光聲與超音波雙模式影像:系統發展與分子探針應用

Abstract

多模式影像乃結合不同的成像機制，在影像中提供互補性資訊，如解剖結構與分子功能，而可作為病情診斷、治療與監測的依據。為加速擷取動態資訊，本論文選擇以光聲與超音波雙模式影像為研究基礎，並從改善系統規格與影像品質出發，延伸至雙模式分子探針在診療的應用。影像的品質可以由解析度來評斷，它包括對時間、空間和對比的解析能力。現今大部分的光聲影像系統幀率限制於雷射規格，成像只在幾十赫茲；為了提高時間解析度，本論文以高重複率的脈衝雷射和商用超音波陣列系統來實現超快光聲成像，陣列可以做平行信號接收，以波束成型組成二維影像;若搭配發送平面波，則超音波影像亦可同時獲得。高速成像的方法則可應用於三維或四維的光聲影像，並且以合成孔徑聚焦技術來改善陣列的水平向聚焦、提升影像品質。除外，因高速成像下的影像信雜比較差，為改善空間和對比分辨率，論文中提出同調因子為基礎的可適性波束成像方法，加入對通道信雜比的評估，修改同調因子定義，改進傳統同調因子受環境雜訊的影響。以超音波和光聲的快速成像的影像作為測試，結果顯示此方式可改善空間解析度與對比度，且能在嘈雜的環境裡保持影像強度。 論文的第二部分為雙模式分子探針的開發，利用超音波顯影劑(微氣泡)與光聲顯影劑(奈米金桿)的結合，做成帶金微氣泡，能在雙模式中做為對比增強劑；而帶金微氣泡經由表面抗體修飾，能夠識別特定分子，增加在血管新生區域的附著量，累積效果可用超音波影像來觀察。該分子探針也能搭配雷射來進行光熱治療，藉由奈米金桿吸光來提升區域溫度，可同時以光聲方式進行溫度監測。並且利用微氣泡的穴蝕效應，可以促使奈米桿的釋放而增加療效，實驗以光聲、光熱方式做巨觀的觀察，再以非線性光學方式作微觀的確認。故以帶金微氣泡做為雙模式顯影劑，不單能提升在光聲與超音波影像對比，亦具有診療監測等多功用途。總結此光聲與超音波的雙模式研究，從系統改良以提高結構影像品質與動態量測的精準，而雙模式分子探針的引入，則結合了光學與聲學的特性，擴展其於生醫診療之應用與功能。

Multi-modality imaging can provide complementary information, such as structure and function. It integrates the advantages from the different modalities and has been a promising approach to improve diagnosis and to monitor therapy. To speed up the acquisition and for accurate measurements, the photoacoustic/ultrasound (PA/US) dual-modality imaging is studied in the research. It starts with system improvement and array processing and explores the potential in theranosis with the PA/US contrast agent. The imaging performance is measured by the resolution, including temporal, spatial and contrast. Ultrafast PA imaging is first implemented with a high pulse-repetition-rate laser and an US array system. With transmitting plane wave, ultrafast US images can be simultaneously obtained. The system is applied to acquire 3D/4D data and its elevational focusing is improved by the synthetic aperture technique. Besides, because high-frame-rate imaging usually suffers from low signal to noise ratio (SNR) and poor spatial and contrast resolution, the coherence based adaptive beamforming is proposed. Specifically, it modifies the definition of coherence factor (CF) according to the aperture SNR. It is tested with US and PA data and found that the spatial resolution and contrast can be improved by the SNR-dependent CF while maintaining the image intensity in the noisy environment. The other topic is to develop the dual-modality molecular probe. The gold microbubbles (AuMBs), which are composed by microbubbles (MB) and gold nanorods (AuNR), provide PA/US contrast enhancement. With surface modification, it can target to the angiogenesis region and the accumulation is observed by US imaging. Photothermal effect can be induced by the plasmonic heating of AuNRs and the temperature rise can be monitored by PA imaging. Moreover, MB cavitation helps to release AuNRs and the improved effect is proven with PA, photothermal, and nonlinear optical methods. In summary, the dual-modality research improves the structural imaging and dynamic measurements by ameliorating system performance and the introduction of dual-modality molecular probe expands the biomedical applications and functions.