基于多波长激光二极管激励的多环阵列传感式三维光声显微成像

Photoacoustic microscopy (PAM) is a novel microscopic imaging technique arising out of photoacoustic spectrometry and acoustic microscopy. By detecting ultrasonic with an ultrasound transducer instead of detecting the scattering photons in optical imaging, it can realize a micrometer-level spatial resolution at centimeter-level depth in biological tissue. However, thus far, most PAM systems generally utilize bulky solid-state laser as a photoacoustic excitation, which makes them inherently difficult to achieve miniaturization and generalization to move out of the lab, because of its high cost, large size and cooling requirement. Therefore, on the basis of the last two generations of PAM prototypes, we are planning to design an integrative compact photoacoustic excitation with 400-700 nm multi-wavelength pulsed laser diodes. In addition, for the disadvantages of low axial resolution and fixed ultrasonic focus spot of focused ultrasonic transducer, a multi-annular plane array transducer combing with dynamic phase-controlled focus technology will be employed to improve the focus detecting capability in depth. Finally, we will set up an in vivo 3D PAM imaging technique and method in terms of being portable, label-free, high resolution, which can obtain structural and functional microscopic imaging on multiple locations of subcutaneous capillaries and veno-arterial network at different depth, and provide a real-time, high contrast and high resolution image reference for clinical diagnosis of various kinds of skin injury and pathological changes.

光声显微镜（PAM）是在光声光谱技术和声学显微镜的基础上兴起的一种新型显微成像技术，其采用超声传感器检测超声波替代光学成像中检测散射光子，可同时实现微米级成像精度和厘米级探测深度的组织影像。但由于常用的光声激励源——固体激光器具有价格高、体积大、需冷却等缺点，使得PAM系统难以小型化、通用化而走出实验室。本项目计划在前两代PAM样机的基础上，研发多个400-700 nm可见光脉冲激光二极管集成一体化的小型化光声激励源，并针对单元式聚焦超声传感器存在的纵向分辨率低且焦点固定的缺点，采用多环平面阵列式光声传感结合动态计算相控聚焦技术接收，以有效提高其在深度方向的动态聚焦探测能力，健全一套便携式、免标记、高分辨率的活体三维光声显微成像技术及其方法，可对皮下不同深度多个位点的毛细血管、动/静脉网络等实现结构与功能的显微成像，为各类皮下损伤与病变的临床诊断提供实时、高对比度、高分辨率的组织影像参考。

本项目旨在研发基于小型化激光二极管激励源和多环阵列超声传感器的光声显微镜技术及其系统，并可实现皮下微血管网络的结构与功能显微成像。为此分别从激励源体积、成像焦深、成像视场、空间分辨率等技术参数最优化入手，分别搭建了多套光声显微成像系统原理样机，有助于推动光声显微技术的产品化而走出实验室，具体执行情况如下：1）开发出了445/520/640nm三款大功率脉冲激光二极管光声激励源，脉冲宽度10-1000ns多档位可调，峰值功率最高可达1.8W，以此分别搭建了一套工作距离高达22mm的便携式光声显微镜和一套超小型的非接触光声显微镜，其空间分辨率可达~10μm，并实现了动物脉管网络和皮下不同深度的微血管网络等显微成像；2）在K-wave仿真平台下对多环超声换能器阵列进行建模仿真，同时设计了一个20MHz中空结构的六环菲涅尔阵列超声换能器，直径仅有~7.4mm，相对带宽高达112.58%，并以此搭建了一套具有10mm范围的长焦深光声显微镜，系统分辨率约为220μm，实现了小动物眼球等结构的高信噪比光声显微成像；3）采用铌酸锂单晶研制了2.5/7.5/10MHz的全透明超声传感器，最大尺寸可达50×50mm，在450-1100nm光谱范围内光学透明度可达60%以上，并以此设计了一套成像视场达20×20mm的快速光声显微镜，系统分辨率约为18μm，实现了动物脉管和皮下微血管网络等的大视场光声显微成像；4）设计了中心频率为10MHz的256阵元环型阵列超声传感器，并结合100MS/s采样率的256转32通道并行数据采集模块，搭建了一套基于高频环型阵列传感的光声显微层析成像系统，系统空间分辨率可达62μm，单次数据采集时间最高约为1.6ms，并实现了不同深度全脑结构及损伤的高分辨率无创光声显微层析成像。