MRI Research Amsterdam UMC

TRIPLET: TaRgeted therapy and Imaging in experimental PLacEnTa insufficiency

Worldwide, 10% of pregnancies are complicated by fetal growth restriction (FGR) and pre-eclampsia (PE). The main cause is a poorly developed placenta, resulting in insufficient nutrients and oxygen for fetal growth. FGR and PE are associated with neonatal morbidity and mortality, partly due to necessary preterm deliveries, leading to a high risk of stillbirths or life-threatening conditions such as sepsis, cerebral hemorrhage, or severe intestinal disorders. Additionally, FGR poses a significant risk for developing adult-onset conditions such as disrupted brain development and cognition, cardiovascular diseases, kidney diseases, or metabolic disorders. None of the current therapies guarantee a safe continuation of pregnancy.

A promising new treatment involves the use of short interfering RNA (siRNA), which has recently shown very promising results in treating PE. Currently, monitoring the fetus is primarily aimed at determining the optimal timing of delivery. Photoacoustic Imaging (PAI) and Blood Oxygen Level Dependent Magnetic Resonance Imaging (BOLD-MRI) are novel imaging techniques enabling measurements of the placenta and fetal oxygenation, providing better insights into the severity of the condition.

In this project proposal, experts in nanomedicine (Schiffelers), imaging (Strijkers), and translational animal and in vitro models (Lely) collaborate to develop a new approach for the treatment and monitoring of FGR and PE. This addresses the urgent need for an effective and safe therapy and an effective monitoring technique for placental and fetal oxygenation. Specifically, we propose developing an siRNA delivery system using nanoparticles to treat placental dysfunction, aiming to prevent placental passage through the nanoparticles, and developing photoacoustic imaging (PAI) and blood oxygen level-dependent MRI (BOLD-MRI) to monitor placental and fetal oxygenation. The main outcome of this project will be a new therapy platform for placental insufficiency, ensuring the safest possible treatment for both the mother and the fetus. Additionally, physicians will have new imaging technology to better assess the condition of the unborn child, facilitating the monitoring of placental insufficiency and improving the evaluation of when preterm delivery or prenatal interventions should commence.