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研究生: 鄭南玉
Cheng, Nan-Yu
論文名稱: 使用漫反射光譜法評估新生兒經皮膽紅素濃度
Evaluation of transcutaneous bilirubin level of neonates using diffuse reflectance spectroscopy
指導教授: 曾盛豪
Tseng, Sheng-Hao
學位類別: 博士
Doctor
系所名稱: 理學院 - 光電科學與工程學系
Department of Photonics
論文出版年: 2019
畢業學年度: 107
語文別: 英文
論文頁數: 74
中文關鍵詞: 漫反射光譜新生兒黃疸膽紅素皮膚光學參數吸收係數散射係數
外文關鍵詞: diffuse reflectance spectroscopy, neonatal jaundice, bilirubin, skin optical properties, absorption coefficient, reduced scattering coefficient
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  • 新生兒黃疸好發於出生一至二週的新生兒,在亞洲有高達六成以上的比例,新生兒黃疸所致之核黃疸,更是開發中國家新生兒死亡的原因之一。現行市售經皮量測黃疸檢測儀除了售價昂貴外,同時具有一些測量限制:易受嬰兒膚色干擾、線性範圍不足、量測部位多局限於頭部、及無法適用於已進行黃疸照光治療的病童上,尚不足以提供可完全信任的膽紅素數值以輔助新生兒黃疸的診斷,因此目前臨床上仍需倚靠抽血為檢驗標準,而抽血檢驗除了造成新生兒疼痛,在一些沒有完善抽血檢驗設備的地區或是國家,更有感染風險及醫療廢棄物處理問題。此外,根據美國兒科醫學會所出版的新生兒高膽紅素血症管理指南,對於接受黃疸光照治療或是膽紅素值上升快速的嬰兒,每日更應頻繁地觀測膽紅素變化,而僅倚靠血液檢查於臨床執行上是困難的。由以上原因,改良經皮量測黃疸儀有其實質的醫學價值。
    本研究使用光擴散理論的基礎原理,架設一套搭配擴散探頭的平台式漫反射光譜系統,利用涵蓋波長450 – 600 nm的光源,量測並計算新生兒皮膚的光學參數,量化皮膚組織的主要色團如帶氧血紅素(HbO_2)、血紅素(Hb)、黑色素(melanin) 與膽紅素(bilirubin)。研究結果顯示我們的系統在具有高膽紅素值的新生兒上仍可準確量測,同時在不同部位(頭、胸、左腳)皆有很好的量測結果,我們並在已接受照光治療後的病童量測上取得了初步驗證,本研究克服了現行經皮量測黃疸儀常見缺失,並對新生兒膽紅素量測提供了更多元的量測方式。

    Neonatal jaundice is a common condition that frequently presents in 1–2 weeks old neonates, and 60% of the Asian neonates ever had neonatal jaundice. The bilirubin-induced brain dysfunction, kernicterus, is also one of the major reasons of neonatal mortality in developing countries. Although there are existing conventional non-invasive transcutaneous bilirubinometers, they are still not accurate and reliable enough to monitor jaundice. Typical transcutaneous bilirubinometers have some measurement limitation, such as affected by skin color, insufficient measurement range, the measurement site is limited at the head, and cannot be used at the neonates who already received the blue-light phototherapy. According to the guideline of hyperbilirubinemia management in the newborn produced by American Academy of Pediatrics, infants who receive phototherapy or who have a rapid increase in bilirubin value, bilirubin changes should be observed frequently every day. It is impractical to monitor via blood tests frequently. Our research has a great impact on the diagnostic method of neonatal hyperbilirubinemia for pediatricians and their little patients.
    We propose a diffuse reflectance spectroscopy system with a diffusing probe for determination of bilirubin value. The recovered absorption spectra were fit to the known absorption spectra of the main chromophores to determine the tissue chromophore concentrations such as oxygen-hemoglobin, hemoglobin, melanin, and bilirubin. Our system could properly determine the transcutaneous bilirubin concentrations at different skin sites (forehead, sternum, and left sole) and high total serum bilirubin levels. Preliminary results also show that our system can reliably determine the transcutaneous bilirubin concentration at the sole of neonates who receive phototherapy.

    摘要 I Abstract II Acknowledgements III Table of Contents IV List of Table VI List of Figures VII List of Symbols X List of Abbreviations XII Chapter 1 Introduction 1 1.1 Neonatal Jaundice 1 1.2 Blood sampling measurement 3 1.3 Transcutaneous bilirubin measurement 4 Chapter 2 Theoretical Background 8 2.1 Diffusion theory 8 2.2 Boundary Conditions 9 2.3 Modified Two-Layered Diffusion Model 12 2.4 Chromophore fitting 14 Chapter 3 Materials and Methods 17 3.1 Diffuse reflectance spectroscopy system 17 3.2 Diffusing probe 20 3.3 Philips BiliChek 21 3.4 Skin-mimicking phantoms fabrication 25 3.5 Measurements of newborns 29 Chapter 4 Results and Discussion 31 4.1 Skin-mimicking phantom measurement by our DRS system 31 4.1.1 Phantoms with different bilirubin concentrations 32 4.1.2 Phantoms with different bilirubin and coffee concentrations 34 4.2 Optical properties of neonatal skin 37 4.3 Neonatal transcutaneous bilirubin measurement 41 4.3.1 At forehead 43 4.3.2 At sternum 46 4.3.3 At soles 51 4.4 Transcutaneous bilirubin measurement of neonates who have high bilirubin concentration 57 4.5 Transcutaneous bilirubin measurement of neonates who received phototherapy 61 Chapter 5 Conclusion and Future Work 65 Bibliography 69

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