Preterm research Placental oxygenation plays a crucial role in a healthy pregnancy and its outcome. Defects in placenta that affects placental oxygenation can cause preeclampsia and intrauterine growth restriction, fetal hypoxia, asphyxia, and cerebral palsy. A fast and non-invasive method that measures placental oxygenation, quantitatively, sounds necessary to detect such abnormalities. Current methods are either not patient-friendly or time consuming. Therefore, we developed a wearable device using near Infrared Spectroscopy (NIRS) that monitors anterior placenta oxygenation non-invasively and dynamically. This device uses two light sources with 760 nm and 840 nm wavelengths because they are sensitive to changes in blood oxyhemoglobin and deoxyhemoglobin. It consists of two photodiodes as detectors and six LED light sources that are placed in six different distances from 10 to 60 mm away from the LEDs. The different source and detector distances help us scan different tissue depths in order to distinguish between placental oxygenation and maternal layers oxygenation. Also, the probe has a flexible geometry that enables us to place it in proper contact with the skin. For the in-vivo study, we have tested this device on subjects in Detroit Michigan in collaboration with Perinatal Research Branch of NICHD(Dr. Roberto Romero) and Wayne State University, and USUHS. Mentioned study focuses on the baseline placental oxygenation for normal term pregnancies scheduled for cesarean section and Ultra-sound imaging gives us the fat and uterus thicknesses we need for the analysis. Thus far, we have measured placental oxygenation of 12 healthy, singleton, pregnant volunteers (33.33.6 weeks pregnant). We are in the process of completing our measurements on the total of 40 subjects to have adequate statistical power (as one can expect the COVID-19 pandemic has temporarily interrupted this study). The placental oxygenation calculated from two source-detector separations (30mm and 40mm) for this group of 12 subjects ranges from 68% to 89%. However, we found that the calculated placental oxygenation is positively correlated with the thickness of the fat layer. A pregnant woman with a thicker fat layer has a higher placental oxygenation. We believe that this correlation was caused by the highly scattering characteristic of the fat. Hence, we are now performing a Monte Carlo simulation on a five-layer model to correct the effect of maternal layers such as fat on placental oxygenation. These simulations are based on thickness and both scattering and absorption coefficient of all maternal layers (dermis, epidermis, fast, uterus) and placenta. In the other hand, placenta as an essential organ for fetal development and successful reproduction, is the least study organ. Thus, we have also measured the scattering coefficients of the human placenta for the range of 659 to 840nm using a well-established frequency domain diffuse optical spectroscopic system (DOSI) and a lab designed diffuse reflectance device (DRS). Measurements were performed in 8 placentas obtained after cesarean deliveries. Absorption and scattering coefficients were then calculated from the measured reflectance using the random walk theory for DRS and frequency domain algorithm for DOSI. Average reduced scattering coefficient was 0.943 0.015 mm-1 at 760 nm and 0.831 0.009 mm-1 at 840 nm and a power function in the form of 1.6619 (wavelengtht/500 nm)**1.426 was derived for the human placental scattering coefficient. These scattering coefficients can be used to improve measurements of placental oxygen saturation. Along with the in-vivo studies, we are studying placental oxygenation in the cellular level using novel biophotonics method named Dynamic Full Field Optical Coherence Tomography (DFFOCT). These experiments use HeLA cells with manually changed oxygenation. The preliminary results established the ability of DFFOCT to detect the changes in intra-cellular activity for different oxygen level. HeLa cell samples were treated with Triton X-100, which causes membrane permeabilization, and paraformaldehyde, which causes cell fixation. Untreated and treated samples were imaged using DFFOCT and analyzed to determine if DFFOCT could detect cellular activity. We were able to isolate cellular signals from environmental and measure changes in cellular activity following various inhibition treatments. This highlights the potential of DFFOCT to uncover new information about dynamic intracellular fluctuations during various cellular processes. Future experiments with targeted cellular treatments can be conducted to further characterize cellular activity. To identify the biological causes of the untreated signal, controlled experiments involving the removal of cellular energetics via mitochondrial inhibitors and glucose decouplers are planned. Cellular energetics are essential for large polymer buildup, disassembly, movement within the cell, and small protein activity. In another study, we aimed to use the PReterm IMaging system based on colposcope to characterize uterine cervix structure in a longitudinal study of low- and high-risk (prior preterm birth (PTB) or a sonographic short cervix) patients. Polarization imaging is an effective tool to measure optical anisotropy in birefringent materials, such as the cervix's extracellular matrix and to predict cervical ripening and potentially to diagnose pre-term birth. We developed a handheld colposcope device for active polarization imaging of the cervix. Through our under-review collaboration with Wayne State University Perinatology Research Branch and Florida International University we will test our system in a control population and those with PTB prevalence. COVID-19 Biosensor: With the pandemic of COVID-19, in collaboration with Biomedical Optics Lab lead by Dr. Bruce Tromberg, we are using our research in oxygenation quantification to develop a multimodal biosensor for early detection, monitoring and screening patients with respiratory infectious diseases including COVID 19 patients. The COVID-19 pandemic has challenged health care system to develop multimodal biosensing devices to identify patients with physiological signs of a COVID-19 infection. Thus, we are in the process of a clinical protocol approval and ultimately testing a wearable multimodal biosensor. This device consists of a near-infrared spectroscopy (NIRS), a photoplethysmogram (PPG) and a thermometer sensor, capable of monitoring skin temperature, tissue oxygenation level, heart rate and respiratory parameters. Data will be collected through a pilot study using this device in 40 healthy subjects who experienced a breathing pattern similar to that seen in pneumonia using hypercapnia, paced breathing and breath holding. Vital parameters extracted from NIRS signal will be identified that could distinguish between normal versus patterned breathing. In the next few months and as soon as the clinical protocol approved, we will start recruiting and will apply our technology to COVID-19 patients, eventually. Our ultimate goal is to use artificial intelligence and machine learning to identify a pattern of NIRS respiration and tissue oxygenation that would be specific to Corona Virus Disease 2019. The end product is going to be a point-of-case home-accessible device with Bluetooth functionality. Cushing syndrome: We are continuing our research on Cushings syndrome (CS ) in collaboration with SEG at NICHD to test a new hand-held multispectral camera to be used a point-of-care system. The device uses a high-resolution CMOS camera with on-chip filters. Images with resolution of 256X256 pixels are acquired simultaneously at eight different near-infrared wavelengths (700-980 nm). We have also developed a user-friendly graphical interface for data processing in Matlab.