Analysis of Cartilage Morphology and sGAG Content via Contrast Enhanced Micro-CT

通过增强显微 CT 分析软骨形态和 sGAG 含量

• 批准号: 7088193
• 负责人: MARC Elliot LEVENSTON
• 金额: $ 19.49万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7088193
• 关键词: articular cartilage; cartilage; joints; model; morphology; tissues

DESCRIPTION (provided by applicant): Osteoarthritis (OA) is a potentially debilitating condition of articular joints characterized by a gradual but progressive degradation of the cartilage extracellular matrix. Interest in OA pathogenesis and in models for testing disease modifying therapies has motivated the development of numerous small animal models for joint degeneration. However, while matrix changes in such models can be evaluated via histology and gross biochemical analysis, determination of detailed spatial information regarding matrix changes is challenging at best. A technique capable of high resolution, nondestructive quantification of cartilage morphology and matrix composition could revolutionize the evaluation of such small animal models. The goal of this Exploratory/Developmental Research Grant proposal is to develop a novel imaging methodology utilizing contrast-enhanced microcomputed tomography (UCT) to obtain high resolution, three-dimensional (3D) data describing the morphology and sulfated glycosaminoglycan distribution of small animal articular cartilage. While a powerful tool for quantitative morphological and microstructural analysis of bone and a variety of biomaterials, UCT has not been useful for analysis of cartilage or other soft tissues because of their minimal X-ray attenuation. We have recently performed preliminary validation of a novel UCT application for quantification of the Equilibrium Partitioning of an Ionic Contrast agent UCT (EPIC-UCT) that relies on preferential exclusion of a negatively charged, radio-opaque contrast agent from tissue regions with a greater negative fixed charge density (primarily due to sulfated glycosaminoglycans (sGAGs) on proteoglycans). The specific aims of the proposed research are to (1) evaluate the use of EPIC-UCT to quantify the morphology of rat articular cartilage; (2) evaluate the use of EPIC-UCT to quantify the sGAG distribution of rat articular cartilage; and (3) evaluate the use of EPIC-UCT for in situ evaluation of articular cartilage in intact rat knees using direct intraarticular injection of the contrast agent. In this 2-year project, we aim to develop a methodology suitable for end-stage analysis of articular cartilage in small rodent models and to have laid the groundwork for studies extending this methodology to longitudinal, in vivo tracking of cartilage matrix changes.

描述(由申请人提供)：骨关节炎(OA)是一种潜在的关节衰弱状态，其特征是软骨细胞外基质逐渐但渐进地降解。对骨关节炎发病机制和疾病修正疗法测试模型的兴趣推动了许多关节退行性变小动物模型的发展。然而，虽然这种模型中的基质变化可以通过组织学和大体生化分析来评估，但确定关于基质变化的详细空间信息充其量也是具有挑战性的。一种能够高分辨率、无损地量化软骨形态和基质成分的技术可能会彻底改变对这种小动物模型的评估。这项探索性/开发性研究资助计划的目标是开发一种新的成像方法，利用对比度增强的显微计算机断层扫描(UCT)获得高分辨率的三维(3D)数据，描述小动物关节软骨的形态和糖胺多糖的分布。虽然UCT是骨和各种生物材料的定量形态和微观结构分析的有力工具，但由于其X射线衰减最小，因此在软骨或其他软组织的分析中并不有用。我们最近对一种新的UCT应用进行了初步验证，该应用用于量化离子造影剂UCT(EPIC-UCT)的平衡分配，该应用依赖于从具有较大负固定电荷密度的组织区域优先排除带负电荷的不辐射不透明的造影剂(主要是由于蛋白多糖上的硫酸化糖胺聚糖(SGAGs))。这项研究的具体目的是：(1)评估EPIC-UCT用于量化大鼠关节软骨的形态；(2)评估EPIC-UCT用于量化大鼠关节软骨SGAG的分布；以及(3)评估EPIC-UCT用于直接关节内注射造影剂对完整大鼠膝关节关节软骨的原位评估。在这个为期两年的项目中，我们的目标是开发一种适合于小型啮齿动物模型中关节软骨的终末期分析的方法，并为将该方法扩展到纵向、活体跟踪软骨基质变化的研究奠定基础。