The survival analysis on histological whole-slide images (WSIs) is one of the most important means to estimate patient prognosis. Although many weakly-supervised deep learning models have been developed for gigapixel WSIs, their potential is generally restricted by classical survival analysis rules and fully-supervision requirements. As a result, these models provide patients only with a completely-certain point estimation of time-to-event, and they could only learn from the well-annotated WSI data currently at a small scale. To tackle these problems, we propose a novel adversarial multiple instance learning (AdvMIL) framework. This framework is based on adversarial time-to-event modeling, and it integrates the multiple instance learning (MIL) that is much necessary for WSI representation learning. It is a plug-and-play one, so that most existing WSI-based models with embedding-level MIL networks can be easily upgraded by applying this framework, gaining the improved ability of survival distribution estimation and semi-supervised learning. Our extensive experiments show that AdvMIL could not only bring performance improvement to mainstream WSI models at a relatively low computational cost, but also enable these models to learn from unlabeled data with semi-supervised learning. Our AdvMIL framework could promote the research of time-to-event modeling in computational pathology with its novel paradigm of adversarial MIL.
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Gigapixel全斜面图像(WSIS)上的癌症预后一直是一项艰巨的任务。大多数现有方法仅着眼于单分辨率图像。利用图像金字塔增强WSI视觉表示的多分辨率方案尚未得到足够的关注。为了探索用于提高癌症预后准确性的多分辨率解决方案,本文提出了双流构建结构,以通过图像金字塔策略对WSI进行建模。该体系结构由两个子流组成:一个是用于低分辨率WSIS,另一个是针对高分辨率的WSIS。与其他方法相比,我们的方案具有三个亮点:(i)流和分辨率之间存在一对一的关系; (ii)添加了一个平方池层以对齐两个分辨率流的斑块,从而大大降低了计算成本并启用自然流特征融合; (iii)提出了一种基于跨注意的方法,以在低分辨率的指导下在空间上在空间上进行高分辨率斑块。我们验证了三个公共可用数据集的计划,来自1,911名患者的总数为3,101个WSI。实验结果验证(1)层次双流表示比单流的癌症预后更有效,在单个低分辨率和高分辨率流中,平均C-指数上升为5.0%和1.8% ; (2)我们的双流方案可以胜过当前最新方案,而C-Index的平均平均值为5.1%; (3)具有可观察到的生存差异的癌症疾病可能对模型复杂性具有不同的偏好。我们的计划可以作为进一步促进WSI预后研究的替代工具。
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组织病理学图像包含丰富的表型信息和病理模式,这是疾病诊断的黄金标准,对于预测患者预后和治疗结果至关重要。近年来,在临床实践中迫切需要针对组织病理学图像的计算机自动化分析技术,而卷积神经网络代表的深度学习方法已逐渐成为数字病理领域的主流。但是,在该领域获得大量细粒的注释数据是一项非常昂贵且艰巨的任务,这阻碍了基于大量注释数据的传统监督算法的进一步开发。最新的研究开始从传统的监督范式中解放出来,最有代表性的研究是基于弱注释,基于有限的注释的半监督学习范式以及基于自我监督的学习范式的弱监督学习范式的研究图像表示学习。这些新方法引发了针对注释效率的新自动病理图像诊断和分析。通过对130篇论文的调查,我们对从技术和方法论的角度来看,对计算病理学领域中有关弱监督学习,半监督学习以及自我监督学习的最新研究进行了全面的系统综述。最后,我们提出了这些技术的关键挑战和未来趋势。
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Learning good representation of giga-pixel level whole slide pathology images (WSI) for downstream tasks is critical. Previous studies employ multiple instance learning (MIL) to represent WSIs as bags of sampled patches because, for most occasions, only slide-level labels are available, and only a tiny region of the WSI is disease-positive area. However, WSI representation learning still remains an open problem due to: (1) patch sampling on a higher resolution may be incapable of depicting microenvironment information such as the relative position between the tumor cells and surrounding tissues, while patches at lower resolution lose the fine-grained detail; (2) extracting patches from giant WSI results in large bag size, which tremendously increases the computational cost. To solve the problems, this paper proposes a hierarchical-based multimodal transformer framework that learns a hierarchical mapping between pathology images and corresponding genes. Precisely, we randomly extract instant-level patch features from WSIs with different magnification. Then a co-attention mapping between imaging and genomics is learned to uncover the pairwise interaction and reduce the space complexity of imaging features. Such early fusion makes it computationally feasible to use MIL Transformer for the survival prediction task. Our architecture requires fewer GPU resources compared with benchmark methods while maintaining better WSI representation ability. We evaluate our approach on five cancer types from the Cancer Genome Atlas database and achieved an average c-index of $0.673$, outperforming the state-of-the-art multimodality methods.
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基于深度学习的半监督学习(SSL)方法在医学图像细分中实现了强大的性能,可以通过使用大量未标记的数据来减轻医生昂贵的注释。与大多数现有的半监督学习方法不同,基于对抗性训练的方法通过学习分割图的数据分布来区分样本与不同来源,导致细分器生成更准确的预测。我们认为,此类方法的当前绩效限制是特征提取和学习偏好的问题。在本文中,我们提出了一种新的半监督的对抗方法,称为贴片置信疗法训练(PCA),用于医疗图像分割。我们提出的歧视器不是单个标量分类结果或像素级置信度图,而是创建贴片置信图,并根据斑块的规模进行分类。未标记数据的预测学习了每个贴片中的像素结构和上下文信息,以获得足够的梯度反馈,这有助于歧视器以融合到最佳状态,并改善半监督的分段性能。此外,在歧视者的输入中,我们补充了图像上的语义信息约束,使得未标记的数据更简单,以适合预期的数据分布。关于自动心脏诊断挑战(ACDC)2017数据集和脑肿瘤分割(BRATS)2019挑战数据集的广泛实验表明,我们的方法优于最先进的半监督方法,这证明了其对医疗图像分割的有效性。
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监督的学习任务,例如GigaiPixel全幻灯片图像(WSIS)等癌症存活预测是计算病理学中的关键挑战,需要对肿瘤微环境的复杂特征进行建模。这些学习任务通常通过不明确捕获肿瘤内异质性的深层多企业学习(MIL)模型来解决。我们开发了一种新颖的差异池体系结构,使MIL模型能够将肿瘤内异质性纳入其预测中。说明了基于代表性补丁的两个可解释性工具,以探测这些模型捕获的生物学信号。一项针对癌症基因组图集的4,479吉普像素WSI的实证研究表明,在MIL框架上增加方差汇总可改善五种癌症类型的生存预测性能。
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高质量注释的医学成像数据集的稀缺性是一个主要问题,它与医学成像分析领域的机器学习应用相撞并阻碍了其进步。自我监督学习是一种最近的培训范式,可以使学习强大的表示无需人类注释,这可以被视为有效的解决方案,以解决带注释的医学数据的稀缺性。本文回顾了自我监督学习方法的最新研究方向,用于图像数据,并将其专注于其在医学成像分析领域的应用。本文涵盖了从计算机视野领域的最新自我监督学习方法,因为它们适用于医学成像分析,并将其归类为预测性,生成性和对比性方法。此外,该文章涵盖了40个在医学成像分析中自学学习领域的最新研究论文,旨在阐明该领域的最新创新。最后,本文以该领域的未来研究指示结束。
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Attention-based multiple instance learning (AMIL) algorithms have proven to be successful in utilizing gigapixel whole-slide images (WSIs) for a variety of different computational pathology tasks such as outcome prediction and cancer subtyping problems. We extended an AMIL approach to the task of survival prediction by utilizing the classical Cox partial likelihood as a loss function, converting the AMIL model into a nonlinear proportional hazards model. We applied the model to tissue microarray (TMA) slides of 330 lung cancer patients. The results show that AMIL approaches can handle very small amounts of tissue from a TMA and reach similar C-index performance compared to established survival prediction methods trained with highly discriminative clinical factors such as age, cancer grade, and cancer stage
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在深度学习研究中,自学学习(SSL)引起了极大的关注,引起了计算机视觉和遥感社区的兴趣。尽管计算机视觉取得了很大的成功,但SSL在地球观测领域的大部分潜力仍然锁定。在本文中,我们对在遥感的背景下为计算机视觉的SSL概念和最新发展提供了介绍,并回顾了SSL中的概念和最新发展。此外,我们在流行的遥感数据集上提供了现代SSL算法的初步基准,从而验证了SSL在遥感中的潜力,并提供了有关数据增强的扩展研究。最后,我们确定了SSL未来研究的有希望的方向的地球观察(SSL4EO),以铺平了两个领域的富有成效的相互作用。
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已经开发了几种深度学习算法,以使用整个幻灯片图像(WSIS)预测癌症患者的存活。但是,WSI中与患者的生存和疾病进展有关的WSI中的图像表型对临床医生而言都是困难的,以及深度学习算法。用于生存预测的大多数基于深度学习的多个实例学习(MIL)算法使用顶级实例(例如Maxpooling)或顶级/底部实例(例如,Mesonet)来识别图像表型。在这项研究中,我们假设WSI中斑块得分分布的全面信息可以更好地预测癌症的生存。我们开发了一种基于分布的多构度生存学习算法(DeepDismisl)来验证这一假设。我们使用两个大型国际大型癌症WSIS数据集设计和执行实验-MCO CRC和TCGA Coad -Read。我们的结果表明,有关WSI贴片分数的分布的信息越多,预测性能越好。包括每个选定分配位置(例如百分位数)周围的多个邻域实例可以进一步改善预测。与最近发表的最新算法相比,DeepDismisl具有优越的预测能力。此外,我们的算法是可以解释的,可以帮助理解癌症形态表型与癌症生存风险之间的关系。
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组织病理学图像提供了癌症诊断的明确来源,其中包含病理学家用来识别和分类恶性疾病的信息,并指导治疗选择。这些图像包含大量信息,其中大部分目前不可用人类的解释。有监督的深度学习方法对于分类任务非常有力,但它们本质上受注释的成本和质量限制。因此,我们开发了组织形态表型学习,这是一种无监督的方法,它不需要注释,并且通过小图像瓷砖中的歧视性图像特征的自我发现进行操作。瓷砖分为形态上相似的簇,这些簇似乎代表了自然选择下出现的肿瘤生长的复发模式。这些簇具有不同的特征,可以使用正交方法识别。应用于肺癌组织,我们表明它们与患者的结局紧密保持一致,组织病理学识别的肿瘤类型和生长模式以及免疫表型的转录组度量。
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Recently deep neural networks, which require a large amount of annotated samples, have been widely applied in nuclei instance segmentation of H\&E stained pathology images. However, it is inefficient and unnecessary to label all pixels for a dataset of nuclei images which usually contain similar and redundant patterns. Although unsupervised and semi-supervised learning methods have been studied for nuclei segmentation, very few works have delved into the selective labeling of samples to reduce the workload of annotation. Thus, in this paper, we propose a novel full nuclei segmentation framework that chooses only a few image patches to be annotated, augments the training set from the selected samples, and achieves nuclei segmentation in a semi-supervised manner. In the proposed framework, we first develop a novel consistency-based patch selection method to determine which image patches are the most beneficial to the training. Then we introduce a conditional single-image GAN with a component-wise discriminator, to synthesize more training samples. Lastly, our proposed framework trains an existing segmentation model with the above augmented samples. The experimental results show that our proposed method could obtain the same-level performance as a fully-supervised baseline by annotating less than 5% pixels on some benchmarks.
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This paper focuses on the task of survival time analysis for lung cancer. Although much progress has been made in this problem in recent years, the performance of existing methods is still far from satisfactory. Traditional and some deep learning-based survival time analyses for lung cancer are mostly based on textual clinical information such as staging, age, histology, etc. Unlike existing methods that predicting on the single modality, we observe that a human clinician usually takes multimodal data such as text clinical data and visual scans to estimate survival time. Motivated by this, in this work, we contribute a smart cross-modality network for survival analysis network named Lite-ProSENet that simulates a human's manner of decision making. Extensive experiments were conducted using data from 422 NSCLC patients from The Cancer Imaging Archive (TCIA). The results show that our Lite-ProSENet outperforms favorably again all comparison methods and achieves the new state of the art with the 89.3% on concordance. The code will be made publicly available.
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变形金刚占据了自然语言处理领域,最近影响了计算机视觉区域。在医学图像分析领域中,变压器也已成功应用于全栈临床应用,包括图像合成/重建,注册,分割,检测和诊断。我们的论文旨在促进变压器在医学图像分析领域的认识和应用。具体而言,我们首先概述了内置在变压器和其他基本组件中的注意机制的核心概念。其次,我们回顾了针对医疗图像应用程序量身定制的各种变压器体系结构,并讨论其局限性。在这篇综述中,我们调查了围绕在不同学习范式中使用变压器,提高模型效率及其与其他技术的耦合的关键挑战。我们希望这篇评论可以为读者提供医学图像分析领域的读者的全面图片。
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人们普遍认为,污渍差异引起的颜色变化是组织病理学图像分析的关键问题。现有方法采用颜色匹配,染色分离,污渍转移或它们的组合以减轻污渍变化问题。在本文中,我们提出了一种用于组织病理学图像分析的新型染色自适应自我监督学习(SASSL)方法。我们的SASSL将一个域 - 交流训练模块集成到SSL框架中,以学习独特的特征,这些功能对各种转换和污渍变化都具有鲁棒性。所提出的SASSL被视为域不变特征提取的一般方法,可以通过对特定下游任务的特征进行细微调整特征来灵活地与任意下游组织病理学图像分析模块(例如核/组织分割)结合。我们进行了有关公开可用的病理图像分析数据集的实验,包括熊猫,乳腺癌和camelyon16数据集,以实现最先进的性能。实验结果表明,所提出的方法可以鲁棒地提高模型的特征提取能力,并在下游任务中实现稳定的性能改善。
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针对组织病理学图像数据的临床决策支持主要侧重于强烈监督的注释,这提供了直观的解释性,但受专业表现的束缚。在这里,我们提出了一种可解释的癌症复发预测网络(Ecarenet),并表明没有强注释的端到端学习提供最先进的性能,而可以通过注意机制包括可解释性。在前列腺癌生存预测的用例上,使用14,479个图像和仅复发时间作为注释,我们在验证集中达到0.78的累积动态AUC,与专家病理学家(以及在单独测试中的AUC为0.77放)。我们的模型是良好的校准,输出生存曲线以及每位患者的风险分数和群体。利用多实例学习层的注意重量,我们表明恶性斑块对预测的影响较高,从而提供了对预测的直观解释。我们的代码可在www.github.com/imsb-uke/ecarenet上获得。
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众所周知,深度学习方法是渴望数据的,它需要大量标记的样本。不幸的是,大量的交互式样品标记工作极大地阻碍了深度学习方法的应用,尤其是对于需要异质样本的3D建模任务。为了减轻对FA \ c {C} ADS的3D建模的数据注释的工作,本文提出了一种半监督的对抗识别策略,该策略嵌入了逆程序建模中。从纹理LOD-2(详细级别)模型开始,我们使用经典的卷积神经网络来识别来自图像补丁的类型并估算Windows的参数。然后将窗口类型和参数组装到程序语法中。一个简单的程序引擎是在现有的3D建模软件中构建的,产生了细粒的窗户几何形状。为了从一些标记的样品中获得有用的模型,我们利用生成对抗网络以半监督的方式训练特征提取器。对抗训练策略还可以利用未标记的数据,使训练阶段更加稳定。使用公开可用的FA \ c {C} ADE图像数据集的实验表明,在同一网络结构下,提出的培训策略可以提高分类精度的提高约10%,参数估计提高了50%。此外,在针对具有不同fa \ c {c} ADE样式的不同数据测试时,性能提高更为明显。
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Molecular and genomic properties are critical in selecting cancer treatments to target individual tumors, particularly for immunotherapy. However, the methods to assess such properties are expensive, time-consuming, and often not routinely performed. Applying machine learning to H&E images can provide a more cost-effective screening method. Dozens of studies over the last few years have demonstrated that a variety of molecular biomarkers can be predicted from H&E alone using the advancements of deep learning: molecular alterations, genomic subtypes, protein biomarkers, and even the presence of viruses. This article reviews the diverse applications across cancer types and the methodology to train and validate these models on whole slide images. From bottom-up to pathologist-driven to hybrid approaches, the leading trends include a variety of weakly supervised deep learning-based approaches, as well as mechanisms for training strongly supervised models in select situations. While results of these algorithms look promising, some challenges still persist, including small training sets, rigorous validation, and model explainability. Biomarker prediction models may yield a screening method to determine when to run molecular tests or an alternative when molecular tests are not possible. They also create new opportunities in quantifying intratumoral heterogeneity and predicting patient outcomes.
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病理诊所中癌症的诊断,预后和治疗性决策现在可以基于对多吉吉像素组织图像的分析,也称为全斜图像(WSIS)。最近,已经提出了深层卷积神经网络(CNN)来得出无监督的WSI表示。这些很有吸引力,因为它们不太依赖于繁琐的专家注释。但是,一个主要的权衡是,较高的预测能力通常以解释性为代价,这对他们的临床使用构成了挑战,通常通常期望决策中的透明度。为了应对这一挑战,我们提出了一个基于Deep CNN的手工制作的框架,用于构建整体WSI级表示。基于有关变压器在自然语言处理领域的内部工作的最新发现,我们将其过程分解为一个更透明的框架,我们称其为手工制作的组织学变压器或H2T。基于我们涉及各种数据集的实验,包括总共5,306个WSI,结果表明,与最近的最新方法相比,基于H2T的整体WSI级表示具有竞争性能,并且可以轻松用于各种下游分析任务。最后,我们的结果表明,H2T框架的最大14倍,比变压器模型快14倍。
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数据分析方法的组合,提高计算能力和改进的传感器可以实现定量颗粒状,基于细胞的分析。我们描述了与组织解释和调查AI方法有关的丰富应用挑战集,目前用于应对这些挑战。我们专注于一类针对性的人体组织分析 - 组织病理学 - 旨在定量表征疾病状态,患者结果预测和治疗转向。
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