The QUILT-1M dataset is the first openly available dataset containing images harvested from various online sources. While it provides a huge data variety, the image quality and composition is highly heterogeneous, impacting its utility for text-conditional image synthesis. We propose an automatic pipeline that provides predictions of the most common impurities within the images, e.g., visibility of narrators, desktop environment and pathology software, or text within the image. Additionally, we propose to use semantic alignment filtering of the image-text pairs. Our findings demonstrate that by rigorously filtering the dataset, there is a substantial enhancement of image fidelity in text-to-image tasks.

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. 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 50.16 % and 52.30 % on the LSCC and LUAD datasets, respectively, and with 62.31 % 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.

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.

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.

Recent advancements in the domain of text-to-image synthesis have culminated in a multitude of enhancements pertaining to quality, fidelity, and diversity. Contemporary techniques enable the generation of highly intricate visuals which rapidly approach near-photorealistic quality. Nevertheless, as progress is achieved, the complexity of these methodologies increases, consequently intensifying the comprehension barrier between individuals within the field and those external to it. In an endeavor to mitigate this disparity, we propose a streamlined approach for text-to-image generation, which encompasses both the training paradigm and the sampling process. Despite its remarkable simplicity, our method yields aesthetically pleasing images with few sampling iterations, allows for intriguing ways for conditioning the model, and imparts advantages absent in state-of-the-art techniques. To demonstrate the efficacy of this approach in achieving outcomes comparable to existing works, we have trained a one-billion parameter text-conditional model, which we refer to as "Paella". In the interest of fostering future exploration in this field, we have made our source code and models publicly accessible for the research community.

International benchmarking competitions have become fundamental for the comparative performance assessment of image analysis methods. However, little attention has been given to investigating what can be learnt from these competitions. Do they really generate scientific progress? What are common and successful participation strategies? What makes a solution superior to a competing method? To address this gap in the literature, we performed a multi-center study with all 80 competitions that were conducted in the scope of IEEE ISBI 2021 and MICCAI 2021. Statistical analyses performed based on comprehensive descriptions of the submitted algorithms linked to their rank as well as the underlying participation strategies revealed common characteristics of winning solutions. These typically include the use of multi-task learning (63%) and/or multi-stage pipelines (61%), and a focus on augmentation (100%), image preprocessing (97%), data curation (79%), and postprocessing (66%). The "typical" lead of a winning team is a computer scientist with a doctoral degree, five years of experience in biomedical image analysis, and four years of experience in deep learning. Two core general development strategies stood out for highly-ranked teams: the reflection of the metrics in the method design and the focus on analyzing and handling failure cases. According to the organizers, 43% of the winning algorithms exceeded the state of the art but only 11% completely solved the respective domain problem. The insights of our study could help researchers (1) improve algorithm development strategies when approaching new problems, and (2) focus on open research questions revealed by this work.

Canine mammary carcinoma (CMC) has been used as a model to investigate the pathogenesis of human breast cancer and the same grading scheme is commonly used to assess tumor malignancy in both. One key component of this grading scheme is the density of mitotic figures (MF). Current publicly available datasets on human breast cancer only provide annotations for small subsets of whole slide images (WSIs). We present a novel dataset of 21 WSIs of CMC completely annotated for MF. For this, a pathologist screened all WSIs for potential MF and structures with a similar appearance. A second expert blindly assigned labels, and for non-matching labels, a third expert assigned the final labels. Additionally, we used machine learning to identify previously undetected MF. Finally, we performed representation learning and two-dimensional projection to further increase the consistency of the annotations. Our dataset consists of 13,907 MF and 36,379 hard negatives. We achieved a mean F1-score of 0.791 on the test set and of up to 0.696 on a human breast cancer dataset.

Manual counts of mitotic figures, which are determined in the tumor region with the highest mitotic activity, are a key parameter of most tumor grading schemes. It is however strongly dependent on the area selection. To reduce potential variability of prognosis due to this, we propose to use an algorithmic field of interest prediction to assess the area of highest mitotic activity in a whole-slide image. Methods: We evaluated two state-of-the-art methods, all based on the use of deep convolutional neural networks on their ability to predict the mitotic count in digital histopathology slides. We evaluated them on a novel dataset of 32 completely annotated whole slide images from canine cutaneous mast cell tumors (CMCT) and one publicly available human mamma carcinoma (HMC) dataset. We first compared the mitotic counts (MC) predicted by the two models with the ground truth MC on both data sets. Second, for the CMCT data set, we compared the computationally predicted position and MC of the area of highest mitotic activity with size-equivalent areas selected by eight veterinary pathologists. Results: We found a high correlation between the mitotic count as predicted by the models (Pearson's correlation coefficient between 0.931 and 0.962 for the CMCT data set and between 0.801 and 0.986 for the HMC data set) on the slides. For the CMCT data set, this is also reflected in the predicted position representing mitotic counts in mostly the upper quartile of the slide's ground truth MC distribution. Further, we found strong differences between experts in position selection. Conclusion: While the mitotic counts in areas selected by the experts substantially varied, both algorithmic approaches were consistently able to generate a good estimate of the area of highest mitotic count. To achieve better inter-rater agreement, we propose to use computer-based area selection for manual mitotic count.