Early in pregnancy migration of trophoblast cells to the lumen of the spiral arteries leads to 5-10 fold terminal dilation of the arteries, thereby increasing blood flow through the placenta. Placental insufficiency is associated with failure of this conversion of the spiral arteries, and results in the most common complications of pregnancy such as fetal growth restriction (FGR) and preeclampsia (PE). In the management and treatment of pregnancies complicated by placental insufficiency, early and reliable detection is critical, because by the time placental dysfunction becomes evident, the pathological changes to the fetus or mother are irreversible. Numerous approaches have been suggested for identifying placental insufficiency in utero. Particularly, there have been various MRI-based methods proposed to measure placental function. However, all of prior studies deployed standard imaging schemes of brain MRI without significant optimization for the placenta or used the methods that are not very sensitive to placental abnormalities. Over the past several years, we have advanced dedicated MRI techniques for placental-specific perfusion and oxygenation measures using velocity-selective arterial spin labeling (VSASL) and quantitative susceptibility mapping (QSM), and have demonstrated promising results in our preliminary data. In this study, we will first optimize placental VSASL at 3 T for improved signal-to-noise ratio and image quality (aim 1). We will then apply our approaches of placental VSASL and QSM in pregnancies diagnosed with FGR or PE and healthy pregnancies to determine differences in placental perfusion and oxygenation between FGR/PE and controls (aim 2). Lastly, we will validate our MR imaging methods by comparing in-vivo placental measures against placental pathology and clinical outcomes (aim 3). Successful completion of this project will determine the association between placental insufficiency and altered in-vivo placental perfusion/oxygenation measurements. Ultimately, this will develop early and reliable biomarkers of placental health and disease, and will assist in developing and assessing new interventional approaches aimed to improve pregnancy outcomes.

Public Health Relevance

In the management and treatment of pregnancies complicated by fetal growth restriction (FGR) and preeclampsia (PE) due to placental insufficiency, early and reliable detection is critical, because once clinically evident, the pathological changes are irreversible. To date, however, there is no validated in-vivo method that can be routinely used in the clinic for non-invasive assessment of placental function. Recently we have developed novel MRI approaches to evaluate placental function such as perfusion and oxygenation. In this study, we will optimize and apply our techniques in pregnancies complicated by FGR and PE as well as healthy pregnancies to determine differences in placental function between FGR/PE and healthy controls. We will also validate our MRI approaches against placental pathology and pregnancy outcomes.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD100012-02
Application #
9989882
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Weinberg, David H
Project Start
2019-08-07
Project End
2023-05-31
Budget Start
2020-06-01
Budget End
2021-05-31
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Children's Research Institute
Department
Type
DUNS #
143983562
City
Washington
State
DC
Country
United States
Zip Code
20010