Ferumoxytol dynamic contrast-enhanced MRI for in vivo longitudinal cotyledon perfusion assessment with pathology correlation in a rhesus macaque thrombotic injury model

Introduction

While placental perfusion and pathology jointly affect pregnancy outcomes, cotyledon-specific perfusion across gestation and its correlation with local injury is not yet well understood. Ferumoxytol dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) offers a promising way to noninvasively identify cotyledons across gestation and quantify longitudinal cotyledon-specific perfusion changes. Additionally, intraplacental injection of bioactive fibrin sealant allows us to model thrombotic placental injury and further assess cotyledon-level relationships between perfusion and significant injury.

Methods

Pregnant rhesus macaques (N=13) received intrauterine saline or fibrin sealant injections at gestational day (GD) ∼101 and underwent ferumoxytol DCE-MRI at GDs ∼100, 115, and 145. Placental perfusion domains derived from contrast arrival time were segmented at each imaging time point and matched to cotyledons identified following tissue collection by cesarean section, with cotyledon perfusion quantified longitudinally and correlated with cotyledon-specific quantitative histopathology.

Results

All pregnancies were successfully carried to term. Fibrin sealant injections induced significantly higher levels of placental pathology compared to saline controls. MRI-derived perfusion domains were largely consistent across gestation and showed predominantly one-to-one correspondence with term cotyledons, with successful perfusion-pathology pairing achieved in 153 cotyledons. Longitudinal cotyledon perfusion changes showed significant positive correlations with villous agglutination injuries.

Conclusions

Feasibility of noninvasively tracking placental cotyledon perfusion using ferumoxytol DCE-MRI was demonstrated, and the efficacy of the rhesus macaque thrombotic injury model was confirmed. The positive perfusion-pathology correlations suggested intrinsic placental regulatory mechanisms and functional plasticity. This new framework is promising for future translational studies and validation of ex vivo cotyledon perfusion models.

Highlights

• Longitudinal tracking of placental perfusion domains with ferumoxytol MRI

• Successful matching of cotyledons and MRI-derived perfusion domains

• Confirmed thrombotic injury-model induced cotyledon pathology

• Maternal perfusion compensation in presence of villous pathology