Smart-phone-integrated, non-invasive, depth-resolved optical spectroscopy for the detection of neonatal jaundice

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PROJECT SUMMARY Newborns have immature liver function that is inefficient at metabolizing bilirubin. Consequently, nearly 80% of preterm and 60% of term babies develop hyperbilirubinemia resulting in neonatal jaundice within a week of their birth. As severe hyperbilirubinemia can be fatal, early, frequent and accurate monitoring of bilirubin is vital to avoid severe health issues and determine appropriate treatment. The gold standard for detecting hyperbilirubinemia is an invasive blood test to measure total serum bilirubin (TSB); however, frequent blood sampling in neonates is costly, painful and increases the chance of infection. Existing non-invasive methods to monitor hyperbilirubinemia lack sufficient accuracy to replace blood tests. Although commercial transcutaneous bilirubinometry (TcB) is clinically accepted for jaundice screening, it has low correlation with TSB for clinical decision-making in dark-skinned neonates and has low availability in low/middle income countries (LMICs). A main reason for the limitation of TcB is spectral cross-talk: the inability to reliably distinguish contributions between skin analytes (i.e., melanin) and blood. Our central hypothesis is that a non-invasive mobile phone-based bilirubin detector can be developed that provides accurate, point-of-care blood bilirubin measurements in dark-skinned neonates. We propose to use spectroscopic optical coherence tomography (sOCT), an imaging technique those depth-resolved capabilities can overcome spectral cross-talk. In Aim 1 we will develop portable, mobile phone-integrated sOCT for non-invasive, depth-resolved measurement of blood spectra. Our working hypothesis is that depth-resolved, sOCT spectra of bilirubin correlate strongly with spectral data from whole blood samples. Our innovative technical design will miniaturize and integrate traditional sOCT components into a compact smartphone attachment. We will also develop a smartphone application to perform data processing, analysis, display and HIPAA-compliant transmission or storage in lieu of a bulky computer. In Aim 2 we will refine and test the sOCT algorithm in vivo. Our working hypothesis is that sOCT measurements correlate better with lab-based TSB than does clinical TcB across a diverse range of skin tones. In a clinical study of 100 neonates, we will compare sOCT data to the TSB blood tests and commercial TcB. In Aim 3 we will validate the performance of sOCT in dark-skinned neonates from Kano, Nigeria. Our working hypothesis is that sOCT performs comparably to lab-based TSB tests in dark-skinned neonates and is acceptable for use in a LMIC setting. We will also assess potential challenges to incorporating sOCT into the clinical workflow of a LMIC hospital. If successful, sOCT can provide an accurate alternative to commercial TcB across diverse skin tones, including dark-skinned neonates and may potentially replace invasive methods to detect and monitor hyperbilirubinemia in LMICs.