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

Introduction: Prior preclinical studies established the utility of liposomal nanoparticle blood-pool contrast agents in visualizing the retro-placental 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. Materials and 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 & POUND;100 & POUND;600 mm3 voxels) and CE-CT was performed at a higher resolu-tion (70 & POUND;70 & POUND;70 mm3 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 showed elevated rates of complicated pregnancy. Contrast-enhanced imaging demonstrated frank infil-tration 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 thin-ner 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.

Automated summary

This study used contrast agents to investigate the effects of abnormal placental implantation on the retro-placental clear space (RPCS). The results showed that the RPCS in the abnormal group of mice was smaller, had a heterogeneous signal, and was significantly damaged. These findings provide a valuable method for early detection of invasive placentation.