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NOVEL NONINVASIVE OPTICAL DIAGNOSTIC TECHNOLOGIES FOR THE MANAGEMENT OF NEONATAL JAUNDICE
Harrison, Brandon K
Harrison, Brandon K
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Thesis/Dissertation
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2022
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Bioengineering
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http://dx.doi.org/10.34944/dspace/8024
Abstract
Optical Diagnostic (OD) approaches are used to assist in real-time disease screening and estimation of physiological parameters. OD techniques such as pulse oximeters, transcutaneous bilirubinometers (TcB) and infrared thermometers have become key components for point-of-care clinical management. TcB is used to screen infants for extreme or prolonged neonatal jaundice (hyperbilirubinemia), a treatable condition that can result in permanent neurological impairment or death. Poor outcomes are common in low- and middle-income countries (LMIC), but rare in high-income countries, where access to newborn TcB screening is one of several factors that contributes to disparities. A low-cost, widely distributable approach for TcB could help expand newborn screening in LMICs. Due to the rapid global adoption of versatile smartphones with onboard camera modules, there is increased interest in transforming mobile phones into OD devices, including for the purpose of performing estimates of circulating bilirubin levels in order to expand access to transcutaneous bilirubinometry (TcB) for neonatal jaundice screening.In this dissertation, the feasibility of performing TcB using spatially resolved diffuse reflectance measurements acquired using a mobile phone is evaluated in human subject studies, as well as using theoretical modeling and optical phantom studies. In Aim 1 of this project, we report on the feasibility of a mobile phone-based TcB device and show the development of this device through Monte Carlo simulations. Theoretical models were constructed and utilized for predicting bilirubin levels and were then evaluated with a small pilot study. We extracted measurements of reflectance from multiple optimized spatial-offset regions of interest (ROIs) and a linear model was developed and cross-validated. This resulted in a correlation between total serum bilirubin and mobile phone-based TcB estimated bilirubin values, with R2 = 0.42 and Bland-Altman limits of agreement of +6.4 mg/dL to -7.0 mg/dL. These results report the feasibility of a mobile phone with a modified adapter that can be utilized to measure neonatal bilirubin values; thus creating a novel tool for neonatal jaundice screening in low-resource settings.
Aim 2 reports further evaluation of a multi-device mobile phone-based TcB study, including calibration for inter-device variability. Measurements of reflectance were extracted from multiple optimized spatial-offset regions of interest (ROIs) and a linear model was developed and cross-validated. This resulted in a correlation between total serum bilirubin and mobile phone-based TcB estimated bilirubin values, with R2 = 0.28 and Bland-Altman limits of agreement of +9.2 mg/dL to -9.3 mg/dL. These results indicate that an adapter-based smartphone can be modified to measure neonatal bilirubin values for neonatal jaundice screening in low-resource settings.
Finally, Aim 3 seeks to guide future developments and evaluate theoretical performance of spatially resolved diffuse reflectance image measurements for regression-based estimation of optical chromophores. We perform a phantom study to explore the impact that increased sample chromophore dimensional variability has on the predictive model correlation. Phantoms were created to simulate the variability of blood, bilirubin and melanin, and then images were captured with mobile phone-based TcB devices. Mean intensities of systematic selection regions of interest based on spatial and spectral images were used as predictive variables for multiple linear regression model construction. The results of this study suggest that 2d spatially resolved diffuse reflectance models benefit the most from unique spatial and spectral regions of interests.
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