基于荧光聚合物纳米探针的动物活体淋巴管结构及功能的多模态多尺度成像研究

准确识别淋巴管是开展淋巴管研究的前提和关键。常规方法通常采用动物尸体或离体组织进行研究，尚未见对活体状态下淋巴管系统进行实时、超高分辨显微成像的研究报道。申请人前期设计合成的近红外荧光聚合物纳米探针，通过淋巴引流可快速、准确显像发生肿瘤转移的淋巴结。本项目拟在已有工作基础上，结合多模态成像技术的优势，包括：探头式活体共聚焦(pCLE)实时、高分辨显微成像，近红外(NIR)荧光高灵敏度、快速成像，光声成像(PA)高空间分辨率，以及磁共振成像(MRI)高穿透深度、软组织对比度强，构建淋巴管特异性显像的NIR/PA/MRI三模态纳米探针，实现对动物活体状态下的不同层次的淋巴管系统的多模态多尺度成像。此外，结合组织透明化技术，实现对离体淋巴管系统的3D超高分辨成像。在此基础上，通过建立不同的动物模型，进一步探讨淋巴管与肿瘤转移、脂质吸收之间的影像学关系，为淋巴管系统的基础研究提供有益的影像学数据。

Accurate identification of lymphatic vessels is the premise and key to the study of the lymphatic system. Conventional methods usually used cadaver or in vitro tissue studies, but there have been no reports on the real-time, ultra-high-resolution microscopic imaging of the lymphatic system in vivo. Previously, we have reported the near-infrared (NIR) fluorescence polymer dots can rapidly and accurately image the metastasis lymph nodes through lymph drainage. In this project, to combine with the advantages of multimodal imaging techniques, which including: real-time and high resolution of probe-based confocal laser endomicroscopy (pCLE), high sensitivity and fast imaging of NIR fluorescence, high spatial resolution of photoacoustic imaging (PA), and the high contrast of soft tissue of magnetic resonance imaging (MRI), we propose to develop NIR/PA/MRI polymer dots for multi-scale and multi-modal imaging of the lymphatic system. In addition, in combination with tissue transparency technology, the 3D ultra-high resolution imaging of lymphatic system in vitro and ex vivo can be achieved. Furthermore, through the establishment of different animal models, the relationship between lymphatic metastasis and lipid absorption can be further explored. Our studies will provide useful imaging data for basic and clinical research.