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Three-dimensional Ultrashort Echo Time Magnetic Resonance Imaging of Entheses

Award Number: R01AR075825
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: 07/01/2019
PERIOD OF PERFORMANCE END DATE: 05/31/2025

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Three-dimensional Ultrashort Echo Time Magnetic Resonance Imaging of Entheses - 7. Abstract Entheses are regions where tendons, ligaments and joint capsules are connected to bone. They are transition zones between flexible and rigid tissues, and stress concentrates at the junction between these two types of tissue as a result of their widely different mechanical properties. Entheses are very commonly involved in many diseases including the overuse syndromes, the early stages of osteoarthritis (OA) and psoriatic arthropathy (PsA). Despite its importance, assessment of enthesitis is difficult. Clinical exam based on tenderness on direct palpation may not be sensitive nor specific. Ultrasound can show enthesial abnormalities, but is operator dependent. Conventional MR imaging has not been helpful in demonstrating the key tissues present in normal entheses which have short T2*s and show little or no signal. As a result normal entheses have not been identifiable with clinical MR imaging. Furthermore, clinical MR imaging biomarkers like T2 (a biomarker of collagen) and T1 (a biomarker of proteoglycan or PG) show strong magic angle effects, which may result in a several fold increase in T2 and T1 when the tissue fibers are oriented ~55 to the B0 field. We have developed 3D ultrashort echo time (UTE) sequences with TEs of 8 µs that are 100~1000 times shorter than the TEs of clinical sequences, allowing us to image entheses. Recent studies show that adiabatic spin-locking and magnetization transfer (MT) imaging are magic angle insensitive. The combination of UTE and adiabatic T1 may allow magic angle insensitive assessment of PG changes in entheses. The combination of UTE and MT may provide magic angle insensitive evaluation of water and collagen proton fractions and exchange rates in entheses. Both UTE-adiabatic-T1 and UTE-MT require T1 compensation. UTE with actual flip angle imaging (AFI) allows accurate T1 mapping of short T2 tissues. Our central hypothesis is that the ability to directly image and quantify the entheses with UTE sequences will provide a new option for correlating structure with mechanical function, and an important method for recognizing change in disease. Our objective is to use UTE for systematic and comprehensive characterization of tendons and entheses in PsA patients. In Aim 1 we will develop UTE sequences for assessment of PG, collagen and water components in tendons and entheses in normal ankles (n=10). In Aim 2 we will compare UTE and clinical sequences for quantitative evaluation of ankle specimens with no abnormality (n=20), and well established PsA (n=20). We will correlate MRI measures with histopathology, PLM, biochemistry and biomechanics. In Aim 3 we will apply UTE sequences to the Achilles tendon enthesis in normal controls (n=30), PsA patients with no clinically evident enthesitis (n=30) and with active enthesitis (n=30). The PsA patients will be treated with tumor necrosis factor (TNF) inhibitors, and will be scanned again at two, six and 12 months to access longitudinal changes. We will correlate the MR measures with physical examination and patient reported outcomes (PROs). We expect that UTE MRI measures will be highly correlated with PROs, enthesial inflammation and subclinical enthesitis.


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 = -$2,259 )
2026	2023	VETERANS MEDICAL RESEARCH FOUNDATION OF SAN DIEGO	3350 LA JOLLA VILLAGE DR	SAN DIEGO	CA	92161	SAN DIEGO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	2/27/2026	NON-COMPETING CONTINUATION	-$2,259
														Subtotal = -$2,259

Issue Date FY: 2023 ( Subtotal = $338,162 )
2023	2023	VETERANS MEDICAL RESEARCH FOUNDATION OF SAN DIEGO	3350 LA JOLLA VILLAGE DR	SAN DIEGO	CA	92161	SAN DIEGO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	5/19/2023	NON-COMPETING CONTINUATION	$338,162
														Subtotal = $338,162

Issue Date FY: 2022 ( Subtotal = $334,777 )
2022	2022	VETERANS MEDICAL RESEARCH FOUNDATION OF SAN DIEGO	3350 LA JOLLA VILLAGE DR STE 151A	SAN DIEGO	CA	92161	SAN DIEGO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	5/4/2022	NON-COMPETING CONTINUATION	$334,777
														Subtotal = $334,777

Issue Date FY: 2021 ( Subtotal = $365,728 )
2021	2021	VETERANS MEDICAL RESEARCH FOUNDATION OF SAN DIEGO	3350 LA JOLLA VILLAGE DR STE 151A	SAN DIEGO	CA	92161	SAN DIEGO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	5/11/2021	NON-COMPETING CONTINUATION	$365,728
														Subtotal = $365,728

Issue Date FY: 2020 ( Subtotal = $435,974 )
2020	2020	VETERANS MEDICAL RESEARCH FOUNDATION OF SAN DIEGO	3350 LA JOLLA VILLAGE DR STE 151A	SAN DIEGO	CA	92161	SAN DIEGO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	6/4/2020	NON-COMPETING CONTINUATION	$435,974
														Subtotal = $435,974

Issue Date FY: 2019 ( Subtotal = $365,750 )
2019	2019	VETERANS MEDICAL RESEARCH FOUNDATION OF SAN DIEGO	3350 LA JOLLA VILLAGE DR STE 151A	SAN DIEGO	CA	92161	SAN DIEGO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	6/28/2019	NEW	$365,750
														Subtotal = $365,750

Grand Total All Awards = $1,838,132

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Three-dimensional Ultrashort Echo Time Magnetic Resonance Imaging of Entheses

Award Number: R01AR075825

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: 07/01/2019

PERIOD OF PERFORMANCE END DATE: 05/31/2025

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