臺灣博碩士論文加值系統

目前臨床上多以生理切片進行診斷消化道癌症，但此種方法對病人而言相當痛苦，將影響其生活品質，而醫生多根據具經驗對可能是病兆區進行切片，其切片區域又常是良性發炎而非癌症區域，這將減少病人持續追中的意願。因此本論文針對早期口腔癌研發一具有高速且高解析之光學同調斷層掃描術於血管造影，使用1310 nm 100 kHz高速掃頻雷射且將探頭端做有效的縮小並可手持式應用於口腔，其系統於空氣中之軸向解析度約為12.11 um、橫向解析度約為8.77 um、每秒可即時顯示100張影像，每張影像由1000條A-line寬度為3 mm所組成，並由370張影像涵蓋9mm2範圍之3D影像僅需30秒，並利用影像強度之都卜勒方差進行血管造影，將可在同一次掃描中獲得組織微結構、組織血管以及組織厚度，將針對正常活體老鼠舌頭、傷口癒合之老鼠耳朵血管新生、人體嘴唇進行研究。

Clinically, there uses a biopsy to detect oral cancer. However, this is too painful for the patient and often mistaken for inflammation rather than cancer. The disadvantage will reduce the patient's willingness to keep treatment. Thus, the goal of this study is to develop an advanced diagnostic instrument for earlier detection of oral cancer. We developed a hand-held oral probe system for in vivo ultrahigh speed optical coherence tomography (OCT) and angiographic imaging of the oral tissue without any contrast agents. Using a 1310 nm swept source laser, the system has a 100 kHz A-scan rate and ~12.11 um axial resolution in air. The system enables two-dimensional imaging of the sample at 100 frames per second (fps) with a ~8.77 um lateral resolution. Volumetric data consisting of 370 two-dimensional images of 1,000 A-scans each over a 3 mm length, covering a ~9 mm2 area is acquired in ~30 seconds. OCT angiography (OCTA) is computed using intensity decorrelation between sequential pairs of two-dimensional scans and enables three-dimensional visualization of micro-vasculature. Volumetric OCT, OCTA imaging and tissue thickness of the mice tongue, wound healing of mice ears with angiogenesis, human lip in vivo were demonstrated.

目錄
致謝 i
摘要 iii
Abstract iv
目錄 v
圖目錄 viii
表目錄 xii
第一章 緒論 1
1-1 研究背景 1
1-2 研究目的 3
1-3 論文架構 6
第二章 理論背景與介紹 7
2-1 光學同調斷層掃描術原理 7
2-1-1 掃頻式光學同調斷層掃描術 7
2-1-2 掃頻式光學同調斷層掃描術成像原理 10
2-2 重新取樣方式 13
2-2-1 振幅偵測 15
2-2-2 相位偵測 15
2-2-3 直接k-clock 取樣 16
2-3 光學同調斷層掃描探頭文獻回顧 18
2-3-1 Side imaging probe 18
2-3-2 Forward imaging probe 21
2-3-3 掃描探頭之血管造影 24
2-4 數值化色散補償 28
2-5 血管影像對比增強演算法(IBDV) 30
第三章 實驗架構與方法 33
3-1 光學架構 33
3-2 架構元件 34
3-2-1 光源 34
3-2-2 掃描探頭 35
3-2-3 掃描模式 36
3-3 訊號處理流程 39
3-3-1 訊號擷取與處理 40
3-3-2 FPGA DAQ (Field-Programmable Gate Array Data Acquisition) 41
3-3-3 色散補償演算法流程 42
3-3-4 影像優化處理方式 43
3-3-5 三維影像處理 44
3-3-6 組織厚度偵測 44
3-4 IBDV測試流體製做 46
3-5 動物實驗 47
3-5-1 老鼠舌頭 47
3-5-2 老鼠耳朵 48
3-5-3 人體嘴唇 48
第四章 實驗結果與討論 49
4-1 空間解析度 49
4-1-1 縱向解析度 50
4-1-2 橫向解析度 52
4-2 系統訊雜比測試 54
4-3 掃描步距計算 55
4-4 影像優化 57
4-5 IBDV驗證 58
4-5-1 仿體測試 58
4-5-2 張數影響測試 59
4-5-3 連續掃描與步階掃描之IBDV結果 60
4-5-4 連續掃描與步階掃描之老鼠耳朵IBDV結果 61
4-5-5 FPGA DAQ 資料格式與IBDV結果 61
4-6 活體實驗 62
4-6-1 正常老鼠舌頭 62
4-6-2 正常老鼠耳朵 65
4-6-3 正常人體嘴唇 68
第五章 總結與未來展望 70
5-1 總結與討論 70
5-2 未來工作 71
參考文獻 73

圖目錄
第一章
圖1-1 鱗狀上皮癌分期 1
圖1-2 臨床消化道診斷方式 3
圖1-3 旋轉光纖內視鏡探頭於活體豬食道之應用 4
圖1-4 旋轉光纖內視鏡探頭利用IBDV演算法之結果 5
第二章
圖2-1 使用麥克森干涉儀的掃頻式雷射光學同調斷層掃描術示意圖 8
圖2-2 掃頻式光學同調斷層掃描術RF調制信號的產生說明 9
圖2-3 掃頻雷射同調長度 11
圖2-4 重新取樣 14
圖2-5 以鏡子模擬生物樣品比較重新取樣前後差異 14
圖2-6 振幅偵測重新取樣 15
圖2-7 相位偵測 16
圖2-8 利用MZI signal做為校正訊號 17
圖2 9 氣球光纖探頭示意圖 18
圖2 10 microelectromechanical endoscopic 19
圖2 11 微小針行探頭 20
圖2 12 Common path endoscopic 21
圖2 13 懸臂樑擺動探頭 22
圖2 14 前向光纖掃描探頭 22
圖2 15 MEMS-based endoscopic 23
圖2 16 手持式掃描探頭 23
圖2 17 Fiber-optic-bundled based probe 24
圖2-18 固定旋轉探頭之架構 24
圖2-19 人體舌側白斑處之OCT強度影像 25
圖2-20 微機電旋轉馬達探頭 25
圖2-21 影像對位後之食道血管照影 26
圖2-22 口腔用探頭 27
圖2-23 眼底用探頭 28
圖2-24 眼底影像對位前後比較 28
圖2-25 數值化色散補償之訊號處理流程圖 29
圖2-26 眼底視網膜層狀結構影像 30
圖2-27 計算IBDV的方式 32
圖2-28 倉鼠皮膚OCT影像 32
第三章
圖3-1 Swept source OCT架構圖 33
圖3-2 探頭架構圖 35
圖3-3 掃描程式介面 37
圖3-4 Laser trigger與掃描波形 38
圖3-5 連續與步階掃描示意圖 38
圖3-6 訊號擷取與影像處理流程圖 39
圖3-7 利用MZI signal做重新取樣 40
圖3-8 LabVIEW人機控制介面 41
圖3-9 FPGA 運算流程 42
圖3-10 數值色散補償流程圖 43
圖3-11 設定閥值後去除影像背景雜訊 43
圖3-12 平均同位置掃描八次的強度影像 44
圖3-13 Avizo影像軟體介面 44
圖3-14 不同分期之口腔癌切片 45
圖3-15 組織厚度偵測流程圖 45
圖3-16 老鼠舌頭結構影像厚度偵測 46
圖3-17 塑膠軟管與掃描位置示意圖 47
圖3-18 夾具固定在老鼠舌頭 47
圖3-19 金屬環固定在老鼠耳朵 48
圖3-20 掃描人體嘴唇 48
第四章
圖4-1 高速成像之手持式OCT探頭 49
圖4-2 光學空間解析度定義 50
圖4-3 點擴散函數數值色散補償前後之比較 51
圖4-4 各深度縱向解析度之比較 52
圖4-5 USAF 1951解析度測試片 52
圖4-6 解析度測試片之OCT三維影像重組後en-face影像 53
圖4-7 第五組區域影像強度波形圖 54
圖4-8 系統靈敏度隨深度變化 54
圖4-9 振鏡掃描位置(0-1:一條寬度為500 m) 55
圖4-10 不同電壓之振鏡掃瞄距離 56
圖4-11 電壓與掃描距離關係圖(linear fitting) 57
圖4-12 影像優化 58
圖4-13 墨汁於塑膠管之停止與流動時IBDV影像變化 59
圖4-14 同一位置靜止仿體之不同張數IBDV計算 59
圖4-15 連續掃描與步階掃描之仿體IBDV結果 60
圖4-16 連續掃描與步階掃描之老鼠耳朵IBDV結果 61
圖4-17 比較資料格式 62
圖4-18 老鼠舌頭微結構 63
圖4-19 正常老鼠血管 64
圖4-20 正常老鼠舌頭組織厚度 65
圖4-21 老鼠耳朵各分期比較 67
圖4-22 人體嘴唇 69
第五章
圖5-1 手持式PS-OCT架構 71
圖5-2 微機電旋轉馬達驅動之側向出光探頭 72

表目錄
表3-1光源規格 34
表4-1 USAF 1951解析度測試片之參照表 53
表4-2 X和Y振鏡之電壓與掃描距離結果對照 56

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