活体颅骨光透明方法及应用(特邀)  

In vivo Skull Optical Clearing Technique and its Applications(Invited)

作　　者：李东宇 俞婷婷 朱京谭[1,2,3] 朱䒟 LI Dongyu;YU Tingting;ZHU Jingtan;ZHU Dan(Britton Chance Center for Biomedical Photonics&MoE Key Laboratory for Biomedical Photonics,Wuhan National Laboratory for Optoelectronics,Huazhong University of Science and Technology,Wuhan 430074,China;Advanced Biomedical Imaging Facility,Huazhong University of Science and Technology,Wuhan 430074,China;Optics Valley Laboratory,Wuhan 430074,China)

机构地区：[1]华中科技大学武汉光电国家研究中心,Britton Chance生物医学光子学研究中心&生物医学光子学教育部重点实验室,武汉430074 [2]华中科技大学高端生物医学成像设施,武汉430074 [3]湖北光谷实验室,武汉430074

出　　处：《光子学报》2022年第8期246-262,共17页Acta Photonica Sinica

基　　金：国家自然科学基金(Nos.61860206009,81870934,82001877);武汉光电国家研究中心创新专项目,光谷实验室创新专项(No.OVL2021BG011)。

摘　　要：颅骨的高散射极大地限制了光学技术在活体脑成像中的应用。开颅窗和磨薄颅骨窗等基于手术的“颅窗”让皮层神经-血管观测成为可能,但各有局限性。近年来发展的活体颅骨光透明技术,以一种更方便、更无创方式建立光透明颅窗。本文主要介绍活体颅骨光透明的发展及应用:1)颅骨光透明方法;2)基于光透明颅窗的细胞及血管成像;3)透过光透明颅窗,实现皮层光操控,包括结合光动力效应打开血脑屏障或实施靶向栓塞、基于激光损伤的靶向出血性脑卒中建立、以及在光遗传学方面的应用等。最后,对活体颅骨光透明技术未来的发展和应用做出展望。In vivo observation of cortical structure and activity is of great significance for understanding the brain functions in the normal state and neurovascular dysfunction associated with various brain diseases.Modern optical imaging techniques has attracted many attentions in the field of neuroscience because it provides an important tool to visualize brain in vivo with high resolution.However,the strong scattering of the turbid skull limits light penetration,causing a serious degradation of imaging depth and imaging quality.In order to overcome such an obstacle,various skull windows have been established to access.The surgery-based skull windows mainly include open-skull window and thinned-skull window which have been widely used for cortical optical imaging.The former allows for large-scale imaging and long-term observation.The latter requires to thin the skull to about 25μm that spine-resolution cortical imaging can be performed.However,each of the two skull windows has its own limitations.The open-skull window would cause inflammation therefore is not suitable for immediate observation,and the thinned-skull window is not capable of large-scale or long-term observation.During the past 10 years,some novel skull window techniques have been developed based on tissue optical clearing technique.Unlike physically remove or thin out the skull,the establishment of the“skull optical clearing window”is realized by using chemical agents to make the skull transparent,therefore no craniotomy is required.Considering the main the components of skull are calcium hydroxyapatite(16%),collagen(16%),lipids(54%),and water(14%),and the refractive index of the calcium hydroxyapatite,collagen and lipids are much higher than water,leading to server scattering,the skull optical clearing technique aims to remove those scattering particles and match the refractive index.WANG Jing et al.demonstrated a skull optical clearing window for the first time in 2012.They used a mixture of laurinol,weak alkaline substances,Ethylene Diamine Tetraa

关 键 词：活体颅骨光透明 光学成像 光操控 神经血管成像 光动力效应 

分 类 号：Q336[生物学—遗传学]