摘要：本計畫中，我們結合光學工程、電機工程及醫學專長，利用同位光學同調斷層及自體螢光掃瞄之非侵入性技術，來建立口腔癌及癌前病變之診斷及治療追蹤的黃金律及標準程序。在能夠進行光學同調斷層與自體螢光之同步同位掃瞄前，我們將先從事以直接目視自體螢光來協助光學同調斷層掃瞄。在台灣大學醫學院附設醫院之臨床診斷工作，不只包括不同口腔癌及癌前病變階段之辨識，如輕度、中度及重度上皮變異、原位癌、早期鱗狀細胞癌、已發展成型之鱗狀細胞癌以及口腔黏膜下纖維化等，也包括以光學同調斷層掃瞄來追蹤口腔癌前病變經光動力治療及冷凍治療後病變之恢復情況。另外，我們也將以高解析度光學同調斷層掃瞄技術，來快速決定口腔癌手術中切除腫瘤塊之安全邊界（亦即切除是否乾淨）。除了標準的光學同調斷層掃瞄外，我們也將建立光學都卜勒及偏振敏感之掃瞄功能，來豐富掃瞄之結果。經由與病理切片影像之比較，我們將找出有效指標及程序來逐步建立口腔病變診斷及手術切除安全邊界之黃金律。依應用所需，我們將使用掃頻光源及頻域光學同調斷層掃瞄兩種系統架構。除了上述工作外，我們也將製作各種不同波長之藍光發光二極體，來尋求激發口腔自體螢光之最佳條件。在口腔癌及癌前病變之診斷應用上，基於光學同調斷層掃瞄之技術有如下之優點：組織掃瞄深(於口腔黏膜可深達3mm，因此可以觀察到輕度上皮變異及口腔黏膜下纖維化，也因此可達到真正的早期診斷)、快速掃瞄和即時診斷、非侵入性、可望取代病理切片、相對便宜等。我們期望在本三年期計畫執行結束後，所建立光學同調斷層掃瞄及分析之黃金律與標準程序能夠達到成熟階段，可用為在病理切片前，口腔病變篩檢之第一步驟，最終或可取代病理切片。本計畫中主要參與研究之教師包括兩位工程教授及兩位醫學教授，共分三個子計畫，分工合作，共同執行所提出之研究課題。
Abstract: In this project, we combine the expertise of optical engineering, electrical engineering, and medicine to build the golden rules for the diagnosis and treatment tracking of oral cancer and precancer based on the noninvasive coregistered oral mucosa scanning of optical coherence tomography (OCT) and autofluorescence. Before the synchronized coregistered scanning, direct autofluorescence visualization-assisted OCT scanning will be investigated first. The clinical diagnosis includes not only the differentiation of different oral precancer and cancer stages, such as mild, moderate, and severe dysplasia, carcinoma in situ, early-stage squamous cell carcinoma, well-developed squamous cell carcinoma, oral submucous fibrosis, etc., but also the tracking of progressive regression of oral precancers after the photodynamic therapy and cryotherapy. Also, fast determination of excision safety margin in oral cancer surgery is implemented by high-resolution OCT scanning. Besides the standard OCT operation, the functions of optical Doppler tomography and polarization-sensitive scanning will be realized for enriching the scanning result. Effective indicators and standard procedures for building the golden rules for oral disease diagnosis and excision safety margin judgment will be identified. Depending on the application, the configurations of swept-source OCT and spectral-domain OCT will be used. In addition, blue light-emitting diodes of various wavelengths will be fabricated for testing the optimized autofluorescence excitation condition. For oral cancer and precancer application, the OCT-based technology has the advantages of deep mucosa scanning (as deep as 3 mm such that the features of mild dysplasia and oral submucous fibrosis can be observed and hence truly early diagnosis of oral precancer can be achieved), fast scanning and real-time diagnosis, noninvasive nature, biopsy free diagnosis, and relatively lower cost, etc. It is expected that after the study of this three-year project, the built golden rules and standard procedures of OCT scanning and image analysis can become mature enough for serving as the first step of lesion screening before biopsy and eventually replacing biopsy. The major involved faculty members of this three-branch-project research proposal include two engineering professors and two medical doctors.
