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

项目摘要 新生儿的肝功能不成熟，不能有效代谢胆红素。因此，近80% 早产儿和60%的足月儿在出生后一周内发生高胆红素血症，导致新生儿黄疸。 他们的诞生由于严重的高胆红素血症可能是致命的，因此早期、频繁和准确地监测胆红素至关重要 以避免严重的健康问题，并确定适当的治疗。检测的黄金标准 高胆红素血症是测量总血清胆红素（TSB）的侵入性血液检查;然而，频繁的血液检查可能导致高胆红素血症。 在新生儿中取样是昂贵的、痛苦的，并且增加了感染的机会。现有的非侵入性方法， 监测高胆红素血症缺乏足够的准确性，以取代血液检查。虽然商业经皮 胆红素测定法（TcB）是临床上公认的黄疸筛查方法， 在深色皮肤的新生儿中，这类药物缺乏决策能力，在低收入/中等收入国家（LMIC）中的可用性较低。 限制TcB的主要原因是光谱串扰：无法可靠地区分 皮肤分析物之间的贡献（即，黑色素）和血液。我们的核心假设是， 可以开发基于移动的电话的胆红素检测器，其提供准确的即时血液胆红素 在深肤色新生儿中进行测量。我们建议使用光谱光学相干断层扫描 （sOCT），一种具有深度分辨能力的成像技术，可以克服光谱串扰。在目标1中， 将开发便携式、移动的手机集成sOCT，用于无创、深度分辨的血液测量 谱我们的工作假设是胆红素的深度分辨sOCT光谱与 来自全血样品的光谱数据。我们创新的技术设计将使我们的产品 将传统的sOCT组件整合到紧凑的智能手机附件中。我们还将开发智能手机 执行数据处理、分析、显示和符合HIPAA的传输或存储的应用程序 一台笨重的电脑。在目标2中，我们将在体内完善和测试sOCT算法。我们的假设是 sOCT测量结果与基于实验室的TSB的相关性优于各种皮肤范围内的临床TcB 音调。在一项100名新生儿的临床研究中，我们将sOCT数据与TSB血液检测和商业 TcB。在目标3中，我们将验证sOCT在来自尼日利亚卡诺的深色皮肤新生儿中的性能。我们 工作假设是sOCT在深肤色新生儿中进行基于实验室的TSB测试， 在LMIC设置中使用是可接受的。我们还将评估将sOCT纳入 LMIC医院的临床工作流程。如果成功的话，sOCT可以提供一个准确的替代商业 TcB在不同肤色中的应用，包括深肤色新生儿，可能会取代侵入性方法 检测和监测低收入国家的高胆红素血症。

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.