Positron Emission Tomography (PET) enables investigators to measure a wide range of in vivo physiology in human beings and laboratory animals with a non-invasive research tool. PET imaging research at Yale focuses on the development and applications of new tracer kinetic modeling methods and algorithms for PET image reconstruction and image quantification. PET radiochemistry research concentrates primarily on the development of new short half-lived radiopharmaceuticals and applying them towards investigation of biochemical transformations and drug mechanisms in primates and humans.
PET is a non-invasive diagnostic scanning technique that provides researchers and clinicians with visual images of organ function. PET scans can detect biochemical changes in body tissues before structural damage occurs from disease. This information allows clinicians to be proactive in their treatments and enables researchers to detect early biomarkers of disease that can aid diagnosis and advance drug development.
Our research uses PET as a tool to measure a wide range of in vivo physiology in human beings and laboratory animals in a non-invasive manner. We focus on the development and applications of new tracer kinetic modeling methods and algorithms for new and existing radiopharmaceuticals, and on research in PET image reconstruction and image quantification. A primary focus of our more neurophysiological applications is the measurement of dynamic changes in neurotransmitters and occupancy of receptors. Recently, we are applying these techniques to studies in diabetes, cardiology, and oncology.
Following administration of a positron-emitting radiopharmaceutical (tracer), PET permits the direct measurement of the four-dimensional radioactivity profile throughout a 3D object over time. Depending on the characteristics of the tracer, physiological parameters can be estimated, such as blood flow, metabolism, and receptor concentration. These measurements can be made with subjects in different states (e.g., stimulus or drug activation), used to compare patient groups to controls, or to assess the efficacy of drug treatment.
The goal of PET tracer kinetic modeling is to devise a biologically validated, quantitatively reliable, and logistically practical method for use in human PET studies. Animal studies are typically performed to characterize the tracers, followed by initially complex human studies, typically leading to the development of simplified methods, e.g., using continuous tracer infusion. Mathematical methodology includes linear and non-linear differential equations, statistical estimation theory, methods to avoid the needs for arterial blood measurements (the input function) such as blind deconvolution, plus the development of novel rapid computational algorithms.
Proper characterization of the PET image data is essential for modeling studies. This requires accurate and carefully characterized corrections for the physics and electronics of coincident event acquisition. Studies of these effects are performed with phantom measurements made on the scanner.
A critical component in the application to real data is the correction for subject motion, particularly as the resolution of modern machines has improved (better than 3-mm in human brain machines). Both hardware and software approaches are employed to address these issues. To produce accurate images with minimum noise, a statistically-based iterative reconstruction algorithm is necessary. Developments in this area include the mathematical aspects of algorithm development, the computer science issues associated with a large cluster-based algorithm, the incorporation of the physics and motion correction, the use of prior information provided from MR images, and the tuning and characterization necessary for practical application for biological studies. The ultimate goal is the combination of the tracer kinetic modeling and image reconstruction to directly process a 4D dataset into parametric images of the physiological parameters of interest.
In whole-body applications, corrections for respiratory and cardiac motion become important. Lack of correction for these motions will blur tumor activity and dramatically affect quantitative interpretation of cardiac uptake of tracers. Thus, full analysis of dynamic PET data can be viewed as a 6-D problem, with cardiac and respiratory cycles as the 5th and 6th dimensions.
PET neuroreceptor studies have focused on determining changes in receptor concentration as a function of disease or measurement of receptor occupancy by drugs. A more recent approach provides an estimate of changes in synaptic neurotransmitter concentration. This method determines the change in tracer binding levels after administration of behavioral or pharmacological stimuli that affect neurotransmitter levels. With careful experimental design and appropriate mathematical modeling techniques, the change in radiotracer binding can be attributed to changes in the level of synaptic neurotransmitter that competes with the radiotracer for receptor binding. Such changes have been successfully demonstrated in the dopaminergic, muscarinic, and serotonergic systems.
PET images of 11C-LSN3172176 (M1 muscarinic acetylcholine receptor) under baseline and blocking conditions, used identify the appropriate kinetic model for quantifying tracer binding.
Our research focuses on the synthesis, preclinical evaluation, and clinical translation of radiopharmaceuticals used to investigate biochemical processes, disease targets, and the action of therapeutic drugs. We develop PET imaging radiopharmaceuticals to study neurotransmitter systems in neuropsychiatric and neurodegenerative diseases and extend our studies to oncology and cardiology applications. We produce radiotracers for targeting proteins, receptors, and transporters like SV2A, opioid and serotonin receptors, and more. Collaborating with academic and industrial partners, we create radiopharmaceuticals for research in various medical fields, support clinical trials, and use PET imaging for disease diagnosis, patient selection, and treatment monitoring.
The National Institute of Mental Health (NIMH) has funded a grant to support the development of PET radioligands to probe high-priority molecular targets implicated in mental illness. (U01MH107803). See more details on our Mental Health PET Radioligand Development (MHPRD) Program page
Vice Chair for Scientific Research, Director PET Center
Elizabeth Mears and House Jameson Professor of Radiology and Biomedical Imaging, Therapeutic Radiology and of Biomedical Informatics & Data Science; Director, PET Center; Vice Chair Scientific Research, Radiology & Biomedical Imaging
Associate Director of PET Center, Director of PET Chemistry
Professor of Radiology and Biomedical Imaging; Director of Radiochemistry, PET Radiochemistry
Director of the PET Core
Associate Professor of Radiology and Biomedical Imaging; Director, Yale PET Core, Radiology & Biomedical Imaging
Associate Research Scientist in Radiology and Biomedical Imaging
Assistant Professor of Radiology and Biomedical Imaging
Associate Professor of Radiology & Biomedical Imaging and of Pharmacology
Professor of Radiology and Biomedical Imaging and of Biomedical Engineering; Director of Graduate Studies, Biomedical Engineering
Associate Professor of Radiology and Biomedical Imaging; Co-Medical Director, Yale University PET Center
Professor of Psychiatry and of Neuroscience and of Radiology and Biomedical Imaging; Co-Director of the T32 Translational Alcohol Research Program, Psychiatry and Public Health
Professor of Psychiatry; Director, Molecular Imaging Program, NCPTSD, VA; Director, Mood, Anxiety, and Cognitive Sciences Division
Research Scientist in Radiology and Biomedical Imaging
Associate Professor Adjunct; Associate Director of Imaging, Positron Emission Tomography (PET)