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Supplement for Development and Translation of Specialized Hyperpolarized C-13 MRI Methods for Alzheimer's Disease

Award Number: U01EB026412
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Supplement for Development and Translation of Specialized Hyperpolarized C-13 MRI Methods for Alzheimer's Disease - Project Summary/Abstract The parent Bioengineering Research Partnership has been highly successful over the past 8 years in developing quantitative, hyperpolarized (HP) stable-isotope MR molecular imaging approaches for monitoring prostate cancer metabolic reprogramming and response to therapy in a fast 2-minute addition to standard mpMRI exams. Our Alzheimer’s Disease (AD) colleagues now want to take advantage of the unique HP MRI measurements of cerebral energy metabolism that is critical for brain function and known to decrease with AD onset. This project has been developed by our AD multidisciplinary team to develop HP pyruvate and urea MRI as a quantitative imaging approach to probe cerebral perfusion and metabolic impairment in AD and related dementias that are a growing public health concern with tremendous impact on patients and their families. Efforts to effectively treat AD are partially confounded by different hypotheses regarding its initiation and progression, as reflected by the range of imaging methods used to study AD, including positron emission tomography (PET) and magnetic resonance imaging (MRI). Dysfunctional glucose metabolism is strongly linked to AD as both an early and critical determinant of disease progression, and the glucose derivative [18F]Fluorodeoxyglucose (FDG) has been widely used to probe cerebral metabolism in AD patients. While this may reflect a decrease in glucose demand, it only informs on uptake and does not provide accurate information on glycolytic metabolism that decreases with AD. Furthermore, FDG-PET has significant limitations in accessibility, cost, and accuracy, and provides no information on metabolic processes downstream of glucose uptake and phosphorylation. The central goal of this supplement proposal is to develop and apply methods of measuring impaired metabolism in AD for the first time using advanced HP C-13 MRI. HP pyruvate MRI is an emerging molecular imaging method that provides dynamic and pathway-specific metabolic information not available with FDG-PET. In the parent BRP, we have developed methods to greatly improve the coverage, speed, and reliability of HP metabolic imaging and techniques to co-polarize pyruvate and urea to simultaneously assess metabolism and perfusion in the prostate. This supplement is designed to extend this approach to measure metabolic impairment in AD. Specialized techniques will be developed to acquire co-polarized data using [2-13C]pyruvate and [13C]urea, providing simultaneous assessment of perfusion, glycolysis, and oxidative metabolism in the human brain. These techniques will then be applied to an initial cohort of patients with mild cognitive impairment (MCI) due to AD and compared to age-matched controls to assess the magnitude of metabolic changes in AD. The data from this pilot project will form the foundation for larger studies to evaluate HP 13C MRI as a tool for clinical assessment and treatment of AD and will have broad applicability for metabolic assessment of other neurogenerative diseases.


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: 2023 ( Subtotal = $1,605,651 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	5	2/24/2023	NON-COMPETING CONTINUATION	$0
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	002	5	5/24/2023	SUPPLEMENT FOR EXPANSION	$403,750
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	5	2/20/2023	NON-COMPETING CONTINUATION	$1,201,901
														Subtotal = $1,605,651

Issue Date FY: 2022 ( Subtotal = $1,241,556 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	002	4	8/3/2022	NON-COMPETING CONTINUATION	$120,336
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	4	3/16/2022	SUPPLEMENT FOR EXPANSION	$38,229
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	4	3/14/2022	NON-COMPETING CONTINUATION	$1,082,991
														Subtotal = $1,241,556

Issue Date FY: 2021 ( Subtotal = $1,266,260 )
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	003	3	7/27/2021	SUPPLEMENT FOR EXPANSION	$85,819
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	002	3	7/26/2021	NON-COMPETING CONTINUATION	-$84,103
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	3	6/2/2021	NON-COMPETING CONTINUATION	$0
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	4/15/2021	NON-COMPETING CONTINUATION	$1,264,544
														Subtotal = $1,266,260

Issue Date FY: 2020 ( Subtotal = $1,242,247 )
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	2	9/17/2020	SUPPLEMENT FOR EXPANSION	$38,229
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	3/19/2020	NON-COMPETING CONTINUATION	$1,204,018
														Subtotal = $1,242,247

Issue Date FY: 2019 ( Subtotal = $1,215,003 )
2019	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	5/27/2019	NEW	$1,215,003
														Subtotal = $1,215,003

Grand Total All Awards = $6,570,717

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Supplement for Development and Translation of Specialized Hyperpolarized C-13 MRI Methods for Alzheimer's Disease

Award Number: U01EB026412

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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