三次谐波显微成像在肿瘤诊断中的应用进展  

Current Progress of Third Harmonic Generation Microscopy in Tumor Diagnosis

作　　者：薄启宇 吴宇辰 邱斯奇 张志清 Bo Qiyu;Wu Yuchen;Qiu Siqi;Zhang Zhiqing(Institute of Modern Optics,Nankai University,Tianjin 300350,China;State Key Laboratory of Applied Optics,Changchun Institute of Optics,Fine Mechanics and Physics,Chinese Academy of Sciences,Changchun 130033,Jilin,China;Tianjin Key Laboratory of Micro-Scale Optical Information Science and Technology,Institute of Modern Optics,Nankai University,Tianjin 300350,China;Diagosis and Treatment Center of Breast Diseases,Shantou Central Hospital,Shantou 515041,Guangdong,China;Clinical Research Center,Shantou Central Hospital,Shantou 515041,Guangdong,China)

机构地区：[1]南开大学现代光学研究所,天津300350 [2]应用光学国家重点实验室,中国科学院长春光学精密机械与物理研究所,吉林长春130033 [3]天津市微尺度光学信息技术科学重点实验室,天津300350 [4]汕头市中心医院乳腺疾病诊疗中心,广东汕头515041 [5]汕头市中心医院临床医学研究中心,广东汕头515041

出　　处：《中国激光》2024年第3期1-12,共12页Chinese Journal of Lasers

基　　金：国家自然科学基金面上项目(82372032);应用光学国家重点实验室开放基金(SKLAO2022001A14)。

摘　　要：三次谐波源于强脉冲激光照射样品时产生的三倍频光响应,可对生物组织实现无标记、亚细胞量级分辨率、近乎实时的成像。通过与二次谐波信号和双/三光子荧光信号相结合,三次谐波显微成像可在肿瘤术中揭示肿瘤组织的典型病理特征信息,比如细胞增生与血管增生等,从而为医生判断肿瘤边界进而做出肿瘤组织彻底切除与否的决策提供实时帮助。本文阐述了三次谐波显微成像的基本原理,讨论了它在肿瘤术中诊断方面的应用,探讨了基于三次谐波的小型化便携术中诊断仪器,并总结了三次谐波内窥成像的发展现状,这些内容的讨论有望推动三次谐波成像技术的临床化。Significance Cancer remains a major life-threatening disease worldwide,as reported by the World Health Organization(WHO).Surgery is the primary therapy for most solid tumors,with the ideal outcome relying on a balance between complete tumor removal and maximal preservation of surrounding normal tissue.Current clinical imaging modalities such as magnetic resonance imaging(MRI),computed tomography(CT),and positron emission tomography(PET)lack the resolution to accurately delineate tumor boundaries.The gold standard in clinics for detecting tumor boundaries and infiltration is the histopathological analysis of surgical specimens via hematoxylin and eosin(H&E)staining.However,the H&E staining workflow requires time-consuming tissue processing,including formalin fixation,paraffin embedding,and manual staining,often taking more than a day before diagnostic results are available to surgeons.Consequently,there is an urgent demand for new real-time microscopic imaging techniques that can be used intraoperatively to provide instant feedback during tumor surgery.Recent years have seen promising developments in label-free nonlinear imaging techniques for real-time tissue pathology in the operating room.These techniques include multiphoton fluorescence microscopy,optical coherence tomography(OCT),Raman microscopy,and harmonic microscopy,which can visualize tumor margins without exogenous labels.Among these,third harmonic generation(THG)combined with second harmonic generation(SHG)offers a unique,label-free subcellular-resolution assessment of fresh and unprocessed tissues.THG signals arise from nonlinear three-photon optical responses at cell-cell and cell-matrix interfaces(Fig.1),effectively detecting proliferative cells and vasculatures,key hallmarks of tumor pathology.THG microscopy stands out by providing sub-cellular resolution,rich cellular and molecular information,and images of H&E quality.Additionally,using a single beam,complementary information from SHG,two-photon excited fluorescence(2PEF),and three-photon excited

关 键 词：医用光学 三次谐波成像 无标记成像 肿瘤诊断 小型化 内窥成像 

分 类 号：O437.1[机械工程—光学工程]