血管内易损斑块组织成分和关键分子成像基础研究

In an attempt to develop a novel technique for detecting atherosclerotic vulnerable plaque, this study was designed to explore an intravascular photoacoustic dual-modality imging system with both morphologic and functional imaging facilities by combining hgh-resolution tissue component imaging and two-dimensional inflammatory cytokine imaging of a whole plaque. A miniaturized photoacoustic imaging catheter will be designd for intravscular imaging. This novel technology will have a penetration at a milimeter scale and a resolution at a micrometer scale that will realize multi-functional imaging by integrating opitcal and ultrasound imaging, optical and acoustic spectroscopy, generation of laser and ultrasound burst as well as detection of near-infrared fluorescent signals. An optimal algorithm will be developed for quantitative imaging of the tissue component in the fibrous cap and the lipid core in a plaque with high-resolution. The methodology, biochemical safety and imaging accuracy of metallaproteinase enzyme-activable probe, monocyte chemotactic protein 1- and NonO protein-targetted microbubbles, and multi-functional "smart" probe will be investigated, and these probes and bubbles will be incorporated into the intravascular photoacoustic dual-modality imaging system to enable two-dimensional imaging of plaque component and inflammation activity within the plaque. A rabbit model of atheroslcerotic vulnerable plaque will be used to validate the accuracy of the new imaging technology in detecting vulnerable plaque.

为了建立检测动脉粥样硬化（AS）易损斑块的新技术，本项目拟研制血管内光、声双模成像系统，实现斑块内组织成分高分辨定量成像与全斑块、多层次、多阶段炎症活动二维分子显像的融合，达到斑块形态显像和功能显像的结合。本项目将研制适于血管内成像的微型化光、声双模成像导管，建立同时具备毫米级穿透力和微米级分辨率的显像技术，实现光学和声学二维成像、光学和声学频谱分析、激光和超声脉冲发放以及近红外光学标记物信号检测的复合功能，通过相关算法研究和优化，实现斑块纤维帽和脂质核内成分的高分辨定量成像，并将研究基质金属蛋白酶酶解活化性光学探针、单核细胞趋化蛋白-1和NonO蛋白靶向声学微泡以及多功能“智能”靶向光学探针的制备方法学、生物安全性和准确性，利用这些探针和所研制的血管内光、声双模成像系统可实现斑块组分和炎症活动的二维分子显像，并以AS易损斑块的兔模型验证成像系统对易损斑块识别的价值。

为建立检测动脉粥样硬化（AS）易损斑块的新技术，本项目研制了血管内光声/超声双模成像系统，对AS斑块易损的关键分子进行了研究和筛选，利用纳米和光声技术对其进行显像，实现了斑块内脂质成分、斑块形态学与炎症活动的三个层次信息的高分辨定量成像的融合，实现了斑块形态显像与功能显像的结合。本项目研制了外径<1mm的适于实时血管内成像的微型化光声/超声双模成像导管，建立了同时具备毫米级穿透力和微米级分辨率的光声显像技术；提出了光声粘弹性成像的理论并加以验证；建立了血管内光声/超声/荧光三模态成像的方法学，实现了光声/光学/声学二维成像、声学频谱分析以及光学标记物信号检测的复合功能；针对斑块内炎症，项目组提出了中性粒细胞-微泡“仿生”复合体、可降解介孔硅及基质金属蛋白酶-纳米金等多种分子探针；通过相关算法研究和优化，实现斑块内脂质成分、纤维帽粘弹力学特征和斑块内炎症活动状态的高分辨成像，利用AS易损斑块的兔模型和高脂喂养的ApoE基因敲除小鼠模型，验证了成像系统对易损斑块识别的价值。该项目为早期识别易损斑块建立了创新性关键技术，具有重要的临床应用前景