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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.

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.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.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.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 in1 h. Overall, C-PET is a cost-effective PET scanner that performs well in a broad variety of clinical applications.

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.

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.

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.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.[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.[18F]EF1 is an excellent radiotracer for noninvasive imaging of tumor hypoxia.

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.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.The SEG technique produced images that were visually less noisy than the ECS method (P0.0001) 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 (P0.0001) 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).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.

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.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.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.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.

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.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.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.Quantitative imaging with 124I appears to be possible under realistic conditions with various PET scanners.

The potential of anatomic imaging to improve the quantitative accuracy of functional brain imaging through refined regional definition is widely accepted. However, there are little data addressing the impact of approach to regional localization on quantitation of metabolic images in the absence of gross structural pathology. We compared MRI-based versus PET-based approaches to the analysis of PET 18F-fluorodeoxyglucose (FDG) images using a standard adjustable template based on simple geometric regions. For the MRI-based approach, templates and individual regions were adjusted to each individual's anatomy, whereas the PET-based definition involved only global proportional adjustment of the standard templates. Metabolic rates for glucose and volume-to-whole brain ratios were determined by two operators for 78 volumes of interest in five subjects. Pairwise correlations indicated high interoperator agreement for each approach and high intraoperator agreement for MRI-based versus PET-based metabolic values. The stability of the metabolic rates and ratios among operators and analysis approaches was supported by low coefficients of variation across measurements and small average differences in paired comparisons. Thus, within the current spatial resolution of PET imaging, quantitation of metabolic images is relatively robust to image analysis approach in the absence of gross structural abnormality. To take advantage of the greater quantitative accuracy promised by high-resolution anatomic and functional imaging, more refined delineation of anatomic images will be necessary.

A standard set of performance measurements is proposed for use with positron emission tomographs. This set of measurements has been developed jointly by the Computer and Instrumentation Council of the Society of Nuclear Medicine and the National Electrical Manufacturers Association. The measurements include tests of spatial resolution, scatter fraction, sensitivity, count rate losses and randoms, uniformity, scatter correction, attenuation correction, and count rate linearity correction.

A standard set of performance measurements is proposed for use with positron emission tomographs. This set of measurements has been developed by the Computer and Instrumentation Council of the Society of Nuclear Medicine and the National Electrical Manufacturers Associations. These measurements are discussed and compared to the set of standard measurements being proposed by the Instrumentation Task Group of the European Economic Community Concerted Action of Cellular Regeneration and Degeneration. The performance of the PENN-PET 240H scanner from UGM Medical Systems is tested with this set of measurements. The PENN-PET scanner consists of six continuous position-sensitive NaI(T1) detectors, which results in a 50 cm transverse field-of-view and a 12.8 cm axial field-of-view. The fine spatial sampling in the axial direction allows the data to be sorted into as many as 64 transverse planes, each 2 mm thick. A large axial acceptance angle, without inter-plane septa, results in a high sensitivity, with a low scatter and randoms fraction, due to the use of a narrow photopeak energy window. This paper emphasizes those performance measurements which illustrate the special characteristics of a volume imaging scanner, compared to a more traditional multi-ring scanner.

A single-slice positron camera has been developed with good spatial resolution and high count rate capability. The camera uses a hexagonal arrangement of six position-sensitive NaI(Tl) detectors. The count rate capability of NaI(Tl) was extended to 800k cps through the use of pulse shortening. In order to keep the detectors stationary, an iterative reconstruction algorithm was modified which ignores the missing data in the gaps between the six detectors and gives artifact-free images. The spatial resolution, as determined from the image of point sources in air, is 6.5 mm full width at half maximum. We have also imaged a brain phantom and dog hearts.