基于光学表面波探测的光声/OCT多模态显微成像研究

Photoacoustic microscopy (PAM) and optical coherence tomography (OCT) is based on the optical-absorption and optical-scattering contrasts, respectively. The integration of these two imaging modalities is able to label-freely reveal structural and functional information of biological tissues, including cells and microcirculations, from multiple perspectives. Determined by the piezoelectric ultrasonic transducer, the axial resolution in PAM is much worse compared with OCT, which thus hinders their integration. In this proposal, we aim to develop multimodal microscopy by integrating PAM and OCT for comprehensively understanding the tissue physiology status. Taking advantage of ultrahigh sensitivity and ultrafast temporal response to the slight variation in refractive index (RI) of the coupling water, optical surface wave technology is utilized for sensing the time-varying low-amplitude photoacoustic transients, leading to the significant improvement in both signal-to-noise ratio (SNR) and bandwidth of PAM imaging. This enables the PAM with axial resolution down to micrometer scale, nearly equivalent with that in OCT. Through the new design of optical-acoustic delivery and detection, high-efficiency transmission is achieved in the illumination lasers (PAM and OCT) and OCT signals, which allows the reflection-mode photoacoustic detection simultaneously. Consequently, in vivo multimodal microscopy demonstrates the combined advantages, including the complementary imaging contrasts, reflection-mode imaging capability, and automatic imaging registration in three dimensions; therefore, the multimodal microscopic approach is potentially invaluable for comprehensively investigating the complicated tissue physiopathological processes.

光学相干层析（OCT）和光声技术分别从光散射和光吸收角度揭示组织的固有光学特性，两者的结合将为观测生物组织复杂多元的形态与功能特征提供无标记、多视角的影像支持。然而，基于压电型超声换能器的光声成像技术的纵向分辨率较低，在深度方向上无法与具有微米级分辨率的OCT相匹配，制约了两种技术的有效融合。本项目拟从光声信号的探测着手，借助于光学表面波传感技术的折射率高敏感与超快时间响应特点，开展基于表面波的宽带、高灵敏度光声检测研究，提高光声成像的信噪比与纵向分辨率，达到与OCT相比拟的深度分辨能力。进而，设计光、声能量的引导与区分方式，既实现多激发光和OCT信号的高效传输，又保证光声波的反射式探测。最终，建立两种技术相融合的多模态在体显微方法与成像系统，兼具反射模式成像能力和三维图像自动配准优势，能够同步提取活体组织的多重互补光学特性，为探索机体的复杂生理病理机制提供革新的技术手段。

研究背景：光声成像技术通过探测生物组织内固有色素物质的光学吸收作用，无需外源标记即可观察细胞核、血液微循环和黑色素等众多元素的复合结构特征，在肿瘤学、脑科学、眼科学、血管生物学等基础生命科学和临床医学诊疗领域展现出巨大的应用价值与前景。光学相干层析成像（OCT）技术通过探测生物组织或材料内部光学反射（散射）特性的空间变化，能够非接触、非侵入、快速的成像生物组织，已经在临床诊疗与科学研究中获得了广泛的应用。将光声成像技术与OCT技术相结合，有望构建出具备两种模态叠加优势的生物医学光学成像技术，可以实现生物组织光吸收和反射（散射）信息的同步三维观测。受传统光声显微系统带宽响应的限制，光声技术的纵向分辨率水平严重低于与OCT技术，制约了两种技术的有机集成。.研究内容与关键结果：针对该问题，本项目借助于光学表面波传感技术的折射率高敏感与超快时间响应特点，将位相光学表面波传感方法引入到光声成像领域，开发了具备高灵敏度（~31 Pa）和大带宽（~218 MHz）的光声波探测技术。以此为核心部件，我们建立了基于光学表面波传感的新型光声显微成像系统，具有~6.0 μm深度分辨率和~3.5 μm横向分辨率，能够无标记的成像活体生物组织。进一步，我们通过构建光束整形、合束分束、以及机电程控等软硬件配置，将光声显微成像技术与OCT相结合，开发了一套光声/OCT多模态显微影像系统，具备反射式成像、微米级空间分辨率、~1.0 mm成像深度、以及无标记观测、图像自动配准等多重优势，能够同时探测活体生物组织的光学吸收和散射信号，从多个角度揭示了视网膜组织的形态结构特征，为评判组织的生理病理状态提供了更为丰富的信息。这一新型光声/OCT多模态显微成像技术有望为生物医学研究提供新的影像工具支持。