of all the scanner designs investigated here, therefore leading to the highest peak NEC value but at a lower activity concentration than that of LaBr(3).

Bromides↗
PubMed2004

Image quality assessment of LaBr3-based whole-body 3D PET scanners: a Monte Carlo evaluation.

The main thrust for this work is the investigation and design of a whole-body PET scanner based on new lanthanum bromide scintillators. We use Monte Carlo simulations to generate data for a 3D PET scanner based on LaBr3 detectors, and to assess the count-rate capability and the reconstructed image quality of phantoms with hot and cold spheres using contrast and noise parameters. Previously we have shown that LaBr3 has very high light output, excellent energy resolution and fast timing properties which can lead to the design of a time-of-flight (TOF) whole-body PET camera. The data presented here illustrate the performance of LaBr3 without the additional benefit of TOF information, although our intention is to develop a scanner with TOF measurement capability. The only drawbacks of LaBr3 are the lower stopping power and photo-fraction which affect both sensitivity and spatial resolution. However, in 3D PET imaging where energy resolution is very important for reducing scattered coincidences in the reconstructed image, the image quality attained in a non-TOF LaBr3 scanner can potentially equal or surpass that achieved with other high sensitivity scanners. Our results show that there is a gain in NEC arising from the reduced scatter and random fractions in a LaBr3 scanner. The reconstructed image resolution is slightly worse than a high-Z scintillator, but at increased count-rates, reduced pulse pileup leads to an image resolution similar to that of LSO. Image quality simulations predict reduced contrast for small hot spheres compared to an LSO scanner, but improved noise characteristics at similar clinical activity levels.

Animals↗
PubMed2002

Noninvasive imaging of tumor hypoxia in rats using the 2-nitroimidazole 18F-EF5.

Tumor hypoxia is an important prognostic indicator for cancer therapy outcome. EF5 [2-(2-nitro-1[ H]-imidazol-1-yl)- N-(2,2,3,3,3-pentafluoropropyl)-acetamide] has been employed to measure tumor hypoxia in animals and humans using immunohistochemical methods. EF5 is a lipophilic molecule designed to have a very uniform biodistribution, a feature of obvious benefit for use in PET imaging. The present study represents the first demonstration of noninvasive PET imaging of rat tumors using fluorine-18 labeled EF5. Because of the small tumor size, partial volume effects may result in underestimation of concentration of the compound. Therefore, validation of the PET data was performed by gamma counting of the imaged tissue. The tumor models studied were the Morris 7777 (Q7) hepatoma (n=5) and the 9L glioma (n=2) grown subcutaneously in rats. Our previous studies have demonstrated that early passage 9L tumors are not severely hypoxic and that Q7 tumors are characterized by heterogeneous regions of tumor hypoxia (i.e., Q7 tumors are usually more hypoxic than early passage 9L tumors). The seven rats were imaged in the HEAD Penn-PET scanner at various time points after administration of 50-100 micro Ci (18)F-EF5 in 30 mg/kg carrier nonradioactive EF5. The carrier was used to ensure drug biodistribution comparable to prior studies using immunohistochemical methods. (18)F-EF5 was excreted primarily via the urinary system. Images obtained 10 min following drug administration demonstrated that the EF5 distributed evenly to all organ systems, including brain. Later images showed increased uptake in most Q7 tumors compared with muscle. Liver uptake remained relatively constant over the same time periods. Tumor to muscle ratios ranged from 0.82 to 1.73 (based on PET images at 120 min post injection) and 1.47 to 2.95 (based on gamma counts at approximately 180 min post injection). Tumors were easily visible by 60 min post injection when the final tumor to muscle ratios (based on gamma counts) were greater than 2. Neither of the 9L tumors nor the smallest Q7 tumor met this criterion, and these tumors were not seen on the PET images. These preliminary results suggest that (18)F-EF5 is a promising agent for noninvasive assessment of tumor hypoxia. Plans are underway to initiate a research project to determine the safety and preliminary evidence for the efficacy of this preparation in patients with brain tumors.

Animals↗
PubMed2002

Design considerations for PET scanners.

In 2-D PET scanners employing septa, scattered radiation is reduced by the septa, placing less importance on good energy resolution. Additionally, the reduced sensitivity in 2-D limits the maximum countrates encountered in clinical FDG studies. In contrast, 3-D PET scanners rely on good energy resolution to reduce the scattered radiation and also must deal with countrates, which are typically 5 times higher than in 2-D mode. To achieve good energy resolution, 3 factors must be considered: 1) choice of a scintillator with good intrinsic energy resolution, 2) choice of a crystal dimension which transmits a uniform amount of light to the PMT in order to avoid light loss along the length of the crystal and 3) choice of a crystal-to-PMT coupling which collects a uniform amount of light from all crystals. As PET scanners are being designed using new, faster scintillators for 3-D imaging, the appropriate trade-off between energy resolution and countrate capability must be found to give the best overall system performance. An example of a fully 3-D PET scanner is the Allegro (ADAC Laboratories), which uses GSO as the detector material. Given the right choice of material and design parameters, good quality, high contrast images can be obtained in 3-D in a relatively short time.

Equipment Design↗
PubMed2001

Imaging in vivo herpes simplex virus thymidine kinase gene transfer to tumour-bearing rodents using positron emission tomography and.

Radiolabelled ganciclovir analogues have shown promise as imaging agents to detect herpes simplex virus thymidine kinase (HSVtk) expression. This study evaluated the use of positron emission tomography (PET) imaging with 9-[(3-[18F]fluoro-1-hydroxy-2-propoxy)methyl]guanine ([18F]FHPG) to assess gene transfer into tumours. HSVtk-positive and HSVtk-negative cell lines were first treated in vitro with [18F]FHPG. To assess the efficacy of PET in detecting HSVtk expression following in vivo gene transfer, mice were injected intravenously with an adenovirus encoding HSVtk (Ad.HSVtk), a control vector (Ad.Bgl2) or saline. Subcutaneous human glioma xenografts were grown in mice and treated by direct injection of Ad.HSVtk or Ad.Bgl2. Imaging was performed 48 h after transduction. Similar experiments were performed using Fischer rats implanted with syngeneic tumours. The presence of the HSVtk protein was confirmed by immunohistochemistry. Biodistribution studies were also obtained in 14 naive mice. In vitro studies showed high and specific uptake of [18F]FHPG in HSVtk-positive cell lines, with an uptake ratio of up to 27:1. PET imaging and direct counting of major organs demonstrated HSVtk-specific tracer retention. In mice, HSVtk-positive tumours retained 3.4% dose/gram as compared to 0.6% for control tumours (P=0.03). They were clearly seen on the PET images as early as 100 min post injection. Similar results were obtained with syngeneic rat tumours. Biodistribution studies demonstrated the rapid distribution and clearance of the tracer in all major organs. Our results demonstrate that PET imaging of HSVtk gene transfer to tumours is feasible and is highly specific for HSVtk expression.

Animals↗
PubMed2001

Performance of a whole-body PET scanner using curve-plate NaI(Tl) detectors.

UNLABELLED: A whole-body PET scanner, without interplane septa, has been designed to achieve high performance in clinical applications. The C-PET scanner, an advancement of the PENN PET scanners, is unique in the use of 6 curved NaI(Tl) detectors (2.54 cm thick). The scanner has a ring diameter of 90 cm, a patient port diameter of 56 cm, and an axial field of view of 25.6 cm. A (137)Cs point source is used for transmission scans. METHODS: Following the protocols of the International Electrotechnical Commission ([IEC] 61675-1) and the National Electrical Manufacturers Association ([NEMA] NU-2-1994 and an updated version, NU2-2001), point and line sources, as well as uniform cylinders, were used to determine the performance characteristics of the C-PET scanner. An image-quality phantom and patient data were used to evaluate image quality under clinical scanning conditions. Data were rebinned with Fourier rebinning into 2-dimensional (slice-oriented) datasets and reconstructed with an iterative reconstruction algorithm. RESULTS: The spatial resolution for a point source in the transaxial direction was 4.6 mm (full width at half maximum) at the center, and the axial resolution was 5.7 mm. For the NU2-1994 analysis, the sensitivity was 12.7 cps/Bq/mL (444 kcps/microCi/mL), the scatter fraction was 25%, and the peak noise equivalent count rate (NEC) for a uniform cylinder (diameter = 20 cm, length = 19 cm) was 49 kcps at an activity concentration of 11.2 kBq/mL. For the IEC protocol, the peak NEC was 41 kcps at 12.3 kBq/mL, and for the NU2-2001 protocol, the peak NEC was 14 kcps at 3.8 kBq/mL. The NU2-2001 NEC value differed significantly because of differences in the data analysis and the use of a 70-cm-long phantom. CONCLUSION: Compared with previous PENN PET scanners, the C-PET, with its curved detectors and improvements in pulse shaping, integration dead time, and triggering, has an improved count-rate capability and spatial resolution. With the refinements in the singles transmission technique and iterative reconstruction, image quality is improved and scan time is shortened. With single-event transmission scans interleaved between sequential emission scans, a whole-body study can be completed in <1 h. Overall, C-PET is a cost-effective PET scanner that performs well in a broad variety of clinical applications.

Adult↗
PubMed2000

Energy-based scatter correction for 3-D PET scanners using NaI(T1) detectors.

Earlier investigations with BGO positron emission tomography (PET) scanners showed that the scatter correction technique based on multiple acquisitions with different energy windows are problematic to implement because of the poor energy resolution of BGO (22%), particularly for whole-body studies. We believe that these methods are likely to work better with NaI(TI) because of the better energy resolution achievable with NaI(TI) detectors (10%). Therefore, we investigate two different choices for the energy window, a low-energy window (LEW) on the Compton spectrum at 400-450 keV, and a high-energy window (HEW) within the photopeak (lower threshold above 511 keV). The results obtained for our three-dimensional (3-D) (septa-less) whole-body scanners [axial field of view (FOV) of 12.8 cm and 25.6 cm] as well as for our 3-D brain scanner (axial FOV of 25.6 cm) show an accurate prediction of the scatter distribution for the estimation of trues method (ETM) using a HEW, leading to a significant reduction of the scatter contamination. The dual-energy window (DEW) technique using a LEW is shown to be intrinsically wrong; in particular, it fails for line source and bar phantom measurements. However, the method is able to produce good results for homogeneous activity distributions. Both methods are easy to implement, are fast, have a low noise propagation, and will be applicable to other PET scanners with good energy resolution and stability, such as hybrid NaI(TI) PET/SPECT dual-head cameras and future PET cameras with GSO or LSO scintillators.

Brain↗
PubMed2000

Noninvasive detection of tumor hypoxia using the 2-nitroimidazole [18F]EF1.

UNLABELLED: The noninvasive assessment of tumor hypoxia in vivo is under active investigation because hypoxia has been shown to be an important prognostic factor for therapy resistance. Various nuclear medicine imaging modalities are being used, including PET imaging of 18F-containing compounds. In this study, we report the development of 18F-labeled EF1 for noninvasive imaging of hypoxia. EF1 is a 3-monofluoro analog of the well-characterized hypoxia marker EF5, 2(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetami de, which has been used to detect hypoxia in tumor and nontumor systems using immunohistochemical methods. METHODS: We have studied 2 rat tumor types: the hypoxic Morris 7777 (Q7) hepatoma and the oxic 9LF glioma tumor, each grown in subcutaneous sites. PET studies were performed using a pharmacological dose of nonradioactive carrier in addition to [18F]EF1 to optimize and assess drug biodistribution. After PET imaging of the tumor-bearing rats, tissues were obtained for gamma-counting of the 18F in various tissues and immunohistochemical detection of intracellular drug adducts in tumors. In one pair of tumors, Eppendorf needle electrode studies were performed. RESULTS: [18F]EF1 was excreted dominantly through the urinary tract. The tumor-to-muscle (T/M) ratio of [18F]EF1 in the Q7 tumors was 2.7 and 2.4 based on PET studies and 2.1, 2.5, and 3.0 based on gamma-counting of the tissues (n = 3). In contrast, the T/M ratio of [18F]EF1 in the 9LF glioma tumor was 0.8 and 0.5 based on PET studies and 1.0, 1.2, and 1.4 based on gamma-counting of the tissues (n = 3). Immunohistochemical analysis of drug adducts for the two tumor types agreed with the radioactivity analysis. In the Q7 tumor, substantial heterogeneous binding was observed throughout the tumor, whereas in the 9LF tumor minimal binding was found. CONCLUSION: [18F]EF1 is an excellent radiotracer for noninvasive imaging of tumor hypoxia.

Animals↗
PubMed1999

Investigation of scattered radiation in 3D whole-body positron emission tomography using Monte Carlo simulations.

The correction of scattered radiation is one of the most challenging tasks in 3D positron emission tomography (PET) and knowledge about the amount of scatter and its distribution is a prerequisite for performing an accurate correction. One concern in 3D PET in contrast to 2D PET is the scatter contribution from activity outside the field-of-view (FOV) and multiple scatter. Using Monte Carlo simulations, we examined the scatter distribution for various phantoms. The simulations were performed for a whole-body PET system (ECAT EXACT HR+, Siemens/CTI) with an axial FOV of 15.5 cm and a ring diameter of 82.7 cm. With (without) interplane septa, up to one (two) out of three detected events are scattered (for a centred point source in a water-filled cylinder that nearly fills out the patient port), whereby the relative scatter fraction varies significantly with the axial position. Our results show that for an accurate scatter correction, activity as well as scattering media outside the FOV have to be taken into account. Furthermore it could be shown that there is a considerable amount of multiple scatter which has a different spatial distribution from single scatter. This means that multiple scatter cannot be corrected by simply rescaling the single scatter component.

Algorithms↗
PubMed1999

Performing 18F-FDG PET studies following injections of 99mTc-sestamibi.

When SPECT studies are followed by PET studies on the same day, substantial 99mTc activity may be present in patients during the PET scans. Degraded PET camera performance results unless the low-energy gamma rays are absorbed by lead shields. Spatial resolution, camera count rates, energy spectra, image contrast and noise, and image quality have been measured for phantoms with varying levels of 99mTc activity, and both with and without thin lead shields placed in front of the detectors. In addition examples of the results of twelve 18F-FDG PET cardiac studies performed within 6 h of 99mTc-sestamibi injections are reported. The presence of 99mTc (140 keV gamma rays) causes light pile-up with 511 keV photons resulting in distorted energy spectra, degraded spatial resolution, increased Compton background and reduced count-rate capability. These effects are avoided using thin lead shields. Studies performed with 99mTc activity in patients but using lead shields are of comparable quality to studies performed without 99mTc or shields. Thin lead shields effectively filter low-energy gamma rays during PET studies leading to improved count-rate capability, contrast and image quality.

Dose-Response Relationship, Radiation↗
PubMed1999

Clinical evaluation of processing techniques for attenuation correction with 137Cs in whole-body PET imaging.

UNLABELLED: Transmission scanning can be successfully performed with a 137Cs single-photon emitting point source for three-dimensional PET imaging. However, the attenuation coefficients provided by this method are underestimated because of the energy difference between 662- and 511-keV photons, as well as scatter and emission contamination when the transmission data are acquired after injection. The purpose of this study was to evaluate, from a clinical perspective, the relative benefits of various processing schemes to resolve these issues. METHODS: Thirty-eight whole-body PET studies acquired with postinjection singles transmission scans were analyzed. The transmission images were processed and applied to the emission data for attenuation correction. Three processing techniques were compared: simple segmentation (SEG) of the transmission scan, emission contamination subtraction with scaling (ECS) of the resulting data to 511-keV attenuation coefficient values and a hybrid technique performing partial segmentation of some tissue densities on the ECS scan (THR). The corrected emission scans were blindly assessed for image noise, the presence of edge artifacts at the lung-soft-tissue interface and for overall diagnostic confidence using a semiquantitative scoring system. The count densities and the SDs in uniform structures were compared among the various techniques. The observations for each method were compared using a paired t test. RESULTS: The SEG technique produced images that were visually less noisy than the ECS method (P < 0.0001) and the THR technique, but at the expense of increased edge artifacts at the boundaries between the lungs and surrounding tissues. The THR technique failed to eliminate these artifacts compared with the ECS technique (P < 0.0001) but preserved the activity gradients in the hilar areas. The count densities (and thus, the standardized uptake values) were similar among the three techniques, but the SEG method tended to underestimate the activity in the lung fields and in chest tumors (slope = 0.79 and 0.94, respectively). CONCLUSION: For many clinical applications, SEG data remain an efficient method for processing 137Cs transmission scans. The ECS method produced noisier images than the other two techniques but did not introduce artifacts at the lung boundaries. The THR technique, more versatile in complex anatomic areas, allowed good preservation of density gradients in the lungs.

Cesium Radioisotopes↗
PubMed1998

Performance of the Fourier rebinning algorithm for PET with large acceptance angles.

The recently proposed Fourier rebinning (FORE) technique of 3D PET reconstruction is investigated over a wide range of axial acceptance angles. In this study we evaluate the performance of the FORE technique using spatial resolution, contrast and noise figures of merit and compare reconstruction performance of the FORE (followed by multislice 2D reconstruction) to the 3D-RP technique for large-acceptance-angle data (+/-26.25 degrees). Our results show that the FORE technique does not affect the transverse resolution. On the other hand the axial resolution using FORE deteriorates faster, compared with the 3D-RP, at large radii as the acceptance angle increases. Concerning the noise behaviour, we have found that filtering has better ability to suppress the noise in the FORE reconstruction, compared with the 3D-RP reconstruction, especially in the slices near the edge of the axial field of view. Overall, the combination of good performance and fast reconstruction time makes the FORE technique a practical choice for 3D PET applications.

Algorithms↗
PubMed1997

Dedicated PET scanners for breast imaging.

We have used computer simulations to compare two designs for a PET scanner dedicated to breast imaging with a whole-body PET scanner. The new designs combine high spatial resolution, high sensitivity, and good energy resolution to detect small, low-contrast masses. The detectors are position sensitive NaI(Tl) scintillators. The first design is a ring scanner surrounding the breast and the second consists of two planar detectors placed on opposite sides of the breast. We have employed standard performance measures to compare the different designs: contrast, percentage standard deviation of the background, and signal-to-noise ratios of reconstructed images. The results of the simulations show that both of the proposed designs have better lesion detectability than a whole-body scanner. The results also show that contrast is higher in the ring breast system but that the noise is lower in the planar breast system. Overall, the ring system yields images with the best signal-to-noise ratios, although the planar system offers practical advantages for imaging the breast and axilla.

Air↗
PubMed1997

Three-dimensional imaging characteristics of the HEAD PENN-PET scanner.

UNLABELLED: A volume-imaging PET scanner, without interplane septa, for brain imaging has been designed and built to achieve high performance, specifically in spatial resolution and sensitivity. The scanner is unique in its use of a single annular crystal of Nal(Tl), which allows a field of view (FOV) of 25.6 cm in both the transverse and axial directions. Data are reconstructed into an image matrix of 128(3) with (2 mm)3 voxels, using three-dimensional image reconstruction algorithms. METHODS: Point-source measurements are performed to determine spatial resolution over the scanner FOV, and cylindrical phantom distributions are used to determine the sensitivity, scatter fraction and counting rate performance of the system. A three-dimensional brain phantom and 18F-FDG patient studies are used to evaluate image quality with three-dimensional reconstruction algorithms. RESULTS: The system spatial resolution is measured to be 3.5 mm in both the transverse and axial directions, in the center of the FOV. The true sensitivity, using the standard NEMA phantom (6 liter), is 660 kcps/microCi/ml, after subtracting a scatter fraction of 34%. Due to deadtime effects, we measure a peak true counting rate, after scatter and randoms subtraction, of 100 kcps at 0.7 mCi for a smaller brain-sized (1.1 liter) phantom, and 70 kcps for a head-sized (2.5 liter) phantom at the same activity. A typical 18F-FDG clinical brain study requires only 2 mCi to achieve high statistics (100 million true events) with a scan time of 30 min. CONCLUSION: The HEAD PENN-PET scanner is based on a cost-effective design using Nal(Tl) and has been shown to achieve high performance for brain studies and pediatric whole-body studies. As a full-time three-dimensional imaging scanner with a very large axial acceptance angle, high sensitivity is achieved. The system becomes counting-rate limited as the activity is increased, but we achieve high image quality with a small injected dose. This is a significant advantage for clinical imaging, particularly for pediatric patients.

Brain↗
PubMed1996

Stimulating technetium-99m cerebral perfusion studies with a three-dimensional Hoffmann brain phantom: collimator and filter selection in SPECT neuroimaging.

The choice of collimator and the selection of a filter can affect the quality of clinical SPECT images of the brain. The compromises that 4 different collimators make between spatial resolution and sensitivity were studied by imaging a three-dimensional Hoffmann brain phantom. The planar data were acquired with each collimator on a three-headed SPECT system and were reconstructed with both a standard Butterworth filter and a Wiener pre-filter. The reconstructed images were then evaluated by specialists in nuclear medicine and were also quantitatively analyzed with specific regions of interest (ROI) in the brain. All observers preferred the Wiener filter reconstructed images regardless of the collimator used to acquire the planar images. With this filter, the ultrahigh-resolution fan-beam collimator was the most subjectively preferable and quantitatively produced the highest contrast ratios. The findings support suggestions that higher resolution collimators are preferable to higher sensitivity collimators, and indicate that fan-beam collimators are preferable to parallel-hole collimators for clinical SPECT studies of cerebral perfusion. The results also suggest that Wiener filter enhances the quality of SPECT brain images regardless of which collimator is used to acquire the data.

Brain↗
PubMed1996

Quantitative imaging of iodine-124 with PET.

UNLABELLED: PET is potentially very useful for the accurate in vivo quantitation of time-varying biological distributions of radiolabeled antibodies over several days. The short half-lives of most commonly used positron-emitting nuclides make them unsuitable for this purpose. Iodine-124 is a positron emitter with a half-life of 4.2 days and appropriate chemical properties. It has not been widely used because of a complex decay scheme including several high energy gamma rays. However, measurements made under realistic conditions on several different PET scanners have shown that satisfactory imaging and quantitation can be achieved. METHODS: Whole-body and head-optimized scanners with different detectors (discrete BGO, block BGO and BaF2 time-of-flight), different septa and different correction schemes were used. Measurements of resolution, quantitative linearity and the ability to quantitatively image spheres of different sizes and activities in different background activities were made using phantoms. RESULTS: Compared with conventional PET nuclides, resolution and quantitation were only slightly degraded. Sphere detectability was also only slightly worse if imaging time was increased to compensate for the lower positron abundance. CONCLUSION: Quantitative imaging with 124I appears to be possible under realistic conditions with various PET scanners.

Half-Life↗
PubMed1995

Sex differences in regional cerebral glucose metabolism during a resting state.

Positron emission tomography was used to evaluate the regional distribution of cerebral glucose metabolism in 61 healthy adults at rest. Although the profile of metabolic activity was similar for men and women, some sex differences and hemispheric asymmetries were detectable. Men had relatively higher metabolism than women in temporal-limbic regions and cerebellum and relatively lower metabolism in cingulate regions. In both sexes, metabolism was relatively higher in left association cortices and the cingulate region and in right ventro-temporal limbic regions and their projections. These results are consistent with the hypothesis that differences in cognitive and emotional processing have biological substrates.

Adult↗