The placenta is a highly vascular organ, responsible for the interaction between mother and developing fetus. Close proximity of maternal blood, in intervillous spaces, and fetal blood, in chorionic villi, enables transport of nutrients, such as oxygen, from mother to fetus and removal of wastes. Perfusion of the intervillous spaces can be impaired by placental diseases, such as preeclampsia. Compromised placental perfusion impairs the exchange between maternal and fetal blood with potentially devastating impact on both mother and fetus. Today, no diagnostic tool can directly monitor regional placental perfusion, intervillous inflow, oxygen response and oxygen state. Clinicians still rely on indirect measures of placental health, such as fetal size and umbilical artery blood velocity. Induced delivery remains the treatment of choice for most placental disorders. New, effective technologies are desperately needed to monitor regional placental health in vivo. We assembled a team of technical MR experts, computational researchers, MR clinician scientists, experienced obstetricians and a internationally recognized placental biologist to address the need for clinically relevant technological advances in MRI for placental imaging. Here we will develop robust, quantitative measures of regional placental perfusion, intervillous inflow, oxygen response and oxygen state from late 2?nd trimester to term, with safety analysis and feasibility testing that pave the way for extension to late 1?st trimester. We will pilot and optimize our placental MRI measures in mothers with typical pregnancy (TP) and preeclampsia (PE) to determine if our novel MRI methods are tolerated by both groups and to evaluate their feasibility and potential as clinical tools to distinguish PE from TP placentas in individuals. Towards this end, we propose the following specific aims: ?1. Map placental perfusion and estimate intervillous inflow: We will develop a new model for diffusion imaging intravoxel incoherent motion (IVIM) for placental perfusion and develop a velocity selective spin labeling (VSSL) approach to estimate intervillous inflow. ?2. Map T1 and T2 to characterize changes in placental oxygen response and oxygen state?: We will develop 2D MR Fingerprinting (MRF) to create rapid joint T1 and T2 maps of placental oxygen response during hyperoxia and 3D MRF or multi-inversion echo planar imaging (MIEPI) to create volumetric joint T1 and T2 maps to determine the placental oxygen state.
For Aims 1 and 2, we will correlate multimodal placental patterns in TP and PE with regional placental histopathology using our placental flattening method for guidance. ?3. Optimize imaging safety throughout pregnancy using temperature simulations?: We will focus on the major safety concern of radiofrequency (RF) tissue heating in the first-through-third trimester of pregnancy. We will build on our anatomically realistic numerical pregnant body models and expertise with electromagnetic simulations and develop accurate and pregnancy-specific thermal models to determine and experimentally validate safe and efficient RF exposure throughout pregnancy.
Disorders of placental structure and function, such as preeclampsia, are common causes of maternal and fetal morbidity and mortality. However, there is no established technology that enables individual placental structure and function to be monitored in real time throughout pregnancy to screen for disease, to monitor for progression, or to assess treatment response. We propose to develop novel magnetic resonance imaging (MRI) strategies combined with innovations in computational analysis that focus on capturing regional placental structure and function and will explore the potential of our new technology to contribute to individual management of preeclampsia.
