Dynamic contrast-enhanced MRI measurements of passive permeability through blood retinal barrier in diabetic rats
Dynamic contrast-enhanced MRI measurements of passive permeability through blood retinal barrier in diabetic rats
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DOI：
10.1167/iovs.03-1381
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发表时间：
2004-07-01
影响因子：
4.4
通讯作者：
Thomas, KA
中科院分区：
文献类型：
--
作者：
Berkowitz, BA;Roberts, R;Thomas, KA
目的。为了验证动态对比增强磁共振成像（DCE-MRI）在实验性糖尿病视网膜病变中提供被动血液视网膜屏障通透性表面积产物（BRB PS）的有效体内测量的假设。采用DCE-MRI和Gd-DTPA （MW 590 Da）测量了脲烷麻醉对照大鼠、碘酸钠治疗大鼠、玻璃体内注射人血清白蛋白（HSA）或血管内皮生长因子/血管通透性因子（VEGF/VPF）大鼠以及糖尿病2、4、6或8个月大鼠的BRB PS （cm(3)/min）。与对照组相比，碘酸钠处理大鼠的BRB PS增加了8倍（P < 0.05）。此外，在碘酸处理的大鼠中，平均玻璃体信号增强与Gd-DTPA剂量呈线性相关（r = 0.91, P < 0.0001）。注射后6小时，VEGF/ vpf处理大鼠的BRB PS比注射HSA的大鼠增加了3倍（P < 0.05）。2、4、6月龄糖尿病大鼠BRB - PS值与对照组无显著差异（P < 0.05）。糖尿病患者8个月后，PS值较对照组增加2倍（P < 0.05）。DCE-MRI显示BRB在死亡前立即发生渗漏，可能在需要去核或视网膜隔离来评估视网膜通透性的方法中人为地增加了视网膜通透性。DCE-MRI提供了一种敏感、无创、线性的检测方法，可以准确测量实验性糖尿病患者被动BRB PS，没有潜在的与死亡和去核相关的伪影。DCE-MRI BRB PS测量有望为药物治疗疗效提供有用的替代标志物。
PURPOSE. To test the hypothesis that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) provides a useful in vivo measure of passive blood retinal barrier permeability surface area product (BRB PS) in experimental diabetic retinopathy.METHODS. BRB PS (cm(3)/min) was measured using DCE-MRI and Gd-DTPA (MW 590 Da) in urethane-anesthetized control rats, sodium iodate-treated rats, rats receiving intravitreally injected human serum albumin (HSA) or vascular endothelial growth factor/vascular permeability factor (VEGF/VPF), or in rats that were diabetic for 2, 4, 6, or 8 months.RESULTS. Sodium iodate-treated rats exhibited an eightfold increase (P < 0.05) in BRB PS compared to that in control animals. Furthermore, in iodate-treated rats, the average vitreous signal enhancement was linearly dependant on Gd-DTPA dose (r = 0.91, P < 0.0001). Six hours postinjection, VEGF/VPF-treated rats exhibited a threefold increase in BRB PS (P < 0.05) compared to eyes injected with HSA. In 2-, 4-, and 6-month diabetic rats, BRB PS was not significantly different (P > 0.05) from control BRB PS values. After 8 months of diabetes, a twofold increase (P < 0.05) in PS over control PS values was found. DCE-MRI demonstrated that the BRB becomes leaky immediately before death, possibly causing an artificial increase in retinal permeability in methods that require enucleation or retinal isolation to assess permeability.CONCLUSIONS. DCE-MRI provides a sensitive, noninvasive, and linear assay that accurately measures, without potential artifacts associated with death and enucleation, passive BRB PS in experimental diabetes. DCE-MRI BRB PS measurements are expected to provide a useful surrogate marker of drug treatment efficacy.