Novel quantitative MRI tools for detection of placental failure in high risk pregnancy.

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Placental dysfunction can manifest as either maternal or fetal disease; in pregnant women, placental dysfunction is commonly seen in hypertensive disorders of pregnancy (HDP), which affects nearly half a million of pregnant women each year in the United States alone. In fetuses, placental dysfunction can result in fetal growth restriction (FGR), which also affects between 10-15% of the pregnant population. Infant survivors of HDP or FGR are at significantly increased risk for lifelong neuropsychiatric morbidity. Given the complexities of fetal brain development, it is unsurprising that any deviation from normal progression during the fetal period could result in lifelong neuropsychiatric injury. However, despite the significant consequences of placental disease, there are no clinical tools to directly and non-invasively assess and measure placental function. In this proposal, we will apply safe, novel and non-invasive tools to quantify placental development and function in healthy pregnancies and those complicated by HDP. The overarching goal of this proposal is to demonstrate that advanced MRI techniques will detect early, in vivo biomarkers of abnormal placental development in the high-risk pregnancy characterized by HDP. Furthermore, we aim to demonstrate that in vivo measures of placental dysfunction will be associated with neurobehavioral assessments of infant survivors. This study will perform advanced MR imaging at two time points: in the fetal period, immediately following the diagnosis of HDP and the immediate neonatal period, and the results will be compared to healthy controls. Specifically, quantitative MRI (qMRI) will be used to measure global and regional placental structure utilizing novel placental signatures of placental geometry and architecture. We will quantitatively measure placental function utilizing global and regional indices of placental perfusion and oxygen transport. This will test the hypothesis that placental structure and function will be abnormal in the HDP group compared to controls. Furthermore, we will develop composite biomarkers of placental structure and function, and relate these to neonatal outcomes of brain development and function using postnatal quantitative MRI and neurodevelopmental testing. The overarching goal is to prevent brain injury and improve neurodevelopmental outcomes in survivors of placental dysfunction. Current management of many high-risk pregnancies, including HDP, cannot address placental maldevelopment or injury, given the standard tools available to clinicians. This important study will address the first steps in the accurate recognition of impaired placental development in real-time by using novel, non- invasive methods. As accurate biomarkers of placental development and function are constructed, the subsequent steps will be to introduce maternal and fetal therapeutics targeting at optimizing placental function, and applying these biomarkers to determine safety and efficacy. In the future, this type of information can translate our understanding of how any number of maternal and environmental factors influence placental development and impact fetal growth and well-being across a spectrum of maternal and fetal diseases.