Bench to Bedside | April 2016

Researchers Developing New Imaging Tools to Assess Placental Dysfunction

As new life forms inside a mother, the placenta becomes a key interface between maternal and fetal health. This temporary disc-shaped organ attaches to the uterine wall and transfers oxygen and nutrients to the fetus, yet the nuances of its structure and function remain enigmatic.

A multidisciplinary research team at The Children’s Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania recently received a $4.2 million grant through the Human Placenta Project launched by the Eunice Kennedy Shriver National Institute of Child Health and Human Development to uncover these mysteries by developing new imaging technologies that allow for a more comprehensive understanding of blood flow and oxygenation in the placenta. Launched in 2014, the Human Placenta Project encourages researchers to explore how the placenta works and then use these insights to help predict complications in pregnancies and eventually assess interventions.

Daniel Licht, MD, one of the study team’s leaders, is in a unique position as a pediatric neurologist studying placental imaging. His research interest in this area evolved from his experience with treating babies born with congenital heart defects (CHD) who also had brain injuries. Fetal imaging has revealed that brain growth stalls in these babies around the third trimester, he noted.

“Alteration of the fetal circulation due to the CHD leads to a vulnerability for brain injury, so fetal circulation is the main problem that we have to tackle if we’re going to figure out how to manage these babies and prevent brain injury,” said Dr. Licht, who is director of the Wolfson Family Laboratory for Clinical and Biomedical Optics at CHOP. “But it’s probably not just fetal circulation; it’s also the placental circulation.”

Blood circulates from the placenta to the fetus and back to the placenta, Dr. Licht explained. If the fetus’ cardiac output is abnormal, then it is likely that this feedback loop also is abnormal, depending on the type of heart anomaly. At birth, some babies with CHD have placentas that are about half the size as would be expected. Abnormal development of the placenta also is related to other pregnancy risks, including poor fetal growth, preeclampsia, and preterm birth.

Physicians need new imaging tools to monitor development and function of the placenta throughout the organ’s lifespan. This can be difficult to accomplish because motion from the mother’s breathing and the fetus’ movement can compromise image quality. The research team will study advanced techniques and sensors in 3D ultrasound, magnetic resonance imaging, and near infrared spectroscopy (NIRS) to determine which modality or combination of modalities will be precise and easy to implement as a screening tool for placental dysfunction in early pregnancy. In the future, their goal also is to use the imaging tools to help determine how treatments, such as future drug therapies, affect the placenta.

“We are using a multimodal experiment design to tackle the problems of: How does maternal blood flow get to the placenta? How does blood flow from the placenta to get to the fetus? How does oxygen transfer occur in vivo? And how do all of these things depend on the placenta’s structure?” Dr. Licht said.

A novel part of the research project is that the team aims to develop a new imaging instrument — an ultrasound probe with optics embedded in it — so that they can measure the placenta’s structure and blood flow while at the same time making optical measurements of oxygen saturation. Part of the challenge is ensuring that the instrument is sensitive and accurate enough to be used at the bedside for pregnant bellies that vary in shapes and size.

The team will rely on a diverse range of technological and clinical expertise in radiology, bioengineering, physics, nursing, and women’s reproductive health as they refine these placental imaging methods. Other team members include co-leader of the CHOP/Penn team Nadav Schwartz, MD, an assistant professor of Maternal Fetal Medicine at Penn; Arjun Yodh, PhD, director of The Laboratory for Research on the Structure of Matter at Penn; Felix Wehrili, PhD, director of the Laboratory for Structural NMR Imaging at Penn; and John Detre, MD, director of the Center for Functional Neuroimaging at Penn.

Once the researchers are able to determine how to best measure placental volumes and changes over time during healthy pregnancies, the next phase of the research project will be to study how maternal nutritional status influences placental development and function.


www.research.chop.edu

Produced by The Children’s Hospital of Philadelphia Research Institute.

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