. Positron Emission Tomography (PET) is a unique tool for investigating the living brain and is used in many research fields and clinical practice to quantify molecular components of neurotransmitter systems as well as the incorporation or metabolism of specific compounds through the injection of tracer doses of radioactively labeled molecules that bind to a brain target. Current PET scanners, however, require the subject to lie still during scanning, and can only be used in centers large enough to support such a device. Newer portable PET cameras, such as CerePETTM (Brain Biosciences, Inc.), are paving the way for a wide array of novel applications, including quantifying metabolic and neurochemical responses to environmental cues relevant to psychiatric/neurological diseases and performing PET close to sites where brain injury occurs. The device?s enhanced sensitivity over current scanners can also result in reduced required injected dose of tracer, greatly facilitating longitudinal assessments of disease progression. Portable scanners can radically transform PET applications, and developing analytic methods for data collected using these devices is critical to facilitate a broader valid use of quantitative PET. A significant limitation in the use of portable PET devices, and PET imaging in general, is the need for arterial blood sampling from the subject?s arm during scan, for current gold- standard quantification of tracer uptake and binding to the target in relation to tracer blood levels. Arterial blood sampling carries risks and is uncomfortable for the subject being imaged. Our group has been developing new methods to estimate outcome measures from PET data, including using simultaneous modeling across multiple brain regions to quantify tracers with reversible kinetics in absence of blood data or a reference region. We seek here to develop a new method to quantify the net influx rate of PET tracers with irreversible kinetics using only PET images. We will gather PET and arterial blood data in 20 healthy volunteers, who will be imaged at rest in two separate scans in two different PET cameras, A) a current PET camera (Siemens BiographTM mCT) and B) the portable CerePETTM, after a bolus infusion of [18F]fluorodeoxyglucose (18F-FDG), a tracer with irreversible kinetics that is the most widely used to quantify glucose metabolism. We propose to: 1) Develop a new tissue-based, blood-free method to quantify the net influx rate of PET irreversible tracers, and optimize it for application with short scan times, common in clinical settings; 2) Validate the method in comparison to arterial blood-based quantification using the newly collected 18F-FDG data; 3) Develop and disseminate a library of software routines for implementation of the validated method for use with current and portable PET scanners, to allow its incorporation into pipelines for analysis of brain imaging data. This method can significantly help widen the application of fully quantitative PET imaging with 18F-FDG and other tracers with irreversible kinetics, and enhance PET contribution to understanding the molecular underpinnings of brain disorders, and identifying clinically useful biomarkers.

Public Health Relevance

Positron Emission Tomography (PET) is a powerful tool for investigating the living brain and new portable PET cameras with increased sensitivity over current PET scanners are paving the way for yet unexplored PET applications, including quantification of metabolic and neurochemical responses to environmental cues relevant to psychiatric and neurological diseases, and potential for PET imaging in environments close to sites of brain injury. However a significant limitation in the use of portable PET devices, and PET imaging in general, is the need for continuous arterial blood sampling from the subject?s arm during scan, for current gold-standard quantification of tracer uptake and binding to the target in relation to tracer blood levels. Because development, validation and dissemination of quantification methods that work for imaging data acquired with both current and portable PET scanners in absence of blood sampling or a reference region are a key step to facilitate a broader valid use of quantitative PET imaging, we propose here to develop a new tissue- based, blood-free method to quantify the net influx rate of PET tracers with irreversible kinetics, validate the method using new collected [18F]fluorodeoxyglucose data, and disseminate the software routines to allow use of this method for analysis of brain imaging data acquired with current and new generation PET scanners.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
1R01EB026481-01
Application #
9577163
Study Section
Clinical Molecular Imaging and Probe Development (CMIP)
Program Officer
Zubal, Ihor George
Project Start
2018-07-15
Project End
2022-03-31
Budget Start
2018-07-15
Budget End
2019-03-31
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
New York State Psychiatric Institute
Department
Type
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032