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 - Mualla, Firas A1 - Aubreville, Marc A1 - Maier, Andreas ED - Maier, Andreas ED - Steidl, Stefan ED - Christlein, Vincent ED - Hornegger, Joachim T1 - Microscopy T2 - Medical Imaging Systems: An Introductory Guide N2 - We perceive the physical world around us using our eyes, but only down to a certain limit. Objects with a diameter smaller than 75 μm cannot be recognized by the naked eye, and due to this reason, they remained undiscovered for the most of human history. UR - https://doi.org/10.1007/978-3-319-96520-8_5 Y1 - 2018 UR - https://doi.org/10.1007/978-3-319-96520-8_5 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-26411 SN - 978-3-319-96520-8 SP - 69 EP - 90 PB - Springer CY - Cham ER - TY - INPR A1 - Ammeling, Jonas A1 - Schmidt, Lars-Henning A1 - Ganz, Jonathan A1 - Niedermair, Tanja A1 - Brochhausen-Delius, Christoph A1 - Schulz, Christian A1 - Breininger, Katharina A1 - Aubreville, Marc T1 - Attention-based Multiple Instance Learning for Survival Prediction on Lung Cancer Tissue Microarrays N2 - Attention-based multiple instance learning (AMIL) algorithms have proven to be successful in utilizing gigapixel whole-slide images (WSIs) for a variety of different computational pathology tasks such as outcome prediction and cancer subtyping problems. We extended an AMIL approach to the task of survival prediction by utilizing the classical Cox partial likelihood as a loss function, converting the AMIL model into a nonlinear proportional hazards model. We applied the model to tissue microarray (TMA) slides of 330 lung cancer patients. The results show that AMIL approaches can handle very small amounts of tissue from a TMA and reach similar C-index performance compared to established survival prediction methods trained with highly discriminative clinical factors such as age, cancer grade, and cancer stage. UR - https://doi.org/10.48550/arXiv.2212.07724 Y1 - 2022 UR - https://doi.org/10.48550/arXiv.2212.07724 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-30642 PB - arXiv CY - Ithaca ER - TY - INPR A1 - Stoeve, Maike A1 - Aubreville, Marc A1 - Oetter, Nicolai A1 - Knipfer, Christian A1 - Neumann, Helmut A1 - Stelzle, Florian A1 - Maier, Andreas T1 - Motion Artifact Detection in Confocal Laser Endomicroscopy Images N2 - Confocal Laser Endomicroscopy (CLE), an optical imaging technique allowing non-invasive examination of the mucosa on a (sub)- cellular level, has proven to be a valuable diagnostic tool in gastroenterology and shows promising results in various anatomical regions including the oral cavity. Recently, the feasibility of automatic carcinoma detection for CLE images of sufficient quality was shown. However, in real world data sets a high amount of CLE images is corrupted by artifacts. Amongst the most prevalent artifact types are motion-induced image deteriorations. In the scope of this work, algorithmic approaches for the automatic detection of motion artifact-tainted image regions were developed. Hence, this work provides an important step towards clinical applicability of automatic carcinoma detection. Both, conventional machine learning and novel, deep learning-based approaches were assessed. The deep learning-based approach outperforms the conventional approaches, attaining an AUC of 0.90. UR - https://doi.org/10.48550/arXiv.1711.01117 Y1 - 2018 UR - https://doi.org/10.48550/arXiv.1711.01117 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-12588 PB - arXiv CY - Ithaca 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 - 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 - Schröter, H. A1 - Rosenkranz, Tobias A1 - Escalante-B, A. N. A1 - Aubreville, Marc A1 - Maier, Andreas T1 - CLCNET: deep learning-based noise reduction for hearing aids using complex linear coding T2 - ICASSP 2020 - 2020 IEEE International Conference on Acoustics, Speech and Signal Processing (ICASSP) UR - https://doi.org/10.1109/ICASSP40776.2020.9053563 KW - noise reduction KW - speech enhancement KW - LPC KW - hearing aid signal processing KW - deep learning Y1 - 2020 UR - https://doi.org/10.1109/ICASSP40776.2020.9053563 SN - 978-1-5090-6631-5 SP - 6949 EP - 6953 PB - IEEE CY - Piscataway 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 - INPR A1 - Aubreville, Marc A1 - Pan, Zhaoya A1 - Sievert, Matti A1 - Ammeling, Jonas A1 - Ganz, Jonathan A1 - Oetter, Nicolai A1 - Stelzle, Florian A1 - Frenken, Ann-Kathrin A1 - Breininger, Katharina A1 - Goncalves, Miguel T1 - Few Shot Learning for the Classification of Confocal Laser Endomicroscopy Images of Head and Neck Tumors N2 - The surgical removal of head and neck tumors requires safe margins, which are usually confirmed intraoperatively by means of frozen sections. This method is, in itself, an oversampling procedure, which has a relatively low sensitivity compared to the definitive tissue analysis on paraffin-embedded sections. Confocal laser endomicroscopy (CLE) is an in-vivo imaging technique that has shown its potential in the live optical biopsy of tissue. An automated analysis of this notoriously difficult to interpret modality would help surgeons. However, the images of CLE show a wide variability of patterns, caused both by individual factors but also, and most strongly, by the anatomical structures of the imaged tissue, making it a challenging pattern recognition task. In this work, we evaluate four popular few shot learning (FSL) methods towards their capability of generalizing to unseen anatomical domains in CLE images. We evaluate this on images of sinunasal tumors (SNT) from five patients and on images of the vocal folds (VF) from 11 patients using a cross-validation scheme. The best respective approach reached a median accuracy of 79.6% on the rather homogeneous VF dataset, but only of 61.6% for the highly diverse SNT dataset. Our results indicate that FSL on CLE images is viable, but strongly affected by the number of patients, as well as the diversity of anatomical patterns. UR - https://doi.org/10.48550/arXiv.2311.07216 Y1 - 2023 UR - https://doi.org/10.48550/arXiv.2311.07216 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-41522 PB - arXiv CY - Ithaca 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 - CHAP A1 - Aubreville, Marc A1 - Ehrensperger, Kai A1 - Maier, Andreas A1 - Rosenkranz, Tobias A1 - Graf, Benjamin A1 - Puder, Henning T1 - Deep Denoising for Hearing Aid Applications T2 - IWAENC Proceedings UR - https://doi.org/10.1109/IWAENC.2018.8521369 KW - noise reduction KW - hearing aid signal processing KW - deep neural networks Y1 - 2018 UR - https://doi.org/10.1109/IWAENC.2018.8521369 SN - 978-1-5386-8151-0 SP - 361 EP - 365 PB - IEEE CY - Piscataway ER - TY - CHAP A1 - Aubreville, Marc A1 - Petrausch, Stefan T1 - Directionality assessment of adaptive binaural beamforming with noise suppression in hearing aids T2 - 2015 IEEE International Conference on Acoustics, Speech, and Signal Processing: Proceedings UR - https://doi.org/10.1109/ICASSP.2015.7177962 KW - spatial processing KW - measurement KW - hearing aids KW - sequential directivity index Y1 - 2015 UR - https://doi.org/10.1109/ICASSP.2015.7177962 SN - 978-1-4673-6997-8 SP - 211 EP - 215 PB - IEEE CY - Piscataway ER - TY - CHAP A1 - Krappmann, Maximilian A1 - Aubreville, Marc A1 - Maier, Andreas A1 - Bertram, Christof A1 - Klopfleisch, Robert ED - Maier, Andreas ED - Deserno, Thomas Martin ED - Handels, Heinz ED - Maier-Hein, Klaus H. ED - Palm, Christoph ED - Tolxdorff, Thomas T1 - Classification of Mitotic Cells BT - Potentials Beyond the Limits of Small Data Sets T2 - Bildverarbeitung für die Medizin 2018 UR - https://doi.org/10.1007/978-3-662-56537-7_66 Y1 - 2018 UR - https://doi.org/10.1007/978-3-662-56537-7_66 SN - 978-3-662-56536-0 SP - 245 EP - 250 PB - Springer CY - Berlin ER - TY - INPR 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 UR - https://doi.org/10.48550/arXiv.1707.08525 Y1 - 2017 UR - https://doi.org/10.48550/arXiv.1707.08525 PB - arXiv CY - Ithaca ER - TY - INPR A1 - Pernias, Pablo A1 - Rampas, Dominic A1 - Aubreville, Marc T1 - Würstchen: Efficient Pretraining of Text-to-Image Models N2 - We introduce Wuerstchen, a novel technique for text-to-image synthesis that unites competitive performance with unprecedented cost-effectiveness and ease of training on constrained hardware. Building on recent advancements in machine learning, our approach, which utilizes latent diffusion strategies at strong latent image compression rates, significantly reduces the computational burden, typically associated with state-of-the-art models, while preserving, if not enhancing, the quality of generated images. Wuerstchen achieves notable speed improvements at inference time, thereby rendering real-time applications more viable. One of the key advantages of our method lies in its modest training requirements of only 9,200 GPU hours, slashing the usual costs significantly without compromising the end performance. In a comparison against the state-of-the-art, we found the approach to yield strong competitiveness. This paper opens the door to a new line of research that prioritizes both performance and computational accessibility, hence democratizing the use of sophisticated AI technologies. Through Wuerstchen, we demonstrate a compelling stride forward in the realm of text-to-image synthesis, offering an innovative path to explore in future research. UR - https://doi.org/10.48550/arXiv.2306.00637 Y1 - 2023 UR - https://doi.org/10.48550/arXiv.2306.00637 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-39160 PB - arXiv CY - Ithaca ER - TY - JOUR A1 - Haghofer, Andreas A1 - Fuchs-Baumgartinger, Andrea A1 - Lipnik, Karoline A1 - Klopfleisch, Robert A1 - Aubreville, Marc A1 - Scharinger, Josef A1 - Weissenböck, Herbert A1 - Winkler, Stephan M. A1 - Bertram, Christof T1 - Histological classification of canine and feline lymphoma using a modular approach based on deep learning and advanced image processing JF - Scientific Reports N2 - AbstractHistopathological examination of tissue samples is essential for identifying tumor malignancy and the diagnosis of different types of tumor. In the case of lymphoma classification, nuclear size of the neoplastic lymphocytes is one of the key features to differentiate the different subtypes. Based on the combination of artificial intelligence and advanced image processing, we provide a workflow for the classification of lymphoma with regards to their nuclear size (small, intermediate, and large). As the baseline for our workflow testing, we use a Unet++ model trained on histological images of canine lymphoma with individually labeled nuclei. As an alternative to the Unet++, we also used a publicly available pre-trained and unmodified instance segmentation model called Stardist to demonstrate that our modular classification workflow can be combined with different types of segmentation models if they can provide proper nuclei segmentation. Subsequent to nuclear segmentation, we optimize algorithmic parameters for accurate classification of nuclear size using a newly derived reference size and final image classification based on a pathologists-derived ground truth. Our image classification module achieves a classification accuracy of up to 92% on canine lymphoma data. Compared to the accuracy ranging from 66.67 to 84% achieved using measurements provided by three individual pathologists, our algorithm provides a higher accuracy level and reproducible results. Our workflow also demonstrates a high transferability to feline lymphoma, as shown by its accuracy of up to 84.21%, even though our workflow was not optimized for feline lymphoma images. By determining the nuclear size distribution in tumor areas, our workflow can assist pathologists in subtyping lymphoma based on the nuclei size and potentially improve reproducibility. Our proposed approach is modular and comprehensible, thus allowing adaptation for specific tasks and increasing the users’ trust in computer-assisted image classification. UR - https://doi.org/10.1038/s41598-023-46607-w Y1 - 2023 UR - https://doi.org/10.1038/s41598-023-46607-w UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-41415 SN - 2045-2322 VL - 13 PB - Springer Nature CY - London ER - TY - JOUR A1 - Hirling, Dominik A1 - Tasnadi, Ervin A1 - Caicedo, Juan A1 - Caroprese, Maria V. A1 - Sjögren, Rickard A1 - Aubreville, Marc A1 - Koos, Krisztian A1 - Horvath, Peter T1 - Segmentation metric misinterpretations in bioimage analysis JF - Nature Methods N2 - Quantitative evaluation of image segmentation algorithms is crucial in the field of bioimage analysis. The most common assessment scores, however, are often misinterpreted and multiple definitions coexist with the same name. Here we present the ambiguities of evaluation metrics for segmentation algorithms and show how these misinterpretations can alter leaderboards of influential competitions. We also propose guidelines for how the currently existing problems could be tackled. UR - https://doi.org/10.1038/s41592-023-01942-8 Y1 - 2023 UR - https://doi.org/10.1038/s41592-023-01942-8 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-40491 SN - 1548-7091 SN - 1548-7105 VL - 21 IS - 2 SP - 213 EP - 216 PB - Springer Nature CY - Berlin ER - TY - JOUR A1 - Sievert, Matti A1 - Mantsopoulos, Konstantinos A1 - Müller, Sarina K. A1 - Eckstein, Markus A1 - Rupp, Robin A1 - Aubreville, Marc A1 - Stelzle, Florian A1 - Oetter, Nicolai A1 - Maier, Andreas A1 - Iro, Heinrich A1 - Goncalves, Miguel T1 - Systematic interpretation of confocal laser endomicroscopy: larynx and pharynx confocal imaging score JF - Acta otorhinolaryngologica italica N2 - Objective. Development and validation of a confocal laser endomicroscopy (CLE) classification score for the larynx and pharynx. Methods. Thirteen patients (154 video sequences, 9240 images) with laryngeal or pharyngeal SCC were included in this prospective study between October 2020 and February 2021. Each CLE sequence was correlated with the gold standard of histopathological examination. Based on a dataset of 94 video sequences (5640 images), a scoring system was developed. In the remaining 60 sequences (3600 images), the score was validated by four CLE experts and four head and neck surgeons who were not familiar with CLE. Results. Tissue homogeneity, cell size, borders and clusters, capillary loops and the nucleus/ cytoplasm ratio were defined as the scoring criteria. Using this score, the CLE experts obtained an accuracy, sensitivity, and specificity of 90.8%, 95.1%, and 86.4%, respectively, and the CLE non-experts of 86.2%, 86.4%, and 86.1%. Interobserver agreement Fleiss’ kappa was 0.8 and 0.6, respectively. Conclusions. CLE can be reliably evaluated based on defined and reproducible imaging features, which demonstrate a high diagnostic value. CLE can be easily integrated into the intraoperative setting and generate real-time, in-vivo microscopic images to demarcate malignant changes. UR - https://doi.org/10.14639/0392-100X-N1643 KW - confocal laser endomicroscopy KW - head and neck cancer KW - classification system KW - non-invasive histological imaging KW - larynx KW - pharynx Y1 - 2022 UR - https://doi.org/10.14639/0392-100X-N1643 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-29175 SN - 1827-675X VL - 42 IS - 1 SP - 26 EP - 33 PB - Pacini CY - Pisa ER - TY - CHAP A1 - Qiu, Jingna A1 - Wilm, Frauke A1 - Öttl, Mathias A1 - Schlereth, Maja A1 - Liu, Chang A1 - Heimann, Tobias A1 - Aubreville, Marc A1 - Breininger, Katharina ED - Greenspan, Hayit ED - Madabhushi, Anant ED - Mousavi, Parvin ED - Salcudean, Septimiu ED - Duncan, James ED - Syeda-Mahmood, Tanveer ED - Taylor, Russell T1 - Adaptive Region Selection for Active Learning in Whole Slide Image Semantic Segmentation T2 - Medical Image Computing and Computer Assisted Intervention – MICCAI 2023: Proceedings, Part II UR - https://doi.org/10.1007/978-3-031-43895-0_9 Y1 - 2023 UR - https://doi.org/10.1007/978-3-031-43895-0_9 SN - 978-3-031-43895-0 SN - 1611-3349 SP - 90 EP - 100 PB - Springer CY - Cham ER - TY - CHAP A1 - Ganz, Jonathan A1 - Lipnik, Karoline A1 - Ammeling, Jonas A1 - Richter, Barbara A1 - Puget, Chloé A1 - Parlak, Eda A1 - Diehl, Laura A1 - Klopfleisch, Robert A1 - Donovan, Taryn A1 - Kiupel, Matti A1 - Bertram, Christof A1 - Breininger, Katharina 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 - Deep Learning-based Automatic Assessment of AgNOR-scores in Histopathology Images 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_49 Y1 - 2023 UR - https://doi.org/10.1007/978-3-658-41657-7_49 SN - 978-3-658-41657-7 SN - 978-3-658-41656-0 SP - 226 EP - 231 PB - Springer Vieweg CY - Wiesbaden ER - TY - CHAP 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 T2 - 2023 IEEE 20th International Symposium on Biomedical Imaging (ISBI) UR - https://doi.org/10.1109/ISBI53787.2023.10230458 KW - Histopathology KW - Domain Shift KW - Representation Learning KW - Barlow Twins Y1 - 2023 UR - https://doi.org/10.1109/ISBI53787.2023.10230458 SN - 978-1-6654-7358-3 PB - IEEE CY - Piscataway ER - TY - JOUR A1 - Aubreville, Marc A1 - Stathonikos, Nikolas A1 - Donovan, Taryn A1 - Klopfleisch, Robert A1 - Ammeling, Jonas A1 - Ganz, Jonathan A1 - Wilm, Frauke A1 - Veta, Mitko A1 - Jabari, Samir A1 - Eckstein, Markus A1 - Annuscheit, Jonas A1 - Krumnow, Christian A1 - Bozaba, Engin A1 - Cayir, Sercan A1 - Gu, Hongyan A1 - Chen, Xiang A1 - Jahanifar, Mostafa A1 - Shephard, Adam A1 - Kondo, Satoshi A1 - Kasai, Satoshi A1 - Kotte, Sujatha A1 - Saipradeep, Vangala A1 - Lafarge, Maxime W. A1 - Koelzer, Viktor H. A1 - Wang, Ziyue A1 - Zhang, Yongbing A1 - Yang, Sen A1 - Wang, Xiyue A1 - Breininger, Katharina A1 - Bertram, Christof T1 - Domain generalization across tumor types, laboratories, and species — Insights from the 2022 edition of the Mitosis Domain Generalization Challenge JF - Medical Image Analysis N2 - 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 majority vote 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 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. However, we also found that domain characteristics not present in the training set (feline as new species, spindle cell shape as new morphology and a new scanner) led to small but significant decreases in performance. When assessed against the immunohistochemistry-assisted reference standard, all methods resulted in reduced recall scores, with only minor changes in the order of participants in the ranking. UR - https://doi.org/10.1016/j.media.2024.103155 Y1 - 2024 UR - https://doi.org/10.1016/j.media.2024.103155 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-58479 SN - 1361-8423 VL - 2024 IS - 94 PB - Elsevier CY - Amsterdam 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 - 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 - INPR A1 - Qiu, Jingna A1 - Aubreville, Marc A1 - Wilm, Frauke A1 - Öttl, Mathias A1 - Utz, Jonas A1 - Schlereth, Maja A1 - Breininger, Katharina T1 - Leveraging Image Captions for Selective Whole Slide Image Annotation UR - https://doi.org/10.48550/arXiv.2407.06363 Y1 - 2024 UR - https://doi.org/10.48550/arXiv.2407.06363 PB - arXiv CY - Ithaca 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 - JOUR A1 - Ganz, Jonathan A1 - Ammeling, Jonas A1 - Jabari, Samir A1 - Breininger, Katharina A1 - Aubreville, Marc T1 - Re-identification from histopathology images JF - Medical Image Analysis N2 - In numerous studies, deep learning algorithms have proven their potential for the analysis of histopathology images, for example, for revealing the subtypes of tumors or the primary origin of metastases. These models require large datasets for training, which must be anonymized to prevent possible patient identity leaks. This study demonstrates that even relatively simple deep learning algorithms can re-identify patients in large histopathology datasets with substantial accuracy. In addition, we compared a comprehensive set of state-of-the-art whole slide image classifiers and feature extractors for the given task. We evaluated our algorithms on two TCIA datasets including lung squamous cell carcinoma (LSCC) and lung adenocarcinoma (LUAD). We also demonstrate the algorithm’s performance on an in-house dataset of meningioma tissue. We predicted the source patient of a slide with 𝐹1 scores of up to 80.1% and 77.19% on the LSCC and LUAD datasets, respectively, and with 77.09% on our meningioma dataset. Based on our findings, we formulated a risk assessment scheme to estimate the risk to the patient’s privacy prior to publication. UR - https://doi.org/10.1016/j.media.2024.103335 Y1 - 2024 UR - https://doi.org/10.1016/j.media.2024.103335 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-53025 SN - 1361-8423 SN - 1361-8415 VL - 2025 IS - 99 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Aubreville, Marc A1 - Ganz, Jonathan A1 - Ammeling, Jonas A1 - Rosbach, Emely A1 - Gehrke, Thomas A1 - Scherzad, Agmal A1 - Hackenberg, Stephan A1 - Goncalves, Miguel T1 - Prediction of tumor board procedural recommendations using large language models JF - European Archives of Oto-Rhino-Laryngology UR - https://doi.org/10.1007/s00405-024-08947-9 Y1 - 2024 UR - https://doi.org/10.1007/s00405-024-08947-9 SN - 1434-4726 SN - 0937-4477 VL - 282 IS - 3 SP - 1619 EP - 1629 PB - Springer CY - Berlin ER - TY - JOUR A1 - Frenken, Ann‐Kathrin A1 - Sievert, Matti A1 - Panuganti, Bharat A1 - Aubreville, Marc A1 - Meyer, Till A1 - Scherzad, Agmal A1 - Gehrke, Thomas A1 - Scheich, Matthias A1 - Hackenberg, Stephan A1 - Goncalves, Miguel T1 - Feasibility of Optical Biopsy During Endoscopic Sinus Surgery With Confocal Laser Endomicroscopy: A Pilot Study JF - The Laryngoscope UR - https://doi.org/10.1002/lary.31503 Y1 - 2024 UR - https://doi.org/10.1002/lary.31503 SN - 1531-4995 VL - 134 IS - 10 SP - 4217 EP - 4224 PB - Wiley CY - Malden 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 - Sievert, Matti A1 - Aubreville, Marc A1 - Mueller, Sarina Katrin A1 - Eckstein, Markus A1 - Breininger, Katharina A1 - Iro, Heinrich A1 - Goncalves, Miguel T1 - Diagnosis of malignancy in oropharyngeal confocal laser endomicroscopy using GPT 4.0 with vision JF - European Archives of Oto-Rhino-Laryngology UR - https://doi.org/10.1007/s00405-024-08476-5 Y1 - 2024 UR - https://doi.org/10.1007/s00405-024-08476-5 SN - 1434-4726 SN - 0937-4477 VL - 281 IS - 4 SP - 2115 EP - 2122 PB - Springer CY - Berlin ER - TY - JOUR A1 - Aubreville, Marc T1 - Developing Robust AI Applications for Clinical Use: The Special Case of Pathology JF - Trillium Pathology UR - https://doi.org/10.47184/tp.2024.01.04 Y1 - 2024 UR - https://doi.org/10.47184/tp.2024.01.04 SN - 2752-1915 VL - 3 IS - 1 SP - 20 EP - 22 PB - Trillium GmbH Medizinischer Fachverlag CY - Grafrath ER - TY - CHAP A1 - Pernias, Pablo A1 - Rampas, Dominic A1 - Richter, Mats Leon A1 - Pal, Christopher A1 - Aubreville, Marc T1 - Würstchen: An Efficient Architecture for Large-Scale Text-to-Image Diffusion Models T2 - The Twelfth International Conference on Learning Representations (ICLR 2024) Y1 - 2024 UR - https://openreview.net/forum?id=gU58d5QeGv PB - OpenReview ER - TY - CHAP A1 - Eisenmann, Matthias A1 - Reinke, Annika A1 - Weru, Vivienn A1 - Tizabi, Minu Dietlinde A1 - Isensee, Fabian A1 - Adler, Tim J. A1 - Ali, Sharib A1 - Andrearczyk, Vincent A1 - Aubreville, Marc A1 - Baid, Ujjwal A1 - Bakas, Spyridon A1 - Balu, Niranjan A1 - Bano, Sophia A1 - Bernal, Jorge A1 - Bodenstedt, Sebastian A1 - Casella, Alessandro A1 - Cheplygina, Veronika A1 - Daum, Marie A1 - De Bruijne, Marleen A1 - Depeursinge, Adrien A1 - Dorent, Reuben A1 - Egger, Jan A1 - Ellis, David G. A1 - Engelhardt, Sandy A1 - Ganz, Melanie A1 - Ghatwary, Noha M. A1 - Girard, Gabriel A1 - Godau, Patrick A1 - Gupta, Anubha A1 - Hansen, Lasse A1 - Harada, Kanako A1 - Heinrich, Mattias A1 - Heller, Nicholas A1 - Hering, Alessa A1 - Huaulmé, Arnoud A1 - Jannin, Pierre A1 - Kavur, A. Emre A1 - Kodym, Oldrich A1 - Kozubek, Michal A1 - Li, Jianning A1 - Li, Hongwei A1 - Ma, Jun A1 - Martín-Isla, Carlos A1 - Menze, Bjoern H. A1 - Noble, Alison A1 - Oreiller, Valentin A1 - Padoy, Nicolas A1 - Pati, Sarthak A1 - Payette, Kelly A1 - Rädsch, Tim A1 - Rafael-Patiño, Jonathan A1 - Bawa, Vivek Singh A1 - Speidel, Stefanie A1 - Sudre, Carole H. A1 - Van Wijnen, Kimberlin M. H. A1 - Wagner, M. A1 - Wei, D. A1 - Yamlahi, Amine A1 - Yap, Moi Hoon A1 - Yuan, C. A1 - Zenk, Maximilian A1 - Zia, A. A1 - Zimmerer, David A1 - Aydogan, Dogu Baran A1 - Bhattarai, B. A1 - Bloch, Louise A1 - Brüngel, Raphael A1 - Cho, J. A1 - Choi, C. A1 - Dou, Q. A1 - Ezhov, Ivan A1 - Friedrich, Christoph M. A1 - Fuller, C. A1 - Gaire, Rebati Raman A1 - Galdran, Adrian A1 - García-Faura, Álvaro A1 - Grammatikopoulou, Maria A1 - Hong, S. A1 - Jahanifar, Mostafa A1 - Jang, I. A1 - Kadkhodamohammadi, Abdolrahim A1 - Kang, I. A1 - Kofler, Florian A1 - Kondo, Satoshi A1 - Kuijf, Hugo Jaco A1 - Li, M. A1 - Luu, M. A1 - Martinčič, Tomaz A1 - Morais, P. A1 - Naser, M. A. A1 - Oliveira, B. A1 - Owen, D. A1 - Pang, S. A1 - Park, Jinah A1 - Park, S. A1 - Płotka, S. A1 - Puybareau, Élodie A1 - Rajpoot, Nasir M. A1 - Ryu, K. A1 - Saeed, N. A1 - Shephard, Adam A1 - Shi, P. A1 - Štepec, Dejan A1 - Subedi, Ronast A1 - Tochon, Guillaume A1 - Torres, Helena R. A1 - Urien, Hélène A1 - Vilaça, João L. A1 - Wahid, Kareem A. A1 - Wang, H. A1 - Wang, J. A1 - Wang, L. A1 - Wang, Xiyue A1 - Wiestler, Benedikt A1 - Wodzinski, Marek A1 - Xia, F. A1 - Xie, J. A1 - Xiong, Z. A1 - Yang, Sen A1 - Yang, Y. A1 - Zhao, Z. A1 - Maier-Hein, Klaus H. A1 - Jäger, Paul F. A1 - Kopp-Schneider, Annette A1 - Maier-Hein, Lena T1 - Why is the Winner the Best? T2 - Proceedings: 2023 IEEE/CVF Conference on Computer Vision and Pattern Recognition UR - https://doi.org/10.1109/CVPR52729.2023.01911 KW - Medical and biological vision KW - cell microscopy Y1 - 2023 UR - https://doi.org/10.1109/CVPR52729.2023.01911 SN - 979-8-3503-0129-8 SN - 2575-7075 SP - 19955 EP - 19967 PB - IEEE CY - Los Alamitos ER - TY - JOUR A1 - Wilm, Frauke A1 - Ihling, Christian A1 - Méhes, Gábor A1 - Terracciano, Luigi A1 - Puget, Chloé A1 - Klopfleisch, Robert A1 - Schüffler, Peter A1 - Aubreville, Marc A1 - Maier, Andreas A1 - Mrowiec, Thomas A1 - Breininger, Katharina T1 - Pan-tumor T-lymphocyte detection using deep neural networks: Recommendations for transfer learning in immunohistochemistry JF - Journal of Pathology Informatics N2 - The success of immuno-oncology treatments promises long-term cancer remission for an increasing number of patients. The response to checkpoint inhibitor drugs has shown a correlation with the presence of immune cells in the tumor and tumor microenvironment. An in-depth understanding of the spatial localization of immune cells is therefore critical for understanding the tumor’s immune landscape and predicting drug response. Computer-aided systems are well suited for efficiently quantifying immune cells in their spatial context. Conventional image analysis approaches are often based on color features and therefore require a high level of manual interaction. More robust image analysis methods based on deep learning are expected to decrease this reliance on human interaction and improve the reproducibility of immune cell scoring. However, these methods require sufficient training data and previous work has reported low robustness of these algorithms when they are tested on out-of-distribution data from different pathology labs or samples from different organs. In this work, we used a new image analysis pipeline to explicitly evaluate the robustness of marker-labeled lymphocyte quantification algorithms depending on the number of training samples before and after being transferred to a new tumor indication. For these experiments, we adapted the RetinaNet architecture for the task of T-lymphocyte detection and employed transfer learning to bridge the domain gap between tumor indications and reduce the annotation costs for unseen domains. On our test set, we achieved human-level performance for almost all tumor indications with an average precision of 0.74 in-domain and 0.72–0.74 cross-domain. From our results, we derive recommendations for model development regarding annotation extent, training sample selection, and label extraction for the development of robust algorithms for immune cell scoring. By extending the task of marker-labeled lymphocyte quantification to a multi-class detection task, the pre-requisite for subsequent analyses, e.g., distinguishing lymphocytes in the tumor stroma from tumor-infiltrating lymphocytes, is met. UR - https://doi.org/10.1016/j.jpi.2023.100301 KW - Tumor-infiltrating lymphocytes KW - Immuno-oncology KW - Immunohistochemistry KW - Deep learning KW - Transfer learning KW - Domain adaptation Y1 - 2023 UR - https://doi.org/10.1016/j.jpi.2023.100301 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-40458 SN - 2153-3539 VL - 2023 IS - 14 PB - Elsevier CY - Amsterdam 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 - JOUR A1 - Krügel, Sebastian A1 - Ammeling, Jonas A1 - Aubreville, Marc A1 - Fritz, Alexis A1 - Kießig, Angelika A1 - Uhl, Matthias T1 - Perceived responsibility in AI-supported medicine JF - AI & Society: Journal of Knowledge, Culture and Communication N2 - In a representative vignette study in Germany with 1,653 respondents, we investigated laypeople’s attribution of moral responsibility in collaborative medical diagnosis. Specifically, we compare people’s judgments in a setting in which physicians are supported by an AI-based recommender system to a setting in which they are supported by a human colleague. It turns out that people tend to attribute moral responsibility to the artificial agent, although this is traditionally considered a category mistake in normative ethics. This tendency is stronger when people believe that AI may become conscious at some point. In consequence, less responsibility is attributed to human agents in settings with hybrid diagnostic teams than in settings with human-only diagnostic teams. Our findings may have implications for behavior exhibited in contexts of collaborative medical decision making with AI-based as opposed to human recommenders because less responsibility is attributed to agents who have the mental capacity to care about outcomes. UR - https://doi.org/10.1007/s00146-024-01972-6 Y1 - 2024 UR - https://doi.org/10.1007/s00146-024-01972-6 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-57874 SN - 1435-5655 VL - 40 SP - 1485 EP - 1495 PB - Springer CY - London ER - TY - CHAP A1 - Ammeling, Jonas A1 - Wilm, Frauke A1 - Ganz, Jonathan A1 - Breininger, Katharina A1 - Aubreville, Marc ED - Sheng, Bin ED - Aubreville, Marc T1 - Reference Algorithms for the Mitosis Domain Generalization (MIDOG) 2022 Challenge T2 - Mitosis Domain Generalization and Diabetic Retinopathy Analysis UR - https://doi.org/10.1007/978-3-031-33658-4_19 Y1 - 2023 UR - https://doi.org/10.1007/978-3-031-33658-4_19 SN - 978-3-031-33658-4 SN - 978-3-031-33657-7 SP - 201 EP - 205 PB - Springer CY - Cham ER - TY - JOUR A1 - Sievert, Matti A1 - Aubreville, Marc A1 - Gostian, Antoniu-Oreste A1 - Mantsopoulos, Konstantinos A1 - Koch, Michael A1 - Müller, Sarina K. A1 - Eckstein, Markus A1 - Rupp, Robin A1 - Stelzle, Florian A1 - Oetter, Nicolai A1 - Maier, Andreas A1 - Iro, Heinrich A1 - Goncalves, Miguel T1 - Validity of tissue homogeneity in confocal laser endomicroscopy on the diagnosis of laryngeal and hypopharyngeal squamous cell carcinoma JF - European Archives of Oto-Rhino-Laryngology and Head & Neck N2 - Purpose Confocal laser endomicroscopy (CLE) allows imaging of the laryngeal mucosa in a thousand-fold magnification. This study analyzes differences in tissue homogeneity between healthy mucosa and squamous cell carcinoma (SCC) via CLE. Materials and methods We included five SCC patients with planned total laryngectomy in this study between October 2020 and February 2021. We captured CLE scans of the tumor and healthy mucosa. Analysis of image homogeneity to diagnose SCC was performed by measuring the signal intensity in four regions of interest (ROI) in each frame in a total of 60 sequences. Each sequence was assigned to the corresponding histological pattern, derived from hematoxylin and eosin staining. In addition, we recorded the subjective evaluation of seven investigators regarding tissue homogeneity. Results Out of 3600 images, 1620 (45%) correlated with benign mucosa and 1980 (55%) with SCC. ROIs of benign mucosa and SCC had a mean and standard deviation (SD) of signal intensity of, respectively, 232.1 ± 3.34 and 467.3 ± 9.72 (P < 0.001). The mean SD between the four different ROIs was 39.1 ± 1.03 for benign and 101.5 ± 2.6 for SCC frames (P < 0.001). In addition, homogeneity yielded a sensitivity and specificity of 81.8% and 86.2%, respectively, regarding the investigator-dependent analysis. Conclusions SCC shows a significant tissue inhomogeneity in comparison to the healthy epithelium. The results support this feature’s importance in identifying malignant mucosa areas during CLE examination. However, the examiner-dependent evaluation emphasizes that homogeneity is a sub-criterion that must be considered in a broad context. UR - https://doi.org/10.1007/s00405-022-07304-y KW - confocal laser endomicroscopy KW - head and neck cancer KW - classification system KW - non-invasive histological imaging KW - larynx KW - pharynx Y1 - 2022 UR - https://doi.org/10.1007/s00405-022-07304-y UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-23180 SN - 1434-4726 SN - 0937-4477 VL - 279 IS - 8 SP - 4147 EP - 4156 PB - Springer Nature CY - Cham ER - TY - JOUR A1 - Sievert, Matti A1 - Mantsopoulos, Konstantinos A1 - Müller, Sarina K. A1 - Rupp, Robin A1 - Eckstein, Markus A1 - Stelzle, Florian A1 - Oetter, Nicolai A1 - Maier, Andreas A1 - Aubreville, Marc A1 - Iro, Heinrich A1 - Goncalves, Miguel T1 - Validation of a classification and scoring system for the diagnosis of laryngeal and pharyngeal squamous cell carcinomas by confocal laser endomicroscopy JF - Brazilian Journal of Otorhinolaryngology N2 - Introduction Confocal laser endomicroscopy is an optical imaging technique that allows in vivo, real-time, microscope-like images of the upper aerodigestive tract’s mucosa. The assessment of morphological tissue characteristics for the correct differentiation between healthy and malignant suspected mucosa requires strict evaluation criteria. Objective This study aims to validate an eight-point score for the correct assessment of malignancy. Methods We performed confocal laser endomicroscopy between March and October 2020 in 13 patients. 197 sequences (11.820 images) originated from the marginal area of pharyngeal and laryngeal carcinomas. Specimens were taken at corresponding locations and analyzed in H&E staining as a standard of reference. A total of six examiners evaluated the sequences based on a scoring system; they were blinded to the histopathological examination. The primary endpoints are sensitivity, specificity, and accuracy. Secondary endpoints are interrater reliability and receiver operator characteristics. Results Healthy mucosa showed epithelium with uniform size and shape with distinct cytoplasmic membranes and regular vessel architecture. Confocal laser endomicroscopy of malignant cells demonstrated a disorganized arrangement of variable cellular morphology. We calculated an accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 83.2%, 81.3%, 85.5%, 86.7%, and 79.7%, respectively, with a κ-value of 0.64, and an area under the curve of 0.86. Conclusion The results confirm that this scoring system is applicable in the laryngeal and pharyngeal mucosa to classify benign and malignant tissue. A scoring system based on defined and reproducible characteristics can help translate this experimental method to broad clinical practice in head and neck diagnosis. UR - https://doi.org/10.1016/j.bjorl.2021.06.002 KW - confocal laser endomicroscopy KW - squamous cell carcinoma KW - head and neck cancer KW - diagnosis Y1 - 2021 UR - https://doi.org/10.1016/j.bjorl.2021.06.002 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-20887 SN - 1808-8694 VL - 2022 IS - 88, S4 SP - 26 EP - 32 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Sievert, Matti A1 - Eckstein, Markus A1 - Mantsopoulos, Konstantinos A1 - Müller, Sarina K. A1 - Stelzle, Florian A1 - Aubreville, Marc A1 - Oetter, Nicolai A1 - Maier, Andreas A1 - Iro, Heinrich A1 - Goncalves, Miguel T1 - Impact of intraepithelial capillary loops and atypical vessels in confocal laser endomicroscopy for the diagnosis of laryngeal and hypopharyngeal squamous cell carcinoma JF - European Archives of Oto-Rhino-Laryngology and Head & Neck N2 - Purpose Confocal laser endomicroscopy (CLE) allows surface imaging of the laryngeal and pharyngeal mucosa in vivo at a thousand-fold magnification. This study aims to compare irregular blood vessels and intraepithelial capillary loops in healthy mucosa and squamous cell carcinoma (SCC) via CLE. Materials and methods We included ten patients with confirmed SCC and planned total laryngectomy in this study between March 2020 and February 2021. CLE images of these patients were collected and compared with the corresponding histology in hematoxylin and eosin staining. We analyzed the characteristic endomicroscopic patterns of blood vessels and intraepithelial capillary loops for the diagnosis of SCC. Results In a total of 54 sequences, we identified 243 blood vessels which were analyzed regarding structure, diameter, and Fluorescein leakage, confirming that irregular, corkscrew-like vessels (24.4% vs. 1.3%; P < .001), dilated intraepithelial capillary loops (90.8% vs. 28.7%; P < .001), and increased capillary leakage (40.7% vs. 2.5%; P < .001), are significantly more frequently detected in SCC compared to the healthy epithelium. We defined a vessel diameter of 30 μm in capillary loops as a cut-off value, obtaining a sensitivity, specificity, PPV, and NPV and accuracy of 90.6%, 71.3%, 57.4%, 94.7%, and 77.1%, respectively, for the detection of malignancy based solely on capillary architecture. Conclusion Capillaries within malignant lesions are fundamentally different from those in healthy mucosa regions. The capillary architecture is a significant feature aiding the identification of malignant mucosa areas during in-vivo, real-time CLE examination. UR - https://doi.org/10.1007/s00405-021-06954-8 KW - confocal laser endomicroscopy KW - head and neck squamous cell carcinoma KW - capillary loops KW - malignant vascularization KW - head and neck malignancies Y1 - 2021 UR - https://doi.org/10.1007/s00405-021-06954-8 UR - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:573-23196 SN - 1434-4726 SN - 0937-4477 VL - 279 IS - 4 SP - 2029 EP - 2037 PB - Springer Nature CY - Cham 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 - JOUR A1 - Pan, Zhaoya A1 - Breininger, Katharina A1 - Aubreville, Marc A1 - Stelzle, Florian A1 - Oetter, Nicolai A1 - Maier, Andreas A1 - Mantsopoulos, Konstantinos A1 - Iro, Heinrich A1 - Goncalves, Miguel A1 - Sievert, Matti T1 - Defining a baseline identification of artifacts in confocal laser endomicroscopy in head and neck cancer imaging JF - American Journal of Otolaryngology UR - https://doi.org/10.1016/j.amjoto.2022.103779 KW - Confocal laser endomicroscopy KW - Head and neck cancer KW - Classification system KW - Non-invasive histological imaging KW - Larynx KW - Pharynx Y1 - 2022 UR - https://doi.org/10.1016/j.amjoto.2022.103779 SN - 1532-818X SN - 0196-0709 VL - 44 IS - 2 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 -