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

描述（由申请人提供）：本项目的总体目标是开发，优化和定量评估用于评估骨骼生物力学特性的磁共振成像（MRI）方法。目前诊断骨骼健康的标准方法是双能x射线吸收仪（DXA），它提供了骨密度的近似测量，但它是一种投影方法，不能将宏观结构、微观结构、胶原蛋白或孔隙度对抗骨折性的全部贡献纳入其中。定量计算机断层扫描（qCT）能够部分规避DXA的这些缺点，但仍有局限性，因为它和其他基于x射线的方法只对骨骼的矿物质含量敏感，而骨骼的矿物质含量仅占骨骼体积的~~40%。最近的研究表明，bbbbh核磁共振（NMR）可以识别骨骼的多种软组织成分，包括胶原蛋白、胶原结合水和孔隙水。此外，在尸体皮质骨样本中，这些核磁共振测量比目前的高分辨率qCT更能预测与骨折风险相关的几种力学特性。本项目旨在通过三个项目目标将这些b[1]H核磁共振结果转化为评估全骨骨折风险的临床MRI方法。在目标1中，来自皮质骨样本的b[1]H NMR测量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Aim 2中，这些MRI方法，以及DXA和qCT，将应用于多个尸体骨部位（包括股骨颈和桡骨远端）。所得的束缚水、孔隙水和横截面惯性矩的MRI测量结果将与从同一部位和腰椎测量的全骨骨折抵抗特性相关。类似的相关性将在DXA和qCT测量之间进行比较。在Aim 3中，MRI方法将被转化为人体MRI系统，在那里它们将被重新优化为3T (c/w 4.7T)，并定量评估用于多个解剖部位（例如，胫骨远端股骨颈等）。最终，该项目将使MRI方法具有改善骨折风险的临床诊断评估的潜力，并为研究骨病和药物治疗反应提供新的成像生物标志物。

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.