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Effects of in situ orientation on quantitative MR-based measures of cartilage endplate health

Award Number: F32AR081139
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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Effects of in situ orientation on quantitative MR-based measures of cartilage endplate health - Project Summary/Abstract Chronic low back pain (cLBP) is a leading cause of disability globally and is thought to relate to intervertebral disc degeneration in some patients. The cartilage endplate (CEP) plays a key role in disc health by influencing nutrient transport between the avascular disc and the vertebral capillaries. By its influence on disc nutrient supply, the CEP may also influence the efficacy of cell-based biologic therapies designed to regenerate the disc, as these therapies increase intradiscal nutrient demands. The premise of this proposal is that non-invasive assessment of CEP composition could provide insight into disc degeneration etiology and guide patient selection for cell-based biologic therapies, in turn helping to address the global health burden associated with cLBP. A novel imaging biomarker of CEP composition—the mean CEP T2* relaxation time measured using ultra- short echo time (UTE) MRI—has recently been shown to correlate with aspects of CEP composition influencing nutrient transport to the disc and the extent of disc degeneration in patients with cLBP. This non-invasive biomarker has major implications for elucidating the role of the CEP in disc degeneration/regeneration. However, the MR signal generated by the CEP depends on its in situ orientation relative in the MRI bore. Differences in T2* caused by orientation during imaging could exceed those associated with biochemical or microstructural deterioration, thus confounding accurate analysis. Without understanding the effects of orientation on CEP T2* values, researchers—and eventually clinicians—cannot accurately assess CEP composition in patients. The studies proposed here address these limitations and facilitate the development and clinical translation of MRI-based biomarkers of CEP composition independent of inter- and intra-individual anatomic variations in CEP orientation. Aim 1a will image cadaveric motion segments with UTE MRI at varying angles to develop a calibration curve for adjusting CEP T2* values based on in situ orientation. Aim 1b will test the clinical utility of this calibration curve in clinical cohorts of patients with cLBP and asymptomatic controls imaged with UTE MRI. Aim 2 will quantify the contributions of CEP microstructure and biochemical composition to inter- and intra-CEP variations in CEP T2* values, enhancing mechanistic understanding of the factors influencing CEP T2* and thus the diagnostic interpretation of UTE-based CEP biomarkers. The proposed training plan involves developing expertise in advanced techniques in MRI, biochemical and microstructural characterization of musculoskeletal tissues, mathematical and statistical modeling, and concepts in clinical medicine with a focus on cLBP. The fellowship is supported by two sponsors—Dr. Aaron Fields (primary sponsor, Department of Orthopaedic Surgery) and Dr. Roland Krug (co-sponsor, Department of Radiology)—who have deep domain expertise in the proposed research areas. The work will be conducted at the University of California, San Francisco, one of the premier biomedical and life sciences research centers in the world.


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 = $82,846 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	5/17/2024	NON-COMPETING CONTINUATION	$5,464
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	1/19/2024	NON-COMPETING CONTINUATION	$77,382
														Subtotal = $82,846

Issue Date FY: 2023 ( Subtotal = $73,800 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	1	1/10/2023	NEW	$0
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	003	1	2/23/2023	NEW	$0
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	1	2/23/2023	NEW	$1,918
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	1/10/2023	NEW	$71,882
														Subtotal = $73,800

Grand Total All Awards = $156,646

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Effects of in situ orientation on quantitative MR-based measures of cartilage endplate health

Award Number: F32AR081139

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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