Quantitative Biophotonics for Tissue Characterization and Function

Eunice Kennedy Shriver National Institute Of Child Health & Human Development

Investigators

Linked publications, trials & patents

Abstract

Placental oxygenation plays a crucial role in a healthy pregnancy, ensuring the fetus receives an adequate supply of oxygen. Defects in the placenta that affects its oxygen saturation level can lead to poor pregnancy outcomes for both the mother and baby, including preeclampsia, intrauterine fetal growth restriction, fetal hypoxia, asphyxia, and cerebral palsy. Additionally, reduced perfusion could cause intrapartum asphyxia and the most severe reduction of perfusion could lead to fetal death. The Section on Translational Biophotonics has developed a wearable optical device to monitor tissue oxygen saturation in the placenta continuously. This placental oxygenation monitor utilizes depth-resolved near-infrared spectroscopy (NIRS) and features six source-detector separations ranging from 10 - 60 mm, which is helpful to target different tissue depths. The NIRS probe is flexible and bendable, which allows the device to fit properly on a curved surface like an abdomen. This device can measure real-time tissue oxygen saturation at a data acquisition rate of 0.5 Hz. Measurements of tissue oxygen saturation were compared with a commercial system (TRS-41 system, Hamamatsu photonics, Japan) to validate performance. The placental oxygenation monitor yields close oxygen saturation levels with the commercial device (R2 = 0.94) with an averaged error of 2.7% 1.8%. Under protocol #090717MP4E, which was approved by the Wayne State University Human Investigations Committee Institutional Review Board (IRB), the placental oxygenation monitor was used to measure tissue oxygen saturation in the placenta of 12 singleton pregnant women in their third trimester at the Center for Advanced Obstetrical Care and Research of the Perinatology Research Branch, located at the Detroit Medical Center (DMC, Detroit, Michigan, USA) (Nguyen et al., Biomed. Optic Exp., 2021). Five of these women had maternal pregnancy complications. Our preliminary results have indicated a significantly lower tissue oxygen saturation level in the placenta of patients with complicated pregnancies (69.4% 6.7%) compared to their peers with normal pregnancies (75.0% 5.8%). After delivery, 10 of the 12 participants placentas were delivered to the pathology department at the DMC to inspect for lesions. Five placentas were found to have chronic or acute lesions, four of which belonged to participants with maternal pregnancy complications. We further found that patients with lesion-free placentas presented a significantly higher placental oxygen saturation (74.2% 5.8%) than patients with lesions (68.7% 5.6%). These results suggest a relationship between the placental oxygen saturation and pregnancy complications and placental pathology. Based on the original plancental oxygenation monitor, we have developed a new wireless and wearable multimodal placental device with an embeded accelerometer. The biosensor has a data acquisition rate of 20 Hz, which allows collection of high frequency signals such as maternal and fetal heart rates. The accelerometer was added to detect fetal movement. The wireless placenta-device has recently been deployed to perform a one-time measurement of 24 pregnant women at their second and third trimesters at DMC (Detroit, Michigan, USA). Ten of the women in this cohort had maternal complications including chronic hypertension, asthma, type II diabetes, renal failure with dyalisis, and prolactinoma, and five had preeclampsia with severe features. The experimental procedure was perfomed in the same way as the previous measurement, where the participant lied down on the examination bed in a supine position. After delivery, the placentas of 22 participants were sent to a pathology labratory to examine for lesions. Seventeen placentas had issues including acute and/or chronic inflammartory lesions, acute funisitis and vasculitis, placental infarct, and lesions associated with maternal vascualar malperfusion. In general, all 24 participants had either maternal complications, placental issues, and/or neonatal complications. The average oxygen saturation of the placenta of all participants were 68.9 4.2%, which was similar to the oxygen saturation level found in the group of pregnant women with maternal complications and/or placental lesions in the first measurment. In order to test the multimodal biosensor in a larger population, we are collaborating with Dr. Guoyang Luo at the INOVA Fairfax Hospital to develop a clinical protocol to monitor pregnancy health in more than 1000 pregnant women. This research was recently awarded with the Scientific Director Award for FY 2023 & FY 2024. In addition, a provisional patent application (Title: System and protocol for monitoring pregnancy health, No. E-198-2022-0-US-01) is associated with the multimodal biosensor. An additional provisional patent application (Title: Single source-detector separation approach to calculate tissue oxygen saturation, No. E-037-2023-0-US-01) is associated with the methodology of the study. DFFOCT: In tandem with our research into the impact of placental oxygenation using the NIRS device, we are concurrently developing an algorithm that assesses the metabolic behavior of placental cells based on varying oxygen levels. This is accomplished through the utilization of the DFFOCT (Dynamic Full-field Optical Coherence Tomography) system. Our experimentation involves employing HeLa cells, which are similar to placental cells and the results of the study can be widely applied. The DFFOCT system is a label-free, non-invasive, and non-destructive method that analyzes the dynamic activity based on the movement of the scattering body within the cell. Capitalizing on the strengths of DFFOCT, we have devised a methodology for scrutinizing the dynamic activity traits of cells (Park, et al. 12(10), 6431-6441, Biomedical Optics Express, 2021), alongside an automated viability evaluation technology (Park, et al. 13(6), 3187-3194, Biomedical Optics Express, 2022). In 2023, we successfully constructed a customized incubator for cell cultivation in conjunction with the DFFOCT system. This incubator addresses past limitations associated with maintaining optimal 'temperature', 'gas concentration control', and the 'continuous supply of nutrients' during extended cell observations using the DFFOCT system. Notably, the incubator's systematic control over the supplied O2 concentration enables a more methodical exploration of the impact of placental oxygen levels on fetal development. Our current efforts revolve around the ongoing acquisition of dynamic activity data from HeLa cells exposed to varying O2 concentrations. Multimodal biosensor: The emergence of the global coronavirus pandemic in 2019 (COVID-19 disease) created a need for remote methods to detect and continuously monitor patients with infectious respiratory diseases. Many different devices, including thermometers, pulse oximeters, smartwatches, and rings, were proposed to monitor the symptoms of infected individuals at home. However, these consumer-grade devices are typically not capable of automated monitoring during both day and night. This study aims to develop a method to continuously monitor patients with respiratory infectious disease and classify breathing patterns in real-time using the measured data and Machine Learning.In a collaboration with Dr. Babak Shadgan at the University of British Columbia, Canada, data were collected in 21 healthy adult volunteers during different breathing exercises through a clinical protocol approved by the Clinical Research Ethics Board at the University of British Columbia. Collected data was used to classify breathing patterns using Random Forest algorithm, which results in a classification accuracy of 87% (Mah et al., 2022) and using Pre-ResNet, which results in a classification accuracy of 92.4% (Park et al., 2023).