An optical technique for measuring placental blood flow and oxygenation in real time provides information about placental hemodynamics that could aid in the early detection of adverse pregnancy outcomes. The technique is the result of a collaboration between the University of Pennsylvania and the Children’s Hospital of Philadelphia. The multimodal instrument developed by the research team combines concurrent frequency-domain diffuse optical spectroscopy with ultrasound imaging. Image-reconstruction algorithms are used to integrate ultrasound information about the morphology of tissue layers with optical information on hemodynamics. This information, once combined, is used to assess the properties of the placenta. The researchers spent three years optimizing the design of the instrument and testing it in preclinical settings. The optimization process involved integrating optical fibers with ultrasound probes, exploring various ultrasound transducers, and improving the multimodal technology to ensure that measurements were stable, accurate, and reproducible while collecting data at the bedside. A key challenge was finding a way to reduce background noise caused by the light scattering as it traveled through deep tissue to reach the placenta. The researchers ultimately reduced the background noise so as to ensure that the amount of light that penetrated the placenta tissue, while small, returned enough data for a high-quality measurement. “We’re sending a light signal that goes through the same deep tissues as the ultrasound,” professor Arjun Yodh said. “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.” The developed instrument can be used to noninvasively probe placental oxygen hemodynamics up to 4.2 cm below the body surface. Combining optical measurements with ultrasound, an interdisciplinary team from the University of Pennsylvania’s School of Arts & Sciences and Perelman School of Medicine and the Children’s Hospital of Philadelphia developed a device to measure blood flow and oxygenation in the placenta. Courtesy of Lin Wang. In a pilot study, 24 pregnant patients in their third trimester (15 with normal placental function and nine with abnormal function) were given supplemental oxygen for a short time to induce placental hyperoxia. The researchers measured oxygenated and deoxygenated blood concentrations in the placentas before and during hyperoxia. The results showed that the device could be used to study placental function in real time and also provided new insights into the relationship between blood flow and maternal vascular malperfusion, a condition that can occur when blood flow to the placenta is disrupted. “Not only do we show that oxygen levels go up when you give the mom oxygen, but when we analyze the data, both for clinical outcomes and pathology, patients with maternal vascular malperfusion did not have as much of an increase in oxygen compared to patients with normal placentas,” said professor Nadav Schwartz. “What was exciting is that, not only did we get an instrument to probe deeper than commercial devices, but we also obtained an early signal that hyperoxygenation experiments can differentiate a healthy placenta from a diseased placenta.” The researchers are refining the instrument to make it faster and more user-friendly. They are also using the instrument in larger studies, including in a study of second-trimester patients. The team is also interested in using the instrument to investigate different regions of the placenta. “From an instrumentation perspective, we want to make the operation more user-friendly, and then we want to carry out more clinical studies,” researcher Lin Wang said. According to Schwartz, the biggest potential of this work is in providing a way to start answering clinical questions about the placenta that remain unanswered. “Without being able to study the placenta directly, we are relying on very indirect science,” Schwartz said. “This is a tool that helps us study the underlying physiology of pregnancy so we can more strategically study interventions that can help support good pregnancy outcomes.” The research was published in Nature Biomedical Engineering (www.doi.org/10.1038/s41551-022-00913-2).