Diffusion and perfusion MRI of normal, preeclamptic and growth-restricted mice models reveal clear fetoplacental differences

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.

Modeling Normal Mouse Uterine Contraction and Placental Perfusion with Non-invasive Longitudinal Dynamic Contrast Enhancement MRI

“…We have optimized the subcutaneous Gd administration and imaging acquisition protocol to enable quantitative placental perfusion mapping with the steepest slope model (38–42). Repetitive intravenous (IV) administration of contrast agent in mice for longitudinal DCE investigation is difficult.…”

“…Administration via common mouse iv administration routes like femoral, jugular, or retro orbital veins is terminal and cannot be used for longitudinal monitoring. Although tail-vein injection (38, 43–45) can be performed multiple times, quantitative DCE requires administration of Gd contrast agent via an IV catheter inside the magnet during DCE acquisition, which is difficult for multiple administration longitudinally. Therefore, most mouse placental DCE studies with the steepest slope model were performed with single imaging time points.…”

“…Although the identification of spatially varying perfusion zones within the mouse placenta has been identified in other studies (38–42, 44, 45), we expanded this knowledge with the addition of a biologically based (22) modeling for automatic localization of the different perfusion chambers. All other previous studies rely on manual analysis and region of interest (ROI) generation after data review.…”

“…We have optimized the subcutaneous Gd administration and imaging acquisition protocol to enable quantitative placental perfusion mapping with the steepest slope model (38)(39)(40)(41)(42).…”

Modeling normal mouse uterine contraction and placental perfusion with non-invasive longitudinal dynamic contrast enhancement MRI

“…We have optimized the subcutaneous Gd administration and imaging acquisition protocol to enable quantitative placental perfusion mapping with the steepest slope model [ 38 – 43 ] repetitive intravenous (IV) administration of contrast agent in mice for longitudinal DCE investigation is difficult. Administration via common mouse iv administration routes like femoral, jugular, or retro orbital veins is terminal and cannot be used for longitudinal monitoring.…”