TY - INPR 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 - Ganz, Jonathan A1 - Scharinger, Josef A1 - Aubreville, Marc A1 - Winkler, Stephan M. A1 - Kiupel, Matti A1 - Bertram, Christof T1 - Nuclear Morphometry using a Deep Learning-based Algorithm has Prognostic Relevance for Canine Cutaneous Mast Cell Tumors 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 (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. UR - https://doi.org/10.48550/arXiv.2309.15031 Y1 - 2023 UR - https://doi.org/10.48550/arXiv.2309.15031 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-41401 PB - arXiv CY - Ithaca 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 - INPR A1 - Ganz, Jonathan A1 - Ammeling, Jonas A1 - Rosbach, Emely A1 - Lausser, Ludwig A1 - Bertram, Christof A1 - Breininger, Katharina A1 - Aubreville, Marc T1 - Is Self-Supervision Enough? Benchmarking Foundation Models Against End-to-End Training for Mitotic Figure Classification N2 - Foundation models (FMs), i.e., models trained on a vast amount of typically unlabeled data, have become popular and available recently for the domain of histopathology. The key idea is to extract semantically rich vectors from any input patch, allowing for the use of simple subsequent classification networks potentially reducing the required amounts of labeled data, and increasing domain robustness. In this work, we investigate to which degree this also holds for mitotic figure classification. Utilizing two popular public mitotic figure datasets, we compared linear probing of five publicly available FMs against models trained on ImageNet and a simple ResNet50 end-to-end-trained baseline. We found that the end-to-end-trained baseline outperformed all FM-based classifiers, regardless of the amount of data provided. Additionally, we did not observe the FM-based classifiers to be more robust against domain shifts, rendering both of the above assumptions incorrect. UR - https://doi.org/10.48550/arXiv.2412.06365 Y1 - 2024 UR - https://doi.org/10.48550/arXiv.2412.06365 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-59672 PB - arXiv CY - Ithaca ER - TY - JOUR A1 - Bertram, Christof A1 - Aubreville, Marc A1 - Gurtner, Corinne A1 - Bartel, Alexander A1 - Corner, Sarah M. A1 - Dettwiler, Martina A1 - Kershaw, Olivia A1 - Noland, Erica L. A1 - Schmidt, Anja A1 - Sledge, Dodd G. A1 - Smedley, Rebecca C. A1 - Thaiwong, Tuddow A1 - Kiupel, Matti A1 - Maier, Andreas A1 - Klopfleisch, Robert T1 - Computerized Calculation of Mitotic Count Distribution in Canine Cutaneous Mast Cell Tumor Sections: Mitotic Count Is Area Dependent JF - Veterinary Pathology UR - https://doi.org/10.1177/0300985819890686 KW - area selection KW - high-power field KW - mitotic activity KW - mitotic figure distribution KW - tumor grading KW - tumor periphery Y1 - 2020 UR - https://doi.org/10.1177/0300985819890686 SN - 1544-2217 VL - 57 IS - 2 SP - 214 EP - 226 PB - Sage CY - London 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 - CHAP A1 - Ganz, Jonathan A1 - Bertram, Christof A1 - Klopfleisch, Robert A1 - Jabari, Samir A1 - Breininger, Katharina A1 - Aubreville, Marc T1 - Classification of visibility in multi-stain microscopy images T2 - Medical Imaging with Deep Learning: MIDL 2022 Short Papers KW - mitotic figure classification KW - digital pathology KW - deep learning KW - dual input networks KW - attention KW - immunohistochemical staining Y1 - 2022 UR - https://openreview.net/forum?id=-GsA-mUVmm ER - TY - INPR A1 - Puget, Chloé A1 - Ganz, Jonathan A1 - Ostermaier, Julian A1 - Konrad, Thomas A1 - Parlak, Eda A1 - Bertram, Christof A1 - Kiupel, Matti A1 - Breininger, Katharina A1 - Aubreville, Marc A1 - Klopfleisch, Robert T1 - Deep Learning model predicts the c-Kit-11 mutational status of canine cutaneous mast cell tumors by HE stained histological slides N2 - 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. UR - https://doi.org/10.48550/arXiv.2401.06169 Y1 - 2024 UR - https://doi.org/10.48550/arXiv.2401.06169 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-46020 PB - arXiv CY - Ithaca ER - TY - CHAP A1 - Aubreville, Marc A1 - Bertram, Christof A1 - Klopfleisch, Robert A1 - Maier, Andreas T1 - Field of Interest Proposal for Augmented Mitotic Cell Count BT - Comparison of Two Convolutional Networks T2 - Proceedings of the 12th International Joint Conference on Biomedical Engineering Systems and Technologies - BIOIMAGING UR - https://doi.org/10.5220/0007365700300037 KW - Mitotic Figure KW - Cell Segmentation KW - Digital Histopathology KW - Tumor Grading Y1 - 2019 UR - https://doi.org/10.5220/0007365700300037 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-19248 SN - 978-989-758-353-7 SN - 2184-4305 VL - 2 SP - 30 EP - 37 PB - SciTePress CY - Setúbal 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 - JOUR A1 - Donovan, Taryn A1 - Moore, Frances M. A1 - Bertram, Christof A1 - Luong, Richard A1 - Bolfa, Pompei A1 - Klopfleisch, Robert A1 - Tvedten, Harold A1 - Salas, Elisa N. A1 - Whitley, Derick A1 - Aubreville, Marc A1 - Meuten, Donald J. T1 - Mitotic Figures - Normal, Atypical, and Imposters: A Guide to Identification JF - Veterinary pathology UR - https://doi.org/10.1177/0300985820980049 KW - mitotic figure KW - mitotic count KW - MC KW - prophase KW - prometaphase KW - metaphase KW - anaphase KW - telophase KW - computational pathology KW - CPATH KW - artificial intelligence KW - AI KW - whole slide image KW - WSI KW - pathology KW - oncology Y1 - 2021 UR - https://doi.org/10.1177/0300985820980049 SN - 1544-2217 VL - 58 IS - 2 SP - 243 EP - 257 PB - Sage CY - London ER - TY - CHAP A1 - Aubreville, Marc A1 - Bertram, Christof A1 - Klopfleisch, Robert A1 - Maier, Andreas ED - Handels, Heinz ED - Deserno, Thomas Martin ED - Maier, Andreas ED - Maier-Hein, Klaus H. ED - Palm, Christoph ED - Tolxdorff, Thomas T1 - Augmented mitotic cell count using field of interest proposal T2 - Bildverarbeitung für die Medizin 2019, Algorithmen – Systeme – Anwendungen, Proceedings des Workshops vom 17. bis 19. März 2019 in Lübeck UR - https://doi.org/10.1007/978-3-658-25326-4_71 Y1 - 2019 UR - https://doi.org/10.1007/978-3-658-25326-4_71 SN - 978-3-658-25325-7 SN - 978-3-658-25326-4 N1 - Access to this content is enabled by Nationallizenz Ebooks Medicine SP - 321 EP - 326 PB - Springer Vieweg CY - Wiesbaden 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 - INPR A1 - Ammeling, Jonas A1 - Hecker, Moritz A1 - Ganz, Jonathan A1 - Donovan, Taryn A1 - Klopfleisch, Robert A1 - Bertram, Christof A1 - Breininger, Katharina A1 - Aubreville, Marc T1 - Automated Volume Corrected Mitotic Index Calculation Through Annotation-Free Deep Learning using Immunohistochemistry as Reference Standard N2 - The volume-corrected mitotic index (M/V-Index) was shown to provide prognostic value in invasive breast carcinomas. However, despite its prognostic significance, it is not established as the standard method for assessing aggressive biological behaviour, due to the high additional workload associated with determining the epithelial proportion. In this work, we show that using a deep learning pipeline solely trained with an annotation-free, immunohistochemistry-based approach, provides accurate estimations of epithelial segmentation in canine breast carcinomas. We compare our automatic framework with the manually annotated M/V-Index in a study with three board-certified pathologists. Our results indicate that the deep learning-based pipeline shows expert-level performance, while providing time efficiency and reproducibility. UR - https://doi.org/10.48550/arXiv.2311.08949 Y1 - 2023 UR - https://doi.org/10.48550/arXiv.2311.08949 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-41549 PB - arXiv CY - Ithaca ER - TY - JOUR A1 - Bertram, Christof A1 - Aubreville, Marc A1 - Gurtner, Corinne A1 - Bartel, Alexander A1 - Corner, Sarah M. A1 - Dettwiler, Martina A1 - Kershaw, Olivia A1 - Noland, Erica L. A1 - Schmidt, Anja A1 - Sledge, Dodd G. A1 - Smedley, Rebecca C. A1 - Thaiwong, Tuddow A1 - Kiupel, Matti A1 - Maier, Andreas A1 - Klopfleisch, Robert T1 - Mitotic count in canine cutaneous mast cell tumours BT - not accurate but reproducible JF - Journal of Comparative Pathology UR - https://doi.org/10.1016/j.jcpa.2019.10.015 Y1 - 2020 UR - https://doi.org/10.1016/j.jcpa.2019.10.015 SN - 1532-3129 VL - 2020 IS - 174 SP - 143 PB - Elsevier CY - London ER - TY - INPR A1 - Wilm, Frauke A1 - Fragoso-Garcia, Marco A1 - Bertram, Christof A1 - Stathonikos, Nikolas A1 - Öttl, Mathias A1 - Qiu, Jingna A1 - Klopfleisch, Robert A1 - Maier, Andreas A1 - Aubreville, Marc A1 - Breininger, Katharina T1 - Mind the Gap: Scanner-induced domain shifts pose challenges for representation learning in histopathology UR - https://doi.org/10.48550/arXiv.2211.16141 KW - Histopathology KW - Domain Shift KW - Representation Learning KW - Barlow Twins Y1 - 2022 UR - https://doi.org/10.48550/arXiv.2211.16141 PB - arXiv CY - Ithaca ER - TY - CHAP A1 - Aubreville, Marc A1 - Krappmann, Maximilian A1 - Bertram, Christof A1 - Klopfleisch, Robert A1 - Maier, Andreas T1 - A Guided Spatial Transformer Network for Histology Cell Differentiation T2 - VCBM '17: Proceedings of the Eurographics Workshop on Visual Computing for Biology and Medicine UR - https://doi.org/10.2312/vcbm.20171233 Y1 - 2017 UR - https://doi.org/10.2312/vcbm.20171233 SN - 978-3-03868-036-9 SP - 21 EP - 25 PB - Eurographics Association CY - Goslar ER - TY - CHAP A1 - Aubreville, Marc A1 - Bertram, Christof A1 - Klopfleisch, Robert A1 - Maier, Andreas T1 - SlideRunner BT - a tool for massive cell annotations in whole slide images T2 - Bildverarbeitung für die Medizin 2018: Algorithmen - Systeme - Anwendungen N2 - Large-scale image data such as digital whole-slide histology images pose a challenging task at annotation software solutions. Today, a number of good solutions with varying scopes exist. For cell annotation, however, we find that many do not match the prerequisites for fast annotations. Especially in the field of mitosis detection, it is assumed that detection accuracy could significantly benefit from larger annotation databases that are currently however very troublesome to produce. Further, multiple independent (blind) expert labels are a big asset for such databases, yet there is currently no tool for this kind of annotation available. To ease this tedious process of expert annotation and grading, we introduce SlideRunner, an open source annotation and visualization tool for digital histopathology, developed in close cooperation with two pathologists. SlideRunner is capable of setting annotations like object centers (for e.g. cells) as well as object boundaries (e.g. for tumor outlines). It provides single-click annotations as well as a blind mode for multi-annotations, where the expert is directly shown the microscopy image containing the cells that he has not yet rated. UR - https://doi.org/10.1007/978-3-662-56537-7_81 Y1 - 2018 UR - https://doi.org/10.1007/978-3-662-56537-7_81 SN - 978-3-662-56537-7 SP - 309 EP - 314 PB - Springer Vieweg CY - Berlin ER -