光声二次谐波非线性成像技术及其应用研究

The applicant begins the study of the photoacoustic conversion efficiency on micro-nano scales during her master and doctor degrees. She has published a series of original research works on the photoacoustic effect of nanoscale and the amplification mechanism of photoacoustic conversion efficiency for nanoprobes. (Nano Research, 2016; Nano Research, 2017.) On this basis, the project intends study the relationship between the nonlinear photoacoustic conversion and the sample's thermal diffusion characteristics, innovatively proposing a high-sensitive, high-contrast photoacoustic second-harmonic imaging with nonlinear thermal diffusiivity as the imaging contrast. The applicant try to clarify the physical mechanism of the photoacoustic second-harmonic imaging and deduce the mathematical relationship between the magnitude of the signal amplitude and the nonlinear thermal diffusivity of the sample; to build the photoacoustic second-harmonic imaging system, making up for the defects of the single contrast of conventional photoacoustic imaging. By using the fact that the photoacoustic second-harmonic signal comes from a smaller region compared with the laser spot, the photoacoustic second-harmonic is expected to become a superresolution imaging technique, which provides new idea for in vivo label-free superresolution imaging.

申报人自硕博期间便开始致力于微纳尺度下的光声转换理论机制研究，已经在纳米尺度下的光声效应及纳米探针光声转换效率放大机制等方面做出了一系列原创性研究成果（Nano Research, 2016/2017）。在上述研究基础上，本项目拟通过研究频率域非线性光声波转换与样品热扩散特性之间的关系，创新性地提出一种高灵敏、高对比、反映样品非线性热扩散特征的光声二次谐波特异性成像技术，阐明光声二次谐波信号产生的物理机制并推理其幅值大小与样品非线性热扩散系数之间的对应数学解析；搭建光声二次谐波非线性成像系统，并探索该技术的生物应用前景，弥补传统光声成像技术成像对比参数单一的缺陷；利用光声二次谐波信号产生自小于激光光斑区域的特点，发展超分辨的光声二次谐波成像技术，为活体深层非标记超分辨成像提供新思路。

发展非线性光声成像理论及新技术方法，是近几年光声成像领域较为有活力的一个研究分支。本项目中，通过研究频率域非线性光声波转换与样品热扩散特性之间的关系，首次提出了一种高灵敏、高对比、反映样品非线性热扩散特征的光声二次谐波特异性成像技术，并阐明了光声二次谐波信号产生的物理机制，推演了其幅值大小与样品非线性热扩散系数之间的对应数学解析。在建立的理论方法基础之上，搭建了光声二次谐波非线性成像系统，探索了该技术的生物应用前景，特别演示了该技术的亚衍射极限成像能力，弥补了传统光声成像技术成像对比参数单一的缺陷。项目执行期间发表了标注的学术论文10余篇，申请发明专利2项，完成了项目既定的全部工作计划和目标。