MRI-Based Assessment of Structural and Mechanical Implications of Osteoporosis

描述（由申请人提供）：骨密度和骨折易感性之间的脱节促使人们寻找导致骨骼强度受损的其他风险因素。该提案的申请人先前开发了基于定量MRI的方法，用于评估骨质量的多种测量，包括通过称为虚拟骨活检（VBB）的程序进行的骨小梁微结构。该技术的潜力已在转化研究中得到证实，表明骨质量的结构测量与骨质疏松性骨折的相关性比区域BMD更强，并且这些结构测量是结构完整性受损患者药物干预疗效的敏感指标。 关键的缺失环节是结构的措施和强度的措施，如刚度和失效载荷之间的关联。有很少的研究，试图在体内骨结构衍生的力学估计从微观有限元（？FE）分析，并结合实际断裂数据。尽管高分辨率CT和MRI都适合于此目的，但MRI比CT具有显著优势，除了不含电离辐射外，还具有上级的骨髓对比度;最重要的是，仅在美国就有超过10，000台的安装基础。 在这个项目中，我们提出了以下假设：1）有限元估计的参数（全截面刚度和极限强度，和子体积松质骨的弹性和剪切模量）来自体内？胫骨远端和桡骨的MR图像与表达测量部位的尺度、拓扑结构和方向的结构参数相关，结构测量共同解释了力学参数高达90%的变化; 2）这些关联比涉及骨体积分数或单独的骨密度的关联更强; 3）替代部位的力学和结构参数与离体评价的椎体结构和力学参数以及体内椎体畸形状态相关。我们建议通过解决以下具体目标来评估上述假设：1。我们将验证所提出的方法在胫骨远端和桡骨标本进行力学测试和比较的数据与？有限元衍生的弹性模量来自微CT和？MR图像以及来自相同供体的椎骨的图像。 2.我们将评估一组绝经后妇女的协议组成的收购高分辨率三维？胫骨远端和桡骨的MRI，匹配解剖位置的pQCT 3D BMD，用于椎体畸形评估的脊柱MRI，以及脊柱和髋关节的DXA aBMD。 3.我们将推导出结构和力学参数在两个周边网站，以测试上述假设，通过比较？FE估计参数与结构和BMD的措施，并与椎体畸形状态。拟议的体内MRI研究将为骨质疏松症的微观结构和力学影响提供新的见解，从而为将该方法转化为临床提供基础，这是该项目的长期目标。 公共卫生相关性：骨强度和结构的措施之间的关系还不清楚，只是最近的技术已经成为可用的形式，高分辨率的非侵入性成像和微观有限元分析，以探索这些协会。在这个项目中，我们解决的假设，骨机械能力可以预测的基础上，高分辨率MRI在人尸体标本比较力学测试结果与计算生物力学和应用的方法，绝经后妇女骨折的风险，通过比较结构和力学参数与椎体畸形状态。

DESCRIPTION (provided by applicant): The disconnect between bone density and fracture susceptibility has spurred the search for other risk factors that cause compromised skeletal strength. The applicants of this proposal previously developed methods, based on quantitative MRI for assessing multiple measures of bone quality, including trabecular bone microstructure via a procedure referred to as virtual bone biopsy (VBB). The potential of this technology has been demonstrated in translational research studies showing that structural measures of bone quality are more strongly associated with osteoporotic fractures than areal BMD and that these structural measures are sensitive indicators of drug intervention efficacy in patients with impaired structural integrity. The critical missing link is the association between measures of structure and measures of strength such as stiffness and failure load. There are very few studies that have attempted to relate in vivo bone- structure derived mechanical estimates from micro-finite element (?FE) analysis, with actual fracture data. Whereas both, high-resolution CT and MRI, are suited for this purpose, MRI has substantial advantages over CT, besides being free of ionizing radiation, in that it has superior bone-to-marrow contrast; and most importantly, an installed base of over 10,000 units in the United States alone. In this project we advance the following hypotheses: 1) that FE-estimated parameters (whole-section stiffness and ultimate strength, and sub-volume trabecular bone elastic and shear moduli) derived from in vivo ?MR images at the distal tibia and radius, are associated with structural parameters expressing scale, topology and orientation at the measurement sites, with structural measures jointly explaining as much as 90% of the variation in the mechanical parameters; 2) that these associations are stronger than those involving bone volume fraction or BMD alone; 3) that the mechanical and structural parameters at the surrogate sites are correlated with vertebral structural and mechanical parameters evaluated ex vivo and vertebral deformity status in vivo. We propose to evaluate the above hypotheses by addressing the following specific aims: 1. We will validate the proposed method in specimens of the distal tibia and radius by performing mechanical testing and comparing the data with ?FE-derived estimates of elastic moduli derived from micro-CT and ?MR images as well as with those from vertebral bone of the same donors. 2. We will evaluate a cohort of postmenopausal women with a protocol consisting of acquisition of high- resolution 3D ?MRI of the distal tibia and radius, 3D BMD by pQCT at matching anatomic locations, MRI of the spine for vertebral deformity assessment, and DXA aBMD at the spine and hip. 3. We will derive structural and mechanical parameters at the two peripheral sites to test the above hypotheses by comparing ?FE-estimated parameters with measures of structure and BMD, and with vertebral deformity status. The proposed in vivo MRI study will provide new insight into the microstructural and mechanical implications of osteoporosis, thereby providing the basis for translation of the methodology to the clinic, which is the long-term objective underlying the project. PUBLIC HEALTH RELEVANCE: The relationship between measures of bone strength and architecture is not understood and only recently technology has become available in the form of high-resolution noninvasive imaging and micro-finite-element analysis to explore these associations. In this project we address the hypothesis that bone mechanical competence can be predicted on the basis of high-resolution MRI in human cadaver specimens comparing mechanical test results with computational biomechanics and apply the methodology to postmenopausal women at risk of fracture by comparing the structural and mechanical parameters with vertebral deformity status.