Ferumoxytol-enhanced MRI of retroplacental clear space disruption in placenta accreta spectrum

Introduction: Placenta accreta spectrum (PAS) occurs when the placenta is pathologically adherent to the myometrium. An intact retroplacental clear space (RPCS) is a marker of normal placentation. In this study, we investigate use of the FDA-approved iron supplement ferumoxytol for contrast-enhanced MRI of the RPCS in mouse models of normal pregnancy and PAS. We then demonstrate the translational potential of this technique in human patients (n = 6) presenting with severe PAS (FIGO Grade 3C), moderate PAS (FIGO Grade 1), and no PAS. Methods: T1-weighted sequences were used to determine the optimal dose of ferumoxytol in pregnant mice. Pregnant Gab3^−/− mice which demonstrate adherent placentation were imaged alongside wild-type (WT) pregnant mice with non-adherent placentation. Fe-MRI was also performed in 6 pregnant subjects using standard T1 and T2 weighted sequences and a 3D magnetic resonance angiography (MRA) sequence. Results: Ferumoxytol administered at 5 mg/kg led to strong placental enhancement in Fe-MRI images. Gab3^−/− mice demonstrated loss of the hypointense region characteristic of the RPCS relative to WT mice. In human patients, Fe-MRI enabled high uteroplacental vasculature signal and quantification of the volume and signal profile in severe and moderate invasion of the placenta relative to non-PAS cases. Discussion: Ferumoxytol, an FDA-approved iron oxide nanoparticle formulation, enabled T1w MRI visualization of abnormal vascularization and loss of uteroplacental interface in a murine model of PAS. The potential of this non-invasive visualization technique was then further demonstrated in human subjects and suggests the possibility of PAS diagnosis using contrast enhanced MRI.