Raman Markers of Allograft Osseointegration

摘要 总体目标是发展非侵入性扩散拉曼层析成像方法，用于评估 大鼠模型中骨同种异体移植物的状态以及骨修复和愈合中的其他问题（即微损伤）。的 应用在两个领域推进了概念，包括骨移植的重要治疗进展 生物学，以及在实现一种全新的类型的成像技术，具有化学特异性 信息.该项目将考虑光学，生物，成像和数据减少方面的 新的体内成像技术将用于研究移植物的成功或失败非侵入性。 将使用大鼠后肢上的微计算机断层扫描（micro-CT）数据定义的几何形状的骨骼， 用于精确地再现骨和覆盖组织的几何形状。明胶将含有明胶（基质 替代物）、羟基磷灰石（矿物替代物）、脂质和光吸收分子来模拟组织光学 和拉曼光谱。这些体模将用于定义和测试光纤拉曼探头几何形状， 以评估诸如运动伪影之类的问题。我们的候选拉曼探针几何形状是圆周的 照明和收集，但将考虑其他几何形状。断层重建软件将 可以被修改以用于低信号/噪声比拉曼数据。一种新的最大似然方法将是 开发用于提取拉曼光谱和计算拉曼强度从数据集的汇出 拉曼散射光拉曼谱带强度比和多元统计参数将区分 新造的大鼠骨组织和光谱相似的同种异体移植物之间的差异。附加空间 可以使用其他成像模式（MRI、微型CT）获得信息。大鼠模型中的纵向研究 将用于评估该技术区分同种异体移植组织和新模型组织的能力。 骨组织同种异体移植物和微损伤实验的结果拉曼成像测量将 与其他生物力学和组织化学技术相关。

Abstract The overall aim is development of noninvasive diffuse Raman tomographic methodology for evaluating the state of bone allografts in a rat model and other problems in bone repair and healing (i.e. microdamage). The applications advance concepts in two areas, including important therapeutic developments in bone graft biology, as well as in the realization of an entirely new type of imaging technology with chemically specific information. The project will consider the optical, biological, imaging, and data reduction aspects of the problem, and the new in vivo imaging technology will be used to study graft success or failure noninvasively. Phantoms with geometries defined by micro-computed tomography (micro-CT) data on rat hind limbs will be used to reproduce bone and overlying tissue geometry accurately. Phantoms will contain gelatin (matrix surrogate), hydroxyapatite (mineral surrogate), lipids, and light absorbing molecules to model both tissue optics and Raman spectra. These phantoms will be used to define and test fiber optic Raman probe geometry, and to assess such problems as motion artifacts. Our candidate Raman probe geometry is circumferential illumination and collection, but other geometries will be considered. Tomographic reconstruction software will be modified for use with low signal/noise ratio Raman data. A new maximum likelihood methodology will be developed for extraction of Raman spectra and calculation of Raman intensities from data sets of remitted Raman-scattered light. Raman band intensity ratios and multivariate statistical parameters will differentiate between newly modeled bone tissue of the rat and the spectroscopically similar allografts. Additional spatial information can be gained using other imaging modalities (MRI, micro-CT). Longitudinal studies in a rat model will be used to assess the ability of this technology to distinguish between allograft tissue and newly modeled bone tissue. Outcome Raman imaging measures of the allograft and microdamage experiments will be correlated with other biomechanical and histochemical techniques.