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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Nucleolar organizer regions (NORs) are parts of the DNA that are involved in RNA transcription. Due to the silver affinity of associated proteins, argyrophilic NORs (AgNORs) can be visualized using silver-based staining. The average number of AgNORs per nucleus has been shown to be a prognostic factor for predicting the outcome of many tumors. Since manual detection of AgNORs is laborious, automation is of high interest. We present a deep learning-based pipeline for automatically determining the AgNOR-score from histopathological sections. An additional annotation experiment was conducted with six pathologists to provide an independent performance evaluation of our approach. Across all raters and images, we found a mean squared error of 0.054 between the AgNOR- scores of the experts and those of the model, indicating that our approach offers performance comparable to humans.
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Mitotic activity is key for the assessment of malignancy in many tumors. Moreover, it has been demonstrated that the proportion of abnormal mitosis to normal mitosis is of prognostic significance. Atypical mitotic figures (MF) can be identified morphologically as having segregation abnormalities of the chromatids. In this work, we perform, for the first time, automatic subtyping of mitotic figures into normal and atypical categories according to characteristic morphological appearances of the different phases of mitosis. Using the publicly available MIDOG21 and TUPAC16 breast cancer mitosis datasets, two experts blindly subtyped mitotic figures into five morphological categories. Further, we set up a state-of-the-art object detection pipeline extending the anchor-free FCOS approach with a gated hierarchical subclassification branch. Our labeling experiment indicated that subtyping of mitotic figures is a challenging task and prone to inter-rater disagreement, which we found in 24.89% of MF. Using the more diverse MIDOG21 dataset for training and TUPAC16 for testing, we reached a mean overall average precision score of 0.552, a ROC AUC score of 0.833 for atypical/normal MF and a mean class-averaged ROC-AUC score of 0.977 for discriminating the different phases of cells undergoing mitosis.
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Computer-aided systems in histopathology are often challenged by various sources of domain shift that impact the performance of these algorithms considerably. We investigated the potential of using self-supervised pre-training to overcome scanner-induced domain shifts for the downstream task of tumor segmentation. For this, we present the Barlow Triplets to learn scanner-invariant representations from a multi-scanner dataset with local image correspondences. We show that self-supervised pre-training successfully aligned different scanner representations, which, interestingly only results in a limited benefit for our downstream task. We thereby provide insights into the influence of scanner characteristics for downstream applications and contribute to a better understanding of why established self-supervised methods have not yet shown the same success on histopathology data as they have for natural images.
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Tumor segmentation in histopathology images is often complicated by its composition of different histological subtypes and class imbalance. Oversampling subtypes with low prevalence features is not a satisfactory solution since it eventually leads to overfitting. We propose to create synthetic images with semantically-conditioned deep generative networks and to combine subtype-balanced synthetic images with the original dataset to achieve better segmentation performance. We show the suitability of Generative Adversarial Networks (GANs) and especially diffusion models to create realistic images based on subtype-conditioning for the use case of HER2-stained histopathology. Additionally, we show the capability of diffusion models to conditionally inpaint HER2 tumor areas with modified subtypes. Combining the original dataset with the same amount of diffusion-generated images increased the tumor Dice score from 0.833 to 0.854 and almost halved the variance between the HER2 subtype recalls. These results create the basis for more reliable automatic HER2 analysis with lower performance variance between individual HER2 subtypes.
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Histopathology imaging is crucial for the diagnosis and treatment of skin diseases. For this reason, computer-assisted approaches have gained popularity and shown promising results in tasks such as segmentation and classification of skin disorders. However, collecting essential data and sufficiently high-quality annotations is a challenge. This work describes a pipeline that uses suspected melanoma samples that have been characterized using Multi-Epitope-Ligand Cartography (MELC). This cellular-level tissue characterisation is then represented as a graph and used to train a graph neural network. This imaging technology, combined with the methodology proposed in this work, achieves a classification accuracy of 87%, outperforming existing approaches by 10%.
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光学相干断层扫描(OCT)是微尺度的体积成像方式,已成为眼科临床标准。 OCT仪器图像通过栅格扫描整个视网膜上的聚焦光点,从而获取顺序的横截面图像以生成体积数据。收购期间的患者眼动作带来了独特的挑战:可能会发生非刚性,不连续的扭曲,从而导致数据和扭曲的地形测量差距。我们提出了一种新的失真模型和相应的全自动,无参考优化策略,用于在正交栅格扫描,视网膜OCT量中进行计算运动校正。使用新型的,域特异性的时空参数化,可以首次连续校正眼睛运动。时间正则化的参数估计提高了先前空间方法的鲁棒性和准确性。我们在单个映射中在3D中单独校正每个A-SCAN,包括OCT血管造影协议中使用的重复采集。专业的3D前向图像扭曲将中位运行时间降低到<9 s,足够快地供临床使用。我们对18名具有眼病理学的受试者进行了定量评估,并在微扫描过程中证明了准确的校正。横向校正仅受眼震颤的限制,而亚微米可重复性是轴向可重复性的(中位数为0.51 UM中位数),这比以前的工作有了显着改善。这允许评估局灶性视网膜病理学的纵向变化,作为疾病进展或治疗反应的标志,并承诺能够使多种新功能(例如Suppersmplempled/Super-Supersmpled/Super-Super-Super-Super-Spemply/Super-Supertolution Reponstruction and Ransition and Anallys in Dealitaligy Eye the Neurologation疾病中发生的病理眼运动分析。
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本文介绍了一个新的多模式介入放射学数据集,称为POCAP(端口导管放置)语料库。该语料库由德语,X射线图像的语音和音频信号组成,以及六名外科医生从31个POCAP干预措施收集的系统命令,平均持续时间为81.4 $ \ pm $ 41.0分钟。该语料库旨在为在手术室中开发智能语音助理提供资源。特别是,它可用于开发语音控制的系统,该系统使外科医生能够控制操作参数,例如C臂运动和表位置。为了记录数据集,我们获得了Erlangen大学医院和患者数据隐私的机构审查委员会和工人委员会的同意。我们描述了录制设置,数据结构,工作流程和预处理步骤,并使用预告片的模型以11.52 $ \%$单词错误率报告了第一个POCAP语料库语音识别分析结果。研究结果表明,数据有可能构建强大的命令识别系统,并将使用医学领域中的语音和图像处理来开发新颖的干预支持系统。
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由于形态的相似性,皮肤肿瘤的组织学切片分化为个体亚型可能具有挑战性。最近,基于深度学习的方法证明了它们在这方面支持病理学家的潜力。但是,这些监督算法中的许多都需要大量的注释数据才能进行稳健开发。我们提供了一个公开可用的数据集,该数据集是七个不同的犬皮肤肿瘤的350张全滑图像,其中有13种组织学类别的12,424个多边形注释,包括7种皮肤肿瘤亚型。在评估者间实验中,我们显示了提供的标签的高稠度,尤其是对于肿瘤注释。我们通过训练深层神经网络来进一步验证数据集,以完成组织分割和肿瘤亚型分类的任务。我们的肿瘤尤其是0.7047的类平均Jaccard系数为0.7047,尤其是0.9044。对于分类,我们达到了0.9857的幻灯片级准确性。由于犬皮肤肿瘤对人肿瘤具有各种组织学同源性,因此该数据集的附加值不限于兽医病理学,而是扩展到更一般的应用领域。
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注释数据,尤其是在医疗领域,需要专家知识和很多努力。这限制了可用医疗数据集的实验量和/或有用性。因此,发展策略以增加注释的数量,同时降低所需的域知识是感兴趣的。可能的策略是使用游戏,即即将注释任务转换为游戏。我们提出了一种方法来游戏从病理整体幻灯片图像中注释肺部流体细胞的任务。由于该域是未知的非专家注释器所知,我们将用视网网架构检测到的细胞图像到花卉图像域。使用Compygan架构执行此域传输,用于不同的小区类型。在这种更科的域名中,非专家注释器可以(t)要求在俏皮的环境中注释不同种类的花朵。为了提供概念证据,该工作表明,通过评估在真实单元图像上培训的图像分类网络并在由Cyclegan网络生成的小区图像上测试的图像分类网络可以进行域传输。分类网络分别达到原始肺液体细胞和转化肺部流体细胞的精度​​为97.48%和95.16%。通过这项研究,我们为使用自行车队进行了未来的游戏研究的基础。
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