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Final Report Summary: Radiation dosimetry of Cu-64-labeled radiotherapy agents using PET [Positron Emission Tomography]

Description: This project began in 1996, and was completed in July 2001. The overall goals were to compare various methods of dosimetry of PET imaging agents, as well as develop more optimal methods. One of the major accomplishments of this grant was the human PET imaging studies of a positron-emitting radiopharmaceutical for somatostatin-receptor imaging, and subsequent dosimetry calculations resulting from this study. In addition, we collaborated with Darrell Fisher and Edmund Hui to develop a MIRD-hamster program for calculating hamster organ and tumor dosimetry in hamster models. Progress was made towards a point kernel approach to more accurately determining absorbed doses to normal organs, as well as towards co-registration of PET and MRI images. This report focuses on the progress made in the last 15 months of the grant, which in general is a summary of the progress over the 5 years the project was ongoing.
Date: September 1, 2002
Creator: Anderson, Carolyn J. & Cutler, P.D.
Partner: UNT Libraries Government Documents Department


Description: A description of some of the methods used in neuroreceptor imaging to distinguish changes in receptor availability has been presented in this chapter. It is necessary to look beyond regional uptake of the tracer since uptake generally is affected by factors other than the number of receptors for which the tracer has affinity. An exception is the infusion method producing an equilibrium state. The techniques vary in complexity some requiring arterial blood measurements of unmetabolized tracer and multiple time uptake data. Others require only a few plasma and uptake measurements and those based on a reference region require no plasma measurements. We have outlined some of the limitations of the different methods. Laruelle (1999) has pointed out that test/retest studies to which various methods can be applied are crucial in determining the optimal method for a particular study. The choice of method will also depend upon the application. In a clinical setting, methods not involving arterial blood sampling are generally preferred. In the future techniques for externally measuring arterial plasma radioactivity with only a few blood samples for metabolite correction will extend the modeling options of clinical PET. Also since parametric images can provide information beyond that of ROI analysis, improved techniques for generating such images will be important, particularly for ligands requiring more than a one-compartment model. Techniques such as the wavelet transform proposed by Turkheimer et al. (2000) may prove to be important in reducing noise and improving quantitation.
Date: April 2, 2001
Creator: Logan, J.
Partner: UNT Libraries Government Documents Department


Description: Nuclear Medicine is the specialty of medical imaging, which utilizes a variety of radionuclides incorporated into specific compounds for diagnostic imaging and therapeutic applications. During recent years, research efforts associated with this discipline have concentrated on the decay characteristics of particular radionuclides and the design of unique radiolabeled tracers necessary to achieve time-dependent molecular images. The specialty is expanding with specific Positron emission tomography (PET) and SPECT radiopharmaceuticals allowing for an extension from functional process imaging in tissue to pathologic processes and nuclide directed treatments. PET is an example of a technique that has been shown to yield the physiologic information necessary for clinical oncology diagnoses based upon altered tissue metabolism. Most PET drugs are currently produced using a cyclotron at locations that are in close proximity to the hospital or academic center at which the radiopharmaceutical will be administered. In November 1997, a law was enacted called the Food and Drug Administration Modernization Act of 1997 which directed the Food and Drug Administration (FDA) to establish appropriate procedures for the approval of PET drugs in accordance with section 505 of the Federal Food, Drug, and Cosmetic Act and to establish current good manufacturing practice requirements for such drugs. At this time the FDA is considering adopting special approval procedures and cGMP requirements for PET drugs. The evolution of PET radiopharmaceuticals has introduced a new class of ''drugs'' requiring production facilities and product formulations that must be closely aligned with the scheduled clinical utilization. The production of the radionuclide in the appropriate synthetic form is but one critical component in the manufacture of the finished radiopharmaceutical.
Date: June 25, 2001
Creator: Finn, R. & Schlyer, D.
Partner: UNT Libraries Government Documents Department

Dynamic neurotransmitter interactions measured with PET

Description: Positron emission tomography (PET) has become a valuable interdisciplinary tool for understanding physiological, biochemical and pharmacological functions at a molecular level in living humans, whether in a healthy or diseased state. The utility of tracing chemical activity through the body transcends the fields of cardiology, oncology, neurology and psychiatry. In this, PET techniques span radiochemistry and radiopharmaceutical development to instrumentation, image analysis, anatomy and modeling. PET has made substantial contributions in each of these fields by providing a,venue for mapping dynamic functions of healthy and unhealthy human anatomy. As diverse as the disciplines it bridges, PET has provided insight into an equally significant variety of psychiatric disorders. Using the unique quantitative ability of PET, researchers are now better able to non-invasively characterize normally occurring neurotransmitter interactions in the brain. With the knowledge that these interactions provide the fundamental basis for brain response, many investigators have recently focused their efforts on an examination of the communication between these chemicals in both healthy volunteers and individuals suffering from diseases classically defined as neurotransmitter specific in nature. In addition, PET can measure the biochemical dynamics of acute and sustained drug abuse. Thus, PET studies of neurotransmitter interactions enable investigators to describe a multitude of specific functional interactions in the human brain. This information can then be applied to understanding side effects that occur in response to acute and chronic drug therapy, and to designing new drugs that target multiple systems as opposed to single receptor types. Knowledge derived from PET studies can be applied to drug discovery, research and development (for review, see (Fowler et al., 1999) and (Burns et al., 1999)). Here, we will cover the most substantial contributions of PET to understanding biologically distinct neurochemical systems that interact to produce a variety of behaviors and disorders. Neurotransmitters are neither static nor ...
Date: April 2, 2001
Creator: Schiffer, W. K. & Dewey, S. L.
Partner: UNT Libraries Government Documents Department

Research symposium proceedings. Final report

Description: THE research symposium was organized to present the cutting edge research for PET by individuals from leading institutions throughout the world. The Institute for Clinical PET (ICP) has focused its annual meeting on the clinical applications of PET.
Date: December 31, 1991
Partner: UNT Libraries Government Documents Department

Developments in functional neuroimaging techniques

Description: A recent review of neuroimaging techniques indicates that new developments have primarily occurred in the area of data acquisition hardware/software technology. For example, new pulse sequences on standard clinical imagers and high-powered, rapidly oscillating magnetic field gradients used in echo planar imaging (EPI) have advanced MRI into the functional imaging arena. Significant developments in tomograph design have also been achieved for monitoring the distribution of positron-emitting radioactive tracers in the body (PET). Detector sizes, which pose a limit on spatial resolution, have become smaller (e.g., 3--5 mm wide) and a new emphasis on volumetric imaging has emerged which affords greater sensitivity for determining locations of positron annihilations and permits smaller doses to be utilized. Electromagnetic techniques have also witnessed growth in the ability to acquire data from the whole head simultaneously. EEG techniques have increased their electrode coverage (e.g., 128 channels rather than 16 or 32) and new whole-head systems are now in use for MEG. But the real challenge now is in the design and implementation of more sophisticated analyses to effectively handle the tremendous amount of physiological/anatomical data that can be acquired. Furthermore, such analyses will be necessary for integrating data across techniques in order to provide a truly comprehensive understanding of the functional organization of the human brain.
Date: March 1, 1995
Creator: Aine, C.J.
Partner: UNT Libraries Government Documents Department

Analysis of Factors Affecting Positron Emission Mammography (PEM) Image Formation

Description: Image reconstruction for positron emission mammography (PEM) with the breast positioned between two parallel, planar detectors is usually performed by backprojection to image planes. Three important factors affecting PEM image reconstruction by backprojection are investigated: (1) image uniformity (flood) corrections, (2) image sampling (pixel size) and (3) count allocation methods. An analytic expression for uniformity correction is developed that incorporates factors for spatial-dependent detector sensitivity and geometric effects from acceptance angle limits on coincidence events. There is good agreement between experimental floods from a PEM system with a pixellated detector and numerical simulations. The analytic uniformity corrections are successfully applied to image reconstruction of compressed breast phantoms and reduce the necessity for flood scans at different image planes. Experimental and simulated compressed breast phantom studies show that lesion contrast is improved when the image pixel size is half of, rather than equal to, the detector pixel size, though this occurs at the expense of some additional image noise. In PEM reconstruction counts usually are allocated to the pixel in the image plane intersected by the line of response (LOR) between the centers of the detection pixels. An alternate count allocation method is investigated that distributes counts to image pixels in proportion to the area of the tube of response (TOR) connecting the detection pixels that they overlay in the image plane. This TOR method eliminates some image artifacts that occur with the LOR method and increases tumor signal-to-noise ratios at the expense of a slight decrease in tumor contrast. Analysis of image uniformity, image sampling and count allocation methods in PEM image reconstruction points to ways of improving image formation. Further work is required to optimize image reconstruction parameters for particular detection or quantitation tasks.
Date: November 1, 2001
Creator: Smith, Mark F.; Majewski, Stan; Weisenberger, Andrew G.; Kieper, Douglas A.; Raylman, Raymond R. & Turkington, Timothy G.
Partner: UNT Libraries Government Documents Department

A High-Performance VME-Based Acquisition System for Positron Emission Mammography

Description: A prototype for a practical and economical breast imaging system for cancer detection is currently under development at Jefferson Lab. The latest advances in bright, fast, crystal scintillators, compact position-sensitive photomultipliers (PSPMT), and high-performance digitizing and readout electronics are being used to develop a compact imager based on Positron Emission Tomography (PET). To facilitate the performance demands of the detector as well as the high number of readout channels, the data acquisition system is built around an intelligent, self-contained, VME form-factor.
Date: November 1, 2001
Creator: Abbott, D.J.; Weisenberger, A.; Majewski, S.; Kieper, D.; Kross, B.; Popov, V. et al.
Partner: UNT Libraries Government Documents Department

Aspects of Three-Dimensional Imaging by Classical Tomography for Dual Detector Positron Emission Mammography (PEM)

Description: Images from dual detector positron emission mammography (PEM) systems are commonly reconstructed by backprojection methods of classical tomography. Characteristics of three-dimensional (3-D) PEM images were investigated using analytic models, computer simulations, and experimental acquisitions with compact pixellated detectors, in particular depth resolution normal to the detectors. An analytic formula was developed using circular image pixels that models blurring normal to the detectors. The amount of blurring is dependent on the acceptance angle for coincidence events and may vary across the field of view due to geometric limitations on the maximum angle of lines of response normal to the detectors. For experimental acquisitions with line sources and a pixellated lutetium gadolinium oxyorthosilicate (LGSO) detector, depth resolution is broader than predicted by numerical simulations, possibly due to uncorrected randoms or scatter within the scintillator arrays. Iterative image reconstruction with the maximum likelihood expectation maximization (MLEM) algorithm of a compressed breast phantom acquisition with a pixellated gadolinium oxyorthosilicate (GSO) detector shows improved contract compared with backprojection reconstruction. Image reconstruction for dual detector PEM with static detectors represents a case of limited angle tomography with truncated projection data, and there is the opportunity to improve three-dimensional PEM imaging by the use of more sophisticated image reconstruction techniques.
Date: December 1, 2001
Creator: Smith, Mark F.; Majewski, Stan; Weisenberger, Andrew G.; Raylman, Raymond R.; Kieper, Douglas A.; Kalen, Joseph D. et al.
Partner: UNT Libraries Government Documents Department

A wavelet phase filter for emission tomography

Description: The presence of a high level of noise is a characteristic in some tomographic imaging techniques such as positron emission tomography (PET). Wavelet methods can smooth out noise while preserving significant features of images. Mallat et al. proposed a wavelet based denoising scheme exploiting wavelet modulus maxima, but the scheme is sensitive to noise. In this study, the authors explore the properties of wavelet phase, with a focus on reconstruction of emission tomography images. Specifically, they show that the wavelet phase of regular Poisson noise under a Haar-type wavelet transform converges in distribution to a random variable uniformly distributed on [0, 2{pi}). They then propose three wavelet-phase-based denoising schemes which exploit this property: edge tracking, local phase variance thresholding, and scale phase variation thresholding. Some numerical results are also presented. The numerical experiments indicate that wavelet phase techniques show promise for wavelet based denoising methods.
Date: July 1, 1995
Creator: Olsen, E.T. & Lin, B.
Partner: UNT Libraries Government Documents Department

Positron ring system using anger-type detectors. Progress report, February 15, 1991--February 14, 1992

Description: The major accomplishments of this year include (1) building and debugging a new set of coincidence electronics for our laboratory setup, (2) performing a series of detector experiments in the dry glove-box aimed at improving the performance of NaI(Tl) position-sensitive detectors, (3) modifying and debugging a Monte Carlo simulation code to test reconstruction algorithms and predict overall performance of a large solid angle PET scanner, (4) significant progress in the 3-D reprojection reconstruction algorithm and comparison to the 2-D single-slice algorithm and a 3-D multi-slice rebinning algorithm, (5) performance comparisons of the two PENN-PET scanners, which lead to a design for a large solid angle scanner with a 25-cm axial extent.
Date: November 15, 1991
Creator: Karp, J. S.
Partner: UNT Libraries Government Documents Department

Measuring dopamine release in the human brain with PET

Description: The dopamine system is involved in the regulation of brain regions that subserve motor, cognitive and motivational behaviors. Disruptions of dopamine (DA) function have ben implicated in neurological and psychiatric illnesses including substance abuse as well as on some of the deficits associated with aging of the human brain. This has made the DA system an important topic in research in the neurosciences and neuroimaging as well as an important molecular target for drug development. Positron Emission Tomography (PET), was the first technology that enabled direct measurement of components of the DA system in the living human brain. Imaging studies of DA in the living brain have been indirect, relying on the development of radiotracers to label DA receptors, DA transporters, compounds which have specificity for the enzymes which degrade synaptic DA. Additionally, through the use of tracers that provide information on regional brain activity (ie brain glucose metabolism and cerebral blood flow) and of appropriate pharmacological interventions, it has been possible to assess the functional consequences of changes in brain DA activity. DA specific ligands have been useful in the evaluation of patients with neuropsychiatric illnesses as well as to investigate receptor blockade by antipsychotic drugs. A limitation of strategies that rely on the use of DA specific ligands is that the measures do not necessarily reflect the functional state of the dopaminergic system and that there use to study the effects of drugs is limited to the investigation of receptor or transporter occupancy. Newer strategies have been developed in an attempt to provide with information on dopamine release and on the functional responsivity of the DA system in the human brain. This in turn allows to investigate the effects of pharmacological agent in an analogous way to what is done with microdialysis techniques.
Date: December 1, 1995
Creator: Volkow, N.D.; Fowler, J.S.; Logan, J. & Wang, G.J.
Partner: UNT Libraries Government Documents Department

Laboratory and cyclotron requirements for PET research

Description: This report describes four types of PET facilities: Clinical PET with no radionuclide production; clinical PET with a small accelerator; clinical PET with research support; and research PET facilities. General facility considerations are also discussed.
Date: June 1, 1993
Creator: Schlyer, D. J.
Partner: UNT Libraries Government Documents Department

High resolution tomographic instrument development

Description: Our recent work has concentrated on the development of high-resolution PET instrumentation reflecting in part the growing importance of PET in nuclear medicine imaging. We have developed a number of positron imaging instruments and have the distinction that every instrument has been placed in operation and has had an extensive history of application for basic research and clinical study. The present program is a logical continuation of these earlier successes. PCR-I, a single ring positron tomograph was the first demonstration of analog coding using BGO. It employed 4 mm detectors and is currently being used for a wide range of biological studies. These are of immense importance in guiding the direction for future instruments. In particular, PCR-II, a volume sensitive positron tomograph with 3 mm spatial resolution has benefited greatly from the studies using PCR-I. PCR-II is currently in the final stages of assembly and testing and will shortly be placed in operation for imaging phantoms, animals and ultimately humans. Perhaps the most important finding resulting from our previous study is that resolution and sensitivity must be carefully balanced to achieve a practical high resolution system. PCR-II has been designed to have the detection characteristics required to achieve 3 mm resolution in human brain under practical imaging situations. The development of algorithms by the group headed by Dr. Chesler is based on a long history of prior study including his joint work with Drs. Pelc and Reiderer and Stearns. This body of expertise will be applied to the processing of data from PCR-II when it becomes operational.
Date: August 1, 1992
Partner: UNT Libraries Government Documents Department

New imaging systems in nuclear medicine. Final report, January 1, 1993--December 31, 1995

Description: The aim of this program has been to improve the performance of positron emission tomography (PET) to achieve high resolution with high sensitivity. Towards this aim, the authors have carried out the following studies: (1) explored new techniques for detection of annihilation radiation including new detector materials and system geometries, specific areas that they have studied include--exploration of factors related to resolution and sensitivity of PET instrumentation including geometry, detection materials and coding, and the exploration of technique to improve the image quality by use of depth of interaction and increased sampling; (2) complete much of the final testing of PCR-II, an analog-coded cylindrical positron tomograph, developed and constructed during the current funding period; (3) developed the design of a positron microtomograph with mm resolution for quantitative studies in small animals, a single slice version of this device has been designed and studied by use of computer simulation; (4) continued and expanded the program of biological studies in animal models. Current studies have included imaging of animal models of Parkinson`s and Huntington`s disease and cancer. These studies have included new radiopharmaceuticals and techniques involving molecular biology.
Date: December 31, 1995
Partner: UNT Libraries Government Documents Department

Visualization of monoamine oxidase in human brain

Description: Monoamine oxidase is a flavin enzyme which exists in two subtypes, MAO A and MAO B. In human brain MAO B predominates and is largely compartmentalized in cell bodies of serotonergic neurons and glia. Regional distribution of MAO B was determined by positron computed tomography with volunteers after the administration of deuterium substituted [11C]L-deprenyl. The basal ganglia and thalamus exhibited the greatest concentrations of MAO B with intermediate levels in the frontal cortex and cingulate gyrus while lowest levels were observed in the parietal and temporal cortices and cerebellum. We observed that brain MAO B increases with are in health normal subjects, however the increases were generally smaller than those revealed with post-mortem studies.
Date: December 31, 1996
Creator: Fowler, J.S.; Volkow, N.D.; Wang, G.J.; Pappas, N.; Shea, C.; MacGregor, R.R. et al.
Partner: UNT Libraries Government Documents Department

A room temperature LSO/PIN photodiode PET detector module that measures depth of interaction

Description: We present measurements of a 4 element PET detector module that uses a 2{times}2 array of 3 mm square PIN photodiodes to both measure the depth of interaction (DOI) and identify the crystal of interaction. Each photodiode is coupled to one end of a 3{times}3{times}25 mm LSO crystal, with the opposite ends of all 4 crystals attached to a single PMT that provides a timing signal and initial energy discrimination. Each LSO crystal is coated with a {open_quotes}lossy{close_quotes} reflector, so the ratio of light detected in the photodiode and PMT depends on the position of interaction in the crystal, and is used to determine this position on an event by event basis. This module is operated at +25{degrees}C with a photodiode amplifier peaking time of 2 {mu}s. When excited by a collimated beam of 511 keV photons at the photodiode end of the module (i.e. closest to the patient), the DOI resolution is 4 mm fwhm and the crystal of interaction is identified correctly 95% of the time. When excited at the opposite end of the module, the DOI resolution is 13 mm fwhm and the crystal of interaction is identified correctly 73% of the time. The channel to channel variations in performance are minimal.
Date: November 1, 1994
Creator: Moses, W.W.; Derenzo, S.E.; Melcher, C.L. & Manente, R.A.
Partner: UNT Libraries Government Documents Department

Robotic control of whole blood processing in functional brain imaging research

Description: This paper describes progress in automation of routine clinical laboratory tasks which support PET. The system examined is based on standard components of Zymark Corporation`s PyTechnology system. The system proved a reliable and robust source of laboratory automation modules suitable for automating a major task associated withe the clinical chemistry portions of PET.
Date: December 31, 1996
Creator: Alexoff, D.L.; King, P. & Gatley, S.J.
Partner: UNT Libraries Government Documents Department

Emittance measurement techniques used in the 1 MeV RFQ for the PET isotope linac at Fermilab

Description: Beam emittance measurements have been performed on the {sup 3}He{sup +} beam at the PET isotope production accelerator, being commissioned at Fermilab for the Biomedical Research Foundation in Shreveport, Louisiana, USA. Emittances have been measured at injection to and extraction from the first RFQ, at 20 keV and 1 MeV, respectively. A single slit followed by a 48 electrode collector is used in the standard way to measure the divergence of the {sup 3}He{sup +} beam as a function of position. Noise reduction operations have been developed, both in hardware and software. These techniques and the emittance measurement results are presented.
Date: September 1, 1996
Creator: McCrory, E.; Popovic, M.; Schmidt, C.W. & Young, P.
Partner: UNT Libraries Government Documents Department

Positron tomographic imaging of tumors using monoclonal antibodies. Final progress report, April 15, 1989--October 31, 1995

Description: The overall objective of this research is to develop methods for utilizing positron emission tomography (PET) to increase the clinical potential of radiolabeled monoclonal antibodies (MAbs). Enhancement of MAb tumor localization by hyperthermia also was proposed. Studies were to have been performed with both {sup 18}F and {sup 124}I; however, the lack of its availability (until quite recently) prevented experiments with {sup 124}I. Instead, two additional lines of inquiry were initiated in which they utilized aspects of the radiofluorination chemistries originally developed for MAbs for labeling chemotactic peptides and meta-iodobenzylguanidine (MIBG) analogues with {sup 18}F. This final report summarizes the original specific aims and the main research accomplishments in studies of mouse, dog and human models.
Date: February 1, 1997
Creator: Zalutsky, M.R.
Partner: UNT Libraries Government Documents Department

Technology transfer at Brookhaven National Laboratory

Description: The Office of Technology Transfer is firmly committed to technology transfer--to the utilization of Laboratory developed technology to the benefit of industry and state and local governments. Such technology utilization can be accomplished in a variety of ways. Brookhaven encourages exchanges of personnel between the Laboratory and industry, as well as cost shared cooperative research efforts with industry. Industry sponsored research and industry use of Brookhaven`s designated user facilities provide access to the Laboratory`s unique research expertise and facilities. The Laboratory`s active patent licensing program is a further tool to accomplish commercialization of Brookhaven developed technology. The Office of Technology Transfer will work to match specific market-driven needs of individual companies with appropriate technologies from Brookhaven National Laboratory. This brochure provides an overview of technology transfer opportunities at BNL.
Date: September 1, 1996
Partner: UNT Libraries Government Documents Department

High Resolution Detector Modules Based on NaI(T1) Arrays for Small Animal Imaging

Description: We are developing high spatial resolution detector modules based on recently available NaI(T1) crystal scintillator arrays that are capable of detecting photons over a range of energies. We report on the testing of an array with individual element sizes of 1 mm x 1 mm arrays over the energy range of 28 keV to 511 keV. It is anticipated that these detector modules could be applied to small animal imaging utilizing single photon emitters such as iodine-125 (28-35 keV) and technetium-99m (140 keV); and also positron emitters such as fluorine-18. The performance of a 5 cm square array of NaI(T1) crystal scintillators in which each element is 1 mm x 1 mm x 5 mm in dimension was measured. The NaI(T1) array manufactured by Saint-Gobain was coupled to Hamamatsu position sensitive photomultiplier tubes and tested over a range of photon energies. In particular, we tested the NaI(T1) array with the Hamamatsu model R2487 position sensitive photomultiplier tube and the new Hamamatsu model 85 00 flat panel position sensitive photomultiplier tube. Though the NaI(T1) module performed best for the single photon emitters its use in positron emission tomography applications for small animal imaging could be possible even though resulting sensitivity is not ideal.
Date: November 1, 2001
Creator: Weisenberger, A.G.; Wojcik, R.; Majewski, S. & Popov, V.
Partner: UNT Libraries Government Documents Department