基于光学分辨模式的便携式实时光声显微成像技术研究

Optical-resolution photoacoustic microscopy (OR-PAM) combines the advantages of high absorption contrast of pure optical imaging and high penetration depth of pure ultrasound imaging, which has been significantly improved in terms of spatial resolution, imaging speed, detection sensitivity and depth. However, thus far, most OR-PAM systems generally utilize bulky solid-state lasers for optical illumination, which makes them inherently difficult to achieve integrative producibility, because of their high cost, large size, cooling requirements, and complex maintenance. As an alternative laser source, semiconductor excitation of laser diodes are relatively inexpensive, compact, and high repetition frequency for noninvasive photoacoustic equipment, which has been explored for photoacoustic imaging studies. In 2012, we has presented the 3D-visual photoacoustic imaging technique with a laser diode excitation [Opt.Express,20(2),2012], and recently design the first generation portable OR-PAM prototype [Appl.Phys.Lett. 102(5),2013]. Therefore, we are planning on this basis to integrate the following techneques of laser galvanometer scanning excitation, multielement array detection, multichannel parallel acquisition, dynamic phase-controlled focus synthesis, and 3D-visual reconstruction, etc., and devote to develop a noninvasive, portable, realtime, and high-resolution OR-PAM system and method.

光学分辨式光声显微成像（OR-PAM）结合了纯光学成像的高对比度和纯声学成像的高穿透性优点，近年来在空间分辨率、成像速度、探测灵敏度和探测深度等方面取得了显著进展。但由于常用的光声激励源--固体激光器具有价格高、体积大、需冷却、维护难等缺点，使得OR-PAM系统难以集成一体化而走出实验室。作为一种新型的光声激励源，半导体激光器--激光二极管具有价格低、体积小、重复率高等优点，并已探索性用于光声成像领域。2012年，本申请人提出基于激光二极管辐射源的三维可视化光声技术[Opt.Express, 20(2),2012]，并开发了第一代的便携式OR-PAM样机系统[Appl.Phys.Lett.102(5),2013]。现计划在此基础上，采用激光振镜扫描激发、多元阵列式传感、多通道并行采集、动态相控聚焦合成、三维可视化重建等技术，建立健全一套无损、便携、实时和高分辨率的光声显微成像系统及其方法。

光学分辨模式光声显微镜（OR-PAM）是从2008年兴起的一种非入侵式和非电离式的新型生物医学影像技术。然而以大型固体激光器作为常规光声激励源的系统方案，导致该技术的研发成本高、整机体积大、后期维护难等。为此，本课题通过研发成本低、体积小、寿命长的脉冲激光二极管（LD）光声激励源，并以此发展可易于集成化、通用化、实用化的OR-PAM系统方案，将有助于推进OR-PAM技术的产品化而走出实验室。在项目执行三年期间，研制和完善了多套系统原理样机，具体情况如下：（1）完善了一套基于905nm激光二极管激励源的光声显微镜系统NIR LD-OR-PAM，系统横向分辨率可达1.5μm，光声激励源体积仅有10×3×3cm，并实现了模拟微血管及小动物等的2D/3D可视化显微成像；（2）研发了一套基于405nm激光二极管激励源的光声显微镜系统VIS LD-OR-PAM，系统横向分辨率提高到0.95μm，单脉冲能量从14μJ降低至52nJ，光声激励源源体积缩小到1.8×1.2×1.2cm，并实现了碳纤维原丝表面缺陷、小鼠皮下毛细血管网络等的2D/3D显微成像；（3）开发了短脉冲的405/445/520/650nm多波长激光二极管光声激励源、15MHz四环阵列式光声传感器等核心模块，并正在完善一套基于2D激光阵镜扫描的下一代实时VIS LD-OR-PAM原理样机；（4）采用主频为7.5MHz的256阵元环形阵列式光声传感器，完善了一套全角度电子扫描的快速光声成像系统，系统横向分辨率约为100μm，成像速度可达3s/frame，并实现了活体小鼠全脑结构及其损伤的无损快速光声层析成像。