@article{MeutenMooreDonovanetal.2021, author = {Meuten, Donald J. and Moore, Frances M. and Donovan, Taryn and Bertram, Christof and Klopfleisch, Robert and Foster, Robert A. and Smedley, Rebecca C. and Dark, Michael and Milovancev, Milan and Stromberg, Paul and Williams, Bruce H. and Aubreville, Marc and Avallone, Giancarlo and Bolfa, Pompei and Cullen, John and Dennis, Michelle M. and Goldschmidt, Michael and Luong, Richard and Miller, Andrew D. and Miller, Margaret A. and Munday, John S. and Roccabianca, Paola and Salas, Elisa N. and Schulman, F. Yvonne and Laufer-Amorim, Renee and Asakawa, Midori G. and Craig, Linden and Dervisis, Nick and Esplin, D. Glen and George, Jeanne W. and Hauck, Marlene and Kagawa, Yumiko and Kiupel, Matti and Linder, Keith and Meichner, Kristina and Marconato, Laura and Oblak, Michelle L. and Santos, Renato L. and Simpson, R. Mark and Tvedten, Harold and Whitley, Derick}, title = {International Guidelines for Veterinary Tumor Pathology: A Call to Action}, volume = {58}, journal = {Veterinary Pathology}, number = {5}, publisher = {Sage}, address = {London}, issn = {1544-2217}, doi = {https://doi.org/10.1177/03009858211013712}, pages = {766 -- 794}, year = {2021}, language = {en} } @unpublished{AubrevilleStathonikosDonovanetal.2023, author = {Aubreville, Marc and Stathonikos, Nikolas and Donovan, Taryn and Klopfleisch, Robert and Ganz, Jonathan and Ammeling, Jonas and Wilm, Frauke and Veta, Mitko and Jabari, Samir and Eckstein, Markus and Annuscheit, Jonas and Krumnow, Christian and Bozaba, Engin and Cayir, Sercan and Gu, Hongyan and Chen, Xiang and Jahanifar, Mostafa and Shephard, Adam and Kondo, Satoshi and Kasai, Satoshi and Kotte, Sujatha and Saipradeep, Vangala and Lafarge, Maxime W. and Koelzer, Viktor H. and Wang, Ziyue and Zhang, Yongbing and Yang, Sen and Wang, Xiyue and Breininger, Katharina and Bertram, Christof}, title = {Domain generalization across tumor types, laboratories, and species - Insights from the 2022 edition of the Mitosis Domain Generalization Challenge}, publisher = {arXiv}, address = {Ithaca}, doi = {https://doi.org/10.48550/arXiv.2309.15589}, year = {2023}, abstract = {Recognition of mitotic figures in histologic tumor specimens is highly relevant to patient outcome assessment. This task is challenging for algorithms and human experts alike, with deterioration of algorithmic performance under shifts in image representations. Considerable covariate shifts occur when assessment is performed on different tumor types, images are acquired using different digitization devices, or specimens are produced in different laboratories. This observation motivated the inception of the 2022 challenge on MItosis Domain Generalization (MIDOG 2022). The challenge provided annotated histologic tumor images from six different domains and evaluated the algorithmic approaches for mitotic figure detection provided by nine challenge participants on ten independent domains. Ground truth for mitotic figure detection was established in two ways: a three-expert consensus and an independent, immunohistochemistry-assisted set of labels. This work represents an overview of the challenge tasks, the algorithmic strategies employed by the participants, and potential factors contributing to their success. With an F1 score of 0.764 for the top-performing team, we summarize that domain generalization across various tumor domains is possible with today's deep learning-based recognition pipelines. When assessed against the immunohistochemistry-assisted reference standard, all methods resulted in reduced recall scores, but with only minor changes in the order of participants in the ranking.}, language = {en} } @unpublished{HaghoferParlakBarteletal.2023, author = {Haghofer, Andreas and Parlak, Eda and Bartel, Alexander and Donovan, Taryn and Assenmacher, Charles-Antoine and Bolfa, Pompei and Dark, Michael and Fuchs-Baumgartinger, Andrea and Klang, Andrea and J{\"a}ger, Kathrin and Klopfleisch, Robert and Merz, Sophie and Richter, Barbara and Schulman, F. Yvonne and Ganz, Jonathan and Scharinger, Josef and Aubreville, Marc and Winkler, Stephan M. and Kiupel, Matti and Bertram, Christof}, title = {Nuclear Morphometry using a Deep Learning-based Algorithm has Prognostic Relevance for Canine Cutaneous Mast Cell Tumors}, publisher = {arXiv}, address = {Ithaca}, doi = {https://doi.org/10.48550/arXiv.2309.15031}, year = {2023}, abstract = {Variation in nuclear size and shape is an important criterion of malignancy for many tumor types; however, categorical estimates by pathologists have poor reproducibility. Measurements of nuclear characteristics (morphometry) can improve reproducibility, but manual methods are time consuming. In this study, we evaluated fully automated morphometry using a deep learning-based algorithm in 96 canine cutaneous mast cell tumors with information on patient survival. Algorithmic morphometry was compared with karyomegaly estimates by 11 pathologists, manual nuclear morphometry of 12 cells by 9 pathologists, and the mitotic count as a benchmark. The prognostic value of automated morphometry was high with an area under the ROC curve regarding the tumor-specific survival of 0.943 (95\% CI: 0.889 - 0.996) for the standard deviation (SD) of nuclear area, which was higher than manual morphometry of all pathologists combined (0.868, 95\% CI: 0.737 - 0.991) and the mitotic count (0.885, 95\% CI: 0.765 - 1.00). At the proposed thresholds, the hazard ratio for algorithmic morphometry (SD of nuclear area ≥9.0μm2) was 18.3 (95\% CI: 5.0 - 67.1), for manual morphometry (SD of nuclear area ≥10.9μm2) 9.0 (95\% CI: 6.0 - 13.4), for karyomegaly estimates 7.6 (95\% CI: 5.7 - 10.1), and for the mitotic count 30.5 (95\% CI: 7.8 - 118.0). Inter-rater reproducibility for karyomegaly estimates was fair (κ = 0.226) with highly variable sensitivity/specificity values for the individual pathologists. Reproducibility for manual morphometry (SD of nuclear area) was good (ICC = 0.654). This study supports the use of algorithmic morphometry as a prognostic test to overcome the limitations of estimates and manual measurements.}, language = {en} } @unpublished{GanzMarzahlAmmelingetal.2024, author = {Ganz, Jonathan and Marzahl, Christian and Ammeling, Jonas and Richter, Barbara and Puget, Chlo{\´e} and Denk, Daniela and Demeter, Elena A. and Tabaran, Flaviu A. and Wasinger, Gabriel and Lipnik, Karoline and Tecilla, Marco and Valentine, Matthew J. and Dark, Michael and Abele, Niklas and Bolfa, Pompei and Erber, Ramona and Klopfleisch, Robert and Merz, Sophie and Donovan, Taryn and Jabari, Samir and Bertram, Christof and Breininger, Katharina and Aubreville, Marc}, title = {On the Value of PHH3 for Mitotic Figure Detection on H\&E-stained Images}, publisher = {arXiv}, address = {Ithaca}, doi = {https://doi.org/10.48550/arXiv.2406.19899}, year = {2024}, abstract = {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.}, language = {en} } @article{BertramAubrevilleGurtneretal.2020, author = {Bertram, Christof and Aubreville, Marc and Gurtner, Corinne and Bartel, Alexander and Corner, Sarah M. and Dettwiler, Martina and Kershaw, Olivia and Noland, Erica L. and Schmidt, Anja and Sledge, Dodd G. and Smedley, Rebecca C. and Thaiwong, Tuddow and Kiupel, Matti and Maier, Andreas and Klopfleisch, Robert}, title = {Computerized Calculation of Mitotic Count Distribution in Canine Cutaneous Mast Cell Tumor Sections: Mitotic Count Is Area Dependent}, volume = {57}, journal = {Veterinary Pathology}, number = {2}, publisher = {Sage}, address = {London}, issn = {1544-2217}, doi = {https://doi.org/10.1177/0300985819890686}, pages = {214 -- 226}, year = {2020}, language = {en} } @inproceedings{MarzahlAubrevilleBertrametal.2020, author = {Marzahl, Christian and Aubreville, Marc and Bertram, Christof and Gerlach, Stefan and Maier, Jennifer and Voigt, J{\"o}rn and Hill, Jenny and Klopfleisch, Robert and Maier, Andreas}, title = {Is crowd-algorithm collaboration an advanced alternative to crowd-sourcing on cytology slides?}, booktitle = {Bildverarbeitung f{\"u}r die Medizin 2020, Algorithmen - Systeme - Anwendungen. Proceedings des Workshops vom 15. bis 17. M{\"a}rz 2020 in Berlin}, editor = {Tolxdorff, Thomas and Deserno, Thomas Martin and Handels, Heinz and Maier, Andreas and Maier-Hein, Klaus H. and Palm, Christoph}, publisher = {Springer Vieweg}, address = {Wiesbaden}, isbn = {978-3-658-29266-9}, doi = {https://doi.org/10.1007/978-3-658-29267-6_5}, pages = {26 -- 31}, year = {2020}, language = {en} } @inproceedings{AubrevilleBertramJabarietal.2020, author = {Aubreville, Marc and Bertram, Christof and Jabari, Samir and Marzahl, Christian and Klopfleisch, Robert and Maier, Andreas}, title = {Inter-species, inter-tissue domain adaptation for mitotic figure assessment}, booktitle = {Bildverarbeitung f{\"u}r die Medizin 2020, Algorithmen - Systeme - Anwendungen. Proceedings des Workshops vom 15. bis 17. M{\"a}rz 2020 in Berlin}, subtitle = {learning new tricks from old dogs}, editor = {Tolxdorff, Thomas and Deserno, Thomas Martin and Handels, Heinz and Maier, Andreas and Maier-Hein, Klaus H. and Palm, Christoph}, publisher = {Springer Vieweg}, address = {Wiesbaden}, isbn = {978-3-658-29266-9}, doi = {https://doi.org/10.1007/978-3-658-29267-6_1}, pages = {1 -- 7}, year = {2020}, language = {en} } @inproceedings{GanzBertramKlopfleischetal.2022, author = {Ganz, Jonathan and Bertram, Christof and Klopfleisch, Robert and Jabari, Samir and Breininger, Katharina and Aubreville, Marc}, title = {Classification of visibility in multi-stain microscopy images}, booktitle = {Medical Imaging with Deep Learning: MIDL 2022 Short Papers}, url = {https://openreview.net/forum?id=-GsA-mUVmm}, year = {2022}, language = {en} } @unpublished{PugetGanzOstermaieretal.2024, author = {Puget, Chlo{\´e} and Ganz, Jonathan and Ostermaier, Julian and Konrad, Thomas and Parlak, Eda and Bertram, Christof and Kiupel, Matti and Breininger, Katharina and Aubreville, Marc and Klopfleisch, Robert}, title = {Deep Learning model predicts the c-Kit-11 mutational status of canine cutaneous mast cell tumors by HE stained histological slides}, publisher = {arXiv}, address = {Ithaca}, doi = {https://doi.org/10.48550/arXiv.2401.06169}, year = {2024}, abstract = {Numerous prognostic factors are currently assessed histopathologically in biopsies of canine mast cell tumors to evaluate clinical behavior. In addition, PCR analysis of the c-Kit exon 11 mutational status is often performed to evaluate the potential success of a tyrosine kinase inhibitor therapy. This project aimed at training deep learning models (DLMs) to identify the c-Kit-11 mutational status of MCTs solely based on morphology without additional molecular analysis. HE slides of 195 mutated and 173 non-mutated tumors were stained consecutively in two different laboratories and scanned with three different slide scanners. This resulted in six different datasets (stain-scanner variations) of whole slide images. DLMs were trained with single and mixed datasets and their performances was assessed under scanner and staining domain shifts. The DLMs correctly classified HE slides according to their c-Kit 11 mutation status in, on average, 87\% of cases for the best-suited stain-scanner variant. A relevant performance drop could be observed when the stain-scanner combination of the training and test dataset differed. Multi-variant datasets improved the average accuracy but did not reach the maximum accuracy of algorithms trained and tested on the same stain-scanner variant. In summary, DLM-assisted morphological examination of MCTs can predict c-Kit-exon 11 mutational status of MCTs with high accuracy. However, the recognition performance is impeded by a change of scanner or staining protocol. Larger data sets with higher numbers of scans originating from different laboratories and scanners may lead to more robust DLMs to identify c-Kit mutations in HE slides.}, language = {en} } @inproceedings{AubrevilleBertramKlopfleischetal.2019, author = {Aubreville, Marc and Bertram, Christof and Klopfleisch, Robert and Maier, Andreas}, title = {Field of Interest Proposal for Augmented Mitotic Cell Count}, volume = {2}, booktitle = {Proceedings of the 12th International Joint Conference on Biomedical Engineering Systems and Technologies - BIOIMAGING}, subtitle = {Comparison of Two Convolutional Networks}, publisher = {SciTePress}, address = {Set{\´u}bal}, isbn = {978-989-758-353-7}, issn = {2184-4305}, doi = {https://doi.org/10.5220/0007365700300037}, pages = {30 -- 37}, year = {2019}, language = {en} }