許多重要疾病如腫瘤的研究，皆與血管有著密切的關係。光聲造影為一種基於光聲效應之新穎生醫造影技術，對於微細血管造影來說，此技術最大優點為不需標定的高光學吸收對比且為非侵入式的成像技術，同時可進行血液相關重要參數如血紅素濃度及血氧飽和濃度的功能性造影。在本研究中，我們基於非聚焦式超音波換能器，建立一套可用於微細血管脈絡造影廣視野之光學式掃描光學解析度光聲顯微鏡。傳統的光學解析度光聲顯微鏡，使用機械式掃描及聚焦式超音波換能器來提升系統之訊雜比，但此架構會增加系統成像時間，本研究採光學式掃描來解決此問題。然傳統系統使用的光學物鏡與聚焦式超音波換能器會限制系統之視野，本系統選用非聚焦式超音波換能器增加系統之視野。目前本系統使用超音波換能器的中心頻率10-MHz時，軸向解析度為120um，橫向解析度為4um，視野至少可達2x2 mm2，並可用於活體小鼠耳中微細血管脈絡造影，於活體實驗穿透深度估計可達0.8 mm。未來工作重點將放在系統成像速度提升至即時影像、空間解析度的改進及多波長功能性血管造影上。

Blood vessels play an important role in many significant disease researches such as cancer study. Photoacoustic imaging is a novel bio-imaging modality based on the photoacoustic effect. For micro-vasculature imaging, it owns the advantages of label free high optical absorption contrast and can be performed non-invasively. It also
can provide blood-related functional imaging capability for the measure of total hemoglobin concentration and hemoglobin oxygen saturation. In this thesis, we developed an unfocused ultrasound transducer based laser
scanning optical resolution photoacoustic microscope (OR-PAM) for
extended large field of view (FOV) in vivo micro-vasculature imaging of
small animals. Conventional OR-PAM employs a focused ultrasound
transducer to improve the signal-to-noise ratio and performs mechanical
scanning for imaging. However, mechanical scanning is time-consuming.
Such a problem is solved by optical scanning in this study while the
optical objective lens and focused ultrasound transducer limit the FOV
instead. In our design, the FOV is improved by using an unfocused
ultrasound transducer plus laser scanning. The experimental results
showed that the developed OR-PAM is with axial resolution of 120m
and lateral resolution of 4m when using a 10-MHz unfocused
transducer. The achievable FOV is at least 2x2 mm2. The resolving
power of the system was also demonstrated by imaging the in vivo
micro-vasculature of a mouse ear. The estimated noise-equivalent
penetration depth is 0.8 mm in vivo. Future work will focus on the
improvement of the imaging frame rate and spatial resolution and the
development of multi-wavelength functional micro-vascular imaging.

摘要
Abstract
圖目錄
表目錄
第一章 序論
1.1 血管影像
1.2 光聲造影
1.2.1 光聲造影原理
1.2.2 聲學解析度與光學解析度之光聲顯微系統
1.3 研究動機與目的
1.4 論文架構
第二章 基於非聚焦式超音波探頭之光學解析度光聲顯微鏡
2.1 技術簡介
2.2 系統架構與設計原理
2.2.1 脈衝雷射與耦合系統
2.2.2 觀測目標與訊號頻率
2.2.3 光聲探頭
2.2.4 超音波換能器的選擇
2.2.5 定位與掃描系統
2.2.6 系統同步的控制
2.2.7 訊號擷取系統
2.3 預掃描流程與C-scan 成像
2.4 系統參數測試
2.4.1 空間解析度
2.4.2 穿透深度
2.4.3 掃描與成像速度
第三章 活體小動物之光聲造影
3.1 皮下微細血管脈絡造影
3.1.1 系統活體驗證
3.1.2 實驗結果與討論
第四章 結論與未來工作
4.1 結論
4.2 未來工作
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