MULTIPARAMETRIC STUDIES OF CARTILAGE INTEGRITY

描述：(改编自《调查者摘要》)骨关节炎和 类风湿关节炎是一种相对流行的疾病，在这些疾病中，关节 软骨逐渐被破坏。能够充分地 了解这些疾病状态并制定合理的诊断， 预防和治疗策略一直受到 无法评估体内软骨的功能状态。这个 申请者的长期目标是建立磁共振(MR) 软骨成分和功能评价技术 并将这些技术应用于软骨生理学和生物力学的研究 病理生理学。他们的方法是开发一种多参数协议 基于对MR对特定的敏感性的基本理解 软骨的功能相关特征。 软骨作为承重组织发挥作用的能力直接 与细胞外基质的组成和结构有关。 糖胺多糖(GAG)和胶原蛋白是主要成分 软骨基质，并在很大程度上负责 组织的抗压强度和抗拉强度。这个 水通过组织的运输是基质结构的一种衡量标准 正直，是药物、营养素和其他物质 溶质可以到达软骨细胞。调查人员最近 表明可以测量软骨中的糖胺多糖含量。 在钠的作用下，胶原蛋白是主要的软骨成分， 有助于产生称为磁化传递的MR效应。他们 最近证明了小分子溶质在溶液中的扩散系数 软骨可以用MR先生测量。 本项目的具体目标如下：(1)将 三个磁共振(MR)实验(钠、磁化 传递和扩散)，用于样本的多参数评估 培养中的活软骨。这些技术将应用于 压缩和挤压引起的生理和病理扰动的研究 白介素1的降解。(2)建立磁共振成像 (MRI)多参数评价完整软骨的方法 异质样本，并将这些技术应用于人类研究 病程不同阶段的软骨标本。 糖胺多聚糖、胶原蛋白和转运的联合测量 (扩散性)软骨的特性应该提供独特的 非破坏性地研究和监测疾病进展的机会 关节炎早期的基质破坏和评估 从补充基质的角度看治疗的效果 体外和体内系统的成分。非破坏性的 磁共振研究的性质提供了强大的进行能力 对同一标本(或病人)进行的动态或连续研究。这 结合非破坏性的、与生活功能相关的研究 软骨目前在实验或临床上是不可行的 布景。

DESCRIPTION: (Adapted From Investigator's Abstract) Osteoarthritis and rheumatoid arthritis are relatively prevalent diseases in which articular cartilages become progressively destroyed. The ability to fully understand these disease states and to formulate sensible diagnostic, preventive, and therapeutic strategies has been hampered by the inability to assess the functional state of cartilage in vivo. The applicants' long term goal is to establish magnetic resonance (MR) techniques for the compositional and functional evaluation of cartilage and to apply these techniques for the study of cartilage physiology and pathophysiology. Their approach is to develop a multiparametric protocol grounded in a basic understanding of the MR sensitivity to specific functionally relevant features of cartilage. The ability of cartilage to function as a load bearing tissue is directly related to the composition and structure of the extracellular matrix. Glycosaminoglycans (GAGs) and collagen are the predominant constituents of cartilage matrix, and are responsible in large part for the compressive and tensile strength of the tissue, respectively. The transport of water through the tissue is a measure of matrix structural integrity and is a direct indicator of how drugs, nutrients and other solutes may reach the cartilage cells. The investigators have recently shown that the glycosaminoglycan content of cartilage can be measured with sodium MR. Collagen is the predominant cartilage constituent which contributes to an MR effect referred to as magnetization transfer. They have recently demonstrated that the diffusivity of small solutes in cartilage can be measured by MR. The specific aims for this project are the following: (1) To combine the three magnetic resonance (MR) experiments (sodium, magnetization transfer, and diffusion) for a multiparametric evaluation of samples of living cartilage in culture. The techniques will be applied to the study of the physiologic and pathologic perturbations of compression and interleukin-1 degradation. (2) To establish magnetic resonance imaging (MRI) protocols for the multiparametric evaluation of cartilage in intact heterogeneous samples, and to apply the techniques to the study of human cartilage samples in various stages of disease. A combined measure of glycosaminoglycans, collagen, and transport (diffusivity) properties of cartilage should provide the unique opportunity to non-destructively study and monitor the progression of matrix destruction during the early stages of arthritis and to evaluate the efficacy of therapeutic endeavors in terms of replenishing matrix constituents both in vitro and in vivo systems. The nondestructive nature of the MR studies provides the powerful capability of conducting kinetic or sequential studies on the same specimen (or patient). This combination of nondestructive, functionally relevant studies of living cartilage is currently not feasible in an experimental or clinical setting.