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.
Competing Interest Statement
AVA is a significant stockholder in Alzeca Inc. and Sensulin LLC. KBG is a research consultant for Alzeca Inc. MS is a stockholder in Alzeca Biosciences. EAT is a consultant and stockholder in Alzeca Biosciences. All remaining authors in this work have no conflicts to disclose.
Footnotes
badachha{at}bcm.edu
prajwal.bhandari{at}bcm.edu
laxman.devkota{at}bcm.edu
mxsrivas{at}texaschildrens.org
eatanifu{at}texaschildrens.org
Verghese.George{at}bcm.edu
kafox{at}bcm.edu
cyallamp{at}bcm.edu
avannapr{at}texaschildrens.org