Dynamic contrast-enhanced MRI measurements of passive permeability through blood retinal barrier in diabetic rats.
OBJECTIVE
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 dependent 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.
Berkowitz
Bruce A
BA
Department of Anatomy and Cell Biology, and Kresge Eye Institute, Wayne State University, Detroit, Michigan 48201, USA. baberko@med.wayne.edu
Roberts
Robin
R
Luan
Hongmei
H
Peysakhov
Jamie
J
Mao
Xianzhi
X
Thomas
Kenneth A
KA
D000818:Animals; D001813:Blood-Retinal Barrier; D002199:Capillary Permeability / Q000187:drug effects; D003287:Contrast Media; D003921:Diabetes Mellitus, Experimental / Q000175:diagnosis*; D003930:Diabetic Retinopathy / Q000175:diagnosis*; D019786:Gadolinium DTPA; D007452:Iodates / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D051381:Rats; D012171:Retinal Vessels / Q000473:pathology*; D012709:Serum Albumin / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D003287:Contrast Media; D007452:Iodates; D012709:Serum Albumin; D042461:Vascular Endothelial Growth Factor A; D019786:Gadolinium DTPA; C032285:sodium iodate