Devising an Imaging Modality to Identify Abnormal Placental Development Early in Pregnancy

Abnormal placental development is widely accepted as the cause of common pregnancy complications, including hypertensive disorders of pregnancy, growth-restricted babies, and stillbirth. Obstetricians and reproductive biologists acknowledge that novel imaging tools are needed to assess the development of the placenta early in gestation in order to identify pregnancies at highest risk of adverse outcomes attributed to placental dysfunction.

Sophisticated 3-D ultrasound technologies have been used to study placental morphology and perfusion in relation to adverse pregnancy outcomes, but these modalities fail to provide robust clinical prediction of adverse pregnancy outcomes. Furthermore, these techniques require offline manual manipulation that limits their use as a point-of-care test.

Thus, in order to better assess placental development in a clinically relevant and noninvasive manner, a more precise and user-friendly approach to evaluating placental structure and function is needed. This requires advances in current technology and new partnerships between experts in technology and experts in clinical care of pregnant women.

Study looks at comprehensive approach to imaging the placenta

To this end, CHOP neurologist Daniel Licht, MD, and Nadav Schwartz, MD, an obstetrician/gynecologist at the Hospital of the University of Pennsylvania (HUP), are collaborating for a study of a logical but comprehensive imaging approach utilizing ultrasound, MRI, and near-infrared spectroscopy (NIRS) to determine placental morphology, perfusion, and oxygenation early in pregnancy. The study is part of the Human Placenta Project Technology Development Working Group, which is organized by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and funded by a U01 cooperative agreement.

“With this study, we are approaching imaging of the placenta with everything we have: ultrasound, optics, and MRI,” says Licht, director of CHOP’s newly named Wolfson Clinical and Biomedical Optical Imaging Lab.

The study team includes experts in imaging technology who have substantial experience researching novel techniques and clinical applications for each of these modalities, along with clinical investigators with expertise in women’s reproductive health (clinical perinatology, nutrition, and placental biology). This diverse team will be crucial for technology development and application as well as analysis of data and decisions regarding research directions over the four-year funding period.

The team’s ultimate objective is to develop a simple, clinically useful imaging modality that can be used at the bedside to identify women early in pregnancy who are at highest risk of developing pregnancy complications attributed to abnormal placental morphology, perfusion, and/or oxygenation. HUP will recruit women in its ultrasound unit into specific case control and cohort studies that will focus on development and validation of 3-D power Doppler ultrasound, functional MRI, and NIRS techniques.

Cross-validation will be employed to identify the most clinically relevant imaging modalities. The study team will then perform a validation cohort study to determine the relationship among maternal BMI, placental imaging (morphology, perfusion, and oxygenation), and neonatal anthropometrics.

Specific aims are to:

• Develop and validate an automated ultrasound segmentation tool to standardize quantitative analysis of placenta morphology in vivo.
• Develop and validate a quantitative MRI measure of placental perfusion.
• Develop novel and noninvasive tools to quantify placental oxygenation using functional MRI and NIRS.
• Conduct a pilot study using the optimal measures obtained in aims 1 to 3 to study the impact of maternal nutritional status on placental development and function.

Licht’s research focuses on abnormal brain development of fetuses and children with congenital heart disease (CHD). Improved survival over the last 15 years has revealed significant neurodevelopmental dysfunction among children who underwent early surgery for CHD, including a high prevalence of white matter injury. Licht’s work has found it’s not the surgery but the uterine environment that sets the brains of these patients up for injury.

“All of this data is pointing to the in utero circulation being abnormal,” says Licht. “And yet we know nothing about the placenta. My hope is that we come up with a good way to image the placenta and that becomes part of the fetal diagnostic workup to help identify — and potentially treat — these patients prior to birth.”