設計開發以自動突聚焦超穎透鏡為基礎之微型光聲顯微鏡

Abstract

光聲成像 (Photoacoustic imaging, PAI) 近年已成為生醫領域中重要的研究方向與應用工具，該技術透過脈衝雷射激發組織產生超音波訊號，再由超音波換能器進行偵測，透過特定光波長脈衝，PAI可在無需標記 (label-free) 的情況下實現血氧與脂肪等生理資訊成像，兼具高光學對比且較純光學系統擁有更好的穿透能力。然而，聲學解析度光聲顯微鏡（Acoustic-resolution photoacoustic microscopy, AR-PAM）通常仰賴體積較大的光學元件與複雜的光學對準機制，導致系統尺寸龐大，限制其在臨床應用與內視鏡發展上的可行性。因此，在維持AR-PAM解析度的同時實現系統微型化，仍為一項關鍵挑戰。本研究提出一種自動突聚焦光聲顯微鏡(AAF-PAM)，其利用光學超穎透鏡（Optical Metalens）所產生之自動突聚焦（Abrupt Autofocusing, AAF）雷射光束來進行微型化，AAF特殊中空光學結構可提供單晶超音波換能器的置入空間，達到傳統AR-PAM光學元件功能的同時大幅縮小探頭體積，並且因整體整合於三軸自動掃描系統中，AAF-PAM可將A-scan訊號重建為最大強度投影與深度影像。在實驗驗證中，所設計之直徑3 mm超穎透鏡成功產生自動突聚焦光束，該光束最大中空結構直徑為1 mm，並可置入中心頻率為20 MHz、-6 dB頻寬約為13 MHz、有效面積0.75 × 0.75 mm2、長度8 mm的方形單晶超音波探頭並於純水環境下進行光聲成像測試，結果顯示AAF-PAM具橫向解析度為165.6 ± 9.4 μm、縱向解析度109.5 ± 30.0 µm，優於本研究所用 20 MHz對應的理論AR-PAM解析度，且能穩定重建葉脈、鼠尾等生物樣本影像。此外，本系統亦為未來微型化光聲內視鏡（Photoacoustic endoscopy, PAE）及微型AR-PAM腦部動態影像應用奠定基礎。綜合而言，本研究證實超穎透鏡所產生之自動突聚焦光束可微型化AR-PAM，不僅突破傳統光學系統尺寸與整合限制，亦具備高度擴展性，展現其於醫學檢測及精準醫療等領域的應用潛力。

Photoacoustic imaging (PAI) has recently become an important research direction and a powerful tool in the biomedical field. It relies on pulsed laser excitation to generate ultrasonic signals that are subsequently detected by an ultrasound transducer. By selecting an appropriate optical wavelength, PAI enables label-free imaging of physiological parameters such as blood oxygenation and lipid distribution, while providing both high optical contrast and better deep tissue penetration compared with pure optical systems like OCT. However, acoustic-resolution photoacoustic microscopy (AR-PAM) typically depends on bulky optical components and complex optical alignment, resulting in a large system size that limits its feasibility for clinical applications and endoscopic integration. Therefore, achieving system miniaturization while maintaining AR-PAM-level resolution remains a critical challenge. In this thesis, an abrupt autofocusing photoacoustic microscope (AAF-PAM) is proposed, which utilizes an abrupt autofocusing (AAF) beam generated by an optical metalens to enable system miniaturization. The unique hollow region of the AAF beam provides sufficient space for the integration of a single-element ultrasound transducer, allowing the system to preserve the functionality of conventional AR-PAM while significantly reducing the probe size. By integrating the system with a three-axis automated scanning platform, the AAF-PAM is capable of reconstructing A-scan signals into maximum intensity projection (MIP) images and depth images. In the experimental validation, the designed metalens with a diameter of 3 mm successfully generates the AAF beam, which exhibits a maximum hollow diameter of 1 mm. This configuration enables the insertion of a square single-crystal ultrasound transducer with a center frequency of 20 MHz, a -6 dB bandwidth of approximately 13 MHz, an active area of 0.75 × 0.75 mm², and a length of 8 mm. Photoacoustic imaging experiments were conducted in a water environment to evaluate system performance. The results demonstrate that the AAF-PAM system achieves a lateral resolution of 165.6 ± 9.4 μm and an axial resolution of 109.5 ± 30.0 µm, comparable to those of conventional AR-PAM systems. In addition, the system is capable of stably reconstructing biological structures such as leaf venation and mouse tail vasculature, confirming its imaging capability. Furthermore, this system lays the foundation for future developments in miniaturized photoacoustic endoscopy (PAE) and compact AR-PAM systems for functional brain imaging. In summary, this thesis verifies that metalens-generated AAF beams provide an effective approach for miniaturizing AR-PAM. The proposed design overcomes the size and integration limitations of conventional optical systems, while offering high scalability and strong potential for applications in medical diagnostics and precision medicine.