Nanoparticle Contrast-enhanced MRI for Visualization of Retroplacental Clear Space Disruption in a Mouse Model of Placental Accreta Spectrum (PAS)

Authors

Andrew A Badachhape
Prajwal Bhandari
Laxman Devkota
Mayank Srivastava
Eric A Tanifum
Verghese George
Karin A Fox
Chandrasekhar Yallampalli
Ananth V Annapragada
Ketan B Ghaghada

Publication Date

7-1-2023

Journal

Academic Radiology

DOI

10.1016/j.acra.2022.08.025

PMID

36167627

PMCID

PMC10036264

PubMedCentral® Posted Date

7-1-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Female, Pregnancy, Animals, Mice, Placenta, Contrast Media, Magnetic Resonance Imaging, Disease Models, Animal, Nanoparticles, Retrospective Studies, Adaptor Proteins, Signal Transducing, Placenta accreta spectrum, accreta, magnetic resonance imaging, blood pool contrast agent, retroplacental space, nanoparticle, liposome, gadolinium

Abstract

Introduction:

Prior preclinical studies established the utility of liposomal nanoparticle blood-pool contrast agents in visualizing the retroplacental clear space (RPCS), a marker of normal placentation, while sparing fetuses from exposure because the agent does not cross the placental barrier. In this work, we characterized RPCS disruption in a mouse model of placenta accreta spectrum (PAS) using these agents.

Methods:

Contrast-enhanced MRI (CE-MRI) and computed tomography (CE-CT) using liposomal nanoparticles bearing gadolinium (liposomal-Gd) and iodine were performed in pregnant Gab3^−/− and wild type (WT) mice at day 16 of gestation. CE-MRI was performed on a 1T scanner using a 2D T1-weighted sequence (100×100×600 μm³ voxels) and CE-CT was performed at a higher resolution (70×70×70 μm³ voxels). Animals were euthanized post-imaging and feto-placental units (FPUs) were harvested for histological examination. RPCS conspicuity was scored through blinded assessment of images.

Results:

Pregnant Gab3^−/− mice show elevated rates of complicated pregnancy. Contrast-enhanced imaging demonstrated frank infiltration of the RPCS of Gab3^−/− FPUs. RPCS in Gab3^−/− FPUs was smaller in volume, demonstrated a heterogeneous signal profile, and received lower conspicuity scores than WT FPUs. Histology confirmed in vivo findings and demonstrated staining consistent with a thinner RPCS in Gab3^−/− FPUs.

Discussion:

Imaging of the Gab3^−/− mouse model at late gestation with liposomal contrast agents enabled in vivo characterization of morphological differences in the RPCS that could cause the observed pregnancy complications. An MRI-based method for visualizing the RPCS would be valuable for early detection of invasive placentation.