Richard Carson, PhD

Professor of Radiology and Biomedical Imaging and of Biomedical Engineering; Director, Yale PET Center; Director of Graduate Studies, Biomedical Engineering

Research Departments & Organizations

Radiology & Biomedical Imaging: Bioimaging Sciences: Positron Emission Tomography (PET): PET Radioligand Development for Mental Health (PRDMH)

Alzheimer's Disease Research Center (ADRC)

Diabetes Research Center

Neuroscience Research Training Program (NRTP)

Stress & Addiction Clinical Research Program

Yale Cancer Center: Radiobiology & Radiotherapy

Office of Cooperative Research

Research Interests

Biomedical Engineering; Nuclear Medicine; Physiology; Positron-Emission Tomography; Radiology

Research Summary

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 synaptic density in a wide range of neuropsychiatric disorders.

Specialized Terms: 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

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 Applications

PET studies are performed in human subjects and preclinical models of a wide variety of diseases. Examples of interest include:

  • Synaptic density imaging in the living human brain (See Science Translational Medicine, 2016)
  • Measuring beta cells in the pancreas for diabetes with novel tracers including ligands for the vesicular monoamine transporter
  • Using PET to measure drug delivery in cancer
  • 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.
  • 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
  • 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 preclinical and clinical applications in oncology

Clinical Trials

Conditions Study Title
Addictive Behaviors, Alcohol Addiction, Diseases of the Nervous System, Mental Health & Behavioral Research, Tobacco Addiction Imaging the Neurochemistry of Drug Addiction With PET
Diseases of the Nervous System, Mental Health & Behavioral Research Examination of Glutamate and mGluR5 in Psychiatric Disorders
Diseases of the Nervous System, Mental Health & Behavioral Research C4 Gene Dose Effects using 11C-UCB-J PET
Mental Health & Behavioral Research Imaging 11B-hydroxysteroid dehydrogenase availability in vivo
Mental Health & Behavioral Research, Alzheimer's Disease Synaptic Density PET tracer evaluation
Mental Health & Behavioral Research Vitamin D as a Therapeutic Adjunct in the Stimulant Treatment of ADHD
Mental Health & Behavioral Research Imaging Microglial Activation in PTSD wITH PET
Diseases of the Nervous System Imaging pancreatic beta-cells with PET neuroimaging agent 11C-PHNO
Mental Health & Behavioral Research Imaging mGluR5 and synaptic density in psychiatric disorders
Lung An Exploratory Study of the Biologic Effects and Biomarkers of Nivolumab in Combination With Ipilimumab in Subjects With Treatment-Naive Stage IV or Recurrent Non-Small Cell Lung Cancer (NSCLC)
Mental Health & Behavioral Research Imaging SV2A in mood disorders
Lung Low-Dose PET/CT for Imaging Small Lung Nodules
Tobacco Addiction Imaging sex differences in smoking-induced dopamine release via novel PET methods
Diseases of the Nervous System, Mental Health & Behavioral Research SV2A PET Imaging in Healthy Subjects and Epilepsy Patients
Addictive Behaviors PET Imaging of mGLuR5 With Drug Challenge
Mental Health & Behavioral Research Translational Neuroscience Optimization of GlyT1 Inhibitor (NCATS)
Mental Health & Behavioral Research, Tobacco Addiction Acetylcholine, Tobacco Smoking, Genes and Nicotinic Receptors (nic_physo)
Mental Health & Behavioral Research Glutamate-Glutamine Cycling (VCYC) During Cocaine Abstinence Using 13C-MRS

Activities

  • PET-RTRC External Advisory Board St. Louis, United States (2018)

    NIBIB Biomedical Technology Resource Center (P41), “PET Radiotracer Translation and Resource Center” External Advisory Board-Member

  • Helmholtz-Zentrum Dresden-Rossendorf Dresden, Germany (2017 - 2017)

    Scientific review panel

  • Dementias Platform UK MR-PET scientific advisory board Manchester, United Kingdom (2016)

  • EPSRC Centre for Mathematical and Statistical Analysis of Multimodal Clinical Imaging Cambridge, United Kingdom (2015)

    Scientific Advisory Board

  • NUS CIRC Scientific Advisory Board Singapore, Singapore (2012 - 2018)

    Member, Scientific Advisory Board, National University of Singapore Clinical Imaging Research Centre

  • EURIPIDES London, United Kingdom (2008 - 2011)

    Member of scientific advisory board for European Research initiative to develop Imaging Probes for early In-vivo Diagnosis and Evaluation of response to therapeutic Substances

Selected Publications

See list of PubMed publications

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