The overarching aim of this proposed project is to develop, optimize, and quantitatively evaluate magnetic resonance imaging (MRI) methods for assessing bone fracture risk. The current standard diagnostic of bone health, dual-energy X-ray absorptiometry (DXA), provides an approximate measure of bone mineral density, but it is a projection method that does not incorporate the full contribution of macro-structure, micro- architecture, collagen, or porosity to fracture resistance. Quantitative computed tomography (qCT) is able to partially circumvent these shortcomings of DXA, but remains limited in that it, and other X-ray based methods, are sensitive only to the mineral content of bone, which accounts for only ?40% of bone by volume. This project has demonstrated that bound- and pore-water signals from cortical bone can be independently measured in vivo using MRI, and that these measures report on mechanical properties of bone. The next phase of this project will undertake a combination of technical developments and imaging studies to prepare these MRI methods for clinical use.
In Aim 1, the current MRI methods will be accelerated by replacing 3D ultra- short-echo time (UTE) MRI with 2D methods, will be modi?ed to provide more accurate and informative measures, and will be extended to the lumbar vertebra.
In Aim 2 the newly developed MRI methods will be evaluated as predictors of the biomechanical properties of cadaver bones (lumbar vertebra and radius).
In Aim 3, the methods will be evaluated in vivo in patients with elevated fracture risk. Ultimately, this project will result in MRI methods with the potential for improved clinical diagnostic evaluation of fracture risk and novel imaging biomarkers for the study of bone diseases and pharmacological treatment response.

Public Health Relevance

Current methods for diagnostic imaging of bone are incomplete and do not fully predict the increase in bone fracture risk with age or advancement of disease. Unlike current X-ray based imaging, MRI can probe soft- tissue characteristics of bone, which may be important in fracture resistance. The proposed research aims to continue development and evaluation of MRI methods that can better predict bone fracture risk and provide more speci?c feedback on bone compositional changes in response to therapy.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
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Medical Imaging Study Section (MEDI)
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Liu, Guoying
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Vanderbilt University Medical Center
Schools of Medicine
United States
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Manhard, Mary Kate; Nyman, Jeffry S; Does, Mark D (2017) Advances in imaging approaches to fracture risk evaluation. Transl Res 181:1-14
Uppuganti, Sasidhar; Granke, Mathilde; Manhard, Mary Kate et al. (2017) Differences in sensitivity to microstructure between cyclic- and impact-based microindentation of human cortical bone. J Orthop Res 35:1442-1452
Manhard, Mary Kate; Harkins, Kevin D; Gochberg, Daniel F et al. (2017) 30-Second bound and pore water concentration mapping of cortical bone using 2D UTE with optimized half-pulses. Magn Reson Med 77:945-950
Uppuganti, Sasidhar; Granke, Mathilde; Makowski, Alexander J et al. (2016) Age-related changes in the fracture resistance of male Fischer F344 rat bone. Bone 83:220-232
Manhard, Mary Kate; Uppuganti, Sasidhar; Granke, Mathilde et al. (2016) MRI-derived bound and pore water concentrations as predictors of fracture resistance. Bone 87:1-10
Granke, Mathilde; Makowski, Alexander J; Uppuganti, Sasidhar et al. (2015) Identifying Novel Clinical Surrogates to Assess Human Bone Fracture Toughness. J Bone Miner Res 30:1290-300
Li, Ke; Dortch, Richard D; Kroop, Susan F et al. (2015) A rapid approach for quantitative magnetization transfer imaging in thigh muscles using the pulsed saturation method. Magn Reson Imaging 33:709-17
Manhard, Mary Kate; Horch, R Adam; Gochberg, Daniel F et al. (2015) In Vivo Quantitative MR Imaging of Bound and Pore Water in Cortical Bone. Radiology 277:221-9
Granke, Mathilde; Does, Mark D; Nyman, Jeffry S (2015) The Role of Water Compartments in the Material Properties of Cortical Bone. Calcif Tissue Int 97:292-307
Harkins, Kevin D; Horch, R Adam; Does, Mark D (2015) Simple and robust saturation-based slice selection for ultrashort echo time MRI. Magn Reson Med 73:2204-11

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