Otálora Sebastian, Atzori Manfredo, Andrearczyk Vincent, Khan Amjad, Müller Henning
Institute of Information Systems, HES-SO University of Applied Sciences and Arts Western Switzerland, Sierre, Switzerland.
Computer Science Centre (CUI), University of Geneva, Geneva, Switzerland.
Front Bioeng Biotechnol. 2019 Aug 23;7:198. doi: 10.3389/fbioe.2019.00198. eCollection 2019.
One of the main obstacles for the implementation of deep convolutional neural networks (DCNNs) in the clinical pathology workflow is their low capability to overcome variability in slide preparation and scanner configuration, that leads to changes in tissue appearance. Some of these variations may not be not included in the training data, which means that the models have a risk to not generalize well. Addressing such variations and evaluating them in reproducible scenarios allows understanding of when the models generalize better, which is crucial for performance improvements and better DCNN models. Staining normalization techniques (often based on color deconvolution and deep learning) and color augmentation approaches have shown improvements in the generalization of the classification tasks for several tissue types. Domain-invariant training of DCNN's is also a promising technique to address the problem of training a single model for different domains, since it includes the source domain information to guide the training toward domain-invariant features, achieving state-of-the-art results in classification tasks. In this article, deep domain adaptation in convolutional networks (DANN) is applied to computational pathology and compared with widely used staining normalization and color augmentation methods in two challenging classification tasks. The classification tasks rely on two openly accessible datasets, targeting Gleason grading in prostate cancer, and mitosis classification in breast tissue. The benchmark of the different techniques and their combination in two DCNN architectures allows us to assess the generalization abilities and advantages of each method in the considered classification tasks. The code for reproducing our experiments and preprocessing the data is publicly available. Quantitative and qualitative results show that the use of DANN helps model generalization to external datasets. The combination of several techniques to manage color heterogeneity suggests that several methods together, such as color augmentation methods with DANN training, can generalize even further. The results do not show a single best technique among the considered methods, even when combining them. However, color augmentation and DANN training obtain most often the best results (alone or combined with color normalization and color augmentation). The statistical significance of the results and the embeddings visualizations provide useful insights to design DCNN that generalizes to unseen staining appearances. Furthermore, in this work, we release for the first time code for DANN evaluation in open access datasets for computational pathology. This work opens the possibility for further research on using DANN models together with techniques that can overcome the tissue preparation differences across datasets to tackle limited generalization.
在临床病理工作流程中,深度卷积神经网络(DCNN)应用的主要障碍之一是其克服载玻片制备和扫描仪配置差异的能力较低,这会导致组织外观发生变化。其中一些变化可能未包含在训练数据中,这意味着模型存在泛化能力不佳的风险。在可重复的场景中解决此类变化并对其进行评估,有助于理解模型何时能更好地泛化,这对于性能提升和更好的DCNN模型至关重要。染色归一化技术(通常基于颜色反卷积和深度学习)以及颜色增强方法已在多种组织类型的分类任务泛化方面取得了进展。DCNN的域不变训练也是一种有前景的技术,可解决针对不同域训练单个模型的问题,因为它包含源域信息以引导训练朝着域不变特征进行,在分类任务中取得了最优结果。在本文中,卷积网络中的深度域自适应(DANN)被应用于计算病理学,并在两项具有挑战性的分类任务中与广泛使用的染色归一化和颜色增强方法进行比较。分类任务依赖于两个可公开获取的数据集,分别针对前列腺癌的Gleason分级和乳腺组织的有丝分裂分类。在两种DCNN架构中对不同技术及其组合进行基准测试,使我们能够评估每种方法在考虑的分类任务中的泛化能力和优势。用于重现我们实验和预处理数据的代码是公开可用的。定量和定性结果表明,使用DANN有助于模型泛化到外部数据集。多种管理颜色异质性技术的组合表明,多种方法一起使用,例如颜色增强方法与DANN训练相结合,可以实现更进一步的泛化。即使在组合使用时,结果也未显示在所考虑的方法中有单一的最佳技术。然而,颜色增强和DANN训练最常获得最佳结果(单独使用或与颜色归一化和颜色增强相结合)。结果的统计显著性和嵌入可视化可为设计能泛化到未见染色外观的DCNN提供有用的见解。此外,在这项工作中,我们首次在开放获取的计算病理学数据集中发布了用于DANN评估的代码。这项工作为进一步研究将DANN模型与能够克服跨数据集组织制备差异的技术结合起来以解决有限泛化问题开辟了可能性。
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