臺灣博碩士論文加值系統

目前腸胃科醫生普遍以內視鏡作食道癌腫瘤初步判斷，在找到懷疑病灶後，再以侵入式的活體組織切片作病理檢查確定癌細胞的存在，步驟繁複且需要切割組織才能取得病理變化資訊。且使用一般白光內視鏡檢查的誤診情況嚴重，過去研究顯示共6943例病例中有7.8％在確診前3至36個月內曾接受內鏡檢查卻沒被診斷為食道癌。另外，市面上雖然有多種影像加強型內視鏡可供選擇，但仍存在使用不方便或操作困難等缺點，且目前尚無內視鏡技術能準確判斷腫瘤邊界及範圍。光學同調斷層掃描技術 (Optical coherence tomography, OCT) 為一種光學斷層造影術，自1991年被提出後已普遍運用於臨床眼科檢查，目前 OCT應用於腫瘤偵測正在發展中，如口腔癌、肺癌、乳腺癌及食道癌等。在過去文獻已發現正常組織和腫瘤組織在光偏振特性上存有差異，但此特性尚未於早期食道癌診斷上研究，因此本實驗利用 OCT 在微觀尺度上非侵入性、高解析的成像特性，並配合光偏振特性作極化靈敏 (Polarization sensitive, PS) 成像，檢測小鼠離體食道和人體食道檢體結構的光強度及雙折射的深度資訊，作為早期食道癌腫瘤檢測觀察工具。透過本研究，我們提供小鼠和人體早期食道癌檢體的光學結構影像和相位延遲影像，並以三維重建後投影的方式呈現量化參數，包括相位延遲標準差（standard deviation of phase retardation）及厚度圖（Thickness map） 以區分正常組織與食道癌病變組織之邊界。

At present, gastroenterologists generally use endoscopy as a preliminary judgment for esophageal cancer. After finding the suspected lesion, the invasive biopsy is used for pathological examination to determine the presence of cancer cells. The steps are complicated, and the tissue needs to be cut to obtain deep structural changes. The misdiagnosis of endoscopic examination is serious. In the past, it was found that 7.8% of the total 6943 cases had undergone endoscopy within 3 to 36 months before diagnosis, but were not diagnosed as esophageal cancer. In addition, although there are many types of endoscopes available on the market, each endoscope has the possibility of false positives. The images show that the range of esophageal cancer tumors is not the same, and the cancer border cannot be distinguished. Optical coherence tomography (OCT) is an optical tomography technique that has been commonly used in clinical ophthalmologic examination since its introduction in 1991. Currently, OCT is used in the development of tumor detection, such as oral cancer, lung cancer, and breast cancer. Since the past literature has pointed out that there are differences in the polarization properties of normal tissues and tumor tissues, and OCT can be used to observe the internal structure of the esophagus, this experiment uses OCT to achieve non-invasive, high-resolution imaging characteristics on a microscopic scale. Moreover, with polarization characteristics for polarization-sensitive (PS) imaging, the light intensity and birefringence depth information of the isolated esophagus and human esophageal specimen structure are detected, and it is used as an observation tool for esophageal cancer detection. Through this study, we provide optical structure images and phase-delay images of mouse and human esophageal cancer specimens, and present quantitative parameters in three-dimensional reconstruction and en-face projection, including phase standard deviation and thickness map to distinguish the boundary between normal tissue and esophageal cancerous tissue.

目錄
中文摘要 i
英文摘要 ii
致謝 iv
目錄 v
圖目錄 viii
表目錄 ix
第 1 章 緒論 1
1.1 食道癌 1
1.1.1 簡介 1
1.1.2 臨床診斷方式 2
1.2 研究動機與目的 4
第 2 章 背景理論 6
2.1 光學同調斷層掃描術(OCT)簡介 6
2.1.1 極化靈敏光學同調斷層掃描技術(PSOCT) 7
2.2 極化靈敏原理 9
2.2.1 極化狀態 9
2.2.2 雙折射晶體 10
2.3 癌症與光學特性的關係 11
2.3.1 光散射差異 12
2.3.2 厚度變化 12
2.3.3 極化改變 13
2.4 OCT應用於食道癌論文回顧 15
第 3 章 系統架構與實驗參數 17
3.1 系統架構簡介 17
3.2 影像處理 19
3.3 參數定義 21
3.3.1 相位延遲標準差 21
3.3.2 厚度分佈 21
3.4 小鼠模型 21
3.5 人體檢體來源 22
第 4 章 影像重建與結果討論 24
4.1 小鼠實驗結果 24
4.1.1 PSOCT Enface投影與螢光激發照片比較 25
4.1.2 PSOCT 二維成像與組織切片對照驗證 32
4.2 人體檢體實驗結果 39
4.2.1 PSOCT 相位延遲標準差enface投影與窄頻內視鏡照片比較 39
4.2.2 PSOCT 二維切面與組織切片對照驗證 44
4.3 討論 59
4.3.1 相位延遲標準差與厚度分佈比較 59
4.3.2 小鼠離體和人體檢體結果比較 61
4.3.3 應用不同處理方式對相位延遲enface影像結果比較 61
第 5 章 總結與未來展望 63
5.1 總結 63
5.2 未來展望 63
參考文獻 65

圖目錄
圖 1 1 2016年台灣食道癌症相關個案報告[7] 2
圖 1 2具有食道鱗狀細胞癌病變的食道內視鏡影像 2
圖 1 3 具有食道病變的食道內視鏡影像 3
圖 1 4經放大之窄頻內視鏡成像從I型到V-N型病例的上皮內乳頭毛細血管環分類。[12] 3
圖 2 1麥克森干涉儀示意圖 6
圖 2 2基礎PS-OCT架構圖 7
圖 2 3 TM MODE與TE MODE之入射光、折射光及反射光示意圖。 9
圖 2 4光經過雙折射特性物質示意圖 11
圖 2 5正常組纖與食道鱗狀細胞癌病變位置之拉曼光譜比較。[34] 12
圖 2 6良性與惡性食道CT影像與特徵比較。[37]（惡性食道包括食道癌） 13
圖 2 7舌頭二維PSOCT成像 13
圖 2 8 通過PSOCT和MT染色分別評估區分四類口腔組織期別回歸圖[38] 14
圖 2 9燒傷疤痕一般照片與相位延遲ENFACE成像 [39] 14
圖 2 10離體豬食道OCT光強度成像以及厚度分佈圖。[40] 16
圖 3 1實驗室SWEPT SOURCE PS-OCT架構圖 17
圖 3 2影像處理流程 19
圖 3 3影像處理流程 20
圖 3 4犧牲老鼠後取出的食道 22
圖 3 5軟木板上的人體食道檢體 23
圖 4 1 小鼠正常食道PSOCT ENFACE投影與螢光激發照片比較。 27
圖 4 2小鼠上皮增生食 道PSOCT ENFACE投影與螢光激發照片比較。 28
圖 4 3 (I)小鼠食道癌食道PSOCT ENFACE投影與螢光激發照片比較。 29
圖 4 4 (II)小鼠食道癌食道PSOCT ENFACE投影與螢光激發照片比較。 30
圖 4 5 (III)小鼠食道癌食道PSOCT ENFACE投影與螢光激發照片比較。 31
圖 4 6小鼠正常食道PSOCT 二維成像與組織切片比較 34
圖 4 7小鼠上皮增生食道PSOCT 二維成像與組織切片比較 35
圖 4 8 (I)小鼠食道癌病變食道PSOCT 二維成像與組織切片比較 36
圖 4 9 (II)小鼠食道癌病變食道PSOCT 二維成像與組織切片比較 37
圖 4 10 (III)小鼠食道癌病變食道PSOCT 二維成像與組織切片比較 38
圖 4 11 (I)人體檢體食道癌PSOCT ENFACE投影與窄頻內視鏡照片比較。 41
圖 4 12 (II)人體檢體食道癌PSOCT ENFACE投影與窄頻內視鏡照片比較。 42
圖 4 13 (III)人體檢體食道癌PSOCT ENFACE投影與窄頻內視鏡照片比較。 43
圖 4 14 (I)人體檢體食道癌病理切片位置示意圖 45
圖 4 15 不同位置下(I)人體檢體食道癌PSOCT二維成像與組織切片比較 49
圖 4 16 (II)人體檢體食道癌病理切片位置示意圖 50
圖 4 17不同位置下(II)人體檢體食道癌PSOCT二維成像與組織切片比較 53
圖 4 18 (III)人體檢體食道癌病理切片位置示意圖 54
圖 4 19不同位置下(III)人體檢體食道癌PSOCT二維成像與組織切片比較 57
圖 4 20 各人體檢體食道癌PSOCT二維成像與組織切片結構比較 58
圖 4 21小鼠食道癌PSOCT 影像與組織切片 60
圖 4 22隨固定深度變化的相位延遲斜率回歸、平均值與標準差ENFACE影像比較 62

表目錄
表 2 1 極化狀態與瓊斯矩陣描述 10

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