Raman Markers of Allograft Osseointegration

描述（由申请人提供）：总体目标是开发非侵入性弥漫拉曼断层扫描方法，用于评估大鼠模型中同种异体骨移植的状态以及骨修复和愈合中的其他问题（即微损伤）。这些应用推进了两个领域的概念，包括骨移植生物学的重要治疗发展，以及实现具有化学特定信息的全新类型的成像技术。该项目将考虑问题的光学、生物、成像和数据缩减方面，新的体内成像技术将用于无创地研究移植物的成功或失败。具有由大鼠后肢的微计算机断层扫描（micro-CT）数据定义的几何形状的体模将用于准确地再现骨骼和覆盖组织的几何形状。模型将包含明胶（基质替代物）、羟基磷灰石（矿物质替代物）、脂质和光吸收分子，以模拟组织光学和拉曼光谱。这些模型将用于定义和测试光纤拉曼探针的几何形状，并评估运动伪影等问题。我们的候选拉曼探针几何形状是圆周照明和收集，但也会考虑其他几何形状。断层扫描重建软件将被修改以用于低信噪比拉曼数据。将开发一种新的最大似然方法，用于从发射拉曼散射光的数据集中提取拉曼光谱和计算拉曼强度。拉曼带强度比和多元统计参数将区分新建模的大鼠骨组织和光谱相似的同种异体移植物。使用其他成像方式（MRI、微型 CT）可以获得额外的空间信息。大鼠模型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建模骨组织的能力。同种异体移植和微损伤实验的拉曼成像结果测量将与其他生物力学和组织化学技术相关。公共健康相关性：同种异体骨移植物（来自尸体捐赠者的无菌骨组织）被用作骨肉瘤和其他骨癌病例中切除的大量组织的替代品。由于这些移植物通常无法融入健康组织，因此开发能够研究失败机制并最终可用于人类受试者的方法非常重要，以早期评估同种异体移植物或其他骨修复手术的成功或失败。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Bone allografts, sterilized bone tissue from a cadaveric donor, are used as replacements for massive amounts of tissue removed in cases of osteosarcoma and other bone cancers. Because these grafts often fail to integrate into the healthy tissue, it is important to develop methods that can study the failure mechanisms and that can ultimately be used in human subjects for early evaluation of the success or failure of allografts or other bone repair procedures.