基于契伦科夫信号增强技术的双模式内窥成像方法研究

It achieves the radionuclide optical molecular imaging by Cerenkov luminescence, which successfully solves the limitations of the probe used in optical molecular imaging. Endoscopic imaging enhances the tissue penetration of optical molecular imaging. Therefore, endoscopic Cerenkov luminescence imaging has great value in promoting the clinical transformation of the molecular imaging of early gastric cancer. However, the clinical application is limited due to the weak signal of Cerenkov luminescence and the gastrointestinal motility in the imaging exposure time. First, we produce targeted fluorescent probes which can be used in clinical practice according the spectral characteristics of Cerenkov luminescence. By the secondary excitation imaging, they can enhance signal strength and tissue penetration. It improves the efficiency of the signal transduction when optimizing the Cerenkov luminescence endoscopic imaging equipment. Finally, we design the dual-mode imaging equipment which can be used for fluorescence imaging but also Cerenkov luminescence imaging to process the secondary excitation imaging of radionuclide and obtain the information of the distribution of the fluorescence probe, to increase the veracity of the location to positive signal. This research aims to further promote the clinical practice of Cerenkov luminescence imaging, to provide a new way in improving the detection rate of early gastric cancer.

契伦科夫光实现了放射性核素光学分子成像，成功解决光学分子影像探针局限性的问题；内窥成像方式成功解决了光学分子成像组织穿透性的问题。因此内窥式契伦科夫光成像在早期胃癌分子成像的临床转化应用方面具有巨大的推动价值。然而由于契伦科夫光信号微弱，在较长的成像曝光时间内易受到胃肠道蠕动的影响，限制了其临床应用。本研究依据契伦科夫光的光谱特点构建多种临床可用的靶向荧光探针，通过级联二次激发成像，增强信号强度及组织穿透性；进一步优化内窥式契伦科夫光成像设备，提高信号传导效率；进而构建荧光-契伦科夫光双模式内窥成像设备，在进行放射性核素级联二次激发成像的同时又能获得荧光探针的分布信息，提高阳性信号定位的准确性。本项目研究成果旨在进一步推动契伦科夫光成像的临床应用，为提高早期胃癌的检出率提供新方法。

胃癌是世界范围内最常见的恶性肿瘤之一，如何提高早期胃癌的检出率成为一个难点。分子成像可以检测在形态学发生改变前分子水平的改变，有助于提高早期肿瘤检出率，契伦科夫内窥成像解决了光学分子成像探针局限性及组织穿透性不足的问题，迅速成为研究热点。如何进一步增强契伦科夫荧光信号强度、降低传导过程中的信号损失率及准定位阳性信号位置，是内窥式CLI技术提高早期胃癌检出率的关键。本研究从提高核素光学信号强度和提高内窥光学信号传导效率两方面入手开展研究工作。在提高光学信号强度方面，首先依据契伦科夫能量转移成像原理，借助荧光素钠作为媒介，通过契伦科夫光内源激发荧光素钠增强信号强度，提高检出率，进而和共聚焦激光显微内镜结合，提出契伦科夫能量转移成像与高分辨共聚焦显微成像的双模式成像方式，从而有助于提高病变检出率和判断病变边界；其次开展了基于氧化铕纳米颗粒的核素放射激发荧光成像，提出了基于纳米化闪烁晶体的内源核素光学成像新模式。在内窥光学信号传导方面，设计了双通道荧光内镜，可以实现契伦科夫光成像与荧光成像的融合，有助于下一步的临床转化应用。