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基于深度学习的生物样本虚拟组织学染色

Deep learning-enabled virtual histological staining of biological samples.

作者信息

Bai Bijie, Yang Xilin, Li Yuzhu, Zhang Yijie, Pillar Nir, Ozcan Aydogan

机构信息

Electrical and Computer Engineering Department, University of California, Los Angeles, CA, 90095, USA.

Bioengineering Department, University of California, Los Angeles, 90095, USA.

出版信息

Light Sci Appl. 2023 Mar 3;12(1):57. doi: 10.1038/s41377-023-01104-7.


DOI:10.1038/s41377-023-01104-7
PMID:36864032
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9981740/
Abstract

Histological staining is the gold standard for tissue examination in clinical pathology and life-science research, which visualizes the tissue and cellular structures using chromatic dyes or fluorescence labels to aid the microscopic assessment of tissue. However, the current histological staining workflow requires tedious sample preparation steps, specialized laboratory infrastructure, and trained histotechnologists, making it expensive, time-consuming, and not accessible in resource-limited settings. Deep learning techniques created new opportunities to revolutionize staining methods by digitally generating histological stains using trained neural networks, providing rapid, cost-effective, and accurate alternatives to standard chemical staining methods. These techniques, broadly referred to as virtual staining, were extensively explored by multiple research groups and demonstrated to be successful in generating various types of histological stains from label-free microscopic images of unstained samples; similar approaches were also used for transforming images of an already stained tissue sample into another type of stain, performing virtual stain-to-stain transformations. In this Review, we provide a comprehensive overview of the recent research advances in deep learning-enabled virtual histological staining techniques. The basic concepts and the typical workflow of virtual staining are introduced, followed by a discussion of representative works and their technical innovations. We also share our perspectives on the future of this emerging field, aiming to inspire readers from diverse scientific fields to further expand the scope of deep learning-enabled virtual histological staining techniques and their applications.

摘要

组织学染色是临床病理学和生命科学研究中组织检查的金标准,它使用彩色染料或荧光标记来可视化组织和细胞结构,以辅助对组织进行显微镜评估。然而,当前的组织学染色工作流程需要繁琐的样品制备步骤、专门的实验室基础设施以及训练有素的组织技术人员,这使得它成本高昂、耗时且在资源有限的环境中无法使用。深度学习技术通过使用经过训练的神经网络以数字方式生成组织学染色,为彻底改变染色方法创造了新机会,为标准化学染色方法提供了快速、经济高效且准确的替代方案。这些技术被广泛称为虚拟染色,多个研究团队对其进行了广泛探索,并证明能够从未染色样品的无标记显微图像中成功生成各种类型的组织学染色;类似的方法也被用于将已染色组织样品的图像转换为另一种类型的染色,即进行虚拟染色到染色的转换。在本综述中,我们全面概述了基于深度学习的虚拟组织学染色技术的最新研究进展。介绍了虚拟染色的基本概念和典型工作流程,随后讨论了代表性作品及其技术创新。我们还分享了对这一新兴领域未来的看法,旨在激发不同科学领域的读者进一步拓展基于深度学习的虚拟组织学染色技术及其应用的范围。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfa4/9981740/84e3351ddce4/41377_2023_1104_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfa4/9981740/e99f210e54e1/41377_2023_1104_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfa4/9981740/d0a4be5b5567/41377_2023_1104_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfa4/9981740/b75da7b73933/41377_2023_1104_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfa4/9981740/18171833ba2e/41377_2023_1104_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfa4/9981740/caaab7f91171/41377_2023_1104_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfa4/9981740/16a0f9516562/41377_2023_1104_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfa4/9981740/4e122025d148/41377_2023_1104_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfa4/9981740/84e3351ddce4/41377_2023_1104_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfa4/9981740/e99f210e54e1/41377_2023_1104_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfa4/9981740/d0a4be5b5567/41377_2023_1104_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfa4/9981740/b75da7b73933/41377_2023_1104_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfa4/9981740/18171833ba2e/41377_2023_1104_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfa4/9981740/caaab7f91171/41377_2023_1104_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfa4/9981740/16a0f9516562/41377_2023_1104_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfa4/9981740/4e122025d148/41377_2023_1104_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfa4/9981740/84e3351ddce4/41377_2023_1104_Fig8_HTML.jpg

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本文引用的文献

[1]
Label-Free Virtual HER2 Immunohistochemical Staining of Breast Tissue using Deep Learning.

BME Front. 2022-10-25

[2]
Deep UV Microscopy Identifies Prostatic Basal Cells: An Important Biomarker for Prostate Cancer Diagnostics.

BME Front. 2022-9-2

[3]
Virtual Staining, Segmentation, and Classification of Blood Smears for Label-Free Hematology Analysis.

BME Front. 2022-7-1

[4]
Emerging Advances to Transform Histopathology Using Virtual Staining.

BME Front. 2020-8-25

[5]
Mitosis domain generalization in histopathology images - The MIDOG challenge.

Med Image Anal. 2023-2

[6]
Improving unsupervised stain-to-stain translation using self-supervision and meta-learning.

J Pathol Inform. 2022-6-20

[7]
Label-free intraoperative histology of bone tissue via deep-learning-assisted ultraviolet photoacoustic microscopy.

Nat Biomed Eng. 2023-2

[8]
Deep Learning-Inferred Multiplex ImmunoFluorescence for Immunohistochemical Image Quantification.

Nat Mach Intell. 2022-4

[9]
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Light Sci Appl. 2022-9-7

[10]
MVFStain: Multiple virtual functional stain histopathology images generation based on specific domain mapping.

Med Image Anal. 2022-8

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