臺灣博碩士論文加值系統

光學同調斷層掃描術(Optical coherence tomography, OCT)，由1991年發展出來，它對於生物組織能產生非接觸、非侵入式的斷層影像。於臨床上，光學同調斷層掃瞄已廣泛的應用在眼科的領域上。OCT除了應用於人類以外，此種技術也被廣泛用於觀察動物的眼睛，包括各種視網膜疾病的模型，在臨床應用和研究中的診斷能力準確度是依賴於其圖像的品質，所以高解析度(Ultrahigh-resolution)的影像就小動物眼底造影相對重要。
本論文致力於開發一套針對大鼠使用的高解析度眼底光學同調斷層掃描系統(Ultrahigh-resolution fundus camera optical coherence tomography)可觀察眼底視網膜的影像，將來可當作藥物篩檢的平台，本系統是以傅立葉域之光學同調斷層掃描(Fourier domain optical coherence tomography, FD-OCT)架構來達到快速擷取(最快45K A-lines/s)、高縱向解析度(軸向:3~5 m)、二維斷層與三維斷層影像組成，以及不需添加螢光染劑就能獲得組織影像對比，且配合眼底鏡(Fundus camera)可以看到OCT的掃描線，幫助我們在取得影像時當作定位的功能。

Optical coherence tomography (OCT), introduced in 1991, is a powerful tool that can produce non-contact, non-invasive tomographic images of biological tissues. Clinically, OCT systems have been widely used for diagnoses in ophthalmology. In addition to being applied to humans, OCT is widely used to observe the animal's eyes, including small animal models of various retinal diseases. The diagnostic accuracy in clinical applications and research is dependent on the quality of the imaging, so the ultrahigh-resolution imaging capability is very important especially for small animal.
In this thesis, we developed an ultrahigh-resolution fundus camera optical coherence tomography system for rat retina imaging. This imaging platform can be used for drug screening in the future. In this system, we used a Fourier domain OCT construction to achieve high scanning rate (45kHz A-scan rate), high axial resolution (3~5m) in air, two-dimensional (2D) and three-dimensional (3D) tomographic images, as well as free of fluorescent dye to get contrast of tissues. The fundus camera can help us to see the OCT scanning line, which is helpful for retina positioning when the OCT images were acquired.

致謝 I
摘要 III
Abstract IV
目錄 V
圖目錄 VII
表目錄 IX
第一章 緒論 1
1-1 研究動機與目的 1
1-2 文獻回顧 3
1-2-1使用光譜域光學同調斷層掃描術對於大鼠眼底視網膜的成像 3
1-2-2使用光譜域光學同調斷層掃描對大鼠視網膜退化的縱向研究 6
1-3 論文架構 7
第二章 理論背景與介紹 8
2-1眼睛功能與組織概述 8
2-2光學同調斷層掃描術簡介 10
2-2-1 干涉儀原理 11
2-3 頻譜域OCT (Spectral domain OCT, SD-OCT) 13
2-4光學同調斷層掃描的空間解析度 15
2-4-1 縱向解析度 16
2-4-2 橫向解析度 17
2-5光譜儀最大掃描深度(Z max) 18
2-6 數值色散補償 19
2-7 增強影像對比度 21
第三章 實驗架構與方法 24
3-1光學系統架構介紹 24
3-2光學元件 26
3-2-1光源 26
3-2-2元件 26
3-2-3光譜儀 28
3-2-4掃描振鏡 29
3-2-5相機 29
3-3訊號影像處理流程 30
3-3-1訊號擷取 31
3-3-2訊號處理 32
3-3-3數值色散補償演算法流程 33
3-4 動物實驗 34
第四章 結果與討論 35
4-1空間解析度 35
4-1-1軸向解析度 35
4-1-2橫向解析度 36
4-2系統最佳化測試 37
4-2-1 硬體色散補償 37
4-2-2 不同深度解析度比較 38
4-3信號訊雜比(Signal to Noise Ratio , SNR) 39
4-4動物實驗前之測試 40
4-4-1 眼底鏡掃描線測試 40
4-4-2 OCT 掃描膠帶測試 40
4-4-3 OCT 掃描手指測試 41
4-5動物實驗 42
4-5-1眼底鏡測試結果 42
4-5-2 OCT測試結果 43
4-6 以不同角度做掃描 49
4-7 增加影像對比度 49
第五章 結果與討論 51
5-1總結與討論 51
5-2未來工作 52
參考文獻 53

圖目錄
第一章
圖1-1 正常視網膜與不正常視網膜 1
圖1-2 (a) Long-Evans (b) Sprague-Dawley大鼠眼底視網膜 4
圖1-3 適應性光學系統。 5
圖1-4 OCT掃描大鼠眼底影像 6
圖1-5 經過接觸式透鏡的光路 6
第二章
圖2-1光線在視網膜上的落點正常情況 8
圖2-2眼底組織示意圖 10
圖2-3 麥克森干涉儀示意圖 12
圖2-4 SD-OCT系統示意圖 13
圖2-5頻域經傅立葉轉換成時域 15
圖2-6光學空間解析力定義 16
圖2-7 NA數值與橫向解析度 18
圖2-8 (a)頻域，(b)時域，兩者之傅立葉轉換關係 18
圖2-9 數值化色散補償之訊號處理流程圖 20
圖2-10 眼底視網膜層狀結構影像：(a)未做色散補償，(b)硬體色散補償，(c)數值色散補償 21
圖2-11 比較兩種演算法結果 23
第三章
圖3-1 SD-OCT系統架構圖，中心波長為860 nm 24
圖3-2光源之各波段輸出強度圖 26
圖3-3實測的光譜形狀，左為干涉前，右為干涉後 28
圖3-4掃描角度與振幅大小關係 29
圖3-5相機與鏡頭 30
圖3-6訊號擷取與影像處理流程圖 30
圖3-7訊號產生器波形與掃描關係 31
圖3-8 光譜儀參數設定 32
圖3-9 LabVIEW人機控制介面 32
圖3-10影像組成與掃描方式 33
圖3-11 數值色散補償流程圖 33
圖3-12 老鼠移動平移台 34
第四章
圖4-1軸向解析度，點擴散函數之色散補償前(Origin)與後(Calibration) 36
圖4-2 USAF 1951解析度測試片 36
圖4-3解析度測試片之OCT三維影像重組後，XY-enface影像 37
圖4-4 使用不同玻璃厚度補償後的解析度值 38
圖4-5 最佳解析度之點擴散函數 38
圖4-6 各深度鏡子反射訊號SNR 39
圖4-7 各深度鏡子反射訊號強度 40
圖4-8 (a)無掃描，(b)掃描的情況 40
圖4-9 掃描膠帶結果，(a)無平均，(b)平均四張 41
圖4-10 (a)手指，光強度約0.75 mw，(b)光強度約3 mw 42
圖4-11 (a)眼底鏡影像，無掃描 (b)掃描情況 43
圖4-12 (a)文獻掃描大鼠影像 (b)眼底組織切片 44
圖4-13 本系統掃描大鼠影像 44
圖4-14 (a) 厚度所算的位置 (b)平均厚度 45
圖4-15 掃1000張B-scan三維影像(a)xyz面(b)xz面(c)yz面(d)xy-enface 46
圖4-16 1000張B-scan三維影像掃描範圍 46
圖4-17 掃2000張B-scan三維影像(a)xyz面(b)xz面(c)yz面(d)xy-enface 47
圖4-18 2000張B-scan三維影像掃描範圍 47
圖4-19 三維影像(a)xyz面(b)xz面(c)yz面(d)xy-enface 48
圖4-20 三維影像掃描範圍 48
圖4-21 以不同電壓做掃描的結果，(a)0.4V(b)0.5V(c)0.6V(d)0.7V 49
圖4-22 原始圖像 50
圖4-23 原始圖像做對比度增強 50
圖4-24 以八張不同位置做平均 50
圖4-25 八張平均後做對比度增強 50

表目錄
第三章
表3-1各元件距離 25
表3-2光源輸出規格 26
表3-3元件規格型號 27
表3-4光譜儀規格 28
表3-5訊號產生器參數設定 31
第四章
表4-1 Thorlabs USAF 1951之解析度參照表 37
表4-2 不同深度的解析度值 38
表4-3 本系統所掃描大鼠的厚度值 45

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