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CONTRAST ENHANCED MRI OF EXPERIMENTAL UVEITIS

实验性葡萄膜炎的增强 MRI

基本信息

批准号：
2164621
负责人：
NANCY H KOLODNY
金额：
$ 10.43万
依托单位：
WELLESLEY COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-06-13 至 1999-06-12
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2164621
关键词：
antiinflammatory agents bioimaging /biomedical imaging blood aqueous barrier chemical synthesis contrast media eye agent eye disorder diagnosis eye pharmacology image enhancement iridocyclitis laboratory rabbit magnetic resonance imaging mathematical model method development noninvasive diagnosis tight junctions vascular endothelium permeability

项目摘要

The long-term objective of this proposal is to demonstrate that contrast- enhanced proton magnetic resonance imaging (1H MRI) can be used as a quantitative, non-invasive method for the study of normal and abnormal ocular processes. We have chosen experimental anterior uveitis as the condition through which to demonstrate this. Contrast in MR images results from the tissue variations of the inherent relaxation times (T1 and T2) of the protons in water molecules. The development of contrast agents, compounds that alter these protons' inherent relaxation rates (T1-1 and T2-1) has led to new types of studies; most recently contrast agents have been used to study dynamic ocular processes such as aqueous humor flow, molecular diffusion between the ciliary processes and the anterior chamber and permeability of the blood-retinal barrier. MRI allows the three-dimensional localization of such dynamic ocular processes, even in structures, such as the posterior chamber, unobservable by other in vivo methodologies. Idiopathic anterior uveitis (AU) is a sterile, non-suppurative inflammation of the anterior uvea. AU reflects a breakdown of the blood- aqueous barrier (BAB) that is characteristically acute and often recurrent. Currently available objective measures of severity provide little information regarding the dynamics of the inflammatory process, especially the process of BAB repair during resolution. Knowledge of these processes depends on a thorough understanding of protein diffusional mechanics in the normal and inflamed eye. To achieve our goals, contrast agents of protein-like molecular weights will be synthesized. The concentration dependence of their T1- or T2- relaxivities and MR image intensity enhancements will be determined. We will complete sequential contrast-enhanced MRI studies to monitor BAB permeability at several stages during the resolution phase of untreated and treated (using representative steroidal and non-steroidal anti- inflammatory agents) endotoxin-induced AU in rabbits. We will use our MRI data, combined with aqueous fluorophotometry and morphology data, and with computational models for the anterior diffusional pathway to assess the extent and location of disruption of the BAB by AU. We will determine if medications alter the mechanics of BAB repair or merely shorten its time course, and whether differences exist between the permeability of treated versus untreated eyes after clinical resolution of anterior uveitis. Using MRI for these studies affords us the unique opportunity to estimate whether these anti- inflammatory agents affect primarily vascular endothelia or ciliary epithelium by discerning whether leakage relents in the posterior chamber before or after it relents in the anterior chamber.

本提案的长期目标是展示这种对比- 增强质子磁共振成像（1H MRI）可用作用于研究正常和异常的定量、非侵入性方法眼突我们选择实验性前葡萄膜炎作为通过这种方式来证明这一点。 MR图像中的对比度是由固有的组织变化引起的。水分子中质子的弛豫时间（T1和T2）。的造影剂的发展，改变这些质子的化合物，固有的弛豫速率（T1-1和T2-1）导致了新类型的研究;最近造影剂已被用于研究动态眼过程，如房水流动，分子扩散之间睫状突和前房以及血视网膜屏障磁共振成像允许三维定位的这种动态的眼过程，甚至在结构中，如后部室，通过其他体内方法无法观察到。特发性前葡萄膜炎（Au）是一种无菌、非化脓性前葡萄膜的炎症。 Au反映了血液的分解水屏障（BAB），其特征是急性的，经常性的目前可用的严重程度客观衡量标准提供了关于炎症过程的动力学的信息很少，尤其是在消退过程中的BAB修复过程。知识这些过程依赖于对蛋白质的透彻理解，正常和发炎眼睛中的扩散机制。为了实现我们的目标，蛋白质样分子量的造影剂将被合成。 T1-或T2-的浓度依赖性将确定弛豫率和MR图像强度增强。我们将完成连续的对比增强MRI研究，以监测BAB 在未处理的药物的消退阶段期间的几个阶段的渗透性和治疗（使用代表性的类固醇和非类固醇抗- 致炎剂）内毒素诱导的家兔Au。我们将使用我们的MRI数据，结合水荧光光度法，形态学数据，并与计算模型的前扩散途径，以评估破坏的程度和位置， BAB由Au。我们将确定药物是否会改变 BAB修复或仅仅缩短其时程，是否存在差异治疗眼与未治疗眼的渗透性之间存在前葡萄膜炎的临床消退。在这些研究中使用MRI 给我们提供了一个独特的机会来评估这些反炎性因子主要影响血管内皮细胞或纤毛通过辨别后房渗漏是否缓解在前房中缓解之前或之后。