Quantitative imaging of bone has been of central importance in medicine since Roentgen produced the first radiograph in 1895. The current gold standard technique DEXA measures bone mineral density (BMD). However, the majority of bone, including the organic matrix and bone water which together occupy ~60% of bone by volume is inaccessible. BMD by itself only predicts osteoporotic fractures with an accuracy of 30-50%. The overall fracture risk increases 13-fold from ages 60 to 80, but BMD alone only predicts a doubling of the fracture risk. In addition, recent studies demonstrate that bone marrow adiposity plays an active role in affecting bone quantity and quality. There is considerable interest in more comprehensive evaluation of bone quality using information not only about bone mineral, but organic matrix, bone water and marrow fat. All of these factors may play a role in maintaining the biomechanical integrity of cortical and trabecular bone. Magnetic resonance imaging (MRI) is routinely used in the diagnosis of soft tissue disease. However, bone is invisible using all clinical sequences due to its short T2*. We have developed 2D and 3D UTE sequences with TEs of 8 s that are ~1000 times shorter than conventional TEs. This makes it possible to detect multiple water components in cortical bone, and fat content and composition in trabecular bone. The pore water content provides a surrogate measure of cortical porosity. Collagen-bound water provides an indirect measure of organic matrix density. Marrow fat content and composition provide BMD independent fracture risk factors. It would be a major advance to develop UTE MRI techniques to evaluate porosity and organic matrix density in cortical bone, as well as marrow fat content and composition in trabecular bone. This study aims to develop and combine novel 3D UTE MRI techniques to evaluate cortical and trabecular bone offering full insight into bone characterization and correlation with function. To achieve thi goal, in Aim 1 we will evaluate 3D UTE MRI techniques for assessment of cortical bone. We will determine the accuracy of UTE measurement of collagen-bound and pore water, and correlate UTE MRI metrics (collagen-bound and pore water content, T1, T2* and MTR) with biomechanical properties of cortical bone.
In Aim 2 we will evaluate 3D UTE MRI techniques for evaluation of trabecular bone. We will determine the accuracy of 3D UTE MRI measurement of marrow fat content and composition and correlate 3D UTE MRI metrics with those from MR spectroscopy (MRS) as well as biomechanical properties of trabecular bone.
In Aim 3 we will apply the validated 3D UTE MRI techniques to study one group of premenopausal women and two groups of postmenopausal women with slow or fast bone loss. We will compare the 3D UTE MRI and MRS metrics in different groups and correlate the results with BMD and biochemical markers. This work will provide accurate panels of 3D UTE MRI and MRS based biomarkers which may be important for assessing bone quality, and may have a major impact on the diagnosis and therapeutic monitoring of OP.

Public Health Relevance

The goal of this project is to develop and combine novel 3D UTE MRI techniques to evaluate cortical and trabecular bone offering full insight into bone characterization and correlation with function. In the cadaveric human bone studies the 3D UTE MRI techniques will be compared with reference techniques including CT imaging and DEXA scanning for quantitative evaluation of bone quality using biomechanical testing as reference standard. In the human studies the 3D UTE MRI techniques will be applied to one group of premenopausal women and two groups of postmenopausal women with slow or fast bone loss for a comprehensive evaluation of bone quality in vivo.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR068987-03
Application #
9344532
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Lester, Gayle E
Project Start
2015-09-17
Project End
2019-08-31
Budget Start
2017-09-01
Budget End
2018-08-31
Support Year
3
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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Ma, Ya-Jun; Shao, Hongda; Du, Jiang et al. (2016) Ultrashort echo time magnetization transfer (UTE-MT) imaging and modeling: magic angle independent biomarkers of tissue properties. NMR Biomed 29:1546-1552

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