Raman Markers of Allograft Osseointegration

同种异体移植骨整合的拉曼标记

• 批准号: 7730698
• 负责人: MICHAEL DAVID MORRIS
• 金额: $ 49.46万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7730698
• 关键词: Address; Algorithms; Allografting; Animal Model; Area; Autologous Transplantation; Biological; Biology; Biomechanics; Bone Regeneration; Bone Tissue; Bone Transplantation; Calibration; Chemicals; Collection; Computer software; Data; Data Set; Defect; Development; Diffuse; Evaluation; Failure; Fiber Optics; Fluorescence; Gelatin; Healed; Histologic; Hydroxyapatites; Image; Imaging technology; Light; Lighting; Limb structure; Lipids; Longitudinal Studies; Magnetic Resonance Imaging; Malignant Bone Neoplasm; Measurement; Measures; Methodology; Methods; Minerals; Modeling; Morphologic artifacts; Motion; Natural regeneration; Noise; Optics; Osseointegration; Outcome; Outcome Measure; Procedures; Production; Property; Public Health; Raman Spectrum Analysis; Rattus; Recovery; Resolution; Signal Transduction; Solid; Solutions; Specialist; Sprague-Dawley Rats; Staging; Statistical Methods; Techniques; Technology; Testing; Time; Tissues; Training; Work; X-Ray Computed Tomography; absorption; allogenic bone transplantation; bone; healing; human subject; image reconstruction; imaging modality; implantation; improved; in vivo; light scattering; long bone; osteosarcoma; phantom model; public health relevance; reconstruction; repaired; research study; response; soft tissue; success; therapeutic development; tibia; tissue phantom; tomography; tool

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.

描述（由申请人提供）：总体目标是开发无创弥漫性拉曼断层扫描方法，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（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，以及具有化学特异性信息的全新类型的成像技术的实现。该项目将考虑该问题的光学、生物学、成像和数据减少方面，新的体内成像技术将用于无创研究移植物的成功或失败。通过对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幻影将用于精确地再现骨骼和上覆组织的几何形状。幻影将包含明胶（基质替代品），羟基磷灰石（矿物替代品），脂质和光吸收分子来模拟组织光学和拉曼光谱。这些幻影将用于定义和测试光纤拉曼探针的几何形状，并评估诸如运动伪影之类的问题。我们的候选拉曼探针几何是周向照明和收集，但其他几何将被考虑。层析成像重建软件将进行修改，以用于低信噪比拉曼数据。将开发一种新的最大似然方法，用于从发射的拉曼散射光数据集提取拉曼光谱和计算拉曼强度。拉曼波段强度比和多元统计参数将区分新模型大鼠骨组织和光谱相似的同种异体移植物。通过其他成像方式（MRI, micro-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模型骨组织的能力。结果同种异体移植和微损伤实验的拉曼成像测量将与其他生物力学和组织化学技术相关。公共卫生相关性：骨同种异体移植物，来自尸体供体的无菌骨组织，在骨肉瘤和其他骨癌病例中被用作大量切除组织的替代品。由于这些移植物经常不能融入健康组织，因此开发能够研究失败机制的方法并最终用于人类受试者，以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是很重要的。