TY - JOUR A1 - Haghofer, Andreas A1 - Parlak, Eda A1 - Bartel, Alexander A1 - Donovan, Taryn A1 - Assenmacher, Charles-Antoine A1 - Bolfa, Pompei A1 - Dark, Michael A1 - Fuchs-Baumgartinger, Andrea A1 - Klang, Andrea A1 - Jäger, Kathrin A1 - Klopfleisch, Robert A1 - Merz, Sophie A1 - Richter, Barbara A1 - Schulman, F. Yvonne A1 - Janout, Hannah A1 - Ganz, Jonathan A1 - Scharinger, Josef A1 - Aubreville, Marc A1 - Winkler, Stephan M. A1 - Kiupel, Matti A1 - Bertram, Christof T1 - Nuclear pleomorphism in canine cutaneous mast cell tumors: Comparison of reproducibility and prognostic relevance between estimates, manual morphometry, and algorithmic morphometry JF - Veterinary Pathology N2 - 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 can improve reproducibility, but current manual methods are time-consuming. The aim of this study was to explore the limitations of estimates and develop alternative morphometric solutions for canine cutaneous mast cell tumors (ccMCTs). We assessed the following nuclear evaluation methods for accuracy, reproducibility, and prognostic utility: (1) anisokaryosis estimates by 11 pathologists; (2) gold standard manual morphometry of at least 100 nuclei; (3) practicable manual morphometry with stratified sampling of 12 nuclei by 9 pathologists; and (4) automated morphometry using deep learning–based segmentation. The study included 96 ccMCTs with available outcome information. Inter-rater reproducibility of anisokaryosis estimates was low (k = 0.226), whereas it was good (intraclass correlation = 0.654) for practicable morphometry of the standard deviation (SD) of nuclear size. As compared with gold standard manual morphometry (area under the ROC curve [AUC] = 0.839, 95% confidence interval [CI] = 0.701–0.977), the prognostic value (tumor-specific survival) of SDs of nuclear area for practicable manual morphometry and automated morphometry were high with an AUC of 0.868 (95% CI = 0.737–0.991) and 0.943 (95% CI = 0.889–0.996), respectively. This study supports the use of manual morphometry with stratified sampling of 12 nuclei and algorithmic morphometry to overcome the poor reproducibility of estimates. Further studies are needed to validate our findings, determine inter-algorithmic reproducibility and algorithmic robustness, and explore tumor heterogeneity of nuclear features in entire tumor sections. UR - https://doi.org/10.1177/03009858241295399 Y1 - 2024 UR - https://doi.org/10.1177/03009858241295399 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-53661 SN - 1544-2217 SN - 0300-9858 VL - 62 IS - 2 SP - 161 EP - 177 PB - Sage CY - London ER - TY - JOUR A1 - Stathonikos, Nikolas A1 - Aubreville, Marc A1 - de Vries, Sjoerd A1 - Wilm, Frauke A1 - Bertram, Christof A1 - Veta, Mitko A1 - van Diest, Paul J T1 - Breast cancer survival prediction using an automated mitosis detection pipeline JF - The Journal of Pathology: Clinical Research N2 - AbstractMitotic count (MC) is the most common measure to assess tumor proliferation in breast cancer patients and is highly predictive of patient outcomes. It is, however, subject to inter‐ and intraobserver variation and reproducibility challenges that may hamper its clinical utility. In past studies, artificial intelligence (AI)‐supported MC has been shown to correlate well with traditional MC on glass slides. Considering the potential of AI to improve reproducibility of MC between pathologists, we undertook the next validation step by evaluating the prognostic value of a fully automatic method to detect and count mitoses on whole slide images using a deep learning model. The model was developed in the context of the Mitosis Domain Generalization Challenge 2021 (MIDOG21) grand challenge and was expanded by a novel automatic area selector method to find the optimal mitotic hotspot and calculate the MC per 2 mm2. We employed this method on a breast cancer cohort with long‐term follow‐up from the University Medical Centre Utrecht (N = 912) and compared predictive values for overall survival of AI‐based MC and light‐microscopic MC, previously assessed during routine diagnostics. The MIDOG21 model was prognostically comparable to the original MC from the pathology report in uni‐ and multivariate survival analysis. In conclusion, a fully automated MC AI algorithm was validated in a large cohort of breast cancer with regard to retained prognostic value compared with traditional light‐microscopic MC. UR - https://doi.org/10.1002/2056-4538.70008 Y1 - 2024 UR - https://doi.org/10.1002/2056-4538.70008 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-53087 SN - 2056-4538 VL - 10 IS - 6 PB - Wiley CY - Chichester ER - TY - JOUR A1 - Glahn, Imaine A1 - Haghofer, Andreas A1 - Donovan, Taryn A1 - Degasperi, Brigitte A1 - Bartel, Alexander A1 - Kreilmeier-Berger, Theresa A1 - Hyndman, Philip S. A1 - Janout, Hannah A1 - Assenmacher, Charles-Antoine A1 - Bartenschlager, Florian A1 - Bolfa, Pompei A1 - Dark, Michael A1 - Klang, Andrea A1 - Klopfleisch, Robert A1 - Merz, Sophie A1 - Richter, Barbara A1 - Schulman, F. Yvonne A1 - Ganz, Jonathan A1 - Scharinger, Josef A1 - Aubreville, Marc A1 - Winkler, Stephan M. A1 - Bertram, Christof T1 - Automated Nuclear Morphometry: A Deep Learning Approach for Prognostication in Canine Pulmonary Carcinoma to Enhance Reproducibility JF - Veterinary Sciences N2 - The integration of deep learning-based tools into diagnostic workflows is increasingly prevalent due to their efficiency and reproducibility in various settings. We investigated the utility of automated nuclear morphometry for assessing nuclear pleomorphism (NP), a criterion of malignancy in the current grading system in canine pulmonary carcinoma (cPC), and its prognostic implications. We developed a deep learning-based algorithm for evaluating NP (variation in size, i.e., anisokaryosis and/or shape) using a segmentation model. Its performance was evaluated on 46 cPC cases with comprehensive follow-up data regarding its accuracy in nuclear segmentation and its prognostic ability. Its assessment of NP was compared to manual morphometry and established prognostic tests (pathologists’ NP estimates (n = 11), mitotic count, histological grading, and TNM-stage). The standard deviation (SD) of the nuclear area, indicative of anisokaryosis, exhibited good discriminatory ability for tumor-specific survival, with an area under the curve (AUC) of 0.80 and a hazard ratio (HR) of 3.38. The algorithm achieved values comparable to manual morphometry. In contrast, the pathologists’ estimates of anisokaryosis resulted in HR values ranging from 0.86 to 34.8, with slight inter-observer reproducibility (k = 0.204). Other conventional tests had no significant prognostic value in our study cohort. Fully automated morphometry promises a time-efficient and reproducible assessment of NP with a high prognostic value. Further refinement of the algorithm, particularly to address undersegmentation, and application to a larger study population are required. UR - https://doi.org/10.3390/vetsci11060278 Y1 - 2024 UR - https://doi.org/10.3390/vetsci11060278 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-48612 SN - 2306-7381 VL - 11 IS - 6 PB - MDPI CY - Basel ER - TY - CHAP A1 - Ammeling, Jonas A1 - Hecker, Moritz A1 - Ganz, Jonathan A1 - Donovan, Taryn A1 - Klopfleisch, Robert A1 - Bertram, Christof A1 - Breininger, Katharina A1 - Aubreville, Marc ED - Maier, Andreas ED - Deserno, Thomas Martin ED - Handels, Heinz ED - Maier-Hein, Klaus H. ED - Palm, Christoph ED - Tolxdorff, Thomas T1 - Automated Mitotic Index Calculation via Deep Learning and Immunohistochemistry T2 - Bildverarbeitung für die Medizin 2024: Proceedings, German Conference on Medical Image Computing, Erlangen, March 10–12, 2024 UR - https://doi.org/10.1007/978-3-658-44037-4_37 Y1 - 2024 UR - https://doi.org/10.1007/978-3-658-44037-4_37 SN - 978-3-658-44037-4 SP - 123 EP - 128 PB - Springer Vieweg CY - Wiesbaden 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 - CHAP A1 - Ammeling, Jonas A1 - Manger, Carina A1 - Kwaka, Elias A1 - Krügel, Sebastian A1 - Uhl, Matthias A1 - Kießig, Angelika A1 - Fritz, Alexis A1 - Ganz, Jonathan A1 - Riener, Andreas A1 - Bertram, Christof A1 - Breininger, Katharina A1 - Aubreville, Marc ED - Stolze, Markus ED - Loch, Frieder ED - Baldauf, Matthias ED - Alt, Florian ED - Schneegass, Christina ED - Kosch, Thomas ED - Hirzle, Teresa ED - Sadeghian, Shadan ED - Draxler, Fiona ED - Bektas, Kenan ED - Lohan, Katrin ED - Knierim, Pascal T1 - Appealing but Potentially Biasing - Investigation of the Visual Representation of Segmentation Predictions by AI Recommender Systems for Medical Decision Making T2 - Mensch und Computer 2023: Building Bridges: Tagungsband (Proceedings) UR - https://doi.org/10.1145/3603555.3608561 Y1 - 2023 UR - https://doi.org/10.1145/3603555.3608561 SN - 979-8-4007-0771-1 SP - 330 EP - 335 PB - ACM CY - New York ER - TY - CHAP A1 - Aubreville, Marc A1 - Ganz, Jonathan A1 - Ammeling, Jonas A1 - Donovan, Taryn A1 - Fick, Rutger H. J. A1 - Breininger, Katharina A1 - Bertram, Christof ED - Deserno, Thomas Martin ED - Handels, Heinz ED - Maier, Andreas ED - Maier-Hein, Klaus H. ED - Palm, Christoph ED - Tolxdorff, Thomas T1 - Deep Learning-based Subtyping of Atypical and Normal Mitoses using a Hierarchical Anchor-free Object Detector T2 - Bildverarbeitung für die Medizin 2023: Proceedings, German Workshop on Medical Image Computing, Braunschweig, July 2-4, 2023 UR - https://doi.org/10.1007/978-3-658-41657-7_40 Y1 - 2023 UR - https://doi.org/10.1007/978-3-658-41657-7_40 SN - 978-3-658-41657-7 SN - 978-3-658-41656-0 SP - 189 EP - 195 PB - Springer Vieweg CY - Wiesbaden ER - TY - CHAP A1 - Lausser, Ludwig A1 - Bertram, Christof A1 - Klopfleisch, Robert A1 - Aubreville, Marc ED - Deserno, Thomas Martin ED - Handels, Heinz ED - Maier, Andreas ED - Maier-Hein, Klaus H. ED - Palm, Christoph ED - Tolxdorff, Thomas T1 - Limits of Human Expert Ensembles in Mitosis Multi-expert Ground Truth Generation T2 - Bildverarbeitung für die Medizin 2023: Proceedings, German Workshop on Medical Image Computing, Braunschweig, July 2-4, 2023 UR - https://doi.org/10.1007/978-3-658-41657-7_27 Y1 - 2023 UR - https://doi.org/10.1007/978-3-658-41657-7_27 SN - 978-3-658-41657-7 SN - 978-3-658-41656-0 SP - 116 EP - 121 PB - Springer Vieweg CY - Wiesbaden 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 -