A Newly-designed Probe for Clinical Oral Cancer Diagnosis with Optical Coherence Tomography

在本論文中，我們架設了一套光纖式光學同調斷層掃瞄系統，系統本身採用中心波長1300奈米，具有頻寬100奈米的超亮二極體作為光源。在這套系統中，為了達到快速掃瞄的需求，我們採用相位延遲器以達到光程差的快速調變，相位延遲器的掃瞄速度為250 Hz。系統本身的縱向解析度為8微米，靈敏度為80 dB。我們針對口腔內掃瞄的需求設計了一個小型、旋轉式的探頭作為掃瞄之用。系統本身的橫向解析度為14微米。利用這個特殊設計的小型探頭，我們先針對皮膚做活體的掃瞄。根據掃瞄結果發現，我們可清楚分辨皮膚中角質層、表皮以及真皮，這三層主要結構。影像的掃瞄深度可達600到800微米。皮膚掃瞄影像的尺寸為1平方釐米，擷取速度則小於一秒。 為了測試臨床掃瞄的可靠性，我們掃瞄了活體口腔黏膜的影像。在我們的掃瞄過程中，我們針對口腔黏膜中，嘴唇黏膜以及特化黏膜（舌頭背面）這兩種做掃瞄。在這些口腔黏膜的掃瞄結果中發現，我們可以觀察到口腔黏膜中上皮層和固有層兩層結構，部分能看到次黏膜的構造。影像的掃瞄深度可達600到700 微米。此外，我們也可在特化黏膜的掃瞄結果中發現，固有層中某些腺體的存在。 目前這套系統將在台灣大學醫學院附設醫院進行口腔癌的臨床掃瞄。In this research, a fiber-based optical coherence tomography (OCT) system is built, which utilized the broadband SLD light source with the central wavelength at 1300 nm and the spectral width at 100 nm. In the OCT system, an optical phase delay line is implemented for the fast scanning requirement with the scanning frequency up to 250 Hz. The axial resolution of the OCT system is 8 microns. Its sensitivity is 80 dB. A compact rotation-type probe specially designed for the oral cavity scanning is fabricated. The lateral resolution of the system is 14 microns. With this hand-held probe, the in vivo scanning results of human skin are first obtained. In such scanning, three major layers, including stratum corneum, epidermis, and dermis, can be clearly identified. The penetration depth of human skin scanning images is 600~800 μm. The image size of human skin scanning of 1 mm x 1mm can be completed in less than one second. To test the clinical application, in vivo scanning of oral mucosa was performed. In such scanning, two types of oral mucosa, including labial mucosa (lip) and specialized mucosa (the dorsal surface of tongue) are scanned. In the labial scanning images, three major layers, including epithelium, lamina propria, and submucosa, can be identified. The scanning depth of labial mucosa was 600~700 μm. In scanning the images of specialized mucosa, some glands inside the layer of lamina propria can be observed. This OCT system will be used for clinical diagnosis of oral cavity cancer at the National Taiwan University Hospital.致謝………………………………………………i 中文摘要…………………………………………ii Abstract..………………………………………iii Contents…………………………………………iv Chapter 1 Introduction..............................................1 1.1 Optical Bioimaging Methods............................1 1.2 Optical Properties of Biological Tissues..............4 1.3 Oral Cavity...........................................8 1.3.1 Oral mucosa Structures............................8 1.3.2 Oral cavity cancer...............................10 1.4 Research Motivations.................................12 Chapter 2 Fundamentals of Optical Coherence Tomograph..............14 2.1 Low-coherence Interferomery..........................17 2.2 Tissue Scattering Models.............................21 2.3 Configurations of Hardware and Scanning Optics.......22 2.3.1 Light Sources for Optical Coherency Tomography...22 2.3.2 Reference Arm Configurations.....................24 2.3.3 Sample Arm Configurations: Probes and Endoscopes.27 2.4 Functional OCT Modalities............................30 2.4.1 Polarization Sensitive OCT (PSOCT) ..............31 2.4.2 Doppler OCT......................................33 2.4.3 Spectroscopic OCT................................34 2.5 Spectral- or Fourier-domain OCT (SDOCT)..............36 2.6 Current Biomedical Applications of OCT...............39 Chapter 3 Optical Coherence Tomography System for Oral Cavity Cancer Studies..................................................40 3.1 OCT System...........................................40 3.2 Light Source.........................................42 3.3 Detector and Signal Processing.......................43 3.3.1 Detector.........................................43 3.3.2 Signal Processing (Software Demodulation)........44 3.4 Reference Arm Configuration (Phase Delay Line).......46 3.5 Sample Arm Configuration (Probe Design)..............50 3.5.1 Lateral Scanning Configuration (Rotation Motor)..51 3.5.2 Probe Design Process.............................53 3.5.3 Alignment Procedures.............................56 Chapter 4 Scanning Results and Discussions.........................58 4.1 In vivo OCT scanning images of Healthy Human Skin....58 4.2 In vivo OCT scanning images of Healthy Human Oral Mucosa..............................................62 Chapter 5 Conclusions and Discussion...............................66 5.1 Summary..............................................66 5.2 Future Work..........................................67 References...............................................6