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Noninvasive tools for assessing muscle structure and function

Award Number: R01AR071162
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/03/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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Noninvasive tools for assessing muscle structure and function - Project Summary Changes in muscle force and stiffness underlie the control of posture and movement. These fundamental abilities are impaired in almost all movement disorders, including those resulting from stroke, cerebral palsy, musculoskeletal injury, or pain. Rehabilitation can be framed in terms of re-establishing healthy patterns of muscle force and stiffness for each patient. Consequently, a fundamental challenge in the fields of biomechanics, motor control, and physical rehabilitation has long been measuring muscle force and stiffness in health and disease, yet there are no rigorous methods for doing so noninvasively. Ultrasound shear wave elastography (SWE) was proposed as a noninvasive tool for measuring stiffness, but we have demonstrated that SWE is sensitive not only to muscle stiffness but also to force, and that these dependencies vary across muscle types. While our results call into question conclusions from many previous studies, they also suggest that SWE could be reimagined as a tool for noninvasively measuring both stiffness and force. The objective of this proposal is to evaluate this intriguing possibility, which could transform the study of human movement and guide rehabilitation protocols for numerous motor disorders. Our long-term goal is to improve treatments for musculoskeletal disorders associated with changes to muscle force or stiffness. Our central hypothesis is that muscle stiffness and force can be uniquely determined from SWE by considering the distinctive structure of muscle. Shear wave propagation is sensitive to changes in muscle stress (force normalized by cross-sectional area) and stiffness, but it remains unknown if SWE can independently measure these quantities. Aims 1 and 2 will quantify how stresses from passive lengthening and active contraction alter shear wave propagation parallel to the direction of muscle fibers, as measured by the one-dimensional ultrasound arrays currently available in clinics. Studies will be conducted in an animal model so that SWE measurements can be compared to direct measures of muscle stiffness and stress (Aim 1), before considering the complexities of several human muscles thought to have internal variations in stress (Aim 2). Finally, we will evaluate the novel technique we have developed that uses multi-directional SWE to determine muscle stress and stiffness noninvasively (Aim 3); this will occur using a combination of 3D-printed biomaterials with known mechanical properties, muscles harvested from our animal model, and human experiments to rigorously test this innovative approach and adapt it as needed to account for the unique structure of muscle. We expect that our aims will clarify precisely what is being measured by current applications of SWE to muscle and determine if a novel approach employing multidirectional SWE can be used to measure muscle force and stiffness noninvasively. Such an ability would be transformative for rehabilitation, providing quantitative assessments of the critical properties of muscle that enable human movement or contribute to its impairment.


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: 2024 ( Subtotal = $604,768 )
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	8	7/9/2024	NON-COMPETING CONTINUATION	$604,768
														Subtotal = $604,768

Issue Date FY: 2023 ( Subtotal = $678,491 )
2023	2023	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	7	6/8/2023	NON-COMPETING CONTINUATION	$678,491
2023	2022	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	6	5/31/2023	COMPETING CONTINUATION	$65,464
2023	2020	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	5/31/2023	NON-COMPETING CONTINUATION	-$65,464
														Subtotal = $678,491

Issue Date FY: 2022 ( Subtotal = $707,365 )
2022	2022	NORTHWESTERN UNIVERSITY	633 CLARK	EVANSTON	IL	60208	COOK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	6	9/3/2022	COMPETING CONTINUATION	$707,365
														Subtotal = $707,365

Issue Date FY: 2020 ( Subtotal = $565,484 )
2020	2020	NORTHWESTERN UNIVERSITY	633 CLARK	EVANSTON	IL	60208	COOK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	8/18/2020	NON-COMPETING CONTINUATION	$565,484
														Subtotal = $565,484

Issue Date FY: 2019 ( Subtotal = $606,645 )
2019	2019	NORTHWESTERN UNIVERSITY	633 CLARK ST EVANSTON	EVANSTON	IL	60208	COOK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	8/16/2019	NON-COMPETING CONTINUATION	$606,645
														Subtotal = $606,645

Issue Date FY: 2018 ( Subtotal = $626,191 )
2018	2018	NORTHWESTERN UNIVERSITY	633 CLARK ST EVANSTON	EVANSTON	IL	60208	COOK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	8/28/2018	NON-COMPETING CONTINUATION	$626,191
														Subtotal = $626,191

Issue Date FY: 2017 ( Subtotal = $571,763 )
2017	2017	NORTHWESTERN UNIVERSITY	633 CLARK ST EVANSTON	EVANSTON	IL	60208	COOK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	8/14/2017	NON-COMPETING CONTINUATION	$571,763
														Subtotal = $571,763

Issue Date FY: 2016 ( Subtotal = $597,038 )
2016	2016	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	9/7/2016	NEW	$597,038
														Subtotal = $597,038

Grand Total All Awards = $4,957,745

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Noninvasive tools for assessing muscle structure and function

Award Number: R01AR071162

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/03/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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