Award Title: Investigating MRI markers of placental function derived from a multiparametric computational model of placental perfusion in a cohort of early onset Fetal Growth Restricted pregnancies
Funder: The Academy of Medical Sciences

Abstract: Placental insufficiency occurs when the placenta cannot supply a fetuses oxygen and nutritional demands, resulting in fetal growth restriction (FGR). This is responsible for over a third of stillbirths. There is no diagnostic test.

I have developed a multi-compartment MRI model of placental function that separates signals relating to fetal and maternal perfusion, and estimates feto-placental blood oxygen saturation (fbO2). Previous research found fbO2 was significantly lower in FGR compared to controls (56±6.2%vs75±9.6%, FGR vs control, P = 0.02). The reduction correlated to disease severity.

Aims
1. Better understand the MRI features of pregnancies diagnosed with early onset FGR through performing multiparametric placental and fetal MRI with multi-modal placental phenotyping using ultrasound, circulatory proteins and targeted histological analysis.

2. Investigate the utility of previously derived novel MRI marker of placental function in diagnosing placental insufficiency, and their correlation with disease severity.

Objectives

•Recruit 39 women diagnosed with FGR
•Phenotype the placenta with blood biomarkers and ultrasound imaging
•Perform multiparametric MRI of the placenta and fetus
•Collect clinical outcome data
•Perform targeted histology of placental lesions to enhance standard histology
•Analyse MRI data, investigating difference in MRI signals within and between placentas, and how these correlate to clinical outcome and histology

Developing imaging that relates to placental function and fetal oxygenation and organ perfusion will improve our understanding of placental insufficiency and fetal adaptive strategies. Novel markers have the potential to transform clinical care by better informing management decisions, and so impact on long-term outcome.

Lay Abstract: Placental insufficiency, where the placenta cannot meet the oxygen and nutritional demands of a growing baby, is responsible for over a third of UK stillbirths.

Currently there are no diagnostic tests to determine placental function. There is no safe way of assessing the baby’s oxygen levels in the womb. Doctors rely on ultrasound markers of the disease to make difficult management decisions, including the best time to deliver a baby. They must weigh up the risk of complications from a preterm birth against the risk of injury or death of the baby from remaining in the womb with low oxygen levels. Optimising the information used to make these decisions is vital to the health of the baby and mother.

This study aims to discover whether a safe medical imaging technology (Magnetic Resonance Imaging (MRI)) can be developed to assess how well the placenta is working during pregnancy.

We have developed an MRI model of placental function that estimates the baby’s blood oxygen level. We want to apply this to investigate:
• How MRI markers of placental function relate to pregnancy outcome and postnatal microscopic placental examination in a group of pregnant women with very small babies
• How babies adapt to low oxygen levels by imaging other organs

Our long-term aim is to establish an effective MRI test of placental function. This will transform clinical care of pregnancies with small babies, by informing doctors on how the placenta is functioning and how this is impacting the baby's health.

Research Activity Codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health Categories: REPRODUCTIVE HEALTH AND CHILDBIRTH