Elucidating Vertebral Microstructure with Diffraction Enhanced Imaging

 描述（由申请人提供）：骨质疏松症是“一种全身性疾病，其特征为骨量低和骨组织微结构退化。“目前的临床评估指标，骨矿物质密度（BMD），揭示了微结构恶化。骨密度与骨微结构的各向异性程度（DA）结合使用，可强烈预测椎体强度和刚度，但关键障碍 排除了对骨中各向异性程度的临床评估，特别是在骨折具有高死亡率并且高度预测未来骨折的椎骨内。能够测量椎骨中DA的低剂量、非侵入性工具将克服这些障碍，并为临床医生提供更具体和个性化的骨强度和骨折风险指标。在这个应用中，我们建议开发这样一个工具的基础上衍射增强成像（DEI），相衬X射线成像技术。DEI可以检测当X射线束被骨骼中的微结构折射时发生的极小的角扩展。DEI具有方向灵敏度，使其能够测量折射微结构中的角取向和各向异性程度。在这项原理验证研究中，我们的目标是阐明DEI测量的各向异性程度与椎骨的强度和刚度之间的关系。在特定目标1中，我们将通过将DEI测量的各向异性程度与显微CT的金标准测量值进行比较，确定DEI测量椎骨各向异性程度的能力。将获得尸体椎骨（年龄60-64岁男性n=3，女性n=3;年龄70-74岁男性n=3，女性n=3;年龄80-84岁男性n=4，女性n=4），并使用临床双能X射线吸收测定系统评估BMD。Micro-CT图像将用于测量每个椎骨的骨形态参数。将获得一系列DEI反射率分布图像，并将这些图像组合成2D图像，映射椎骨中每个位置处的优选取向方向和DA。将使用线性回归分析阐明金标准骨测量值与基于DEI的测量值之间的数学关系。在具体目标2中，我们将阐明椎体强度和刚度与各向异性的DE测量程度之间的关系。将进行生物力学测试，以评估椎骨的强度和刚度。将计算每个椎骨的刚度和强度与DE I测量的DA之间的相关系数。多元回归分析将确定结合BMD的DEI测量用于评估骨强度的有效性。在这项研究中，我们将建立DEI的敏感性DA在椎骨微结构和验证一个新的微结构评估工具，预测骨折强度和刚度在完整的椎骨。DEI的独特能力，评估微结构恶化，否则无法分辨的尺寸尺度将给临床医生一个强大的新工具，评估骨折的风险。这些发现将推动未来的多项研究，我们将把这项技术应用于临床。

 DESCRIPTION (provided by applicant): Osteoporosis is "a systemic disease characterized by low bone mass and microarchitectural deterioration of bone tissue." The current clinical assessment metric, bone mineral density (BMD), sheds little light on microarchitectural deterioration. BMD used in combination with the degree of anisotropy (DA) in the bone microarchitecture is strongly predictive of vertebral strength and stiffness, but critical barriers preclude the clinical assessment of the degree of anisotropy in bone, especially within vertebrae where fractures have a high mortality and are highly predictive of future fractures. A low dose, non-invasive tool capable of measuring DA in vertebrae would overcome these barriers and provide clinicians with a more specific and individualized metric for bone strength and fracture risk. In this application, we propose to develop such a tool based on diffraction enhanced imaging (DEI), a phase contrast x-ray imaging technique. DEI can detect extremely small angular spreading that occurs when an x-ray beam is refracted by microstructures in bone. DEI has directional sensitivity that enables it to measure the angular orientation and the degree of anisotropy in the refracting microarchitecture. In this proof-of-principle study, our goal is to elucidate the relationship between the DEI- measured degree of anisotropy and the strength and stiffness of the vertebrae. In Specific Aim 1, we will establish DEI's ability to measure the degree of anisotropy in vertebrae through comparing the DEI-measured degree of anisotropy to the gold standard measure from micro-CT. Cadaveric vertebrae (age 60-64 male n=3, female n=3; age 70-74 male n=3, female n=3; and ages 80-84 male n=4, female n=4) will be obtained and the BMD will be assessed with a clinical dual-energy x-ray absorptiometry system. Micro-CT images will be used to measure bone morphology parameters of each vertebra. A series of DEI reflectivity profile images will be obtained and these images will be combined into 2D images mapping the preferred orientation direction and DA at each position in the vertebra. Linear regression analysis will be used to elucidate the mathematical relationship between gold standard bone measurements and the DEI-based measures. In Specific Aim 2, we will elucidate the relationship between vertebral strength and stiffness and the DEI-measured degree of anisotropy. Biomechanical testing will be performed to assess the strength and stiffness of the vertebrae. The correlation coefficient between the stiffness and strength of each vertebra and the DEI-measured DA will be calculated. Multiple regression analysis will determine the effectiveness of the DEI-measures in combination with BMD for assessing bone strength. In this study, we will establish DEI's sensitivity to DA in vertebral microarchitecture and validate a nove microarchitectural assessment tool for predicting fracture strength and stiffness in intact vertebrae. DEI's unique capability for assessing microarchitectural deterioration at otherwise non-resolvable size-scales will give clinicians a powerful new tool for assessing fracture risk. These findings will drive multiple future studies where we will translate this technology into the clinic.