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Ultrashort Echo Time (UTE) Magnetic Resonance Imaging of Bone

Award Number: R01AR068987
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: 09/17/2015
PERIOD OF PERFORMANCE END DATE: 02/28/2026

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Ultrashort Echo Time (UTE) Magnetic Resonance Imaging of Bone - 7. Abstract Metabolic bone diseases including osteoporosis (OP), osteopenia, osteomalacia and renal osteodystrophy (ROD) affect more than 55 million Americans with an annual cost of more than $17B. The gold standard, dual energy X-ray absorptiometry (DEXA) measures bone mineral density (BMD). However, the majority of bone, the organic matrix and water which together occupy ~60% of bone by volume, is inaccessible. A recent study of over 14,613 participants found that ~80% of all non-vertebral fractures occurred among individuals with BMD above the WHO definition of OP. Furthermore, the etiologies and treatments for OP/osteopenia (reduced bone content) and osteomalacia/ROD (reduced mineralization) are different, but DEXA cannot differentiate between these diseases. More comprehensive techniques are needed for the evaluation of cortical and trabecular bone quantity/quality with information not only about mineral, but about organic matrix and water. Bone is “invisible” with clinical MRI sequences due to its short T2*. Ultrashort echo time (UTE) sequences with minimal TEs of 8 µs make it possible to detect signal from bone. In the first four years of this award (1R01 AR068987, 09/2015 – 08/2019), we investigated 3D UTE Cones imaging of bound and pore water content as well as T1, T2* and magnetization transfer (MT) ratio. However, those biomarkers showed only low to moderate correlation with biomechanics, likely due to inaccurate measure of bound and pore water as well as incomplete assessment of organic matrix and mineral in bone. UTE with a soft-hard composite pulse suppresses chemical shift artifact, thus allowing more accurate measure of total water. Double adiabatic inversion recovery UTE (DIR-UTE) provides more complete suppression of pore water, thus allowing more accurate measure of bound water. UTE with MT (UTE-MT) modeling measures collagen proton fraction, exchange and relaxation. UTE with quantitative susceptibility mapping (UTE-QSM) maps bone susceptibility, providing information about BMD. Our goal is to develop a package for fast and accurate mapping of total, bound and pore water, collagen proton fraction, exchange, relaxation, and mineral, and to apply it to OP, osteopenia and ROD patients. Aim 1 targets UTE techniques for fast and accurate mapping of water, collagen and mineral in femur (midshaft, head and neck), using µCT, histomorphometry, Raman and gravimetry as reference standard. Aim 2 will evaluate UTE techniques for water, collagen and mineral in femur from donors with OP (n=20), osteopenia (n=20) and ROD (n=20), with UTE biomarkers correlated with µCT, histomorphometry, Raman and biomechanical testing. Aim 3 targets translational UTE sequences to measure water, collagen and mineral in femur of young (<40y, n=30) and older women (>70y) with (n=30) and without (n=30) OP, with osteopenia (n=30) and with ROD (n=30). UTE biomarkers in different groups will be compared, and correlated with BMD, biochemical markers and fracture history. This work will provide panels of 3D UTE biomarkers for more accurate assessment of bone quantity and quality, and may have a major impact on the diagnosis of various metabolic bone diseases.


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 = $559,184 )
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	9	3/6/2024	NON-COMPETING CONTINUATION	$518,832
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	9	5/20/2024	NON-COMPETING CONTINUATION	$40,352
														Subtotal = $559,184

Issue Date FY: 2023 ( Subtotal = $578,564 )
2023	2023	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	8	5/26/2023	NON-COMPETING CONTINUATION	$57,855
2023	2023	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	8	2/7/2023	NON-COMPETING CONTINUATION	$520,709
														Subtotal = $578,564

Issue Date FY: 2022 ( Subtotal = $592,050 )
2022	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	7	4/26/2022	NON-COMPETING CONTINUATION	$592,050
														Subtotal = $592,050

Issue Date FY: 2021 ( Subtotal = $646,875 )
2021	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	6	3/29/2021	NON-COMPETING CONTINUATION	$600,195
2021	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	6	6/16/2021	NON-COMPETING CONTINUATION	$46,680
														Subtotal = $646,875

Issue Date FY: 2020 ( Subtotal = $688,861 )
2020	2020	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	5	3/25/2020	COMPETING CONTINUATION	$688,861
2020	2018	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	4	6/26/2020	NON-COMPETING CONTINUATION	$0
2020	2018	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	11/5/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $688,861

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2018	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	1/30/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $436,384 )
2018	2018	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	9/11/2018	NON-COMPETING CONTINUATION	$436,384
														Subtotal = $436,384

Issue Date FY: 2017 ( Subtotal = $417,970 )
2017	2017	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	8/14/2017	NON-COMPETING CONTINUATION	$417,970
														Subtotal = $417,970

Issue Date FY: 2016 ( Subtotal = $479,376 )
2016	2016	UNIVERSITY OF CALIFORNIA-SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	9/2/2016	NON-COMPETING CONTINUATION	$479,376
														Subtotal = $479,376

Issue Date FY: 2015 ( Subtotal = $519,588 )
2015	2015	UNIVERSITY OF CALIFORNIA-SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	9/17/2015	NEW	$519,588
														Subtotal = $519,588

Grand Total All Awards = $4,918,852

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Ultrashort Echo Time (UTE) Magnetic Resonance Imaging of Bone

Award Number: R01AR068987

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: 09/17/2015

PERIOD OF PERFORMANCE END DATE: 02/28/2026

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