Sunday, December 21, 2025 12/21/2025

In vivo Mapping of Muscle Specific Metabolism

Award Number: R01AG071725
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2022
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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In vivo Mapping of Muscle Specific Metabolism - In vivo Mapping of Muscle Specific Metabolism ABSTRACT Phosphorus-31 magnetic resonance spectroscopy (31P-MRS) has long been the method of choice to study muscle bioenergetics in humans. 31P-MRS measures relative amounts of phosphocreatine (PCr) and adenosine triphosphate (ATP), and can be used to estimate muscle creatine kinase (CK) kinetics. During exercise, PCr, a high-energy “reserve” source of ATP, is depleted to meet transient energy demands. The rate of PCr re-synthesis after exercise is commonly used as a measure of skeletal muscle oxidative phosphorylation (OXPHOS) capacity. Studies using 31P-MRS and multiple other modalities have suggested that abnormal creatine metabolism and deficient OXPHOS may contribute to the pathophysiology of aging. In addition, it is well established that muscle groups vary with respect to these metabolic properties, and also in their response to aging. Despite its strengths, 31P-MRS has low anatomic resolution, and does not readily provide muscle group specific estimates of creatine metabolism. The currently available option for measuring muscle group specific metabolism is invasive biopsy. Thus, there is a clear unmet need for high-resolution, non-invasive strategies to assess muscle metabolism simultaneously across heterogeneous muscle groups. Our group recently introduced a new magnetic resonance imaging (MRI) technique known as the Cr-amine chemical exchange saturation transfer (CrCEST), which measures free Cr formed from PCr utilization. CrCEST provides over three orders of magnitude higher sensitivity compared to 31P-MRS and can also be used to investigate CK kinetics and muscle bioenergetics. In this proposal, we further develop and optimize the CrCEST for use in humans, by improving time resolution, characterizing reproducibility, and assessing the effects of pH. As a critical part of interrogating the optimized CrCEST technique, we will test the effects of age, sex, race and physical activity on high-resolution CrCEST in healthy adults. We expect to demonstrate muscle group specific differences in creatine metabolism and OXPHOS capacity using non-invasive techniques that were not feasible until now. Successful accomplishment of this project will i) yield quantitative imaging biomarkers of muscle creatine metabolism, lactate metabolism and OXPHOS capacity that provide anatomic specificity without the invasiveness of biopsy-based approaches; ii) provide reference data to support future studies using CrCEST signal as a non-invasive index of muscle quality in aging and other conditions, including but not limited to diabetes, muscular dystrophy, peripheral arterial disease, and genetic mitochondrial disorders. We anticipate that CrCEST (iii) will also serve as a non-invasive muscle group specific monitoring tool to evaluate response to potential therapies targeting abnormal muscle metabolism in aging, in neuromuscular disorders, and myriad other conditions. Thus, CrCEST based technologies have the potential to fill a number of important unmet needs and are expected to exert sustained impact on the field.


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: 2026 ( Subtotal = $544,236 )
2026	2026	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Aging Research	000	5	12/11/2025	NON-COMPETING CONTINUATION	$544,236
														Subtotal = $544,236

Issue Date FY: 2025 ( Subtotal = $613,849 )
2025	2025	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Aging Research	000	4	12/9/2024	NON-COMPETING CONTINUATION	$563,738
2025	2025	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Aging Research	001	4	8/12/2025	NON-COMPETING CONTINUATION	$50,111
														Subtotal = $613,849

Issue Date FY: 2024 ( Subtotal = $626,376 )
2024	2024	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Aging Research	000	3	12/1/2023	NON-COMPETING CONTINUATION	$563,738
2024	2024	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Aging Research	001	3	5/10/2024	NON-COMPETING CONTINUATION	$62,638
														Subtotal = $626,376

Issue Date FY: 2023 ( Subtotal = $636,606 )
2023	2023	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Aging Research	000	2	1/19/2023	NON-COMPETING CONTINUATION	$636,606
														Subtotal = $636,606

Issue Date FY: 2022 ( Subtotal = $644,539 )
2022	2022	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Aging Research	000	1	1/21/2022	NEW	$644,539
														Subtotal = $644,539

Grand Total All Awards = $3,065,606

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In vivo Mapping of Muscle Specific Metabolism

Award Number: R01AG071725

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/2022

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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