PROJECT SUMMARY 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 modified 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.