近年來為了增加三維成像速度，雷射掃描式光學解析度光聲顯微鏡已被提出並使用。此系統常使用水聽筒或是非聚焦式探頭以得到較大的掃描視野，然而這兩類探頭將使掃描視野及訊雜比出現折衷。此外非聚焦式探頭的使用還會產生空間脈衝響應效應─由掃描視野內的光聲源所導致的不均勻探頭壓電響應。此效應將使軸向解析度下降，並降低高頻寬超音波探頭應用於光譜式顯微鏡上的效果。為了解決這些問題，我們提出一個適用於光學解析度光聲顯微鏡的「虛擬點偵測器」概念，此概念除了同時增加訊雜比、降低空間脈衝響應之效應外，還能維持系統的高速掃描能力及足夠的掃描視野。聚焦式探頭的聚焦點將被視作虛擬點偵測器，目的是為了在具有光聲束結合器的情況下仍能夠盡可能地靠近樣品，並可被當作是一個真實的點偵測器。我們利用Filed II模擬及現有的超音波成像系統來初步驗證此概念之可行性。模擬及實驗結果皆呈現了訊雜比及掃描視野之間確實會有折衷的情況，此折衷情況由虛擬點偵測器與樣品之間的距離所決定，故可根據不同的應用來決定掃描視野及訊雜比的大小。其中使用虛擬點偵測器概念相較於非聚焦式探頭確實可得到較高的訊雜比，而空間脈衝響應效應的抑制也被A-line訊號、頻譜及相關度圖所驗證。不同中心頻率探頭間的比較、鼠耳活體造影及初步的鼠腦影像結果也已被呈現。

Recently, laser-scanning optical-resolution photoacoustic microscopy (LSOR-PAM) has been proposed to increase the 3D imaging speed; however, its use of a needle hydrophone or an unfocused ultrasound transducer for obtaining large field-of-view (FOV) compromises the signal-to-noise ratio (SNR). LSOR-PAM with an unfocused transducer also suffers the spatial impulse response (SIR) effect – the non-uniform piezoelectric response of the transducer to the photoacoustic sources in the FOV. The SIR effect also deteriorates the axial resolution and hinders the use of the high frequency broadband transducer required for spectroscopic applications. To solve these problems, we propose a virtual point detector concept for LSOR-PAM to improve the SNR and mitigate the SIR effect while retaining the imaging speed and minimizing the loss in the FOV. The focal point of a focused transducer is viewed as a virtual point detector which can be placed as close to the sample as possible to act like a real one even though the LSOR-PAM is with an optical and acoustic beam combiner. We preliminarily verify the feasibility of the concept by Field II simulation and existing ultrasound imaging system. Simulation results and experimental results both showed that there was a trade-off between the SNR and FOV determined by the distance between the virtual point detector and sample, which can be well tailored for different applications. The higher SNR than that of LSOR-PAM using an unfocused transducer could be obtained. Moreover, the suppression of the SIR effect was proven by A-line signals, spectrums and correlation maps. Comparison between the transducers with different center frequencies, in vivo micro-vascular imaging of a mouse ear and the preliminary results of a mouse brain were also drawn.

摘要 I
Abstract II
Table of Contents III
List of Figures V
Chapter 1 Introduction 1
1.1 Transcranial Imaging of Neuro-vascular Coupling 1
1.2 Photoacoustic Imaging 2
1.2.1 Principles of Photoacoustic Imaging 2
1.2.2 Optical-resolution Photoacoustic Microscopy 3
1.3 Motivations 6
1.4 Thesis Organization 6
Chapter 2 Materials and Methods 8
2.1 Reflection-mode Laser-scanning OR-PAM 8
2.1.1 System Architectures and Specifications 8
2.1.2 Scanning Mechanism 10
2.1.3 LSOR-PAM with an Unfocused Transducer 12
2.1.4 Spatial Impulse Response Effect 13
2.1.5 LSOR-PAM with a Needle Transducer 15
2.2 Virtual Point Detector Concept 16
2.3 Field II Simulation 18
2.3.1 Acoustic Field 18
2.3.2 Spatial Impulse Response Effect 23
2.3.3 Further Improvement of the Proposed Method 24
Chapter 3 Experimental Results and Discussion 27
3.1 System Improvement 27
3.1.1 Improvement of the Imaging Speed 27
3.1.2 Setup of a Custom-made Digital Microscope 28
3.1.3 Fast-adjustment of the Scanning Misalignment 30
3.1.4 Enhancement of the Signal Bandwidth 31
3.2 Verification of the Proposed Method 33
3.2.1 Ultrasound Imaging System 33
3.2.2 Trade-off between the SNR and FOV 35
3.2.3 Mitigation of Spatial Impulse Response Effect 42
3.3 LSOR-PAM of a Mouse Ear In Vivo 48
3.3.1 Small FOV Case 48
3.3.2 Large FOV Case 52
Chapter 4 Conclusions and Future Work 56
4.1 Conclusions 56
4.2 Future Work 57
Reference 59

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