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[Effects of upstream laboratory processes on the digitization of histological slides]. [上游实验室流程对组织学切片数字化的影响]。
Pub Date : 2024-03-01 Epub Date: 2024-02-22 DOI: 10.1007/s00292-024-01303-y
Leander Schwaibold, Sven Mattern, Markus Mählmann, Leon Lobert, Thomas Breunig, Christian M Schürch

Background: Several factors in glass slide (GS) preparation affect the quality and data volume of a digitized histological slide. In particular, reducing contamination and selecting the appropriate coverslip have the potential to significantly reduce scan time and data volume.

Goals: To objectify observations from our institute's digitization process to determine the impact of laboratory processes on the quality of digital histology slides.

Materials and methods: Experiment 1: Scanning the GS before and after installation of a central console in the microtomy area to reduce dirt and statistical analysis of the determined parameters. Experiment 2: Re-coverslipping the GS (post diagnostics) with glass and film. Scanning the GS and statistical analysis of the collected parameters.

Conclusion: The targeted restructuring in the laboratory process leads to a reduction of GS contamination. This causes a significant reduction in the amount of data generated and scanning time required for the digitized sections. Film as a coverslip material minimizes processing errors in contrast to glass. According to our estimation, all the above-mentioned points lead to considerable cost savings.

背景:玻璃载玻片(GS)制备过程中的几个因素会影响数字化组织学载玻片的质量和数据量。特别是,减少污染和选择合适的盖玻片有可能显著减少扫描时间和数据量:将本研究所数字化过程中的观察结果客观化,以确定实验室过程对数字化组织学玻片质量的影响:实验 1:在显微切片区安装中央控制台以减少污垢之前和之后扫描 GS,并对确定的参数进行统计分析。实验 2:用玻璃和胶片重新盖上 GS(诊断后)。扫描 GS 并对收集的参数进行统计分析:结论:对实验室流程进行有针对性的重组可减少 GS 污染。结论:通过对实验室流程进行有针对性的重组,减少了 GS 污染,从而大大减少了生成的数据量和数字化切片所需的扫描时间。与玻璃相比,胶片作为盖玻片材料可最大限度地减少处理错误。根据我们的估算,上述各点都能节省大量成本。
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引用次数: 0
[Histomolecular classification of urothelial carcinoma of the urinary bladder : From histological phenotype to genotype and back]. [膀胱尿路上皮癌的组织分子分类 :从组织学表型到基因型再到组织学表型]。
Pub Date : 2024-03-01 Epub Date: 2024-01-29 DOI: 10.1007/s00292-024-01305-w
Alexandra K Stoll, Florestan J Koll, Markus Eckstein, Henning Reis, Nadine Flinner, Peter J Wild, Jochen Triesch

Background: Of all urothelial carcinomas (UCs), 25% are muscle invasive and associated with a 5-year overall survival rate of 50%. Findings regarding the molecular classification of muscle-invasive urothelial carcinomas (MIUCs) have not yet found their way into clinical practice.

Objectives: Prediction of molecular consensus subtypes in MIUCs with artificial intelligence (AI) based on histologic hematoxylin-eosin (HE) sections.

Methods: Pathologic review and annotation of The Cancer Genome Atlas (TCGA) Bladder Cancer (BLCA) Cohort (N = 412) and the Dr. Senckenberg Institute of Pathology (SIP) BLCA Cohort (N = 181). An AI model for the prediction of molecular subtypes based on annotated histomorphology was trained.

Results: For a five-fold cross-validation with TCGA cases (N = 274), an internal TCGA test set (N = 18) and an external SIP test set (N = 27), we reached mean area under the receiver operating characteristic curve (AUROC) scores of 0.73, 0.8 and 0.75 for the classification of the used molecular subtypes "luminal", "basal/squamous" and "stroma-rich". By training on correlations to individual molecular subtypes, rather than training on one subtype assignment per case, the AI prediction of subtypes could be significantly improved.

Discussion: Follow-up studies with RNA extraction from various areas of AI-predicted molecular heterogeneity may improve molecular classifications and thereby AI algorithms trained on these classifications.

背景:在所有尿路上皮癌(UC)中,25%为肌层浸润癌,5年总生存率为50%。有关肌层浸润性尿路上皮癌(MIUC)分子分类的研究结果尚未应用于临床实践:基于组织学苏木精-伊红(HE)切片,用人工智能(AI)预测肌浸润性尿路上皮癌的分子共识亚型:方法:对癌症基因组图谱(TCGA)膀胱癌(BLCA)队列(N = 412)和森肯伯格博士病理研究所(SIP)膀胱癌队列(N = 181)进行病理学审查和注释。训练了一个基于注释组织形态学预测分子亚型的人工智能模型:在使用 TCGA 病例(N = 274)、内部 TCGA 测试集(N = 18)和外部苏州工业园区测试集(N = 27)进行的五倍交叉验证中,我们对所用分子亚型 "管腔型"、"基底/鳞状 "和 "富基质 "的分类得出的平均接收者操作特征曲线下面积(AUROC)分数分别为 0.73、0.8 和 0.75。通过对各个分子亚型的相关性进行训练,而不是对每个病例的一个亚型分配进行训练,可以显著提高亚型的人工智能预测能力:讨论:从人工智能预测的分子异质性的不同区域提取 RNA 进行后续研究,可能会改进分子分类,从而改进根据这些分类训练的人工智能算法。
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引用次数: 0
[Explainable artificial intelligence in pathology]. [病理学中可解释的人工智能]。
Pub Date : 2024-03-01 Epub Date: 2024-02-05 DOI: 10.1007/s00292-024-01308-7
Frederick Klauschen, Jonas Dippel, Philipp Keyl, Philipp Jurmeister, Michael Bockmayr, Andreas Mock, Oliver Buchstab, Maximilian Alber, Lukas Ruff, Grégoire Montavon, Klaus-Robert Müller

With the advancements in precision medicine, the demands on pathological diagnostics have increased, requiring standardized, quantitative, and integrated assessments of histomorphological and molecular pathological data. Great hopes are placed in artificial intelligence (AI) methods, which have demonstrated the ability to analyze complex clinical, histological, and molecular data for disease classification, biomarker quantification, and prognosis estimation. This paper provides an overview of the latest developments in pathology AI, discusses the limitations, particularly concerning the black box character of AI, and describes solutions to make decision processes more transparent using methods of so-called explainable AI (XAI).

随着精准医疗的发展,对病理诊断的要求也越来越高,需要对组织形态学和分子病理学数据进行标准化、定量化和综合评估。人们对人工智能(AI)方法寄予厚望,人工智能方法已证明有能力分析复杂的临床、组织学和分子数据,以进行疾病分类、生物标记物量化和预后评估。本文概述了病理学人工智能的最新发展,讨论了其局限性,特别是人工智能的黑箱特性,并介绍了使用所谓的可解释人工智能(XAI)方法使决策过程更加透明的解决方案。
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引用次数: 0
[Challenges of automation in quantitative evaluation of liver biopsies : Automatic quantification of liver steatosis]. [肝活检定量评估自动化面临的挑战 :肝脏脂肪变性的自动量化]。
Pub Date : 2024-03-01 Epub Date: 2024-02-21 DOI: 10.1007/s00292-024-01298-6
Jessica Darling, Nada Abedin, Paul K Ziegler, Steffen Gretser, Barbara Walczak, Ana Paula Barreiros, Falko Schulze, Henning Reis, Peter J Wild, Nadine Flinner

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), or non-alcoholic fatty liver disease (NAFLD), is a common disease that is diagnosed through manual evaluation of liver biopsies, an assessment that is subject to high interobserver variability (IBV). IBV can be reduced using automated methods.

Objectives: Many existing computer-based methods do not accurately reflect what pathologists evaluate in practice. The goal is to demonstrate how these differences impact the prediction of hepatic steatosis. Additionally, IBV complicates algorithm validation.

Materials and methods: Forty tissue sections were analyzed to detect steatosis, nuclei, and fibrosis. Data generated from automated image processing were used to predict steatosis grades. To investigate IBV, 18 liver biopsies were evaluated by multiple observers.

Results: Area-based approaches yielded more strongly correlated results than nucleus-based methods (⌀ Spearman rho [ρ] = 0.92 vs. 0.79). The inclusion of information regarding tissue composition reduced the average absolute error for both area- and nucleus-based predictions by 0.5% and 2.2%, respectively. Our final area-based algorithm, incorporating tissue structure information, achieved a high accuracy (80%) and strong correlation (⌀ Spearman ρ = 0.94) with manual evaluation.

Conclusion: The automatic and deterministic evaluation of steatosis can be improved by integrating information about tissue composition and can serve to reduce the influence of IBV.

背景:代谢功能障碍相关性脂肪性肝病(MASLD)或非酒精性脂肪肝(NAFLD)是一种常见疾病,通过人工评估肝活检组织进行诊断,这种评估方法的观察者间变异性(IBV)很高。使用自动化方法可以降低 IBV:目标:现有的许多基于计算机的方法并不能准确反映病理学家的实际评估结果。目的:现有的许多基于计算机的方法并不能准确反映病理学家的实际评估结果,我们的目标是证明这些差异如何影响肝脏脂肪变性的预测。此外,IBV 使算法验证变得复杂:对 40 个组织切片进行分析,以检测脂肪变性、细胞核和纤维化。自动图像处理生成的数据用于预测脂肪变性等级。为了研究 IBV,多位观察者对 18 例肝脏活检进行了评估:结果:与基于细胞核的方法相比,基于面积的方法得出的结果具有更强的相关性(Spearman rho [ρ] = 0.92 vs. 0.79)。加入组织组成信息后,基于面积和基于细胞核的预测的平均绝对误差分别减少了 0.5% 和 2.2%。我们最终的基于区域的算法结合了组织结构信息,达到了很高的准确率(80%),并且与人工评估结果有很强的相关性(Spearman ρ = 0.94):结论:通过整合组织成分信息,可改善脂肪变性的自动确定性评估,并可减少 IBV 的影响。
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引用次数: 0
Mitteilungen der Deutschen Gesellschaft für Pathologie. Mitteilungen der Deutschen Gesellschaft für Pathologie.
Pub Date : 2024-03-01 DOI: 10.1007/s00292-024-01304-x
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引用次数: 0
Mitteilungen der Österreichischen Gesellschaft für Klinische Pathologie und Molekularpathologie. Mitteilungen der Österreichischen Gesellschaft für Klinische Pathologie und Molekularpathologie.
Pub Date : 2024-03-01 DOI: 10.1007/s00292-024-01301-0
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引用次数: 0
[Melanin bleaching-an (almost) forgotten technique]. 黑色素漂白——一种(几乎)被遗忘的技术。
Pub Date : 2024-03-01 Epub Date: 2023-11-23 DOI: 10.1007/s00292-023-01256-8
Antonia Herrmann, Kirsten Utpatel, Matthias Evert
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引用次数: 0
[Digital Pathology]. [数字病理学]
Pub Date : 2024-03-01 Epub Date: 2024-02-28 DOI: 10.1007/s00292-024-01306-9
Nadine Flinner, Peter Boor, Peter J Wild
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引用次数: 0
[Bone marrow histology of cytopenias : Contribution to hematological differential diagnosis]. [细胞减少症的骨髓组织学 :对血液学鉴别诊断的贡献]。
Pub Date : 2024-03-01 Epub Date: 2024-02-21 DOI: 10.1007/s00292-024-01302-z
Hans Kreipe

Besides microscopic evaluation of smears, flow cytometric analysis, chromosomal and molecular studies, histological analysis of bone marrow biopsies (BMbx) is an important component of multiparameter diagnostics of cytopenias in hematology. More than in other fields of histopathology, correct interpretation of BMbx requires correlation with the results of these further studies and other clinical findings. Microcytic, normocytic and macrocytic anemia, isolated granulocytopenia and thromobocytopenia as well as pancytopenia represent frequent and recurrent diseases. With regard to aetiology, reactive and neoplastic causes must be differentiated. Reactive causes of cytopenia include substrate deficiencies, enhanced turn over and loss, and inflammatory processes. Neoplastic disorders with the exception of myeloproliferative neoplasms generally manifest as cytopenia and comprise myelodysplastic syndromes (MDS), acute myeloid leukemia (AML) and lymphoma.

除了对涂片进行显微镜评估、流式细胞分析、染色体和分子研究外,骨髓活检组织学分析(BMbx)也是血液学中细胞减少症多参数诊断的重要组成部分。与组织病理学的其他领域相比,骨髓活检的正确解读更需要与这些进一步研究的结果和其他临床发现相关联。小红细胞性贫血、正常红细胞性贫血和大红细胞性贫血、孤立的粒细胞减少症和血栓性血小板减少症以及全血细胞减少症是常见病和多发病。关于病因,必须区分反应性病因和肿瘤性病因。反应性细胞减少症的病因包括底物缺乏、翻转和丢失增强以及炎症过程。肿瘤性疾病(骨髓增生性肿瘤除外)通常表现为全血细胞减少,包括骨髓增生异常综合征(MDS)、急性髓性白血病(AML)和淋巴瘤。
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引用次数: 0
[The model transferability of AI in digital pathology : Potential and reality]. [数字病理学中人工智能的模型可移植性:潜力与现实]。
Pub Date : 2024-03-01 Epub Date: 2024-02-19 DOI: 10.1007/s00292-024-01299-5
Robin S Mayer, Maximilian N Kinzler, Alexandra K Stoll, Steffen Gretser, Paul K Ziegler, Anna Saborowski, Henning Reis, Arndt Vogel, Peter J Wild, Nadine Flinner

Objective: Artificial intelligence (AI) holds the potential to make significant advancements in pathology. However, its actual implementation and certification for practical use are currently limited, often due to challenges related to model transferability. In this context, we investigate the factors influencing transferability and present methods aimed at enhancing the utilization of AI algorithms in pathology.

Materials and methods: Various convolutional neural networks (CNNs) and vision transformers (ViTs) were trained using datasets from two institutions, along with the publicly available TCGA-MIBC dataset. These networks conducted predictions in urothelial tissue and intrahepatic cholangiocarcinoma (iCCA). The objective was to illustrate the impact of stain normalization, the influence of various artifacts during both training and testing, as well as the effects of the NoisyEnsemble method.

Results: We were able to demonstrate that stain normalization of slides from different institutions has a significant positive effect on the inter-institutional transferability of CNNs and ViTs (respectively +13% and +10%). In addition, ViTs usually achieve a higher accuracy in the external test (here +1.5%). Similarly, we showcased how artifacts in test data can negatively affect CNN predictions and how incorporating these artifacts during training leads to improvements. Lastly, NoisyEnsembles of CNNs (better than ViTs) were shown to enhance transferability across different tissues and research questions (+7% Bladder, +15% iCCA).

Discussion: It is crucial to be aware of the transferability challenge: achieving good performance during development does not necessarily translate to good performance in real-world applications. The inclusion of existing methods to enhance transferability, such as stain normalization and NoisyEnsemble, and their ongoing refinement, is of importance.

目的:人工智能(AI)具有在病理学领域取得重大进展的潜力。然而,人工智能的实际应用和实际使用认证目前还很有限,这通常是由于与模型可移植性相关的挑战造成的。在此背景下,我们研究了影响可移植性的因素,并提出了旨在提高病理学中人工智能算法利用率的方法:使用来自两家机构的数据集以及公开可用的 TCGA-MIBC 数据集训练了各种卷积神经网络(CNN)和视觉转换器(ViT)。这些网络对尿道组织和肝内胆管癌(iCCA)进行了预测。目的是说明染色正常化的影响、训练和测试过程中各种伪影的影响以及 NoisyEnsemble 方法的效果:我们能够证明,对来自不同机构的切片进行染色归一化处理对 CNN 和 ViT 的机构间可转移性有显著的积极影响(分别为 +13% 和 +10%)。此外,ViT 在外部测试中通常能获得更高的准确率(此处为 +1.5%)。同样,我们还展示了测试数据中的人工痕迹如何对 CNN 预测产生负面影响,以及在训练过程中纳入这些人工痕迹如何带来改进。最后,CNN 的 NoisyEnsembles(优于 ViTs)被证明可提高不同组织和研究问题之间的可转移性(膀胱 +7%,iCCA +15%):意识到可转移性的挑战至关重要:在开发过程中取得良好性能并不一定能在实际应用中转化为良好性能。因此,将染色归一化和 NoisyEnsemble 等现有方法纳入其中以提高可移植性,并对其进行不断完善是非常重要的。
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引用次数: 0
期刊
Pathologie (Heidelberg, Germany)
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