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

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.

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.

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.

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.