Bio-imaging/Molecular Imaging Research Overview

Benveniste, Helene

Chair, Medical Department

Benveniste@bnl.gov

Summary : Benveniste's Laboratory focuses on (1) exploring, characterizing and understanding diagnostic MR contrast parameters suitable to visualize neuro-pathology in neurodegenerative diseases; (2) investigate transgenic animal models were specific genes are modified to understand mechanism(s) and treatment of addiction and of drug-induced neurotoxicity using high resolution MR imaging, (3) advance technologies in molecular MR imaging.

Bluestein, Danny

Professor

Danny.Bluestein@sunysb.edu

Summary : Despite major progress, cardiovascular diseases remain the leading cause of death in the western world. One of the major culprits in cardiovascular disease and in devices designed to treat or restore impaired cardiovascular function is the non-physiologic flow pattern that enhances the hemostatic response mainly through platelet activation. Platelets have long been regarded as the preeminent cell involved in physiologic hemostasis and pathologic thrombosis. An innovative technique for measuring flow induced platelet activation has been developed, and its utility demonstrated in experiments conducted in recirculation devices (models of arterial stenosis, Left Ventricular Assist Device (LVAD), and mechanical heart valves). The mechanisms by which the non-physiologic flow patterns induce platelet activation and generate free emboli, that enhance the risk of cardioembolic stroke, was demonstrated in vivo with mechanical heart valves implanted in the sheep model. The results of this research will aid in elucidating physical forces that regulate cellular function in flowing blood, and may be applied to improve the design of blood recirculating devices and to develop more potent drugs for treating cardiovascular diseases.

Brouzes, Eric

Research Assistant Professor

ebrouzes@gmail.com

Summary : Our goal is to better describe and understand the role of tissue heterogeneity in normal tissues and in the onset and development of diseases like cancer. Most tissues are comprised of a complex mixture of different cell types, and even cells within a clonal population exhibit a high degree of heterogeneity. However, the detailed behavior of individual cells is obscured in typical measurements which are averaged over cell populations. As a result, it has been difficult to comprehend the functional relevance of this heterogeneity due to the lack of adequate techniques. In order to enable the analysis of tissue heterogeneity we are developing an experimental approach based on droplet microfluidics that allows the manipulation of single cells by suspending them in drops carried in an inert fluid. These drops can then be automatically combined with reaction solutions, interrogated with fluorescent dyes or sorted to carry out sample preparation and analysis. My research exploits the advantages conferred by droplet microfluidics over conventional technologies and other microfluidics techniques in terms of automation, throughput and combinatorial power for the manipulation and analysis of single-cells.

Button, Terry

Associate Professor

Terry.Button@sunysb.edu

Summary : Dr. Button's research work in the past has focused on Advanced Magnetic Resonance Mammography and Dynamic Infrared Imaging. His current research projects are infrared imaging, breast cancer detection, magnetic resonance and computer aided diagnosis (CAD)

Carlson, Josh

Research Assistant Professor

carlsonjm79@gmail.com

Summary : The human brain is highly tuned for detecting salience within one’s environment. In particular, social signals of threat such as fearful facial expressions are preferentially processed and automatically capture observers’ attention. Indeed, these social signals are so powerful that they can influence behavior even when subliminally processed. Much of my research is aimed at understanding the neural mechanisms underlying salience detection within low signal-to-noise environments including subliminal processing conditions. Furthermore, my research examines how differences in brain activity relate to individual differences in one’s ability to detect salience. The hope is that by understanding the brain mechanisms underlying individual differences in human behavior clinicians will be able to better focus treatment efforts for psychopathological behaviors. Functional magnetic resonance imaging (fMRI), structural MRI, electroencephalogram event-related potentials (EEG/ERP), genetics, and peripheral physiology (e.g., cortisol and heart rate) are all utilized in this research.

Chon, Ki

Professor

Ki.Chon@sunysb.edu

Summary : The cardiac autonomic nervous system is responsible for maintaining proper homeostasis, or balance, of the cardiovascular system. One of our major areas of research is to detect, quantify, and interpret differences in dynamic characteristics of the cardiac autonomic nervous system between normal and diseased subjects, in an attempt to find a marker for increased risk of sudden cardiac death. Identifying and quantifying differences in the dynamic characteristics of autonomic function between normal and diseased conditions may lead to a better understanding of the role of autonomic function imbalance in diseased conditions, and should have important clinical diagnostic and prognostic applications. Another active research area is the development of computational modeling approaches to understand differences in dynamics of renal autoregulatory mechanisms between normotensive and hypertensive conditions. For both areas of research, we are developing novel linear and nonlinear signal processing techniques that can be successfully applied to achieve the research objectives.

Dilmanian, F. Avraham

Associate Professor

Dilmanian@bnl.gov

Summary : The focus of Avraham Dilmanian's work is on the use of X-ray beams from the National Synchrotron Light Source (NSLS), Brookhaven National Laboratory, in radiation therapy and medical imaging. The radiotherapy program, microbeam radiation therapy (MRT), uses arrays of parallel, microplanar X-rays and has two remarkable effects on laboratory vertebrates. First, it does not damage normal tissues at doses where conventional, broad beams produce severe tissue damage. Second, MRT kills some types of malignant tumors by irradiation from a single angle, at doses that are safe to normal tissues. Dilmanian's imaging programs pivot around computed tomography using monoenergetic X-ray beams. In particular, he and his colleagues recently implemented a new X-ray imaging method, Diffraction-Enhance Imaging (DEI), in the CT mode, studying phantoms and small animals. In both MRT and the imag-ing methods, technical challenges after the feasibility studies at the NSLS would be to develop compact sources for implementing the methods in hospitals.

Du, Congwu

Associate Professor and Scientist

congwu@bnl.gov

Summary : The broad goal of this laboratory is to develop advanced optical instrumentation to detect and characterize the physiological processes in the living biological systems such as brain and heart. More specifically, cutting-edge optical spectroscopy and imaging techniques are developed that permit simultaneous detection of cerebral blood flow, blood volume and tissue oxygenation, as well as intracellular calcium in vivo. We are interested in studying drug-induced abnormalities of the brain function. Cocaine is chosen as one of the preliminary drugs for our research applications because it affects cerebral hemodynamcs, metabolism, and neuronal activities in the brain. The mechanisms that underlie cocaine’s neurotoxic effects are not fully understood, partially due to the technical limitations of current neuroimage techniques to differentiate cerebrovascular from neuronal effects at sufficiently high temporal and spatial resolutions. To solve this problem, we have developed a multimodal imaging platform that combines multi-wavelength laser speckle imaging, optical coherence tomography, and calcium fluorescence imaging to enable simultaneous detection of cortical hemodynamics, cerebral metabolism, and neuronal activities of animal brain in vivo, as well as its integration with microprobes for imaging neuronal function in deep brain regions in vivo. Promising results of in vivo animal brain functional studies demonstrate the potential of this novel multimodality approach to compliment other neuroimaging modalities (e.g., PET, fMRI) for investigating brain functional changes such as those induced by drugs of abuse.

Entcheva, Emilia

Associate Professor

Emilia.Entcheva@sunysb.edu

Summary : The Cardiac Cell Engineering Laboratory develops new optical modalities for actuation and sensing of the electromechanical function in cardiac cells and tissues. Our lab leads pioneering work in the field of cardiac optogenetics - the use of light for the precise interrogation, stimulation and control of excitable tissue, including heart, that has been genetically altered to become light-sensitive. We develop useful tools for physiomics type of studies, drug, gene and stem cell therapy testing 3D cellular platforms, also needed for experimental validation of computer models of excitable tissue. This research is multidisciplinary in nature and involves a spectrum of experimental molecular and cell biology procedures, along with the application of design concepts from electrical, optical, mechanical and chemical engineering to create the enabling technology for our studies. New imaging modalities, image processing algorithms and computer modeling are essential complementary tools developed and applied by our team. Key research areas include: 1) cardiac optogenetics; 2) optical mapping of excitation; 3) advanced signal and image processing; 4) cardiac cell and tissue engineering; 5) unraveling the mechanisms of cardiac arrhythmias.

Fowler, Joanna

Professor

Fowler@bnl.gov

Summary : A senior chemist at Brookhaven National Laboratory, she focuses on the biochemical effects of drugs, aging, and selected diseases on the brain. Fowler received a Jacob Javits Investigator Award in the Neurosciences, in 1986 and 1993; a Gustavus John Esselen Award for Chemistry in the Public Interest in 1988; Brookhaven Laboratory's R&D Award, in 1994; the Aebersold Award from the Society of Nuclear Medicine in 1997; and the Francis P. Garvan-John M. Olin Medal in 1998.

Frame, Molly

Associate Professor & Undergraduate Program Director

Mary.Frame@sunysb.edu

Summary : " Our emerging understanding of oxygen delivery to the tissues is that the blood flow within the smallest arterioles is tightly organized within repeating networks across the tissue. Central to this new paradigm are the concepts of vascular communication between the beginning and end of the network (via gap junctions), and its relation to flow sensing by the vascular endothelium. Our work has shown that different types of microvascular flow patterns can be triggered by direct stimulation of the focal adhesions (alpha-v-beta-3 integrins, i.e., wound healing), compared to adenosine (i.e., metabolic change), compared to nitric oxide (i.e., inflammation), hence we can control the flow patterns. Among the goals of this work are in vitro construction of transplantable microvascular networks, using bionanotechnology to create the sturdy scaffolding, and verification of nanofabricated drug delivery units within the vasculature. To this end, equally important are mechanotransduction of the physical forces associated with flow change (i.e., wall shear stress), the pharmacologic signal transduction systems involved (which guide drug discovery and intervention), and the molecular basis for the committed step that ensures healthy flow delivery. Our work employs computational modeling of the fluid mechanics, the physiology of arteriolar network blood flow (in vivo and in vitro), and precise genomic manipulation of key proteins in healthy and vascular disease states. "

Gindi, Gene R.

Associate Professor

Gindi@clio.rad.sunysb.edu

Summary : Algorithm development for medical imaging, particularly the application of applied mathematical methods to image reconstruction and to quantitative metrics for image quality. Gindi has been working in the area of nuclear medicine, where probabilistic methods must be used to reconstruct the image from the quantum limited acquired data. His team's approach has been to use Bayesian methods able to accurately model the image formation process as well as to model assorted forms of prior information concerning the object to be reconstructed. Such prior information includes knowledge of piecewise smoothness of the object as well as side information that can be gleaned from MRIs of the same patient. Image quality involves the formulation of crisp mathematical criteria. A considerable effort in signal processing is required in formulating how noise and object variation affect these criteria. Gindi and his students have made recent progress in the formulation of methods to describe noise propagation in nonlinear reconstruction algorithms.

Goldfarb, James W.

Magnetic Resonance Imaging Scientist

James.Goldfarb@chsli.edu

Summary : The application of magnetic resonance imaging (MRI) to the cardiovascular system, particularly in the areas of myocardial function and blood vessels. Cardiovascular disease is the major cause of death in industrialized nations. Magnetic resonance’s ability for both anatomic and physiological imaging has enormous clinical potential as a noninvasive alternative to conventional invasive procedures. However, significant hurdles remain for cardiovascular MRI. Dr. Goldfarb has been developing, refining and evaluating novel methods that allow improved temporal and spatial resolution, which is needed to transform proposed methods into reliable clinical protocols. Active areas of research include contrast-enhanced angiography, myocardial viability and the development of fast imaging techniques.

Goldstein, Rita

Assistant Scientist

rgoldstein@bnl.gov

Summary : In this study of the brain-behavior mechanisms that underlie drug addiction, I place a special emphasis on the role of the prefrontal cortex and the mesocortical and mesolimbic dopamine brain circuits in the impaired ability to change ongoing behavior (willed-behavior) in response to an emotionally salient feedback. This intricate study of the interaction between brain and behavior incorporates the interrelated yet distinct research disciplines of neuroimaging, cognitive neuroscience, and neuropsychology. My research embraces this multidisciplinary approach, translating into patient-oriented clinical research settings the principles of non-invasive techniques to measure brain function such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), event-related potential (ERP) recordings, and neuropsychology.

Hainfeld, James F.

hainfeld@bnl.gov

Summary : James Hainfeld develops organometallic cluster compounds to be used as high resolution molecular labels. These heavy metal clusters are covalently attached to peptides, antibodies, other proteins, nucleic acids, carbohydrates or lipids to map sites of macromolecules or complexes for visualization in the Scanning Transmission Electron Microscope (STEM). Such clusters have been useful in studying the proteasome, pyruvate dehydrogenase enzyme complex, actin filaments, viruses, blood clotting components, nuclear proteins, and other structures. Use of clusters in anomalous X-ray scattering or for isomorphous replacements is being investigated also. Gold, platinum, palladium, silver, iridium, and other metal clusters have been synthesized. Recently, gold clusters having Nickel-NTA for binding 6x-His tagged proteins, gold-liposomes, gold-cluster-ATP, and giant platinum clusters have been studied. Dr. Hainfeld also founded Nanoprobes, Inc., a bio-nanotechnology biotech company, and serves as the CEO. Nanoprobes researches and develops organometallic nanoparticles for use in biomedical and material science applications. for more information see: www.biology.bnl.gov/stem/stem.html and www.nanoprobes.com

Harrington, Donald

Professor

Donald.Harrington@sunysb.edu

Summary : In 1991, Donald Harrington joined Stony Brook's Department of Radiology as a professor and University Hospital as radiologist-in-chief. Previously, he had taught at Johns Hopkins University School of Medicine and Harvard Medical School. Harrington's major research interests include Magnetic Resonance Imaging in medicine; telecommunications of imaging and data for patient care and medical teaching; and medical image processing. He has published his findings in over 100 journals, including Radiology, the American Journal of Cardiology, the Johns Hopkins Medical Journal, the Annals of Thoracic Surgery, Surgery, Applied Radiology, and many others. He is also an associate editor of Cardiovascular and Interventional Radiology and a reviewer for the American Journal of Roentgenology.

Kaufman, Arie E.

Professor

Arie.Kaufman@sunysb.edu

Summary : Arie Kaufman is the director of the Center of Visual Computing (CVC) and the director of the Cube project for volume visualization supported by the National Science Foundation, Department of Energy, Office of Naval Research, Hughes Aircraft Company, Hewlett-Packard Company, Silicon Graphics Company, Howard Hughes Medical Institute, and many others. His research interests include computer graphics and specifically computer graphics architectures, algorithms, and languages; visualization including volume visualization and scientific visualization; user interfaces; virtual reality; and multimedia. Kaufman is the editor-in-chief of the IEEE Transaction on Visualization and Computer Graphics. He has lectured widely and published numerous technical papers in these areas, including the IEEE tutorial book on Volume Visualization. He has been the papers chair and program cochair for Visualization 1990-1994 and the chairman of the IEEE CS Technical Committee on Computer Graphics.

Liang, Jerome Z.

Professor of Radiology, Computer Science, and Physics

jzl@mil.sunysb.edu

Summary : Jerome Liang focuses his attention on the development of quantitative SPECT systems, 3D virtual endoscopy, and computer aided diagnosis. This work includes creating a quantitative SPECT imaging modality as a cost-effective means for patient diagnosis as well as developing a high resolution PET as a functional research imaging modality. Liang is also striving to create a virtual colonoscopy as a cost-effective procedure for colon screening and to construct an automatic method for brain-tissue segmentation for diagnosis of disorders. In addition, he plans to build various models, in terms of physics, mathematics, and statistics, to simulate the practical problems above and then to validate the models by experiments. Liang has published his findings in journals such as Magnetic Resonance Medicine.

Lin, Wei

Research Assistant Professor

Wei.Lin@sunysb.edu

Summary : Embedded system is the key component of a medical instrument. It is a computer system that performs specific measurement and control functions within a device. It can be a complete computer system on a single circuit board running real time operating system or a miniature system using a microcontroller. Recently, Field Programmable Array (FPGA) has become a versatile integrated circuit component that can be programmed to perform specific functions in hardware. This allows us to build multiple computing cores on one chip for deterministic parallel processing. Our lab is specialized in the development of embedded systems for medical applications. We use LabVIEW from National Instrument extensively for system integration and the development of real time systems with FPGA technology. One of our research focuses is the development of a low cost wireless platform for hospital patient care and home healthcare. The system includes a patient portable unit that can perform measurements of the patient vital signs and send the patient data wirelessly and securely to the data gateway. The data can be forwarded through internet to data center such as electronic health record (EHR) for analysis and review by physicians. The system will provide mobility to non-critical patients, enhance the efficiency of healthcare professionals and reduce the overall healthcare cost.

Liu, Jonathan

Assistant Professor

Jonathan.Liu@stonybrook.edu

Summary : Our laboratory develops biomedical optical devices for diagnostics and therapy. Examples include miniature microscopes for real-time optical biopsy of living tissues, as well as spectral imaging devices for in vivo molecular screening of disease biomarkers. Our projects are multi-disciplinary and collaborative, involving the development of advanced optical instrumentation, the use of molecularly-targeted contrast agents, the validation of technologies with preclinical animal models and tissue culture, as well as the translation of devices into the clinic.

Logan, Jean

Scientist

Summary : Jean Logan has worked in the positron emission tomography (PET) group at BNL since her post-doctoral in theoretical chemistry. Her research interests are primarily the kinetic modeling of data from PET experiments. PET measures radioactivity concentration in tissue after the introduction of a radiotracer. The PET group has developed radiotracers for a number of brain receptors (for example the dopamine D2 receptor, the dopamine transporter, the norepinephrine transporter) and enzymes (monoamine oxidase A and B which occur in the brain as well as in many peripheral organs). Since PET measures the total radiotracer concentration in the tissue it is necessary to separate the tissue accumulation due to functioning receptor etc. from other processes such as tracer delivery via blood flow. She developed a simple technique for analyzing PET data extracting information related to available receptor concentration that is frequently used in PET research today.

Mueller, Klaus

mueller@cs.sunysb.edu

Summary : Klaus Mueller's areas of interest are medical, scientific and information visualization, visual analytics, medical imaging, computer graphics, virtual and augmented reality, and high-performance computing. He has pioneered the use of programmable commodity graphics hardware boards (GPUs) for the acceleration of a wide variety of computer tomographic (CT) reconstruction algorithms and medical physics phenomena. Applications include diagnostic imaging, radiotherapy, electron microscopy, ultrasound tomography for breast mammography, and others. In the visual analytics area he works on devising new high-dimensional data visualization frameworks and combining them with statistical pattern recognition and machine learning to create intuitive interactive analytical reasoning environments for medical professionals. He is also working towards a comprehensive visual data mining environment for neuroscientists, called BrainMiner, to enable a more targeted and experiential derivation of brain functional models from large collections of knowledge and data.

Mujica-Parodi, Lilianne

Assistant Professor

lmujicaparodi@gmail.com

Summary : The Laboratory for the Study of Emotion and Cognition (LSEC) performs clinical research on the neurobiology of emotional arousal, and its effects on physiology and cognition. LSEC studies provide simultaneous measurement of neural, cardiac, endocrine, cognitive, immune, genetic and clinical components of the human emotional response. These data are then analyzed using statistics, system identification, and complex systems analyses adapted from control systems engineering to develop data-driven modeling and simulations with wide-ranging applications. LSEC performs integrative multi-disciplinary research on areas as diverse as: the neurobiological etiology, diagnosis, and treatment of schizophrenia and other mental illnesses; factors responsible for and predictive of individual variability among healthy individuals in their vulnerability and resilience to chronic and acute high-stress environments; the impact of high-stress environments on cognitive processing, pre-attentive sensorimotor gating, and strategic decision-making; functional and anatomical connectivity in fMRI, and the biochemistry/physiological effects of human alarm pheromones.

Pan, Yingtian

Professor

Yingtian.Pan@sunysb.edu

Summary : 2D and 3D cross-sectional optical imaging of biological tissue at close to cellular resolution (e.g., 10um) and at depths of 1-3mm can have significant impacts on noninvasive or minimally invasive clinical diagnosis of tissue abnormalities, e.g., tumorigenesis. Laser scanning endoscopes, based on optical coherence tomography (OCT), have been developed and tested on a wide variety of tissues both ex vivo and in vivo. Encouraging results based on animal and human studies show that LSE can provide morphological details correlated well with excisional histology, suggesting its potential for optical biopsy or optically guided biopsy to reduced negative biopsies in clinical practice. Current research of Dr. Pan’s lab is focused on early-stage epithelial cancer detection, diagnosis of cartilage injury and healing, and assessment of engineering tissue growth. In addition, Dr. Pan’s lab studies skin dehydration, geriatric incontinence and laser/biochemical attack to the eye using OCT and light microscopy.

Qin, Yi-Xian

Professor

Yi-Xian.Qin@sunysb.edu

Summary : Early diagnostic of osteoporosis allows for accurate prediction of fracture risk and effective options for early treatment of the bone disease. A new ultrasound technology, based on focused transmission and reception of the acoustic signal, has been developed by Dr. Qin and his team which represents the early stages of development of a unique diagnostic tool for the measure of both bone quantity (density) and quality (strength). These data show a strong correlation between non-invasive ultrasonic prediction and micro-CT determined bone mineral density (r>0.9), and significant correlation between ultrasound and bone stiffness (r>0.8). Considering the ease of use, the non-invasive, non-radiation based signal, and the accuracy of the device, this work opens an entirely new avenue for the early diagnosis of metabolic bone diseases.

Sitharaman, Balaji

Assistant Professor

Balaji.Sitharaman@sunysb.edu

Summary : Our laboratory seeks to integrate advances in nanoscience and technology with the biological sciences and clinical medicine to achieve significant advances in simultaneous molecular diagnostics and therapeutics (theragnosis), drug delivery, and bioengineering. Towards these ends, our research interests involve a multidisciplinary approach for the development of functional (electronic, optical, magnetic, or structural) bionanosystems as contrast agents for molecular imaging, as carriers for drug delivery, and as structural scaffolds for tissue engineering. Our current projects capitalize on the unique properties of carbon nanobiomaterials to develop a) advanced contrast agents (CAs) for molecular magnetic resonance imaging (MRI), b) nanocomposites to improve the physical and biological (osteoconduction and osteoinduction) properties of polymer scaffolds for bone tissue engineering and c) non-viral vectors for gene transfection. We have exploited the potential of Gd-based carbon nanostructures: Gd@C60 metallofullerenes (gadofullerenes) and Gd@Ultrashort-tubes (gadonanotubes) as a new generation of advanced CAs for MRI and shown them to have efficacies up to 100 times greater than current clinical CAs. Our recent studies show that they are particularly well suited for passive (magnetic labels for cellular MRI) and active (pH sensitive probes for cancer detection) MRI-based Molecular Imaging. Single-walled carbon nanotubes (SWNTs) have been proposed as the ideal foundation for the next generation of materials due to their excellent mechanical properties. We have dispersed SWNTs and ultra short SWNTs into fumarate-based polymers to form nanocomposite scaffolds that exhibit mechanical properties far superior to the polymers alone and are osteoconductive as well osteoinductive. Our research work involves material synthesis techniques, physico-chemical characterization techniques, tissue culture and in vivo studies.

Thanos, Panayotis (Peter) K.

Assisant Professor

thanos@bnl.gov

Summary : "Gene therapy and dopaminergic mechanisms of alcohol and drug abuse Funded by NIDA, NIAAA and DOE # The role of dopamine and its receptors on alcohol, drug abuse and obesity using animal models (knockout mice, rats). -Developing gene therapy techniques for treatment of these addictions. -microPET imaging of the rodent brain treated with gene therapy -Correlating these findings with clinical studies on alcoholism, drug abuse and obesity)"

Vaska, Paul

Professor and Scientist

vaska@bnl.gov

Summary : Medical imaging techniques have undergone substantial growth in recent years, in both the research and clinical arenas. The standard anatomical imaging modalities of computed tomography (CT) and magnetic resonance imaging (MRI) have been complemented by quantitative functional approaches like positron emission tomography (PET) and single photon emission computed tomography (SPECT). Our lab develops new instrumentation and processing techniques not only to enhance the functional capabilities of PET, but also to combine it with synergistic modalities such as MRI to provide unprecedented, multidimensional information for cancer diagnosis, brain research, and many other applications. We have developed a miniaturized brain scanner for rodents (RatCAP) which avoids the potentially confounding effects of general anesthesia in rat brain studies, and even allows for the simultaneous study of behavior along with neurochemistry by PET. We have also developed new approaches for very high spatial resolution in PET, including a solid-state imager using cadmium zinc telluride (CZT) which achieves sub-mm resolution, and a monolithic scintillator detector with depth-encoding capability via a novel maximum likelihood positioning algorithm. And we have developed multiple imaging systems for simultaneous imaging with PET and high-field MRI, including a rodent brain scanner, a whole-body rodent system, and a prototype clinical breast imager. The research encompasses the development of new detector materials and concepts, low-noise microelectronic signal processing, high-throughput data acquisition methods, Monte Carlo simulation, and new data processing techniques to optimize the extraction of quantitative information from the PET data.