Routine clinical evaluation of osteoporosis (OP) has been limited to the assessment of bone mineral density (BMD) using dual energy X-ray absorptiometry (DEXA) and/or CT. The majority of bone, the organic matrix and water, which together represent ~57% of bone by volume, are not accessible with these techniques. BMD alone predicts fractures with only a 30-50% success rate. The missing factor may be the contribution of bone organic matrix and water. Bone water occurs at various locations and in different states. It is bound to the organic matrix or in 'free'form in the Haversian and the lacunar-canalicular systems. The bound water content reflects organic matrix density. The free water content can potentially provide a surrogate measure of bone porosity. However, neither DEXA nor CT can detect either bound or free water in cortical bone. We have developed Ultrashort Time-to-Echo (UTE) magnetic resonance imaging (MRI) sequences with minimum TEs of 8 ?s, and this makes it possible to detect water signal from bone. Total bone water can be quantified by comparing UTE signal from bone and a water phantom. Bound water can be selectively imaged with SIR-UTE sequences which use a single adiabatic inversion pulse to invert and null the free water magnetization. Free water can be selectively imaged with DIR-UTE sequences which saturate bound water while leave free water magnetization unaffected. Bound water has ~10 times shorter T2* than free water. The two components may be separated with bi-component fitting. Free water has a short T2* but long T2, and may be imaged with FSE sequences. The UTE approach may detect the effect of Gadolinium chelates within cortical bone and study its perfusion at high resolution. This provides a new way to characterize cortical bone. In this proposal we hypothesize that bone water content and bone perfusion can be non-invasively assessed by novel MRI techniques, and can serve as sensitive biomarkers of bone quality.
We aim to develop novel UTE, SIR-UTE, DIR-UTE and FSE techniques to measure total, bound and free water in cortical bone (Aim 1), to evaluate the accuracy of MR measures of two groups of women cadaveric human tibia specimens, the younger group (<60 years old) and the older group (>80 years old), and correlate the results with cortical porosity determined by mCT and organic matrix content determined by ashing, as well as elastic properties (modulus, yield stress and strain) and failure properties (ultimate stress, failure strain and energy) determined by 4-point bending test (Aim 2), and to develop translational MR techniques to quantify total, bound and free water as well as bone perfusion in two groups of postmenopausal women: i.e., below 60 without OP and above 80 with OP (Aim 3). The intention is to develop and validate these techniques in tissue studies and a small number of patients to provide preliminary data for an RO1 grant application on the use of MR in diffuse bone disease including OP, renal osteodystrophy, paget disease and osteomalacia. The comprehensive characterization of bone in these conditions could have a profound impact in their diagnosis and treatment.

Public Health Relevance

This study aims to develop novel UTE, SIR-UTE, DIR-UTE and FSE MR techniques to measure total, bound and free bone water and evaluate their correlations with cortical porosity, organic matrix and biomechanical properties in tissue samples, and to develop translational MR techniques to quantify bone water and perfusion.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1-DTCS-A (81))
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Lester, Gayle E
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University of California San Diego
Schools of Medicine
La Jolla
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Shao, H; Chang, E Y; Pauli, C et al. (2016) UTE bi-component analysis of T2* relaxation in articular cartilage. Osteoarthritis Cartilage 24:364-73
Chen, Jun; Carl, Michael; Ma, Yajun et al. (2016) Fast volumetric imaging of bound and pore water in cortical bone using three-dimensional ultrashort-TE (UTE) and inversion recovery UTE sequences. NMR Biomed 29:1373-80
Chen, Jun; Grogan, Shawn P; Shao, Hongda et al. (2015) Evaluation of bound and pore water in cortical bone using ultrashort-TE MRI. NMR Biomed 28:1754-62
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Chang, Eric Y; Du, Jiang; Chung, Christine B (2015) UTE imaging in the musculoskeletal system. J Magn Reson Imaging 41:870-83
Chang, Eric Y; Bae, Won C; Shao, Hongda et al. (2015) Ultrashort echo time magnetization transfer (UTE-MT) imaging of cortical bone. NMR Biomed 28:873-80
Li, Shihong; Ma, Lanqing; Chang, Eric Y et al. (2015) Effects of inversion time on inversion recovery prepared ultrashort echo time (IR-UTE) imaging of bound and pore water in cortical bone. NMR Biomed 28:70-8
Li, Shihong; Chang, Eric Y; Bae, Won C et al. (2014) The effect of excitation and preparation pulses on nonslice selective 2D UTE bicomponent analysis of bound and free water in cortical bone at 3T. Med Phys 41:022306
Carl, Michael; Chiang, Jing-Tzyh Alan; Du, Jiang (2014) Maximizing MR signal for 2D UTE slice selection in the presence of rapid transverse relaxation. Magn Reson Imaging 32:1006-11
Chiang, Jing-Tzyh Alan; Carl, Michael; Du, Jiang (2014) Signal and contrast effects due to T2 decay during k-space readout of UTE (ultrashort TE) sequences. Magn Reson Imaging 32:259-69

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