MULTIPARAMETRIC STUDIES OF CARTILAGE INTEGRITY

描述：（改编自研究者摘要）骨关节炎和 类风湿性关节炎是一种相对普遍的疾病， 软骨逐渐被破坏。 能够充分 了解这些疾病状态并制定合理的诊断， 预防和治疗战略受到阻碍， 不能评估体内软骨的功能状态。 的 申请人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 基于对特定MR敏感性的基本理解， 软骨的功能相关特征。 软骨作为承重组织的能力直接影响着 与细胞外基质的组成和结构有关。 糖胺聚糖（GAG）和胶原蛋白是主要成分 软骨基质，并在很大程度上负责 组织的压缩和拉伸强度。 的 水通过组织的运输是基质结构的量度。 完整性，是药物、营养素和其他 溶质可以到达软骨细胞。 调查人员最近 显示软骨的糖胺聚糖含量可以测量 胶原蛋白是主要的软骨成分， 有助于称为磁化转移的MR效应。 他们 最近已经证明，小溶质的扩散率， 可以通过MR测量软骨。 本项目的具体目标是：（1）将联合收割机 三个磁共振（MR）实验（钠，磁化 转移和扩散）进行多参数评价的样品 活的软骨细胞 这些技术将应用于 研究压迫的生理和病理扰动， 白细胞介素-1降解。 (2)建立磁共振成像 (MRI)完整软骨的多参数评估方案 异质性样品，并将该技术应用于人类的研究 软骨样本在疾病的各个阶段。 糖胺聚糖、胶原蛋白和转运的联合测量 软骨的（扩散率）特性应该提供独特的 有机会非破坏性地研究和监测的进展， 在关节炎的早期阶段基质破坏，并评估 在补充基质方面的治疗效果 在体外和体内系统中的成分。 无损 MR研究的性质提供了强大的能力， 对同一样本（或患者）进行动力学或连续研究。 这 结合非破坏性的，功能相关的研究， 软骨目前在实验或临床上是不可行的 设置.

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.