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(Investigative Ophthalmology and Visual Science. 2004;45:2391-2398.)
© 2004 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.03-1381
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Dynamic Contrast-Enhanced MRI Measurements of Passive Permeability through Blood Retinal Barrier in Diabetic Rats

Bruce A. Berkowitz,1,2 Robin Roberts,1 Hongmei Luan,1 Jamie Peysakhov,1 Xianzhi Mao,3 and Kenneth A. Thomas3

1From the Department of Anatomy and Cell Biology, Wayne State University, Detroit, Michigan; 2Kresge Eye Institute, Wayne State University, Detroit, Michigan; and 3Department of Cancer Research, Merck Research Laboratories, West Point, Pennsylvania.

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 (cm3/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.




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