Assessment of Placental Perfusion in the Preeclampsia L-NAME Rat Model with High-Field Dynamic Contrast-Enhanced MRI

Abstract

Purpose: To evaluate placental function and perfusion in a rat model of preeclampsia infused with L-nitro-arginine methyl ester (L-NAME) by dynamic contrast-enhanced (DCE) MRI using gadolinium chelates. Methods: Pregnant female Sprague-Dawley rats were fitted on embryonic day 16 (E16) with subcutaneous osmotic minipumps loaded to deliver, continuously, L-NAME (50 mg/day per rat; case group) or saline solution (control group). DCE MRI was performed on E19 using gadolinium chelates and a 4.7-T MRI apparatus for small animals. Quantitative analysis was performed using an image software program: placental blood flow (perfusion in mL/min/100 mL of placenta) and fractional volume of the maternal vascular placental compartment (ratio between the placental blood volume and the placental volume, Vb in %) were calculated by compartmental analysis. Results: A total of 176 placentas (27 rats) were analyzed by DCE MRI (97 cases and 79 controls). The model was effective, inducing intrauterine growth retardation, as there was a significant difference between the two groups for placental weight (p < 0.01), fetal weight (p = 0.019), and fetal length (p < 0.01). There was no significant difference in placental perfusion between the L-NAME and control groups (140.1 ± 74.1 vs. 148.9 ± 97.4, respectively; p = 0.496). There was a significant difference between the L-NAME and control groups for Vb (53 ± 12.9 vs. 46.7 ± 9%, respectively; p < 0.01). Conclusion: In the L-NAME preeclampsia model, placental perfusion is normal and the fractional blood volume is increased, suggesting that preeclampsia is not always expressed as a result of decreased placental perfusion. This highlights the usefulness of MRI for investigating the physiopathology of preeclampsia.

Efficacy of Low Molecular Heparin on Preeclampsia by Inhibiting Apoptosis of Trophoblasts via the p38MAPK Signaling Pathway

“…In this study, we constructed preeclampsia rat models through L-nitroarginine methyl ester [ 17 ], finding that blood pressure and 24 h proteinuria levels of the rats significantly increased and the number of fetal rats and weight of them and the weight of placenta in them decreased significantly. In addition, we also found that the apoptosis rate of placenta tissue cells of the rats increased significantly, while after intervention of low molecular heparin, those manifestations were improved.…”

Human placental perfusion measured using dynamic contrast enhancement MRI

“…Kinetic signal intensity curves demonstrate the relative signal intensity in a region of interest plotted over time. MR images were analyzed on a workstation using software (PhysioD3D) [ 19 ] that was locally developed using MATLAB (R2012b; MathWorks, USA) [ 9 – 14 ]. Manual segmentation of the arterial input function (AIF) and the placenta was performed.…”

“…Functional MRI has already been used to evaluate cerebral, cardiac, tumor and hepatic perfusion [ 6 – 8 ], and could provide new insights into placental function. Our team has previously developed animal models of dynamic contrast enhanced (DCE) MRI [ 9 – 14 ]. The feasibility of DCE MRI has also been demonstrated in primates [ 15 ].…”

Advances in imaging feto-placental vasculature: new tools to elucidate the early life origins of health and disease

“…gadolinium chelate) has been used to quantify placental function such as blood volume, blood flow, oxygenation and perfusion rate in different placental compartments. 169 Recently, DCE-MRI has been used to investigate placental perfusion in hypoxic-induced FGR rodents, [170][171][172] pre-eclamptic rats (induced by continuous delivery of L-nitro-arginine methyl ester to chronically inhibit nitric oxide synthase) 173 and prenatal alcohol exposure in monkeys. 151 Placental blood flow and perfusion rate were reduced significantly in the animal models of hypoxia and ethanol exposure 151,170,171 but not in a model of pre-eclampsia.…”

“…151 Placental blood flow and perfusion rate were reduced significantly in the animal models of hypoxia and ethanol exposure 151,170,171 but not in a model of pre-eclampsia. 173 A combination of DCE-MRI and fluorescence imaging has also been used to delineate and quantify the volume of maternal and fetal compartments in mouse placenta. 174 Therefore, both BOLD-MRI and DCE-MRI can be used for in vivo 3D assessment of placental and fetal function, blood flow and oxygenation.…”