Monitoring the placental oxygenation is critical to ensure a healthy pregnancy outcome. Abnormalities in placental oxygenation has been associated with preeclampsia and intrauterine growth restriction, fetal hypoxia, asphyxia, and cerebral palsy. Quantifying placental oxygenation can help early detection of such complications. This project is driven by the lack of patient-friendly devices to measure the oxygenation of the anterior placenta. A wearable, wireless system that can monitor the placental oxygenation dynamically are realized using Functional Near Infrared Spectroscopy (fNIRS). In parallel to the in-vivo studies, we are also interested in investigating placenta at cellular level to control the oxygen levels and understand its effect on cell metabolism. We intend to 1) find the baseline for the normal pregnancies and standardize the oxygenation data across pregnancies, 2) correlate the oxygenation data with the pregnancy outcomes and 3) study placental cell metabolism in-vitro at physiologically relevant variations of oxygen level using a novel biophotonic methodology, Dynamic Full Field Optical Coherence Tomography (DFFOCT). For the in-vivo study, we designed a wearable, wireless, non-invasive and inexpensive device to measure the anterior placental oxygenation in a subject-friendly environment. This prototype is light-weight and compact that can be placed at different abdominal locations for efficient and localized measurement of oxygenation. The NIRS device uses near infrared light with two different wavelengths of 760 nm and 840 nm that are sensitive to changes in oxy-hemoglobin and deoxy-hemoglobin. Our system consists of two light detectors and six LED sources to probe different tissue depth and distinguish the oxygenation between maternal layers and placental tissue. Flexible geometry of the optical probe of the device ensures effective optical contact with the skin without exerting excess pressure. The efficiency of the device was examined for different melanin volume fractions, fat thicknesses and uterus thicknesses to separate the placental oxygenation from the maternal layers contamination. Since the light passes through several tissue compartments, we have developed the multi-layer model based on Monte Carlo simulation that includes optical properties (scattering and absorption) of skin (dermis and epidermis), fat, uterus and placental tissue. For precise calculation of the oxygenation, prior knowledge of the optical properties of the given tissues such as scattering (how much tissue scatters the light) and absorption (how well tissue absorbs the light) is needed. We use a dual wavelength LED source with photodiode array unit built in-house to find the optical properties of the placenta. The attenuation coefficient (as a function of scattering and absorption coefficient) is calculated based on the reflection curve (light intensity as a function of source-detector distance) from placental tissues with and without blood. Monte Carlo simulations along with our multi-layer model helped us build a system that considers skin melanin content, fat and uterus thickness into the calculation of oxygenation index. In collaboration with Maternal-Fetal Medicine, Imaging, and Behavioral Development Affinity Group (Dr. Roberto Romero) at NICHD, Wayne State University, and USUHS we have the opportunity to test our device through pilot studies. We have started our first pilot study with Wayne State University, where we measure the oxygenation of the placenta during the last trimester in normal pregnancies to find a baseline of placental oxygenation. Meanwhile, we refine our data analysis software by incorporating anatomical data from subjects. Ultra-sound imaging gives us the fat and uterus thicknesses we need for the analysis. We hope to detect pregnancy complications in their earlier stages to improve both maternal and fetal health. Our initial in-vitro experiments on HeLa cells confirmed the ability of DFFOCT to detect the changes in intra-cellular activity as a function of ambient oxygenation. We use our segmentation algorithm to identify the DFFOCT signal from the cells grown on porous membrane and use Fourier analysis to understand the dynamic activity occurring within the cells. We compared the signal from cells grown under hypoxia and physoxia (physiological oxygenation) and observed unique differences in the Fourier spectra at these conditions. Control experiments with Cobalt chloride were used to mimic hypoxia. We also ran Western blot to ensure the effects of hypoxia on expression of Hif-1 protein in the cells. We plan to do further experiments to understand the link between oxygenation and the DFFOCT signal. This will help us in using DFFOCT as a tool to asses activity of placental cells under altered oxygenation. Facial plethora is one of the earliest described clinical features of Cushings syndrome (CS). In collaboration with SEG at NICHD, we have quantified changes of facial plethora in CS as an early assessment of cure. Non-invasive multi-spectral near-infrared imaging was performed on the right cheek of the patients before and after surgery. Patients were defined as cured by post-operative measurements of plasma cortisol less than 3 (mcg/dl), and/or adrenocortical insufficiency for which they received replacement. Results indicate that a decrease in facial plethora after surgery, as evidenced by decrease in blood volume fraction, is correlated with cure of CS. The first set of results were published in the journal of clinical endocrinology & metabolism. We also showed that water content fraction could be used as a new biomarker of early cure in patients with CS. We ran our methodology for first (3-6 months after surgery, N=22) and second (6 months after the first follow up, N=10) post-surgery follow up, where all subjects are identified clinically in remission state. As a next step for our bench to bedside goal, we have developed 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. Assessment of tumor development in patients can facilitate treatment strategies and early intervention. In our recent published study, we designed time-resolved fluorescence lifetime imaging to distinguish bound Human Epidermal Growth Factor 2 (HER2) specific affibody probes to HER2 receptors in live animals. Our results show that changes in fluorescence lifetime of the bound contrast agent can be used to rapidly assess the high to mid-level expression of HER2 expressing tumors in-vivo. 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 Universitys Perinatology Research Branch and Florida International University we will test our system in a control population and those with PTB prevalence.
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