Bone Fracture Risk Assessment Through Bound - and Pore - Water MRI

描述（由申请人提供）：本拟议项目的总体目标是开发、优化和定量评价用于评价骨生物力学特性的磁共振成像（MRI）方法。目前骨健康的标准诊断，双能X射线吸收测定法（DXA），提供了骨矿物质密度的近似测量，但它是一种投影方法，不包括宏观结构，微观结构，胶原蛋白或孔隙率对抗骨折性的全部贡献。定量计算机断层扫描（qCT）能够部分规避DXA的这些缺点，但仍然受到限制，因为它和其他基于X射线的方法仅对骨的矿物质含量敏感，骨的矿物质含量仅占骨体积的~~40%。最近的研究表明，[1] H核磁共振（NMR）可以辨别骨的多种软组织成分，包括胶原蛋白、胶原蛋白结合水和孔隙水。此外，在尸体皮质骨样本中，发现这些NMR测量比当前高分辨率qCT更好地预测与骨折风险相关的几种机械性能。该项目旨在通过三个项目目标将这些[1] H NMR结果转化为临床MRI方法，用于评估全骨折风险。在目标1中，[1]皮质骨样本的H NMR测量值将用于设计和测试定量测量骨结合水和孔隙水的MRI方法。在目标2中，这些MRI方法以及沿着DXA和qCT将应用于多个尸体骨部位（包括股骨颈和桡骨远端）。结合水、孔隙水和横截面惯性矩的所得MRI测量值将与从相同部位和腰椎测量的全骨抗骨折性能相关。将在DXA和qCT测量值之间建立类似的相关性以进行比较。在目标3中，MRI方法将被转换为人体MRI系统，其中它们将针对3T（c/w 4.7T）进行重新优化，并定量评价在多个解剖部位（例如，胫骨远端股骨颈，.）。最终，该项目将导致MRI方法具有改善骨折风险的临床诊断评价的潜力，以及研究骨骼疾病和药物治疗反应的新型成像生物标志物。

DESCRIPTION (provided by applicant): The overarching aim of this proposed project is to develop, optimize and quantitatively evaluate magnetic resonance imaging (MRI) methods for evaluating the biomechanical properties of bone. 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. Recent studies have shown that [1]H nuclear magnetic resonance (NMR) can discern multiple soft- tissue components of bone, including collagen, collagen-bound water, and pore water. Further, in cadaveric cortical bone samples, these NMR measures were found to better predict several mechanical properties related to bone fracture risk than current high resolution qCT. This project seeks to translate these [1]H NMR findings into clinical MRI methods for assessing whole bone fracture risk through three project aims. In Aim 1, [1]H NMR measurements from cortical bone samples will be used to design and test MRI methods for quantitatively measuring bound- and pore-water from bone. In Aim 2, these MRI methods, along with DXA and qCT, will be applied to multiple cadaveric bone sites (including the femoral neck and distal radius). The resulting MRI measures of bound-water, pore-water, and cross-sectional moment of inertia will be correlated with whole bone fracture resistance properties measured from the same sites and a lumbar vertebra. Similar correlations will be made between DXA and qCT measures for comparison. In Aim 3, the MRI methods will be translated to a human MRI system where they will be re-optimized for 3T (c/w 4.7T) and quantitatively evaluated for use at multiple anatomical sites (e.g., distal tibia femoral neck, ...). 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 bone disease and pharmacological treatment response.