Nonlinear optical microscopy for skin in vivo:Basics,development and applications

Multi-photon microscopy(MPM)and coherent anti-Stokes Raman scattering(CARS)are two advanced nonlinear optical imaging techniques,which provide complementary information and have great potential in combination for noninvasive in vrito biomedical applications.This paper provides a detailed discussion of the basics,development and applications of these technologies for in vrivo skin research,covering the following topics:The principle and advantage of MPM and CARS,instrumentation development for in vino applications,MPM and CARS of normal skin,application of MPM and CARS in skin cancer and disease diagnosis;application of MPM in skin disease intervention,ie.,imaging guided two-photon photothermolysis.

RAMAN SPECTROSCOPY FOR IN VIVO TISSUE ANALYSIS AND DIAGNOSIS,FROM INSTRUMENT DEVELOPMENT TO CLINICAL APPLICATIONS

Raman spectroscopy is a noninvasive,nondestructive analytical method capable of determining the biochemical constituents based on molecular vibrations.It does not require sample preparation or pretreatment.However,the use of Raman spectroscopy for in vivo clinical applications will depend on the feasibility of measuring Raman spectra in a relatively short time period(a few seconds).In this work,a fast dispersive-type nearinfrared(NIR)Raman spectroscopy system and a skin Raman probe were developed to facilitate real-time,noninvasive,in vivo human skin measurements.Spectrograph image aberration was corrected by a parabolic-line fiber array,permitting complete CCD vertical binning,thereby yielding a 16-fold improvement in signal-to-noise ratio.Good quality in vivo skin NIR Raman spectra free of interference from fiber fluorescence and silica Raman scattering can be acquired within one second,which greatly facilitates practical noninvasive tissue characterization and clinical diagnosis.Currently,we are conducting a large clinical study of various skin diseases in order to develop Raman spectroscopy into a useful tool for non-invasive skin cancer detection.Intermediate data analysis results are presented.Recently,we have also successfully developed a technically more challenging endoscopic Laser-Raman probe for early lung cancer detection.Preliminary in vivo results from endoscopic lung Raman measurements are discussed.

实时拉曼光谱分析技术及其在临床早期癌症检测中的应用

拉曼光谱分析技术可以在分子水平上研究物质分子结构和生化组成信息,具有快速、准确、无创(或低创)等优点,已成为临床早期癌症检测和组织病理生理分析的重要工具。近年来,激光技术、光纤探测器件和光电检测技术的发展,不仅极大促进了新型拉曼光谱分析仪器与技术的研发,更进一步扩展了其临床应用的广度和深度,彰显出其独特的科学内涵与应用价值。对临床拉曼光谱分析技术的理论基础进行了阐述,归纳总结了临床快速拉曼光谱分析集成系统设计思路。在此基础上,以作者相关研究工作为例,探讨了拉曼光谱分析技术在临床癌症早期检测与病理分析中的应用特点,为推动相关基础研究及技术创新提供有益参考。