Thursday, May 15, 2025 5/15/2025

Imaging of Joint Response to Physiological Stress with Age, Sex and in Osteoarthritis

Award Number: R01AR079431
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Imaging of Joint Response to Physiological Stress with Age, Sex and in Osteoarthritis - PROJECT SUMMARY Osteoarthritis (OA) is a leading cause of pain and disability worldwide and results in a reduced quality of life due to pain from common tasks such as walking or climbing and descending stairs. A particular challenge of OA is detection of disease at an early and reversible stage before irreversible structural damage has occurred. However, current imaging methods are performed in a static fashion and have limited sensitivity to joint function or the tissue response to loading. There is a major need to evaluate the joint response from everyday loading tasks, and how this response is altered in OA. Further, as age is a key risk factor of osteoarthritis, which predominantly affects older adults, the role of aging in tissue changes and response to loading stress is of particular interest. PET-MRI offers simultaneous evaluation of multiple early markers of OA in all joint tissues. In particular, [18F]NaF uptake can quantitatively evaluate bone metabolism, including bone perfusion and deposition of [18F] ions into the bone matrix. Further, we have observed that joint loading acutely alters the bone physiology affecting [18F]NaF uptake. This suggests that [18F]NaF uptake may be sensitive to increases in the metabolic response of bone where there is breakdown of the whole-joint unit that results in focal increases in bone loading. This project aims to develop a novel imaging “stress test”, based on [18F]NaF PET-MRI, that is able to evaluate at a single time point, both the function of the whole-joint unit after physiological joint loading and multiple early markers of OA. Our Specific Aims are to (1) develop a rapid, quantitative, dose- and time-minimized [18F]NaF PET-MRI protocol to evaluate joint function from a stair ascent/descent exercise “stress” test ; (2) evaluate [18F]NaF PET-MRI imaging to detect and characterize differences in joint function associated with age and between sexes; and (3) evaluate tissue response to loading stresses measured with PET-MRI in early OA and whether abnormal response is predictive of OA disease progression. The innovation of this project is the development of novel PET and MRI methods to assess the whole-joint response to loading and evaluation of early degenerative disease changes affecting joint function and future OA progression. The significance of this work is an imaging method that is able to rapidly assess joint function in response to physiological loads, and evaluation of how this joint response evolves with age and between genders, as well as the role of altered joint physiology in OA. This may allow us to detect early joint dysfunction at a single time point, to not only study OA pathophysiology, risk factors, and phenotypes, but also to develop targeted interventions.


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 = $513,480 )
2025	2025	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	3/10/2025	NON-COMPETING CONTINUATION	$513,480
														Subtotal = $513,480

Issue Date FY: 2024 ( Subtotal = $569,540 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	2/29/2024	NON-COMPETING CONTINUATION	$528,439
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	3	6/17/2024	NON-COMPETING CONTINUATION	$41,101
														Subtotal = $569,540

Issue Date FY: 2023 ( Subtotal = $875,771 )
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	9/8/2023	SUPPLEMENT FOR EXPANSION	$360,089
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	2/24/2023	NON-COMPETING CONTINUATION	$515,682
														Subtotal = $875,771

Issue Date FY: 2022 ( Subtotal = $392,528 )
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	4/22/2022	NEW	$392,528
														Subtotal = $392,528

Grand Total All Awards = $2,351,319

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Imaging of Joint Response to Physiological Stress with Age, Sex and in Osteoarthritis

Award Number: R01AR079431

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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