It is widely accepted that the in utero environment of the developing fetus influences health outcomes that extend well beyond the perinatal period into adulthood. Aberrant placental development has been linked to virtually every adverse obstetric outcome including abnormalities in fetal growth, preterm delivery and stillbirth. Yet, despite its importance as the mediator between maternal-fetal exchange, the placenta remains the least understood human organ. Adequate blood flow and oxygen delivery are central determinants of placental function and fetal growth. The lack of imaging modalities that facilitate the in vivo study of both normal and abnormal placentas impedes our understanding of placental blood flow and oxygenation. We propose to overcome these limitations using magnetic resonance imaging (MRI) technology. One of the challenges faced in the development of placenta-specific MRI methods is the complex structure of the placental vasculature in primates. Over the past 5 years we have utilized the nonhuman primate (NHP), which shares developmental features including placenta structure and function with humans, to develop a dynamic contrast enhanced MRI (DCE-MRI) method that allows for the quantification of placental blood flow from each spiral artery. Although we recently demonstrated that the level of fetal gadolinium exposure resulting from maternal administration of gadolinium-based contrast reagent during DCE-MRI is extremely low, the abundance of caution when imaging pregnant patients makes it highly pertinent to develop functional MRI methods that do not rely on contrast reagent administration. Importantly, we have acquired preliminary data in our NHP model that demonstrates the feasibility of the approach we are proposing. We are proposing to use our clinically relevant NHP model for non-contrast MRI sequence development and optimization. Simultaneous use of DCE-MRI in these studies will allow us to utilize our contrast dependent quantitative measure of placental perfusion as a benchmark for non-contrast modeling. We propose to transition our studies to human subjects to implement newly developed MR imaging procedures and assess their utility for clinical use. The potential clinical benefits of developing MRI protocols for the in vivo assessment of placental blood flow and oxygenation are tremendous; understanding normal placental function will improve clinical monitoring of pregnancy, permit early identification of women at-risk for placental insufficiency, and facilitate intervention to improve fetal outcome. If the proposed studies are successful, then we will have developed a protocol that allows for rapid, reproducible non-contrast mediated means of visualizing and quantifying both placental perfusion and oxygenation.
The placenta is the key mediator of maternal-fetal exchange; an adequate supply of oxygen and nutrients are critical for fetal growth and are dependent on both placental blood flow and maternal oxygen content. The goal of this proposal is to develop and validate advanced non-invasive magnetic resonance imaging protocols for the in vivo assessment of placental perfusion and oxygenation. This imaging modality has the potential to improve the clinical management and early identification of pregnancies at-risk for placental insufficiency.
