Richard E Carson PhD
Professor of Diagnostic Radiology and of Biomedical Engineering; Director, Yale PET Center; Director of Graduate Studies, Biomedical Engineering
Positron emission tomography (PET) modeling and physics; Tracer kinetic modeling methods and parametric imaging techniques for PET tracers; Application of receptors ligands to assess neurotransmitter dynamic; 3D and 4D PET image reconstruction; Medical imaging
- Awake nonhuman primate PET imaging
- 4D/5D Image reconstruction for PET
- Mathematical model development for novel radiopharmaceuticals
- Imaging of beta cells in the pancreas
- Neuroinflammation imaging in a wide variety of disorders
- Novel prelcinial and clinical applications in oncology
- Synaptic density imaging
Dr. Richard Carson's research uses Positron Emission Tomography (PET) as a tool to noninvasively measure a wide range of in vivo physiology in human beings and laboratory animals. His focus is on the development and applications of new tracer kinetic modeling methods and algorithms and on research in PET image reconstruction and image quantification. These quantitative techniques are then applied in clinical populations and preclinical models of disease. Application areas include neuropsychiatric populations, diabetes, cardiology, and oncology. A primary focus of his more biological applications is the measurement of dynamic changes in neurotransmitters.
Extensive Research Description
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.
Tracer Kinetic Modeling
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. These techniques are also applied on a pixel-by-pixel level to produce images of PET physiological and pharmacological parameters, such as blood flow and receptor binding. 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.
PET Physics and Reconstruction.
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. When applied in the thorax, respiratory and cardiac motion must be included, raising the problem to 5D and 6D analysis.
PET studies are performed in human subjects and preclinical models of a wide variety of diseases. Examples of interest include:
- Measuring beta cells in the pancreas for diabetes with a tracer for the vesicular monoamine transporter
- Neuroreceptor studies have focused on determining changes in receptor concentration as a function of disease or measurement of receptor occupancy by drugs. Such changes have been successfully demonstrated in the dopaminergic, muscarinic, and serotonergic systems.
- Development of awake nonhuman primate PET imaging for various neuroreceptor investigations
- Assessment of spinal cord injury and repair with a serotonin transporter ligand.
- Measurement of the relationship between dopamine receptors and impulsivity
- New methods for quantification of myocardial blood flow
- Hypoxia assessment in tumors before and after radiation treatment
- Differentiation of radiation necrosis vs. tumor recurrence
- Imaging synaptic density