Raman Markers of Allograft Osseointegration

描述（由申请人提供）：总体目标是开发无创扩散拉曼断层扫描方法，用于评价大鼠模型中骨同种异体移植物的状态以及骨修复和愈合（即微损伤）中的其他问题。这些应用在两个领域推进了概念，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。该项目将考虑光学，生物，成像和数据减少方面的问题，新的体内成像技术将用于研究移植物的成功或失败的非侵入性。将使用具有由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重建器来准确地再现骨和覆盖组织的几何形状。生物样品将含有明胶（基质替代物）、羟基磷灰石（矿物替代物）、脂质和光吸收分子，以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，并评估运动伪影等问题。我们的候选拉曼探针的几何形状是圆周照明和收集，但其他的几何形状将被考虑。将修改断层重建软件，以用于低信噪比拉曼数据。一种新的最大似然方法将开发用于提取拉曼光谱和计算拉曼强度从数据集的拉曼散射光。拉曼谱带强度比和多变量统计参数将区分新建模的大鼠骨组织和光谱学上相似的同种异体移植物。可以使用其他成像模式（MRI、micro-CT）获得额外的空间信息。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建模骨组织的能力。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联。公共卫生相关性：同种异体骨移植，即来自尸体供体的灭菌骨组织，用于替代骨肉瘤和其他骨癌病例中切除的大量组织。因为这些移植物通常不能整合到健康组织中，所以重要的是开发可以研究失败机制并且最终可以用于人类受试者的方法，用于早期评估同种异体移植物或其他骨修复程序的成功或失败。

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.