A study published in Nature Biomedical Engineering details a new method of imaging the placenta in pregnant patients as well as the results of a pilot clinical study. By combining optical measurements with ultrasound, the results show how oxygen levels can be monitored non-invasively and offer a new way to generate a better understanding of this complex and crucial organ. This research is the result of a collaboration of the groups of Arjun Yodh and Nadav Schwartz at the University of Pennsylvania with colleagues at Children’s Hospital of Philadelphia (CHOP) and was led by postdoc Lin Wang.
Schwartz describes the placenta as the “engine” of pregnancy, an organ that plays a crucial role in delivering nutrients and oxygen to the fetus. Placental dysfunction can lead to complications such as fetal growth restriction, preeclampsia, and stillbirth. To increase knowledge about this crucial organ, the National Institute of Child Health and Human Development launched the Human Placenta Project in 2014. One of the goals of the program is to develop tools to assess the structure and real-time human placenta function, including optical devices.
For three years, the researchers optimized the design of their instrument and tested it in a preclinical environment. The process involved integrating fiber optics with ultrasound probes, exploring various ultrasound transducers, and improving multimodal technology so that measurements are stable, accurate, and repeatable during bedside data collection. patient. The resulting instrumentation now allows researchers to study the anatomy of the placenta while collecting detailed functional information about blood flow and oxygenation of the placenta, capabilities that existing commercial devices do not have, according to the researchers. researchers.
Because the placenta is located far below the surface of the body, one of the main technical challenges faced by Wang, a postdoctoral fellow at Yodh’s lab, was to reduce background noise in the optoelectronic system. Light is scattered and absorbed as it passes through thick tissue, Yodh says, and the key to success was to reduce background interference so that the small amount of light that goes deep into the placenta and then comes back is still big enough for a high quality measurement.
“We send a light signal that goes through the same deep tissues as the ultrasound. The extremely small amount of light that returns to the surface probe is then used to accurately assess tissue properties, which is only possible with very stable lasers, optics and detectors,” says Yodh. “Lin had to overcome many hurdles to improve the signal-to-noise ratio to the point where we trusted our data.”
Notably, the article also describes the results of a pilot study where 24 pregnant patients in their third trimester received supplemental oxygen for a short time, creating placental hyperoxia. Using the device, the team collected measurements of oxygenated and deoxygenated placental blood concentrations before and during hyperoxia; the results demonstrated that the device could be used to study placental function in real time. The research also provided new insights into the relationship between blood flow and maternal vascular malperfusion, which occurs when blood flow through the placenta is impeded.
“Not only do we show that oxygen levels increase when you give oxygen to the mother, but when we analyze the data, both for clinical outcomes and pathology, patients with maternal vascular malperfusion don’t didn’t have as much of an increase in oxygen compared to patients with normal placentas,” says Schwartz. “What was exciting is that not only did we get an instrument to probe deeper than commercial devices, but we also got an early signal that hyperoxygenation experiments can differentiate a healthy placenta from a diseased placenta.”
While the device is still in development, researchers are currently tweaking their instrument to make it more user-friendly and allow it to collect data faster. The team is also currently working on larger studies, recently including data from patients in their second trimester, and they are also interested in studying different regions of the placenta. “From the instrumentation point of view, we want to make the operation more user-friendly, and then we want to conduct more clinical studies,” Wang says of the future of this work. “We have a lot of interesting ideas.”
And because there are many unanswered clinical questions about the placenta, for Schwartz the greatest potential of this work is to provide a way to begin to answer those questions. “Without being able to study the placenta directly, we rely on very indirect science,” he says. “It’s a tool that helps us study the underlying physiology of pregnancy so that we can more strategically investigate interventions that can help support good pregnancy outcomes.”
The authors are Lin Wang, Jeffrey M. Cochran, Kenneth Abramson, Lian He, Venki Kavuri, Samuel Parry, Arjun G. Yodh, and Nadav Schwartz of Penn; Tiffany Ko, Wesley B. Baker, and Rebecca L. Linn of Children’s Hospital of Philadelphia, and David R. Busch, formerly a research associate at Penn and now at the University of Texas Southwestern Medical School .
Arjun Yodh is the James M. Skinner Professor of Science in the Department of Physics and Astronomy at the University of Pennsylvania School of Arts and Science.
Nadav Schwartz is an Associate Professor in the Department of Obstetrics and Gynecology at Penn’s Perelman School of Medicine.
Lin Wang is a postdoc in the Department of Physics and Astronomy at Penn’s School of Arts & Sciences.
This research was supported by grants F31HD085731, R01NS113945, R01NS060653, P41EB015893, P41EB015893, T32HL007915, and U01HD087180 from the National Institutes of Health.