以光聲顯影劑進行超解析光聲定位顯微術之研究

Super-Resolution Photoacoustic Localization Microscopy with Contrast Agents

呂虹緯(Hung-Wei Lu)

指導教授 ： 李百祺

國立臺灣大學/電機資訊學院/生醫電子與資訊學研究所/碩士(2018年)

https://doi.org/10.6342/NTU201800538

摘要

光聲影像系統結合了光能量的激發與聲學偵測的特性，相較於傳統光學系統，光聲系統提供了較大的偵測深度。最近的文獻顯示利用顯影劑能增強光聲影像之偵測靈敏度及辨識特異性。目前存在多種光聲成像系統，光學解析度的光聲顯微術可以用來得到更好的解析度，但是此系統的成像深度有限。聲學解析度光聲顯微術則可以以空間解析度來換取更深的成像深度。因此本研究提出利用聲學解析度光聲顯微術配合顯影劑以提升其空間解析度，而成像深度能達到數公分。其主要原理是利用追踪單顆的顯影劑粒子，找出其中心以作定位之用。而此定位方法可以超越繞射極限的限制。本論文的第一部份為證明此前提假設的實驗，以532 nm Nd:YAG 雷射作光源訊號，配合超音波陣列系統以接收光聲訊號。而顯影劑主要利用53~63um黑色聚乙烯微粒。經過定位及重建，結果顯示利用此方法可以分辨兩個相距僅150um之細塑膠管，證明了低於繞射極限解析度的光聲成像可能性。接著第二部份嘗試使用金奈米液滴作為顯影劑。相較於一般使用熱膨脹效應產生光聲訊號，在此，汽化效應產生的光聲訊號被用於實現更高的信噪比。實驗結果顯示，液滴濃度需大於〖10〗^7~〖10〗^8droplets/mL才能夠偵測到明顯的氣化光聲信號。而在此系統下要使一顆顆金奈米液滴彼此分開大於解析度的距離，金奈米液滴濃度需要在〖10〗^5droplets/mL以下，但由於單顆金奈米液滴訊號能量非常小，目前難以同時滿足此超解析方法並達到足夠的信噪比。而另一方面，我們也證明了汽化所產生的氣態液滴可以用做超音波成像的顯影劑。對於未來的工作，我們將著重於如何使用這種方法以量化金奈米液滴的汽化效應。

關鍵字

超解析 ； 光聲影像 ； 定位顯微術 ； 金奈米液滴 ； 液滴汽化

並列摘要

Photoacoustic (PA) imaging combines light excitation and ultrasound detection. It can achieve a larger imaging depth than that of conventional optical imaging. Recent studies in the literature show that the use of contrast agents can enhance specificity and sensitivity of PA detection. There are different forms of PA imaging. To achieve better spatial resolution, optical resolution PA microscopy (OR-PAM) can be used. However, it has a limited imaging depth. Another approach is the acoustic resolution photoacoustic microscopy (AR-PAM), which can achieve deeper penetration at the price of degraded spatial resolution. In this study, we propose the use of AR-PAM and contrast agents to improve the resolution while maintaining the imagine depth. The proposed method is based on the tracking of the centroid of an isolated particle. By tracking and accumulating the particles, one is able to enhance the lateral resolution. In the first part of this study, experiments were performed for proof of concept by using a 532 nm Nd:YAG laser and a 128 channel ultrasound array system. Microspheres with a size of 53~63um were used as the contrast agent. The experimental results show that this method is capable of resolving two adjacent tubes placed 150um apart, which is beyond the theoretical diffraction limit of the imaging system. In the second part, gold nanodroplets were used as the contrast agent. Nonetheless, instead of the thermal expansion effect that generates the PA signal, the vaporization signal was used to achieve higher SNR. Experimental results show that a concentration of the nanodroplets about 〖10〗^7~〖10〗^8droplets/mL is required for sufficient signal generation. Given that the droplets have to be sufficiently sparse (i.e., concentration lower than 〖10〗^5droplets/mL) for the proposed super resolution approach, it is difficult to achieve a feasible tradeoff between SNR and the sparsity required for super resolution imaging. On the other hand, we also demonstrated that the resulting gaseous phase of the vaporized droplets can also be used as the contrast agent for ultrasound imaging. For future works, we will focus on how to quantify the vaporization effect of gold nano-droplets using this approach.

並列關鍵字

super-resolution ； photoacoustic ； localization ； microscopy ； gold nanodroplets ； droplet vaporization

參考文獻

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