基于动态增强磁共振的大鼠糖尿病视网膜病变生物标记物的实验研究

Diabetic retinopathy(DR) is the most common and serious complication associated with diabetes, which is the leading cause of legal blindness and vision loss among working-age adults in the world-wide focus. The pathological mechanism is thought to result from breakdown of the blood-retinal barrier(BRB). However traditional methods for evaluating the damage to the BRB have many substantial limitations, and can not be analyzed quantitatively. Which retinal abnormalities can be found early before these traditional available methods. This is the timing associated with treatment. As a keytiming, subsequet abnormalities can be prevented effectually during this period and a better understanding of DR mechanisms associated with BRB breakdown is also expected..Based upon the acquired multi-modal information from animal(rats) experiment in this study, we will try to quantitatively ananlyze the degree of BRB damage and predilection site,screen biological marker and determine its sensibility and specificity by correlating acquisitional data on dynamic contrast enhanced magnetic resonance imaging(DCE-MRI), including passive blood retinal barrier permeability surface area product (BRB PS),time to peak enhancement(Tpeak),the first signal intensity(SIpeak),slope,washout ratio, with pathological findings. All these findings can be expected to facilitate the assessment of the effective timing of medical therapy and provide objective support for early treatment.

糖尿病视网膜病变(DR)是糖尿病所致不可逆盲的最严重的并发症，已经成为世界性的难题之一。血-视网膜屏障（BRB）破坏是DR主要的发生机制，然而采用传统方法检测BRB的破坏情况有很多局限性，且不能进行定位及定量分析。在这些检查发现异常变化之前视网膜组织在疾病早期会有哪些改变？这些均关系到临床干预的时间窗问题。作为关键的时间窗，在此阶段进行有效的干预可能延缓甚至阻止病情向不可逆的方向发展，也为研究DR的发病机制提供了契机。.本项目着眼于动物实验，通过对大鼠DR的动态增强磁共振各项参数的系列研究，包括表面积渗透量值、早期峰值强化时间、最大强化时间、动态增强曲线的斜率、流出率等，与病理学改变进行对照，量化分析DR大白鼠BRB的破坏程度及好发部位，筛选并确定大白鼠DR不同病程BRB渗漏部位的生物标记物及其敏感性、特异性，探讨DR进行干预的有效时间窗，为DR的早期干预提供客观依据。

糖尿病视网膜病变(DR)是糖尿病所致不可逆盲的最严重的并发症，血-视网膜屏障（BRB）破坏是DR 主要的发生机制，然而采用传统方法检测BRB 的破坏情况有很多局限性，且不能进行定位及定量分析。本项目着眼于动物实验，通过对大鼠DR 的动态增强磁共振各项参数的系列研究，与病理学改变进行对照，量化分析DR 大白鼠BRB 的破坏程度及好发部位，筛选并确定大白鼠DR不同病程BRB渗漏部位的生物标记物，探讨DR进行干预的有效时间窗，为DR 的早期干预提供客观依据。研究结果表明大鼠视网膜的高场磁共振成像可分为三个带：紧邻玻璃体的高信号内带，由神经节细胞层、内核层及相应的视网膜血管组成；无血管的外核层及其感受器节段，表现为低信号；高信号的外带，巩膜血管层。BRB破坏处可显示视网膜前区玻璃体腔内高信号的顺磁性对比剂渗漏，且随着时间的延长范围逐渐扩大，其时间-信号曲线（TIC）呈持续上升型，这印证了进展期糖尿病视网膜病变会出现BRB的破坏，血管通透性增加，最终可能会发展成视网膜黄斑水肿及视网膜脱离。TIC曲线及BRB 破坏处被动渗透性的示踪影像学生物标记物BRB表面积渗透量（BRB PS）可用于检测BRB破坏范围及程度，且这种病理性变化早于视网膜脱离和临床症状，因此有望成为活体内监测病变进展的可靠参考指标。DCE-MRI可用于监测糖尿病视网膜病变BRB的破坏情况，可为糖尿病视网膜眼病的深入研究提供一种新方法、新思路，也可为糖尿病视网膜病变的疗效评估提供客观依据及必要的理论基础。