细胞核实例分割与分类研究综述:利用上下文和注意力机制。

A survey on cell nuclei instance segmentation and classification: Leveraging context and attention.

机构信息

INESC TEC - Institute for Systems and Computer Engineering, Technology and Science, R. Dr. Roberto Frias, Porto, 4200-465, Portugal; University of Porto - Faculty of Engineering, R. Dr. Roberto Frias, Porto, 4200-465, Portugal.

IMP Diagnostics, Praça do Bom Sucesso, 4150-146 Porto, Portugal; Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)/[RISE@CI-IPOP], Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), R. Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal; Doctoral Programme in Medical Sciences, School of Medicine and Biomedical Sciences - University of Porto (ICBAS-UP), Porto, Portugal.

出版信息

Med Image Anal. 2025 Jan;99:103360. doi: 10.1016/j.media.2024.103360. Epub 2024 Oct 5.

Abstract

Nuclear-derived morphological features and biomarkers provide relevant insights regarding the tumour microenvironment, while also allowing diagnosis and prognosis in specific cancer types. However, manually annotating nuclei from the gigapixel Haematoxylin and Eosin (H&E)-stained Whole Slide Images (WSIs) is a laborious and costly task, meaning automated algorithms for cell nuclei instance segmentation and classification could alleviate the workload of pathologists and clinical researchers and at the same time facilitate the automatic extraction of clinically interpretable features for artificial intelligence (AI) tools. But due to high intra- and inter-class variability of nuclei morphological and chromatic features, as well as H&E-stains susceptibility to artefacts, state-of-the-art algorithms cannot correctly detect and classify instances with the necessary performance. In this work, we hypothesize context and attention inductive biases in artificial neural networks (ANNs) could increase the performance and generalization of algorithms for cell nuclei instance segmentation and classification. To understand the advantages, use-cases, and limitations of context and attention-based mechanisms in instance segmentation and classification, we start by reviewing works in computer vision and medical imaging. We then conduct a thorough survey on context and attention methods for cell nuclei instance segmentation and classification from H&E-stained microscopy imaging, while providing a comprehensive discussion of the challenges being tackled with context and attention. Besides, we illustrate some limitations of current approaches and present ideas for future research. As a case study, we extend both a general (Mask-RCNN) and a customized (HoVer-Net) instance segmentation and classification methods with context- and attention-based mechanisms and perform a comparative analysis on a multicentre dataset for colon nuclei identification and counting. Although pathologists rely on context at multiple levels while paying attention to specific Regions of Interest (RoIs) when analysing and annotating WSIs, our findings suggest translating that domain knowledge into algorithm design is no trivial task, but to fully exploit these mechanisms in ANNs, the scientific understanding of these methods should first be addressed.

摘要

核衍生的形态特征和生物标志物为肿瘤微环境提供了相关的见解,同时也允许在特定癌症类型中进行诊断和预后。然而,从千兆像素的苏木精和伊红(H&E)染色全切片图像(WSI)中手动注释细胞核是一项费力且昂贵的任务,这意味着用于细胞细胞核实例分割和分类的自动化算法可以减轻病理学家和临床研究人员的工作量,同时为人工智能(AI)工具自动提取临床可解释的特征。但是,由于细胞核形态和颜色特征的高内类和类间可变性,以及 H&E 染色易受伪影影响,最先进的算法无法以必要的性能正确检测和分类实例。在这项工作中,我们假设人工神经网络(ANN)中的上下文和注意力归纳偏差可以提高细胞细胞核实例分割和分类算法的性能和泛化能力。为了了解上下文和基于注意力的机制在实例分割和分类中的优势、用例和局限性,我们首先回顾计算机视觉和医学成像领域的相关工作。然后,我们对来自 H&E 染色显微镜成像的细胞细胞核实例分割和分类的上下文和注意力方法进行了全面调查,同时全面讨论了上下文和注意力解决的挑战。此外,我们还说明了当前方法的一些局限性,并提出了未来研究的思路。作为案例研究,我们将上下文和基于注意力的机制扩展到一般(Mask-RCNN)和定制(HoVer-Net)实例分割和分类方法中,并在一个用于结肠细胞核识别和计数的多中心数据集上进行了比较分析。尽管病理学家在分析和注释 WSI 时在多个层面上依赖上下文,并关注特定的感兴趣区域(ROI),但我们的研究结果表明,将该领域知识转化为算法设计并非易事,但要充分利用这些机制在人工神经网络中,首先应该解决对这些方法的科学理解。

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