多靶点全景数字病理:从原理到应用  

Multi-target panoramic digital pathology: from principle to application

作　　者：张新华 李才伟 张瑜 黄胜男 石晗 吴俊楠 任仕杰 刘珂含 高彤璐 史冰 ZHANG Xin-hua;LI Cai-wei;ZHANG Yu;HUANG Sheng-nan;SHI Han;WU Jun-nan;REN Shi-jie;LIU Ke-han;GAO Tong-lu;SHI Bing(Key Laboratory of Biomedical Engineering of Hainan Province,School of Biomedical Engineering,Hainan University,Haikou 570100,China;School of Computer Science and Technology,Hainan University,Haikou 570100,China)

机构地区：[1]海南省生物医学工程重点实验室,海南大学生物医学工程学院,海南海口570100 [2]海南大学计算机科学与技术学院,海南海口570100

出　　处：《中国光学（中英文）》2022年第6期1258-1274,共17页Chinese Optics

基　　金：国家自然科学基金地区项目(No.82160345);海南省重点研发项目(No.ZDYF2021GXJS017);海口市重点科技计划项目(No.2021-016);海南省自然科学基金(No.620RC558)。

摘　　要：数字病理凭借其便捷的存储、管理、浏览、传输等特点,为远程病理会诊及联合会诊带来了新契机。然而,显微镜的视场有限,在保证分辨率的前提下,无法兼顾全景成像。全景数字病理的提出弥补了这一缺陷,其在保证分辨率的同时可兼顾全景成像。但单张切片仅能实现单靶点检测,而疾病诊断需同时观测多个靶点的表达情况。近年来,多靶点全景数字病理技术发展迅速,因其在药物研发、临床科研以及基础科研等领域有巨大的应用潜力而广受关注。该系统凭借视场大、颜色多、通量高的特点,可在短时间内原位检测整张组织切片上的多种生物标记物的表达情况,借以识别组织上每个细胞表型、丰度、状态及其相互关系。本文首先梳理了数字病理、全景数字病理以及多靶点全景数字病理的发展过程,并简要介绍发展过程中技术的更新迭代,以及发展多靶点全景数字病理的重要性。然后,分别从生物样本准备、多色光学成像以及图像处理3个部分重点介绍多靶点全景数字病理。接下来,阐述了多靶点全景数字病理在肿瘤微环境与肿瘤分子分型等生物医学领域的应用情况。最后,对多靶点全景数字病理的技术优势、目前面临的挑战及其未来的发展趋势进行了总结。Digital pathology has brought new opportunities for remote pathological consultation and joint consultation owing to its convenient storage, management, browsing and transmission. However, because of the limited field of view of a microscope, panoramic imaging cannot be achieved while ensuring a high resolution. The proposal of panoramic digital pathology makes up for this defect and achieves panoramic imaging while ensuring high resolution. However, a single slice can only detect a single target, and disease diagnosis needs to observe the expression of multi-target at the same time. In recent years, multi-target panoramic digital pathology technology has developed rapidly. It has attracted much attention because of its great application potential in drug research and development, clinical research and basic research. Owing to its large field of view, wide range of colors and high flux, the system can detect the expression of various biomarkers on a whole tissue section in situ in a short time to identify the phenotype, abundance, state, and relationship of each cell. Firstly, this paper reviews the development process of digital pathology, panoramic digital pathology and multi-target panoramic digital pathology, as well as the update and iteration of technology in the development process, and illustrates the importance of developing multi-target panoramic digital pathology.Then, the multi-target panoramic digital pathology is described in detail from three perspectives: biological sample preparation, multi-color imaging system and image processing. Next, the applications of multi-target panoramic digital pathology in biomedical fields, such as tumor microenvironments and tumor molecular typing are described. Finally, the advantages, challenges and future development of multi-target panoramic digital pathology are summarized.

关 键 词：多靶点全景数字病理 生物标记物 多色成像 图像处理 

分 类 号：TP394.1[自动化与计算机技术—计算机应用技术] TH691.9[自动化与计算机技术—计算机科学与技术]