TY - JOUR A1 - Marzahl, Christian A1 - Aubreville, Marc A1 - Bertram, Christof A1 - Maier, Jennifer A1 - Bergler, Christian A1 - Kröger, Christine A1 - Voigt, Jörn A1 - Breininger, Katharina A1 - Klopfleisch, Robert A1 - Maier, Andreas T1 - EXACT: a collaboration toolset for algorithm-aided annotation of images with annotation version control JF - Scientific Reports N2 - In many research areas, scientific progress is accelerated by multidisciplinary access to image data and their interdisciplinary annotation. However, keeping track of these annotations to ensure a high-quality multi-purpose data set is a challenging and labour intensive task. We developed the open-source online platform EXACT (EXpert Algorithm Collaboration Tool) that enables the collaborative interdisciplinary analysis of images from different domains online and offline. EXACT supports multi-gigapixel medical whole slide images as well as image series with thousands of images. The software utilises a flexible plugin system that can be adapted to diverse applications such as counting mitotic figures with a screening mode, finding false annotations on a novel validation view, or using the latest deep learning image analysis technologies. This is combined with a version control system which makes it possible to keep track of changes in the data sets and, for example, to link the results of deep learning experiments to specific data set versions. EXACT is freely available and has already been successfully applied to a broad range of annotation tasks, including highly diverse applications like deep learning supported cytology scoring, interdisciplinary multi-centre whole slide image tumour annotation, and highly specialised whale sound spectroscopy clustering. UR - https://doi.org/10.1038/s41598-021-83827-4 Y1 - 2021 UR - https://doi.org/10.1038/s41598-021-83827-4 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-10943 SN - 2045-2322 VL - 11 PB - Springer Nature CY - London ER - TY - INPR A1 - Ganz, Jonathan A1 - Marzahl, Christian A1 - Ammeling, Jonas A1 - Richter, Barbara A1 - Puget, Chloé A1 - Denk, Daniela A1 - Demeter, Elena A. A1 - Tabaran, Flaviu A. A1 - Wasinger, Gabriel A1 - Lipnik, Karoline A1 - Tecilla, Marco A1 - Valentine, Matthew J. A1 - Dark, Michael A1 - Abele, Niklas A1 - Bolfa, Pompei A1 - Erber, Ramona A1 - Klopfleisch, Robert A1 - Merz, Sophie A1 - Donovan, Taryn A1 - Jabari, Samir A1 - Bertram, Christof A1 - Breininger, Katharina A1 - Aubreville, Marc T1 - On the Value of PHH3 for Mitotic Figure Detection on H&E-stained Images N2 - The count of mitotic figures (MFs) observed in hematoxylin and eosin (H&E)-stained slides is an important prognostic marker as it is a measure for tumor cell proliferation. However, the identification of MFs has a known low inter-rater agreement. Deep learning algorithms can standardize this task, but they require large amounts of annotated data for training and validation. Furthermore, label noise introduced during the annotation process may impede the algorithm's performance. Unlike H&E, the mitosis-specific antibody phospho-histone H3 (PHH3) specifically highlights MFs. Counting MFs on slides stained against PHH3 leads to higher agreement among raters and has therefore recently been used as a ground truth for the annotation of MFs in H&E. However, as PHH3 facilitates the recognition of cells indistinguishable from H&E stain alone, the use of this ground truth could potentially introduce noise into the H&E-related dataset, impacting model performance. This study analyzes the impact of PHH3-assisted MF annotation on inter-rater reliability and object level agreement through an extensive multi-rater experiment. We found that the annotators' object-level agreement increased when using PHH3-assisted labeling. Subsequently, MF detectors were evaluated on the resulting datasets to investigate the influence of PHH3-assisted labeling on the models' performance. Additionally, a novel dual-stain MF detector was developed to investigate the interpretation-shift of PHH3-assisted labels used in H&E, which clearly outperformed single-stain detectors. However, the PHH3-assisted labels did not have a positive effect on solely H&E-based models. The high performance of our dual-input detector reveals an information mismatch between the H&E and PHH3-stained images as the cause of this effect. UR - https://doi.org/10.48550/arXiv.2406.19899 Y1 - 2024 UR - https://doi.org/10.48550/arXiv.2406.19899 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-50155 PB - arXiv CY - Ithaca ER - TY - CHAP A1 - Marzahl, Christian A1 - Aubreville, Marc A1 - Bertram, Christof A1 - Gerlach, Stefan A1 - Maier, Jennifer A1 - Voigt, Jörn A1 - Hill, Jenny A1 - Klopfleisch, Robert A1 - Maier, Andreas ED - Tolxdorff, Thomas ED - Deserno, Thomas Martin ED - Handels, Heinz ED - Maier, Andreas ED - Maier-Hein, Klaus H. ED - Palm, Christoph T1 - Is crowd-algorithm collaboration an advanced alternative to crowd-sourcing on cytology slides? T2 - Bildverarbeitung für die Medizin 2020, Algorithmen – Systeme – Anwendungen. Proceedings des Workshops vom 15. bis 17. März 2020 in Berlin UR - https://doi.org/10.1007/978-3-658-29267-6_5 Y1 - 2020 UR - https://doi.org/10.1007/978-3-658-29267-6_5 SN - 978-3-658-29266-9 SN - 978-3-658-29267-6 N1 - Access to this content is enabled by Nationallizenz Ebooks Medicine SP - 26 EP - 31 PB - Springer Vieweg CY - Wiesbaden ER - TY - CHAP A1 - Aubreville, Marc A1 - Bertram, Christof A1 - Jabari, Samir A1 - Marzahl, Christian A1 - Klopfleisch, Robert A1 - Maier, Andreas ED - Tolxdorff, Thomas ED - Deserno, Thomas Martin ED - Handels, Heinz ED - Maier, Andreas ED - Maier-Hein, Klaus H. ED - Palm, Christoph T1 - Inter-species, inter-tissue domain adaptation for mitotic figure assessment BT - learning new tricks from old dogs T2 - Bildverarbeitung für die Medizin 2020, Algorithmen – Systeme – Anwendungen. Proceedings des Workshops vom 15. bis 17. März 2020 in Berlin UR - https://doi.org/10.1007/978-3-658-29267-6_1 Y1 - 2020 UR - https://doi.org/10.1007/978-3-658-29267-6_1 SN - 978-3-658-29266-9 SN - 978-3-658-29267-6 N1 - Access to this content is enabled by Nationallizenz Ebooks Medicine SP - 1 EP - 7 PB - Springer Vieweg CY - Wiesbaden ER - TY - JOUR A1 - Bertram, Christof A1 - Aubreville, Marc A1 - Donovan, Taryn A1 - Bartel, Alexander A1 - Wilm, Frauke A1 - Marzahl, Christian A1 - Assenmacher, Charles-Antoine A1 - Becker, Kathrin A1 - Bennett, Mark A1 - Corner, Sarah M. A1 - Cossic, Brieuc A1 - Denk, Daniela A1 - Dettwiler, Martina A1 - Garcia Gonzalez, Beatriz A1 - Gurtner, Corinne A1 - Haverkamp, Ann-Kathrin A1 - Heier, Annabelle A1 - Lehmbecker, Annika A1 - Merz, Sophie A1 - Noland, Erica L. A1 - Plog, Stephanie A1 - Schmidt, Anja A1 - Sebastian, Franziska A1 - Sledge, Dodd G. A1 - Smedley, Rebecca C. A1 - Tecilla, Marco A1 - Thaiwong, Tuddow A1 - Fuchs-Baumgartinger, Andrea A1 - Meuten, Donald J. A1 - Breininger, Katharina A1 - Kiupel, Matti A1 - Maier, Andreas A1 - Klopfleisch, Robert T1 - Computer-assisted mitotic count using a deep learning–based algorithm improves interobserver reproducibility and accuracy JF - Veterinary Pathology N2 - The mitotic count (MC) is an important histological parameter for prognostication of malignant neoplasms. However, it has inter- and intraobserver discrepancies due to difficulties in selecting the region of interest (MC-ROI) and in identifying or classifying mitotic figures (MFs). Recent progress in the field of artificial intelligence has allowed the development of high-performance algorithms that may improve standardization of the MC. As algorithmic predictions are not flawless, computer-assisted review by pathologists may ensure reliability. In the present study, we compared partial (MC-ROI preselection) and full (additional visualization of MF candidates and display of algorithmic confidence values) computer-assisted MC analysis to the routine (unaided) MC analysis by 23 pathologists for whole-slide images of 50 canine cutaneous mast cell tumors (ccMCTs). Algorithmic predictions aimed to assist pathologists in detecting mitotic hotspot locations, reducing omission of MFs, and improving classification against imposters. The interobserver consistency for the MC significantly increased with computer assistance (interobserver correlation coefficient, ICC = 0.92) compared to the unaided approach (ICC = 0.70). Classification into prognostic stratifications had a higher accuracy with computer assistance. The algorithmically preselected hotspot MC-ROIs had a consistently higher MCs than the manually selected MC-ROIs. Compared to a ground truth (developed with immunohistochemistry for phosphohistone H3), pathologist performance in detecting individual MF was augmented when using computer assistance (F1-score of 0.68 increased to 0.79) with a reduction in false negatives by 38%. The results of this study demonstrate that computer assistance may lead to more reproducible and accurate MCs in ccMCTs. UR - https://doi.org/10.1177/03009858211067478 KW - canine cutaneous mast cell tumors KW - artificial intelligence KW - digital pathology KW - deep learning KW - mitotic figures KW - mitotic count KW - automated image analysis KW - computer assistance Y1 - 2021 UR - https://doi.org/10.1177/03009858211067478 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-13141 SN - 1544-2217 VL - 59 IS - 2 SP - 211 EP - 226 PB - Sage CY - London ER - TY - JOUR A1 - Marzahl, Christian A1 - Aubreville, Marc A1 - Bertram, Christof A1 - Stayt, Jason A1 - Jasensky, Anne-Katherine A1 - Bartenschlager, Florian A1 - Fragoso-Garcia, Marco A1 - Barton, Ann K. A1 - Elsemann, Svenja A1 - Jabari, Samir A1 - Krauth, Jens A1 - Madhu, Prathmesh A1 - Voigt, Jörn A1 - Hill, Jenny A1 - Klopfleisch, Robert A1 - Maier, Andreas T1 - Deep Learning-based quantification of pulmonary hemosiderophages in cytology slides JF - Scientific Reports N2 - Exercise-induced pulmonary hemorrhage (EIPH) is a common condition in sport horses with negative impact on performance. Cytology of bronchoalveolar lavage fluid by use of a scoring system is considered the most sensitive diagnostic method. Macrophages are classified depending on the degree of cytoplasmic hemosiderin content. The current gold standard is manual grading, which is however monotonous and time-consuming. We evaluated state-of-the-art deep learning-based methods for single cell macrophage classification and compared them against the performance of nine cytology experts and evaluated inter- and intra-observer variability. Additionally, we evaluated object detection methods on a novel data set of 17 completely annotated cytology whole slide images (WSI) containing 78,047 hemosiderophages. Our deep learning-based approach reached a concordance of 0.85, partially exceeding human expert concordance (0.68 to 0.86, mean of 0.73, SD of 0.04). Intra-observer variability was high (0.68 to 0.88) and inter-observer concordance was moderate (Fleiss’ kappa = 0.67). Our object detection approach has a mean average precision of 0.66 over the five classes from the whole slide gigapixel image and a computation time of below two minutes. To mitigate the high inter- and intra-rater variability, we propose our automated object detection pipeline, enabling accurate, reproducible and quick EIPH scoring in WSI. UR - https://doi.org/10.1038/s41598-020-65958-2 Y1 - 2020 UR - https://doi.org/10.1038/s41598-020-65958-2 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-11783 SN - 2045-2322 VL - 10 PB - Springer Nature CY - London ER - TY - CHAP A1 - Marzahl, Christian A1 - Wilm, Frauke A1 - Tharun, Lars A1 - Perner, Sven A1 - Kröger, Christine A1 - Voigt, Jörn A1 - Klopfleisch, Robert A1 - Maier, Andreas A1 - Aubreville, Marc A1 - Breininger, Katharina T1 - Robust quad-tree based registration on whole slide images T2 - Proceedings of Machine Learning Research: Proceedings of COMPAY 2021 KW - Registration KW - Microscopy KW - Pathology Y1 - 2021 UR - https://proceedings.mlr.press/v156/marzahl21a.html IS - 156 SP - 181 EP - 190 PB - PMLR CY - [s. l.] ER - TY - INPR A1 - Ganz, Jonathan A1 - Marzahl, Christian A1 - Ammeling, Jonas A1 - Rosbach, Emely A1 - Richter, Barbara A1 - Puget, Chloé A1 - Denk, Daniela A1 - Demeter, Elena A. A1 - Tabaran, Flaviu A. A1 - Wasinger, Gabriel A1 - Lipnik, Karoline A1 - Tecilla, Marco A1 - Valentine, Matthew J. A1 - Dark, Michael A1 - Abele, Niklas A1 - Bolfa, Pompei A1 - Erber, Ramona A1 - Klopfleisch, Robert A1 - Merz, Sophie A1 - Donovan, Taryn A1 - Jabari, Samir A1 - Bertram, Christof A1 - Breininger, Katharina A1 - Aubreville, Marc T1 - Information Mismatch in PHH3-Assisted Mitosis Annotation Leads to Interpretation Shifts in H&E Slide Analysis T2 - Research Square N2 - The count of mitotic figures (MFs) observed in hematoxylin and eosin (H&E)-stained slides is an important prognostic marker, as it is a measure for tumor cell proliferation. However, the identification of MFs has a known low inter-rater agreement. In a computer-aided setting, deep learning algorithms can help to mitigate this, but they require large amounts of annotated data for training and validation. Furthermore, label noise introduced during the annotation process may impede the algorithms' performance. Unlike H&E, where identification of MFs is based mainly on morphological features, the mitosis-specific antibody phospho-histone H3 (PHH3) specifically highlights MFs. Counting MFs on slides stained against PHH3 leads to higher agreement among raters and has therefore recently been used as a ground truth for the annotation of MFs in H&E. However, as PHH3 facilitates the recognition of cells indistinguishable from H&E staining alone, the use of this ground truth could potentially introduce an interpretation shift and even label noise into the H&E-related dataset, impacting model performance. This study analyzes the impact of PHH3-assisted MF annotation on inter-rater reliability and object level agreement through an extensive multi-rater experiment. Subsequently, MF detectors, including a novel dual-stain detector, were evaluated on the resulting datasets to investigate the influence of PHH3-assisted labeling on the models' performance. We found that the annotators' object-level agreement significantly increased when using PHH3-assisted labeling (F1: 0.53 to 0.74). However, this enhancement in label consistency did not translate to improved performance for H&E-based detectors, neither during the training phase nor the evaluation phase. Conversely, the dual-stain detector was able to benefit from the higher consistency. This reveals an information mismatch between the H&E and PHH3-stained images as the cause of this effect, which renders PHH3-assisted annotations not well-aligned for use with H&E-based detectors. Based on our findings, we propose an improved PHH3-assisted labeling procedure. UR - https://doi.org/10.21203/rs.3.rs-4900505/v1 Y1 - 2024 UR - https://doi.org/10.21203/rs.3.rs-4900505/v1 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-57630 SN - 2693-5015 PB - Research Square CY - Durham ER - TY - JOUR A1 - Aubreville, Marc A1 - Bertram, Christof A1 - Marzahl, Christian A1 - Gurtner, Corinne A1 - Dettwiler, Martina A1 - Schmidt, Anja A1 - Bartenschlager, Florian A1 - Merz, Sophie A1 - Fragoso-Garcia, Marco A1 - Kershaw, Olivia A1 - Klopfleisch, Robert A1 - Maier, Andreas T1 - Deep learning algorithms out-perform veterinary pathologists in detecting the mitotically most active tumor region JF - Scientific reports N2 - Manual count of mitotic figures, which is determined in the tumor region with the highest mitotic activity, is a key parameter of most tumor grading schemes. It can be, however, strongly dependent on the area selection due to uneven mitotic figure distribution in the tumor section. We aimed to assess the question, how significantly the area selection could impact the mitotic count, which has a known high inter-rater disagreement. On a data set of 32 whole slide images of H&E-stained canine cutaneous mast cell tumor, fully annotated for mitotic figures, we asked eight veterinary pathologists (five board-certified, three in training) to select a field of interest for the mitotic count. To assess the potential difference on the mitotic count, we compared the mitotic count of the selected regions to the overall distribution on the slide. Additionally, we evaluated three deep learning-based methods for the assessment of highest mitotic density: In one approach, the model would directly try to predict the mitotic count for the presented image patches as a regression task. The second method aims at deriving a segmentation mask for mitotic figures, which is then used to obtain a mitotic density. Finally, we evaluated a two-stage object-detection pipeline based on state-of-the-art architectures to identify individual mitotic figures. We found that the predictions by all models were, on average, better than those of the experts. The two-stage object detector performed best and outperformed most of the human pathologists on the majority of tumor cases. The correlation between the predicted and the ground truth mitotic count was also best for this approach (0.963–0.979). Further, we found considerable differences in position selection between pathologists, which could partially explain the high variance that has been reported for the manual mitotic count. To achieve better inter-rater agreement, we propose to use a computer-based area selection for support of the pathologist in the manual mitotic count. UR - https://doi.org/10.1038/s41598-020-73246-2 Y1 - 2020 UR - https://doi.org/10.1038/s41598-020-73246-2 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-11794 SN - 2045-2322 VL - 10 PB - Springer Nature CY - London ER - TY - CHAP A1 - Marzahl, Christian A1 - Bertram, Christof A1 - Aubreville, Marc A1 - Petrick, Anne A1 - Weiler, Kristina A1 - Gläsel, Agnes C. A1 - Fragoso-Garcia, Marco A1 - Merz, Sophie A1 - Bartenschlager, Florian A1 - Hoppe, Judith A1 - Langenhagen, Alina A1 - Jasensky, Anne-Katherine A1 - Voigt, Jörn A1 - Klopfleisch, Robert A1 - Maier, Andreas T1 - Are Fast Labeling Methods Reliable? A Case Study of Computer-Aided Expert Annotations on Microscopy Slides T2 - Medical Image Computing and Computer Assisted Intervention – MICCAI 2020 UR - https://doi.org/10.1007/978-3-030-59710-8_3 KW - Pathology KW - Microscopy KW - Computer-aided labelling KW - Expert-algorithm collaboration Y1 - 2020 UR - https://doi.org/10.1007/978-3-030-59710-8_3 SN - 978-3-030-59710-8 SN - 1611-3349 SP - 24 EP - 32 PB - Springer CY - Cham ER - TY - CHAP A1 - Marzahl, Christian A1 - Aubreville, Marc A1 - Voigt, Jörn A1 - Maier, Andreas T1 - Classification of leukemic b-lymphoblast cells from blood smear microscopic images with an attention-based deep learning method and advanced augmentation techniques T2 - ISBI 2019 C-NMC challenge: classification in cancer cell imaging UR - https://doi.org/10.1007/978-981-15-0798-4_2 Y1 - 2019 UR - https://doi.org/10.1007/978-981-15-0798-4_2 SN - 978-981-15-0797-7 SN - 978-981-15-0798-4 SN - 978-981-15-0800-4 SN - 2195-271X SN - 2195-2728 SP - 13 EP - 22 PB - Springer CY - Singapore ER - TY - CHAP A1 - Bertram, Christof A1 - Veta, Mitko A1 - Marzahl, Christian A1 - Stathonikos, Nikolas A1 - Maier, Andreas A1 - Klopfleisch, Robert A1 - Aubreville, Marc T1 - Are Pathologist-Defined Labels Reproducible? Comparison of the TUPAC16 Mitotic Figure Dataset with an Alternative Set of Labels T2 - Interpretable and Annotation-Efficient Learning for Medical Image Computing UR - https://doi.org/10.1007/978-3-030-61166-8_22 KW - Breast cancer KW - Mitotic figures KW - Computer-aided annotation KW - Deep learning Y1 - 2020 UR - https://doi.org/10.1007/978-3-030-61166-8_22 SN - 978-3-030-61166-8 SN - 1611-3349 SP - 204 EP - 213 PB - Springer CY - Cham ER - TY - JOUR A1 - Ganz, Jonathan A1 - Marzahl, Christian A1 - Ammeling, Jonas A1 - Rosbach, Emely A1 - Richter, Barbara A1 - Puget, Chloé A1 - Denk, Daniela A1 - Demeter, Elena A. A1 - Tabaran, Flaviu A. A1 - Wasinger, Gabriel A1 - Lipnik, Karoline A1 - Tecilla, Marco A1 - Valentine, Matthew J. A1 - Dark, Michael A1 - Abele, Niklas A1 - Bolfa, Pompei A1 - Erber, Ramona A1 - Klopfleisch, Robert A1 - Merz, Sophie A1 - Donovan, Taryn A1 - Jabari, Samir A1 - Bertram, Christof A1 - Breininger, Katharina A1 - Aubreville, Marc T1 - Information mismatch in PHH3-assisted mitosis annotation leads to interpretation shifts in H&E slide analysis JF - Scientific Reports N2 - The count of mitotic figures (MFs) observed in hematoxylin and eosin (H&E)-stained slides is an important prognostic marker, as it is a measure for tumor cell proliferation. However, the identification of MFs has a known low inter-rater agreement. In a computer-aided setting, deep learning algorithms can help to mitigate this, but they require large amounts of annotated data for training and validation. Furthermore, label noise introduced during the annotation process may impede the algorithms’ performance. Unlike H&E, where identification of MFs is based mainly on morphological features, the mitosis-specific antibody phospho-histone H3 (PHH3) specifically highlights MFs. Counting MFs on slides stained against PHH3 leads to higher agreement among raters and has therefore recently been used as a ground truth for the annotation of MFs in H&E. However, as PHH3 facilitates the recognition of cells indistinguishable from H&E staining alone, the use of this ground truth could potentially introduce an interpretation shift and even label noise into the H&E-related dataset, impacting model performance. This study analyzes the impact of PHH3-assisted MF annotation on inter-rater reliability and object level agreement through an extensive multi-rater experiment. Subsequently, MF detectors, including a novel dual-stain detector, were evaluated on the resulting datasets to investigate the influence of PHH3-assisted labeling on the models’ performance. We found that the annotators’ object-level agreement significantly increased when using PHH3-assisted labeling (F1: 0.53 to 0.74). However, this enhancement in label consistency did not translate to improved performance for H&E-based detectors, neither during the training phase nor the evaluation phase. Conversely, the dual-stain detector was able to benefit from the higher consistency. This reveals an information mismatch between the H&E and PHH3-stained images as the cause of this effect, which renders PHH3-assisted annotations not well-aligned for use with H&E-based detectors. Based on our findings, we propose an improved PHH3-assisted labeling procedure. UR - https://doi.org/10.1038/s41598-024-77244-6 Y1 - 2024 UR - https://doi.org/10.1038/s41598-024-77244-6 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-53559 SN - 2045-2322 VL - 14 IS - 1 PB - Springer Nature CY - London ER - TY - JOUR A1 - Fragoso-Garcia, Marco A1 - Wilm, Frauke A1 - Bertram, Christof A1 - Merz, Sophie A1 - Schmidt, Anja A1 - Donovan, Taryn A1 - Fuchs-Baumgartinger, Andrea A1 - Bartel, Alexander A1 - Marzahl, Christian A1 - Diehl, Laura A1 - Puget, Chloe A1 - Maier, Andreas A1 - Aubreville, Marc A1 - Breininger, Katharina A1 - Klopfleisch, Robert T1 - Automated diagnosis of 7 canine skin tumors using machine learning on H&E-stained whole slide images JF - Veterinary Pathology N2 - Microscopic evaluation of hematoxylin and eosin-stained slides is still the diagnostic gold standard for a variety of diseases, including neoplasms. Nevertheless, intra- and interrater variability are well documented among pathologists. So far, computer assistance via automated image analysis has shown potential to support pathologists in improving accuracy and reproducibility of quantitative tasks. In this proof of principle study, we describe a machine-learning-based algorithm for the automated diagnosis of 7 of the most common canine skin tumors: trichoblastoma, squamous cell carcinoma, peripheral nerve sheath tumor, melanoma, histiocytoma, mast cell tumor, and plasmacytoma. We selected, digitized, and annotated 350 hematoxylin and eosin-stained slides (50 per tumor type) to create a database divided into training, n = 245 whole-slide images (WSIs), validation ( n = 35 WSIs), and test sets ( n = 70 WSIs). Full annotations included the 7 tumor classes and 6 normal skin structures. The data set was used to train a convolutional neural network (CNN) for the automatic segmentation of tumor and nontumor classes. Subsequently, the detected tumor regions were classified patch-wise into 1 of the 7 tumor classes. A majority of patches-approach led to a tumor classification accuracy of the network on the slide-level of 95% (133/140 WSIs), with a patch-level precision of 85%. The same 140 WSIs were provided to 6 experienced pathologists for diagnosis, who achieved a similar slide-level accuracy of 98% (137/140 correct majority votes). Our results highlight the feasibility of artificial intelligence-based methods as a support tool in diagnostic oncologic pathology with future applications in other species and tumor types. UR - https://doi.org/10.1177/03009858231189205 KW - computer-aided diagnosis KW - computational pathology KW - digital pathology KW - dog KW - machine learning KW - skin KW - veterinary oncology Y1 - 2023 UR - https://doi.org/10.1177/03009858231189205 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-38321 SN - 0300-9858 VL - 60 IS - 6 SP - 865 EP - 875 PB - Sage CY - London ER - TY - JOUR A1 - Aubreville, Marc A1 - Stathonikos, Nikolas A1 - Bertram, Christof A1 - Klopfleisch, Robert A1 - Hoeve, Natalie ter A1 - Ciompi, Francesco A1 - Wilm, Frauke A1 - Marzahl, Christian A1 - Donovan, Taryn A1 - Maier, Andreas A1 - Breen, Jack A1 - Ravikumar, Nishant A1 - Chung, Youjin A1 - Park, Jinah A1 - Nateghi, Ramin A1 - Pourakpour, Fattaneh A1 - Fick, Rutger H. J. A1 - Ben Hadj, Saima A1 - Jahanifar, Mostafa A1 - Shepard, Adam A1 - Dexl, Jakob A1 - Wittenberg, Thomas A1 - Kondo, Satoshi A1 - Lafarge, Maxime W. A1 - Kolezer, Viktor H. A1 - Liang, Jingtang A1 - Wang, Yubo A1 - Long, Xi A1 - Liu, Jingxin A1 - Razavi, Salar A1 - Khademi, April A1 - Yang, Sen A1 - Wang, Xiyue A1 - Erber, Ramona A1 - Klang, Andrea A1 - Lipnik, Karoline A1 - Bolfa, Pompei A1 - Dark, Michael A1 - Wasinger, Gabriel A1 - Veta, Mitko A1 - Breininger, Katharina T1 - Mitosis domain generalization in histopathology images — The MIDOG challenge JF - Medical Image Analysis UR - https://doi.org/10.1016/j.media.2022.102699 KW - Domain generalization KW - Histopathology KW - Challenge KW - Deep Learning KW - Mitosis Y1 - 2022 UR - https://doi.org/10.1016/j.media.2022.102699 SN - 1361-8423 SN - 1361-8415 VL - 2023 IS - 84 PB - Elsevier CY - Amsterdam ER - TY - CHAP A1 - Theelke, Luisa A1 - Wilm, Frauke A1 - Marzahl, Christian A1 - Bertram, Christof A1 - Klopfleisch, Robert A1 - Maier, Andreas A1 - Aubreville, Marc A1 - Breininger, Katharina T1 - Iterative Cross-Scanner Registration for Whole Slide Images T2 - 2021 IEEE/CVF International Conference on Computer Vision Workshops (ICCVW) UR - https://doi.org/10.1109/ICCVW54120.2021.00071 KW - Pathology KW - Computer vision KW - Image resolution KW - Microscopy KW - Conferences KW - Estimation KW - Registers Y1 - 2021 UR - https://doi.org/10.1109/ICCVW54120.2021.00071 SN - 978-1-6654-0191-3 SN - 2473-9944 N1 - Eine frei zugängliche Version ist veröffentlicht unter: https://openaccess.thecvf.com/content/ICCV2021W/CDPath/html/Theelke_Iterative_Cross-Scanner_Registration_for_Whole_Slide_Images_ICCVW_2021_paper.html SP - 582 EP - 590 PB - IEEE CY - Piscataway ER - TY - CHAP A1 - Aubreville, Marc A1 - Bertram, Christof A1 - Stathonikos, Nikolas A1 - ter Hoeve, Natalie A1 - Ciompi, Francesco A1 - Klopfleisch, Robert A1 - Veta, Mitko A1 - Donovan, Taryn A1 - Marzahl, Christian A1 - Wilm, Frauke A1 - Breininger, Katharina A1 - Maier, Andreas T1 - Quantifying the Scanner-Induced Domain Gap in Mitosis Detection T2 - MIDL: Medical Imaging with Deep Learning 2021 Y1 - 2021 UR - https://2021.midl.io/papers/i6 PB - MIDL Foundation CY - Nijmegen ER - TY - CHAP A1 - Wilm, Frauke A1 - Marzahl, Christian A1 - Breininger, Katharina A1 - Aubreville, Marc ED - Aubreville, Marc ED - Zimmerer, David ED - Heinrich, Mattias T1 - Domain Adversarial RetinaNet as a Reference Algorithm for the MItosis DOmain Generalization Challenge T2 - Biomedical Image Registration, Domain Generalisation and Out-of-Distribution Analysis : MICCAI 2021 Challenges UR - https://doi.org/10.1007/978-3-030-97281-3_1 Y1 - 2022 UR - https://doi.org/10.1007/978-3-030-97281-3_1 SN - 978-3-030-97281-3 SP - 5 EP - 13 PB - Springer CY - Cham ER - TY - JOUR A1 - Bertram, Christof A1 - Marzahl, Christian A1 - Bartel, Alexander A1 - Stayt, Jason A1 - Bonsembiante, Federico A1 - Beeler-Marfisi, Janet A1 - Barton, Ann K. A1 - Brocca, Ginevra A1 - Gelain, Maria Elena A1 - Gläsel, Agnes C. A1 - du Preez, Kelly A1 - Weiler, Kristina A1 - Weissenbacher-Lang, Christiane A1 - Breininger, Katharina A1 - Aubreville, Marc A1 - Maier, Andreas A1 - Klopfleisch, Robert A1 - Hill, Jenny T1 - Cytologic scoring of equine exercise-induced pulmonary hemorrhage: Performance of human experts and a deep learning-based algorithm JF - Veterinary Pathology N2 - Exercise-induced pulmonary hemorrhage (EIPH) is a relevant respiratory disease in sport horses, which can be diagnosed by examination of bronchoalveolar lavage fluid (BALF) cells using the total hemosiderin score (THS). The aim of this study was to evaluate the diagnostic accuracy and reproducibility of annotators and to validate a deep learning-based algorithm for the THS. Digitized cytological specimens stained for iron were prepared from 52 equine BALF samples. Ten annotators produced a THS for each slide according to published methods. The reference methods for comparing annotator’s and algorithmic performance included a ground truth dataset, the mean annotators’ THSs, and chemical iron measurements. Results of the study showed that annotators had marked interobserver variability of the THS, which was mostly due to a systematic error between annotators in grading the intracytoplasmatic hemosiderin content of individual macrophages. Regarding overall measurement error between the annotators, 87.7% of the variance could be reduced by using standardized grades based on the ground truth. The algorithm was highly consistent with the ground truth in assigning hemosiderin grades. Compared with the ground truth THS, annotators had an accuracy of diagnosing EIPH (THS of < or ≥ 75) of 75.7%, whereas, the algorithm had an accuracy of 92.3% with no relevant differences in correlation with chemical iron measurements. The results show that deep learning-based algorithms are useful for improving reproducibility and routine applicability of the THS. For THS by experts, a diagnostic uncertainty interval of 40 to 110 is proposed. THSs within this interval have insufficient reproducibility regarding the EIPH diagnosis. UR - https://doi.org/10.1177/03009858221137582 KW - artificial intelligence KW - automated image analysis KW - bronchoalveolar lavage fluid KW - computational pathology KW - digital pathology KW - equine KW - pulmonary hemorrhage KW - respiratory disease KW - total hemosiderin score Y1 - 2022 UR - https://doi.org/10.1177/03009858221137582 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-35196 SN - 1544-2217 VL - 60 IS - 1 SP - 75 EP - 85 PB - Sage CY - London ER - TY - CHAP A1 - Wilm, Frauke A1 - Bertram, Christof A1 - Marzahl, Christian A1 - Bartel, Alexander A1 - Donovan, Taryn A1 - Assenmacher, Charles-Antoine A1 - Becker, Kathrin A1 - Bennett, Mark A1 - Corner, Sarah M. A1 - Cossic, Brieuc A1 - Denk, Daniela A1 - Dettwiler, Martina A1 - Garcia Gonzalez, Beatriz A1 - Gurtner, Corinne A1 - Heier, Annabelle A1 - Lehmbecker, Annika A1 - Merz, Sophie A1 - Plog, Stephanie A1 - Schmidt, Anja A1 - Sebastian, Franziska A1 - Smedley, Rebecca C. A1 - Tecilla, Marco A1 - Thaiwong, Tuddow A1 - Breininger, Katharina A1 - Kiupel, Matti A1 - Maier, Andreas A1 - Klopfleisch, Robert A1 - Aubreville, Marc T1 - Influence of inter-annotator variability on automatic mitotic figure assessment T2 - Bildverarbeitung für die Medizin 2021 UR - https://doi.org/10.1007/978-3-658-33198-6_56 Y1 - 2021 UR - https://doi.org/10.1007/978-3-658-33198-6_56 SN - 978-3-658-33198-6 SP - 241 EP - 246 PB - Springer CY - Wiesbaden ER -