Abstract
Diffusion-weighted MRI on rodents could be valuable to evaluate pregnancy-related dysfunctions, particularly in knockout models whose biological nature is well understood. Echo Planar Imaging’s sensitivity to motions and to air/water/fat heterogeneities, complicates these studies in the challenging environs of mice abdomens. Recently developed MRI methodologies based on SPatiotemporal ENcoding (SPEN) can overcome these obstacles, and deliver diffusivity maps at ≈150 µm in-plane resolutions. The present study exploits these capabilities to compare the development in wildtype vs vascularly-altered mice. Attention focused on the various placental layers—deciduae, labyrinth, trophoblast, fetal vessels—that the diffusivity maps could resolve. Notable differences were then observed between the placental developments of wildtype vs diseased mice; these differences remained throughout the pregnancies, and were echoed by perfusion studies relying on gadolinium-based dynamic contrast-enhanced MRI. Longitudinal monitoring of diffusivity in the animals throughout the pregnancies also showed differences between the development of the fetal brains in the wildtype and vascularly-altered mice, even if these disparities became progressively smaller as the pregnancies progressed. These results are analyzed on the basis of the known physiology of normal and preeclamptic pregnancies, as well as in terms of the potential that they might open for the early detection of disorders in human pregnancies.
Highlights
Abbreviations ADC Apparent diffusion coefficient dynamic contrast-enhanced (DCE) Dynamic contrast enhanced EPI Echo planar imaging diffusion-weighted imaging (DWI) Diffusion weighted imaging intrauterine growth-restriction (IUGR) Intrauterine growth restriction FOV Field of view l-NAME Nitro-l-arginine methyl ester hydrochloride PE Preeclampsia reference images scanner-provided fast spin-echo (RARE) Rapid acquisition with relaxation enhancement spatiotemporal encoding (SPEN) Spatio-temporal encoding
EPI, is sensitivite to field inhomogeneities, to water/fat interferences and to other non-idealities, that often prevents it from delivering information in the challenging conditions placed by the abdomens of pregnant, living rodents. This has led to a number of alternative proposals that rely on multiple pulses to overcome these distortions[4,16,17]; we have shown that spatiotemporal encoding (SPEN) techniques[18,19,20] have the potential to deal with these limitations
Quality, high-definition ADC maps using SPEN DWI, for an eNOS-defficient mouse in its E14.5 pregnancy day as case example. Presented in these panels are a multiscan RARE image serving as anatomical reference, as well as interleaved SPEN and reversed-gradient EPI experiments collected on this animal in the absence (b0) and in presence of the bipolar diffusion-weighting module; included are the ADC maps derived from these data
Summary
Abbreviations ADC Apparent diffusion coefficient DCE Dynamic contrast enhanced EPI Echo planar imaging DWI Diffusion weighted imaging IUGR Intrauterine growth restriction FOV Field of view l-NAME Nitro-l-arginine methyl ester hydrochloride PE Preeclampsia RARE Rapid acquisition with relaxation enhancement SPEN Spatio-temporal encoding. Perfusion is usually associated with the active flow of biological fluids, and can be measured by the addition of an exogenous agent changing certain aspects of the NMR/MRI signature—for instance, the water’s T 1 relaxation time As this contrast agent is carried by the circulatory system and its influence is mapped, a 3D description reflecting the hemodynamics of a tissue will arise. The aim of this study was to explore the insight provided by these new methods when used to monitor the progress of fetoplacental units from day E14.5 onwards, in studies comparing the development of wildtype and of vascularly-altered mice The latter were assessed for two kinds of knock-out mice models: eNOS (endothelial nitric oxide synthase) deficient (−/−) animals, which are associated with intrauterine growth-restriction (IUGR) symptoms[23,24], and IL10 knockout mice, exhibiting hypertension and proteinuria during pregnancy and serving as models for preeclampsia (PE,[25,26]). Potential rationalization of these observations on the bases of known physiological features associated to IUGR and PE, as well as their implications to human pregnancies, are briefly discussed
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