Clinical Bone Mechanics Using HR-pQCT and ??MRI

描述（由申请人提供）：高分辨率成像的最新进展允许开发新工具，特别是微磁共振（5 MR）成像和高分辨率外周定量计算机断层扫描（HR-pQCT），这些工具有望通过双能X射线吸收测定法（DXA）提供比面积骨矿物质密度（aBMD）更好的总体骨强度特征。在本申请中，我们试图确定基于图像的显微结构和5 FE分析是否可以区分患有椎骨骨折的个体与没有椎骨骨折的个体。在本研究中，我们提出以下假设：1.来自离体5 MRI和HR-pQCT的胫骨远端和桡骨的刚度和失效载荷的形态测量和5 FE预测与来自5CT和直接机械测试的那些高度相关，并且，此外，来自两个外周部位的参数与椎骨中的参数平行。2.从体内5 MR和HR-pQCT图像中获得的弹性刚度和失效载荷的5 FE估计值可以区分椎体骨折和无椎体骨折的个体，优于单独通过两种成像方式或DXA获得的aBMD的微结构测量值。我们计划通过以下具体目标来解决上述假设：具体目标1a：在体内可实现的信噪比和分辨率条件下，对胫骨远端和桡骨进行离体5 MRI和HR-pQCT扫描，并将以这种方式获得的骨小梁和皮质骨显微结构测量值与高分辨率5CT测量值进行比较。具体目标1b：将通过HR-pQCT和基于5 MR图像的非线性5 FE分析预测的胫骨远端和桡骨的整个骨段的刚度和失效载荷与通过基于5CT图像的5 FE分析和直接机械测试预测的刚度和失效载荷进行比较。具体目标2a：对与目标1a和1b中使用的胫骨远端和桡骨相同的受试者的腰椎进行5次CT扫描，具体目标2b：将目标1a和1b中基于HR-pQCT和5次MRI获得的成像数据的骨小梁和皮质骨显微结构测量值和5次FE预测值与目标2a中相应椎骨的5次CT测量值和直接力学测试值进行比较。具体目标3a：将目标1和2中确认的显微结构和5 FE技术应用于健康女性的体内5 MRI和HR-pQCT扫描，并比较两种成像模式之间的这些测量值。具体目标3b：将目标1和2中确认的显微结构和5 FE技术应用于两种外周成像模式，并使用研究者实验室先前进行或目前正在进行的两项成像研究的数据，确定区分椎体骨折受试者和非骨折受试者的方法的有效性。 公共卫生相关性：高分辨率外周定量计算机断层扫描（HR-pQCT）和微型磁共振成像（5 MRI）是骨骼的最新临床高分辨率成像模式，将确认其用于确定力学能力和预测椎骨骨折。这项研究将测试的可行性，并建立高分辨率骨骼成像在评估骨健康的标准，超越了双能X射线骨密度仪（DXA）获得的面积骨密度测量。

DESCRIPTION (provided by applicant): Recent advances in high-resolution imaging have permitted the development of new tools, notably micro- magnetic resonance (5MR) imaging and high-resolution peripheral quantitative computed tomography (HR- pQCT), that promise to provide a better profile of overall bone strength beyond areal bone mineral density (aBMD) by dual-energy x-ray absorptiometry (DXA). In this application, we seek to determine whether image- based microstructural and 5FE analyses can distinguish between individuals who have vertebral fractures from their counterparts without vertebral fractures. In the proposed project we advance the following hypotheses: 1. Morphological measurements and 5FE predictions of stiffness and failure load of the distal tibia and radius from ex vivo 5MRI and HR-pQCT correlate highly with those from 5CT and direct mechanical testing, and, furthermore, that parameters from the two peripheral sites parallel those in the vertebrae. 2. 5FE-derived estimates of elastic stiffness and failure load from in vivo 5MR and HR-pQCT images can differentiate between individuals with vertebral fractures from those without vertebral fractures better than microstructural measures derived by the two imaging modalities alone or aBMD by DXA. We plan to address the above hypotheses with the following specific aims: Specific Aim 1a: Perform 5MRI and HR-pQCT scans of the distal tibia and radius ex vivo under signal-to-noise and resolution conditions achievable in vivo, and compare trabecular and cortical bone microstructural measurements obtained in this manner with those from high-resolution 5CT. Specific Aim 1b: Compare the stiffness and failure load of whole bone segments of the distal tibia and radius as predicted by HR-pQCT and 5MR image-based nonlinear 5FE analyses to those predicted by 5CT image- based 5FE analysis and direct mechanical testing. Specific Aim 2a: Perform 5CT scans of lumbar vertebrae from the same subjects as the distal tibia and radius used in Aims 1a and 1b Specific Aim 2b: Compare trabecular and cortical bone microstructural measurements and 5FE predictions based on the imaging data obtained by HR-pQCT and 5MRI in Aims 1a and 1b with the 5CT measurements and direct mechanical testing of the corresponding vertebrae in Aim 2a. Specific Aim 3a: Apply the microstructural and 5FE techniques validated in Aims 1 and 2 to in vivo 5MRI and HR-pQCT scans from healthy women and compare these measurements between the two imaging modalities. Specific Aim 3b: Apply the microstructural and 5FE techniques validated in Aims 1 and 2 to the two peripheral imaging modalities and determine the effectiveness of methods in distinguishing between vertebral fracture subjects and their non-fractured peers using data from two imaging studies previously performed or currently in progress in the investigators' laboratories. PUBLIC HEALTH RELEVANCE: High-resolution peripheral quantitative computed tomography (HR-pQCT) and micro magnetic resonance imaging (5MRI), which are state-of-the-art clinical high-resolution imaging modalities for the skeleton, will be validated for the determination of mechanical competence and prediction of vertebral fractures. This research will test the feasibility and establish the standard of high-resolution skeletal imaging in assessing bone health beyond the areal bone mineral density measurements obtained by dual-energy x-ray absorptiometry (DXA).