Richard E. Carson

Professor of Biomedical Engineering & Radiology and Biomedical Imaging
Room / Office: LMP 89A
Office Address:
801 Howard Avenue
New Haven, CT 06519
Mailing Address:
P.O. Box 208048
New Haven, CT 06520
Phone: (203) 737-2814
Fax: (203) 785-3107

Ph.D., University of California at Los Angeles


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.

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.

These issue are now all being taken to the next level for the building and optimization of the NeuroEXPLORER (a.k.a. NX), which will have 10-fold higher sensitivity than the previous state-of-the-art HRRT. This system, scheduled to arrive at Yale late in 2022 will open new vista for brain PET investigations.

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

  • Develop the highest resolution and sensitivity human brain PET system (U01EB029811)
  • Synaptic density imaging in the living human brain (See Science Translational Medicine, 2016 and subsequent clinical and preclinical paper)
  • 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

Selected Publications:

  • Finnema SJ, Nabulsi NB, Eid T, Detyniecki K, Lin SF, Chen MK, Dhaher R, Matuskey D, Baum E, Holden D, Spencer DD, Mercier J, Hannestad J, Huang Y, Carson RE. Imaging synaptic density in the living human brain. Science Translational Medicine 2016, 8: 348ra96. PMID: 27440727, DOI: 10.1126/scitranslmed.aaf6667.
  • Hooker JM, Carson RE. Human Positron Emission Tomography Neuroimaging. Annual Review Of Biomedical Engineering 2019, 21: 551-581. PMID: 31167104, DOI: 10.1146/annurev-bioeng-062117-121056.
  • Finnema SJ, Toyonaga T, Detyniecki K, Chen MK, Dias M, Wang Q, Lin SF, Naganawa M, Gallezot JD, Lu Y, Nabulsi NB, Huang Y, Spencer DD, Carson RE. Reduced synaptic vesicle protein 2A binding in temporal lobe epilepsy: A [11 C]UCB-J positron emission tomography study. Epilepsia 2020, 61: 2183-2193. PMID: 32944949, DOI: 10.1111/epi.16653.
  • Matuskey D, Tinaz S, Wilcox KC, Naganawa M, Toyonaga T, Dias M, Henry S, Pittman B, Ropchan J, Nabulsi N, Suridjan I, Comley RA, Huang Y, Finnema SJ, Carson RE. Synaptic Changes in Parkinson Disease Assessed with in vivo Imaging. Annals Of Neurology 2020, 87: 329-338. PMID: 31953875, PMCID: PMC7065227, DOI: 10.1002/ana.25682.
  • Holmes SE, Scheinost D, Finnema SJ, Naganawa M, Davis MT, DellaGioia N, Nabulsi N, Matuskey D, Angarita GA, Pietrzak RH, Duman RS, Sanacora G, Krystal JH, Carson RE, Esterlis I. Lower synaptic density is associated with depression severity and network alterations. Nature Communications 2019, 10: 1529. PMID: 30948709, PMCID: PMC6449365, DOI: 10.1038/s41467-019-09562-7.
  • Mecca AP, O'Dell RS, Sharp ES, Banks ER, Bartlett HH, Zhao W, Lipior S, Diepenbrock NG, Chen MK, Naganawa M, Toyonaga T, Nabulsi NB, Vander Wyk BC, Arnsten AFT, Huang Y, Carson RE, van Dyck CH. Synaptic density and cognitive performance in Alzheimer's disease: A PET imaging study with [11 C]UCB-J. Alzheimer's & Dementia : The Journal Of The Alzheimer's Association 2022 PMID: 35174954, DOI: 10.1002/alz.12582.
  • Chen MK, Mecca AP, Naganawa M, Finnema SJ, Toyonaga T, Lin SF, Najafzadeh S, Ropchan J, Lu Y, McDonald JW, Michalak HR, Nabulsi NB, Arnsten AFT, Huang Y, Carson RE, van Dyck CH. Assessing Synaptic Density in Alzheimer Disease With Synaptic Vesicle Glycoprotein 2A Positron Emission Tomographic Imaging. JAMA Neurology 2018, 75: 1215-1224. PMID: 30014145, PMCID: PMC6233853, DOI: 10.1001/jamaneurol.2018.1836.
  • Naganawa M, Nabulsi NB, Henry S, Matuskey D, Lin SF, Slieker L, Schwarz AJ, Kant N, Jesudason C, Ruley K, Navarro A, Gao H, Ropchan J, Labaree D, Carson RE, Huang Y. First-in-Human Assessment of 11C-LSN3172176, an M1 Muscarinic Acetylcholine Receptor PET Radiotracer. Journal Of Nuclear Medicine : Official Publication, Society Of Nuclear Medicine 2021, 62: 553-560. PMID: 32859711, PMCID: PMC8049371, DOI: 10.2967/jnumed.120.246967.
  • Toyonaga T, Smith LM, Finnema SJ, Gallezot JD, Naganawa M, Bini J, Mulnix T, Cai Z, Ropchan J, Huang Y, Strittmatter SM, Carson RE. In Vivo Synaptic Density Imaging with 11C-UCB-J Detects Treatment Effects of Saracatinib in a Mouse Model of Alzheimer Disease. Journal Of Nuclear Medicine : Official Publication, Society Of Nuclear Medicine 2019, 60: 1780-1786. PMID: 31101744, PMCID: PMC6894376, DOI: 10.2967/jnumed.118.223867.
  • Finnema SJ, Nabulsi NB, Mercier J, Lin SF, Chen MK, Matuskey D, Gallezot JD, Henry S, Hannestad J, Huang Y, Carson RE. Kinetic evaluation and test-retest reproducibility of [11C]UCB-J, a novel radioligand for positron emission tomography imaging of synaptic vesicle glycoprotein 2A in humans. Journal Of Cerebral Blood Flow And Metabolism : Official Journal Of The International Society Of Cerebral Blood Flow And Metabolism 2018, 38: 2041-2052. PMID: 28792356, PMCID: PMC6259313, DOI: 10.1177/0271678X17724947.
  • Ren S, Jin X, Chan C, Jian Y, Mulnix T, Liu C, Carson RE. Data-driven event-by-event respiratory motion correction using TOF PET list-mode centroid of distribution. Physics In Medicine And Biology 2017, 62: 4741-4755. PMID: 28520558, PMCID: PMC6048592, DOI: 10.1088/1361-6560/aa700c.
  • Germino M, Gallezot JD, Yan J, Carson RE. Direct reconstruction of parametric images for brain PET with event-by-event motion correction: evaluation in two tracers across count levels. Physics In Medicine And Biology 2017, 62: 5344-5364. PMID: 28504644, PMCID: PMC5783541, DOI: 10.1088/1361-6560/aa731f.
  • Normandin MD, Petersen KF, Ding YS, Lin SF, Naik S, Fowles K, Skovronsky DM, Herold KC, McCarthy TJ, Calle RA, Carson RE, Treadway JL, Cline GW. In vivo imaging of endogenous pancreatic β-cell mass in healthy and type 1 diabetic subjects using 18F-fluoropropyl-dihydrotetrabenazine and PET. Journal Of Nuclear Medicine : Official Publication, Society Of Nuclear Medicine 2012, 53: 908-16. PMID: 22573821, PMCID: PMC3737743, DOI: 10.2967/jnumed.111.100545.
  • Yan J, Planeta-Wilson B, Carson RE. Direct 4-D PET list mode parametric reconstruction with a novel EM algorithm. IEEE Transactions On Medical Imaging 2012, 31: 2213-23. PMID: 22929383, PMCID: PMC3660152, DOI: 10.1109/TMI.2012.2212451.
  • Innis RB, Cunningham VJ, Delforge J, Fujita M, Gjedde A, Gunn RN, Holden J, Houle S, Huang SC, Ichise M, Iida H, Ito H, Kimura Y, Koeppe RA, Knudsen GM, Knuuti J, Lammertsma AA, Laruelle M, Logan J, Maguire RP, Mintun MA, Morris ED, Parsey R, Price JC, Slifstein M, Sossi V, Suhara T, Votaw JR, Wong DF, Carson RE. Consensus nomenclature for in vivo imaging of reversibly binding radioligands. Journal Of Cerebral Blood Flow And Metabolism : Official Journal Of The International Society Of Cerebral Blood Flow And Metabolism 2007, 27: 1533-9. PMID: 17519979, DOI: 10.1038/sj.jcbfm.9600493.
  • Ichise M, Liow JS, Lu JQ, Takano A, Model K, Toyama H, Suhara T, Suzuki K, Innis RB, Carson RE. Linearized reference tissue parametric imaging methods: application to [11C]DASB positron emission tomography studies of the serotonin transporter in human brain. Journal Of Cerebral Blood Flow And Metabolism : Official Journal Of The International Society Of Cerebral Blood Flow And Metabolism 2003, 23: 1096-112. PMID: 12973026, DOI: 10.1097/01.WCB.0000085441.37552.CA.
  • Wu Y, Carson RE. Noise reduction in the simplified reference tissue model for neuroreceptor functional imaging. Journal Of Cerebral Blood Flow And Metabolism : Official Journal Of The International Society Of Cerebral Blood Flow And Metabolism 2002, 22: 1440-52. PMID: 12468889, DOI: 10.1097/01.WCB.0000033967.83623.34.
  • Ichise M, Toyama H, Innis RB, Carson RE. Strategies to improve neuroreceptor parameter estimation by linear regression analysis. Journal Of Cerebral Blood Flow And Metabolism : Official Journal Of The International Society Of Cerebral Blood Flow And Metabolism 2002, 22: 1271-81. PMID: 12368666, DOI: 10.1097/01.WCB.0000038000.34930.4E.
  • Carson RE. PET physiological measurements using constant infusion. Nuclear Medicine And Biology 2000, 27: 657-60. PMID: 11091108, DOI: 10.1016/s0969-8051(00)00138-4.
  • Carson RE, Breier A, de Bartolomeis A, Saunders RC, Su TP, Schmall B, Der MG, Pickar D, Eckelman WC. Quantification of amphetamine-induced changes in [11C]raclopride binding with continuous infusion. Journal Of Cerebral Blood Flow And Metabolism : Official Journal Of The International Society Of Cerebral Blood Flow And Metabolism 1997, 17: 437-47. PMID: 9143226, DOI: 10.1097/00004647-199704000-00009.
  • Carson RE, Channing MA, Blasberg RG, Dunn BB, Cohen RM, Rice KC, Herscovitch P. Comparison of bolus and infusion methods for receptor quantitation: application to [18F]cyclofoxy and positron emission tomography. Journal Of Cerebral Blood Flow And Metabolism : Official Journal Of The International Society Of Cerebral Blood Flow And Metabolism 1993, 13: 24-42. PMID: 8380178, DOI: 10.1038/jcbfm.1993.6.
  • Lange K, Carson R. EM reconstruction algorithms for emission and transmission tomography. Journal Of Computer Assisted Tomography 1984, 8: 306-16. PMID: 6608535.


  • Director of the Yale PET Center
  • Director of Graduate Studies, Biomedical Engineering