基于新型液态氟碳纳米颗粒的光声超声双模成像及光声治疗研究

Photoacoustic and ultrasound dual-modality imaging is currently a research hot spot. Meanwhile a lot of studies have been focused on developing integrated contrast agents for the dual-modality imaging application. The combination of ultrasound microbubble with photoacoustic contrast agent has been a popular choice for this purpose, but it is limited by the micro-scale size of microbubble, making it hard to extravasate out of blood vessles to reach the centre core of tumor regime. In this proposal, we will design novel nano-sized dual-modality imaging contrast agent that can provide enhanced photoacoustic and ultrasound contrast based on optically triggered vaporization of liquid perfluorocarbon. In vitro and in vivo photoacoustic/ultrasound dual-modality tumor imaging, mechanism study of perfluorocarbon vaporization process, as well as tumor photoacoustic therapy based on the dual-modality imaging contrast agent will be carried out. The nano-sized novel contrast agent developed in this proposal is capable of extravasating out of blood vessel to reach the tumor tissue area. Furthermore, upon vaporization, it can provide significantly enhanced temporal photoacoustic signal, steady state ultrasound contrast, as well as can be used for photoacoustic therapy. The goal of this proposal is to boost the development of photoacosutic/ultrasound dual-modality tumor imaging and tumor photoacoustic therapy, to provide new idea and scheme for theranostics application, as well as to push photoacoustic technology further into clinical use.

肿瘤组织的光声超声双模成像方法目前发展迅速，而一体化光声超声双模成像对比剂的研究也得到迅速开展，其中多数研究采用超声微泡耦合光声对比剂的方式，局限性在于超声微泡尺寸较大，难以穿透血管膜进入肿瘤组织内部。本项目拟设计基于光学激发液态氟碳纳米颗粒气化机制的新型纳米尺寸光声超声双模成像对比剂，开展在体双模态光声超声肿瘤成像研究，液态氟碳气化过程机制研究，以及基于双模成像对比剂的光声治疗机制研究。项目研制的新型对比剂具备纳米级尺寸特性，能够穿透血管壁进入肿瘤组织内部，且气化过程能够产生显著增强的瞬态光声信号，气化产物能够提供稳态超声对比信号，同时能够用于光声治疗研究。本项目的实施将有力促进肿瘤光声超声双模成像以及肿瘤治疗技术的发展，为一体化治疗诊断学提供新的思路和方案，推动光声技术的进一步临床转化。

肿瘤组织的光声/超声双模分子影像诊断方法近年来发展迅速，影像分子探针的研究也得到迅速开展，其中多数探针的设计采用超声微泡耦合光声对比剂的方法，但由于其尺寸较大，难以穿透血管膜进入肿瘤组织内部，达到靶向成像诊断的目的。为此，本项目设计了基于光学激发液态氟碳纳米颗粒气化机制的新型纳米尺度光声/超声双模成像探针，开展了在体双模态光声/超声肿瘤成像研究，液态氟碳气化过程机制研究，以及基于双模成像对比剂的光声治疗机制研究。本项目研制的新型对比剂具备纳米级尺寸特性，能够穿透血管壁进入肿瘤组织内部，且气化过程能够产生显著增强的瞬态光声信号，气化产物能够提供稳态超声对比信号，同时能够用于光声治疗研究。相关研究成果发表了5篇SCI文章，3篇会议文章，4项发明专利。本项目所取得的研究成果为一体化治疗诊断学提供新的思路和方案，有利于光声技术的进一步临床转化。