Elucidating Vertebral Microstructure with Diffraction Enhanced Imaging

 描述(申请人提供)：骨质疏松症是一种以骨量减少和骨组织微结构恶化为特征的全身性疾病。目前的临床评估指标，骨密度(BMD)，几乎没有揭示微结构的恶化。骨密度结合骨骼微结构中的各向异性程度(DA)可以很好地预测脊柱的强度和僵硬，但关键障碍 排除了对骨的各向异性程度的临床评估，特别是在椎骨内，那里的骨折死亡率很高，并且对未来的骨折有很高的预测性。一种能够测量椎骨中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。在这一应用中，我们建议开发一种基于衍射增强成像(DEI)的工具，这是一种相位对比X射线成像技术。DEI可以探测到当X射线束被骨骼中的微结构折射时发生的极小的角扩散。DEI具有方向敏感性，使其能够测量折射微体系结构中的角方向和各向异性程度。在这项原则验证研究中，我们的目标是阐明各向异性的确切程度与椎骨的强度和硬度之间的关系。在具体目标1中，我们将通过比较Dei测量的各向异性程度与来自Micro-CT的金标准测量来确定Dei测量椎体各向异性程度的能力。取身体椎体标本(年龄60-，男3例，女3例；年龄70-74岁，男3例，女3例；年龄80-84岁，男4例，女4例)，采用临床双能X线骨密度仪进行骨密度测量。将使用Micro-CT图像来测量每个椎体的骨形态参数。将获得一系列DEI反射率轮廓图像，并将这些图像组合成2D图像，以绘制椎体中每个位置的首选方向和DA。将使用线性回归分析来阐明黄金标准骨测量和基于DEI的测量之间的数学关系。在特定的目标2中，我们将阐明椎体强度和刚度之间的关系以及明显的各向异性程度。将进行生物力学测试，以评估椎骨的强度和刚度。计算每个椎体的刚度和强度与测量的DA之间的相关系数。多元回归分析将确定这些指标结合BMD评估骨强度的有效性。在这项研究中，我们将在椎体微结构中建立DEI对DA的敏感性，并验证一种新的微结构评估工具来预测完整椎体的骨折强度和刚度。Dei评估微结构恶化的独特能力将为临床医生提供一个强大的新工具来评估骨折风险。这些发现将推动未来的多项研究，我们将把这项技术转化为临床。

 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.