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Simultaneous Multi-Tracer Positron Emission Tomography for Interrogating Molecular Pathways of Neurological Disorders

Award Number: F31CA265205
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 03/23/2023
PERIOD OF PERFORMANCE END DATE: 06/08/2026

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Simultaneous Multi-Tracer Positron Emission Tomography for Interrogating Molecular Pathways of Neurological Disorders - Project Summary/Abstract Positron emission tomography (PET) is a method of medical imaging that employs positron emitting radionuclides attached to probe molecules (tracers) for non-invasively interrogating biological processes in vivo. Each radionuclide decay emits a positron, which then combines with an electron and creates two oppositely directed, colinear 511 keV annihilation photons. These annihilation photons are detected in opposing elements of a photon detector ring forming lines of response (LOR) along which each positron emission originated. After collecting millions of such photon pair events and positioning them along system LORs, an image can be reconstructed to visualize and quantify the 3D distribution of tracer probe molecules within the body. Up to now, PET systems detect only one tracer per study. However, more complete understanding of the disease biology often requires the study of multiple biological processes simultaneously. Alzheimer’s Disease specifically is characterized by presence of neuroinflammation, β-amyloid, phosphor-τ, and neurodegeneration. This project aims to enable simultaneous imaging of multiple tracers by strategically choosing at least one PET tracer that emits gamma photons in cascade with their positron. These gamma photons can be differentiated from annihilation photons through their higher energy measured by the photon detector. Thus, LORs can be associated with this positron + gamma tracer when a high energy photon arrives nearly the same time as a pair of 511 keV photons. Challenges associated with using prompt gamma emitters come from the lower probability of detecting both the annihilation photons and gamma photon within the appropriate timing and energy windows. Another challenge associated with using multiple tracers is misclassification of events among tracers due to missed, tissue scattered, or random photons detected. Low detection efficiency and misclassification will reduce image quality and accuracy of the associated multi-tracer images; thus, methods must be developed to mitigate these issues. This project proposes to develop and characterize a position-sensitive endcap detector that will cover the open end of an existing PET ring system to increase the detection efficiency for 3-photon events through increasing the solid angle coverage of the system photon detectors. Signal processing algorithms will also be employed using multiple temporal and energy windows to mitigate misclassification of photons coming from the two emitters in addition to compensating for sensitivity differences between two- and three-photon emitters. These techniques will include use of delayed time windows to estimate the different random coincidence rates and joint maximum likelihood estimation of coincidence events based on system geometry. We will also use deep learning to improve the image quality of the low dose images and to accurately separate the images obtained. Through these techniques, this project aims to develop the first system capable of simultaneous multi-tracer PET imaging.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $42,139 )
2025	2025	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Research Manpower	000	3	5/19/2025	NON-COMPETING CONTINUATION	$42,139
														Subtotal = $42,139

Issue Date FY: 2024 ( Subtotal = $42,139 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Research Manpower	001	2	5/7/2024	NON-COMPETING CONTINUATION	$1,430
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Research Manpower	002	2	6/11/2024	NON-COMPETING CONTINUATION	$0
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Research Manpower	000	2	2/26/2024	NON-COMPETING CONTINUATION	$40,709
														Subtotal = $42,139

Issue Date FY: 2023 ( Subtotal = $57,219 )
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Research Manpower	002	1	3/15/2023	NEW	$0
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Research Manpower	001	1	3/15/2023	NEW	$791
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Research Manpower	000	1	2/16/2023	NEW	$56,428
														Subtotal = $57,219

Grand Total All Awards = $141,497

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Simultaneous Multi-Tracer Positron Emission Tomography for Interrogating Molecular Pathways of Neurological Disorders

Award Number: F31CA265205

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 03/23/2023

PERIOD OF PERFORMANCE END DATE: 06/08/2026

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