Simultaneous PET MR is a new imaging modality that offers clear advantages over previous technologies for the mapping of neurotransmitter release. Theoretical analyses, as well as preliminary studies in nonhuman primates, support the hypothesis that sensitivity for detection and quantitative measurement will be can be significantly improved allowing us to extend the range of research questions which can be asked and answered. In this application we propose further development of the methodology, experimental validation, and proof-of-principal studies in depressed patients. In our currently funded R21 application, we proposed that changes in MR measurements blood volume elicited by specific pharmacological challenges were functions of time-varying neurotransmitter levels. Preliminary work with amphetamine and dopamine receptor blockade supports and extends that idea. The dopamine system is but one example of what we postulate is a more general approach, which in this application includes the serotonergic system. We hypothesize that concurrent PET and fMRI will yield synergistic data that, combined with our kinetic analysis methods, can dramatically improve our ability to detect and quantify the spatiotemporal patterns of serotonergic and dopaminergic neurotransmission in the brain. Our interdisciplinary team puts forth an application encompassing technical development and psychiatric investigation in which we propose to refine our kinetic modeling methods, develop methods to quantitatively integrate fMRI and PET data, and assess the translational value of these methods to study dopamine and serotonin transmission in clinical depression.

Public Health Relevance

The goals of the proposed research program are to extend methods for mapping neurochemical signaling in the brain and to apply these imaging techniques toward the study of the neurobiological underpinnings of depression. Approaches will be refined and validated to integrate the molecular specificity of positron emission tomography (PET) with the sensitivity and temporal resolution of functional magnetic resonance imaging (fMRI) with an eye toward use in the burgeoning generation of hybrid PET/MR scanners. Our new neuroimaging procedures and analysis routines will be used to investigate deficits in dopamine and serotonin signaling in subpopulations of depressed patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH100350-05
Application #
9265515
Study Section
Neuroscience and Ophthalmic Imaging Technologies Study Section (NOIT)
Program Officer
Rumsey, Judith M
Project Start
2013-04-09
Project End
2018-03-31
Budget Start
2017-04-01
Budget End
2018-03-31
Support Year
5
Fiscal Year
2017
Total Cost
$400,361
Indirect Cost
$158,537
Name
Massachusetts General Hospital
Department
Type
Independent Hospitals
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02114
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