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

描述(由申请人提供)：该项目的总体目标是开发、优化和定量评估磁共振成像(MRI)方法，以评估骨的生物力学特性。目前诊断骨健康的标准方法，即双能X射线骨密度仪(DXA)，提供了一种骨密度的近似测量方法，但它是一种投影法，没有包含宏观结构、微观结构、胶原蛋白或孔隙率对骨折抗力的全部贡献。定量计算机断层扫描(QCT)能够部分克服DXA的这些缺点，但仍然有限，因为它和其他基于X射线的方法一样，仅对骨的矿物质含量敏感，按体积计算，骨含量仅占骨体积的~40%。最近的研究表明，[1]H核磁共振可以识别骨的多种软组织成分，包括胶原、胶原结合水和孔隙水。此外，在身体皮质骨样本中，这些核磁共振测量被发现比目前的高分辨率QCT更好地预测与骨折风险相关的几个力学特性。该项目旨在通过三个项目目标将这些[1]H核磁共振结果转化为临床MRI方法，用于评估全骨骨折的风险。在目标1中，将使用皮质骨样本的氢核磁共振测量来设计和测试定量测量骨骼结合水和孔隙水的MRI方法。在目标2中，这些MRI方法，连同DXA和QCT，将应用于多个身体骨骼部位(包括股骨颈和桡骨远端)。由此产生的结合水、孔隙水和横截面转动惯量的MRI测量将与从相同部位和腰椎测量的整个骨断裂阻力特性相关联。将在DXA和QCT测量之间建立类似的相关性以进行比较。在目标3中，MRI方法将被转化为人类MRI系统，在那里它们将针对3T(C/W 4.7T)进行重新优化，并针对多个解剖位置(例如，胫骨股骨颈远端，...)进行定量评估。最终，该项目将产生MRI方法，有可能改进骨折风险的临床诊断评估，并为研究骨骼疾病和药物治疗反应提供新的成像生物标记物。

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.