- 學位論文
可用於微細血管脈絡造影光學解析度光聲顯微鏡之開發
Development of Optical Resolution Photoacoustic Microscope for Micro-vasculature Imaging
摘要
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。
並列摘要
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 120m and lateral resolution of 4m 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.