Photoacoustic characteristics of lipid-rich plaques under ultra-low temperature and formaldehyde treatment

The research team enables simultaneous photoacoustic and ultrasound imaging of blood vessels by improving intravascular photoacoustic imaging system. The diameter of this imaging probe is only 1.00 mm, which lays the foundation for in vivo experiments.

Cardiovascular diseases are the number one cause of death worldwide, among which, atherosclerosis is the fundamental pathology. Intravascular photoacoustic imaging (IVPAI), a newly developed non-destructive imaging technology, is of great importance for atherosclerotic plaque study by providing both structure and lipid component information. Comparative study with histology is pivotal to verify the accuracy of IVPAI.

When a biological tissue is excited by the pulse laser, it generates ultrasonic signals that will be detected and recorded. The structure and the optical-absorption distribution of the tissue can be visualized by reconstructing the ultrasonic signals with a back projection algorithm. Therefore, the anatomical images obtained by photoacoustic imaging possess innate advantages of high contrast, high resolution and satisfactory penetration depth. These merits shed light on the application of IVPAI on atherosclerotic plaque identification.

To date, most of IVPAI studies involve samples stored in formaldehyde or under ultra-low temperature, both of which might alter the photoacoustic characteristics of the artery, cause bias on the results explanation and affect the pre-clinically translational research on photoacoustic imaging. Therefore, estimation of effects posed by these two treatments on photoacoustic characteristics of artery is extremely important.

Researchers from a joint research team of Qilu Hospital of Shandong University and South China Normal University made an improvement of the previously reported IVPAI imaging system to enable simultaneous photoacoustic and ultrasound imaging of blood vessels. Then they compared the IVPAI results before and after ultra-low temperature or formaldehyde treatments with histology the golden standard, to validate the effects they made on plaque photoacoustic features. The researchers found that both treatments have little effect on photoacoustic characteristics of the artery samples. Lipid ratios pre- and post-ultra-low temperature treatment were 0.334±0.130 vs. 0.329±0.122 (p=0.299). The ratios pre- and post- formaldehyde treatment were 0.317±0.045 vs. 0.316±0.040 (p=0.854). All these IVPAI derived lipid ratios correlated highly with histological results. This work has been published in Chinese Optics Letters, Volume 16, No. 3, 2018 (Mingjun Xu, et al., Photoacoustic characteristics of lipid-rich plaques under ultra-low temperature and formaldehyde treatment)

Associate Professor Pengfei Zhang and Professor Sihua Yang, directors of the joint research group, believed that these results verified the accuracy of intravascular photoacoustic imaging technology. Moreover, the diameter of this improved IVPAI imaging catheter is only 1.00 mm. Their work laid a solid foundation for in vivo experiments and pre-clinical photoacoustic experiments in the future.

Based on these findings, further work will be focused on translational research from ex vivo to in vivo, and application of IVPAI in monitoring the development or regression of atherosclerotic plaques.

心血管疾病病理学研究进展——超低温及福尔马林处理后富含脂质斑块的光声特性

研究团队改进后的光声血管内窥成像系统。该系统能够同时实现血管内光声和超声成像，并且该成像探头的直径仅为1.00 mm，为进行活体实验奠定了基础。

心血管疾病是世界范围内的首要死因，动脉粥样硬化是其病理学基础。近些年发展起来的一种无损成像技术——血管内光声成像，对动脉粥样硬化斑块的组织结构和脂质成分能够进行非常有价值的研究。与组织学对比研究以验证光声成像技术的准确性尤为重要。

脉冲激光激发下的生物组织产生超声信号，超声信号被接收后，通过反投影算法将其携带的时间信息和强度信息转化为能够反映生物组织结构和吸收分布的可视化图像。因此，该技术获得的组织解剖图像兼具对比度高、分辨率高和成像深度大的优点，为应用血管内光声成像技术识别易损斑块提供了依据。

目前，大部分关于粥样硬化斑块的组织病理学研究仍采用超低温或福尔马林处理的标本，但上述两种方式可能改变血管的光声特性，导致结果解释的偏倚并影响光声成像技术的临床前转化研究。因此，评估上述两种方式对血管光声特性的影响极为重要。

山东大学齐鲁医院和华南师范大学的联合研究团队改进了已报道的光声血管内窥成像系统，实现血管内同时光声和超声成像。利用改进后的系统，通过比较两种处理方式前后光声成像结果，并与组织学这一金标准进行比对，探究两种处理方式对血管光声特性的影响。研究人员发现不同的处理方式对血管光声特性无显著影响 (超低温及福尔马林处理前后脂质占比分别是0.334±0.130 vs. 0.329±0.122, p=0.299和0.317±0.045 vs. 0.316±0.040, p=0.854)，并与组织学结果高度相关。该成果发表在Chinese Optics Letters 2018年第3期上 (Mingjun Xu, et al., Photoacoustic characteristics of lipid-rich plaques under ultra-low temperature and formaldehyde treatment)。

该团队的张鹏飞副教授和杨思华教授认为光声成像实验结果与组织学对比研究验证了血管内光声成像技术的准确性。并且，改进的血管内窥光声成像导管直径仅为1.00 mm。这些都为以后载体实验以及预临床相关光声实验结果分析打下坚实基础。

基于上述发现，下一步工作将侧重体外到体内的转化研究，以及应用光声成像技术监测动脉粥样硬化斑块的进展或消退。