心血管疾病是威胁人类健康的头号杀手，实现对斑块易损性的精准诊断是降低该病死亡率的关键。新兴的光声成像技术既可实现高分辨的结构成像，又可借助光声光谱方法检测斑块脂质成份，是一种具有重大应用潜力的成像技术。但是目前在体获取的脂质光声光谱，与其它组织的光谱对比度低，浓度解析精度不理想。新近出现的基于Gruneisen弛豫效应的光声信号非线性增强，有望为解决这一问题带来机遇。我们在前期研究首次发现，该非线性效应在波长维度也有体现，即将其与波长扫描结合，将会获得与样品吸收系数成平方关系的非线性光声光谱，这有望为提高光声光谱的对比度带来新的帮助。本项目拟从光声信号非线性增强的定量分析入手，探索光声光谱非线性化的产生机制，构建非线性光谱对比度的模型，实现主动调控脂质光谱对比度，从而突破光谱对比度低的难题，促进脂质的在体光谱成像和浓度定量提取。预期通过本项目的研究，有望推动光声光谱在体成像技术的发展及应用

Cardiovascular disease (CVD) is the leading cause of death worldwide. The rupture of vulnerable plaques is the major cause of acute cardiovascular events such as heart attacks and strokes, which claim more than 3 million lives annually in China. Accurate diagnosis of plaque vulnerability is the key to reducing mortality. Photoacoustic imaging is an emerging technology capable of providing multi-contrast (anatomic, functional, and molecular) information of intact biological tissue. It can potentially improve the plaque composition (such as lipid core) identification, which will open new avenues for significant application potential. However, the photoacoustic spectroscopy of lipid obtained in vivo has much lower contrast than other tissues, which cause the concentration resolution accuracy is not capable for clinical application. The nonlinear enhancement of photoacoustic signals generated by the Gruneisen relaxation effect is expected to bring opportunities to solve this issue. We have theoretically deduced that the nonlinear change also occurs in wavelength dimension. It means that by wavelength scanning, a nonlinear photoacoustic spectrum with a square relationship to the absorption coefficient of the sample will be obtained, which is expected to improve the contrast of the photoacoustic spectrum. In this proposal, we plan to start from the quantitative analysis of nonlinear enhancement of photoacoustic signals, explore the mechanism of nonlinearization of photoacoustic spectroscopy, construct the parameter model of nonlinear changes of spectra, optimize the spectral of lipids, and breakthrough the low contrast issue. And we aim to perform in vivo spectroscopic imaging and quantitative extraction of lipid concentrations. With the proposed methods, development of photoacoustic spectroscopy in vivo imaging technology and its clinical application breakthrough is expected to promote.