Domain generalization across tumor types, laboratories, and species -- insights from the 2022 edition of the Mitosis Domain Generalization Challenge

Recognition of mitotic figures in histologic tumor specimens is highly relevant to patient outcome assessment. This task is challenging for algorithms and human experts alike, with deterioration of algorithmic performance under shifts in image representations. Considerable covariate shifts occur when assessment is performed on different tumor types, images are acquired using different digitization devices, or specimens are produced in different laboratories. This observation motivated the inception of the 2022 challenge on MItosis Domain Generalization (MIDOG 2022). The challenge provided annotated histologic tumor images from six different domains and evaluated the algorithmic approaches for mitotic figure detection provided by nine challenge participants on ten independent domains. Ground truth for mitotic figure detection was established in two ways: a three-expert consensus and an independent, immunohistochemistry-assisted set of labels. This work represents an overview of the challenge tasks, the algorithmic strategies employed by the participants, and potential factors contributing to their success. With an $F_1$ score of 0.764 for the top-performing team, we summarize that domain generalization across various tumor domains is possible with today's deep learning-based recognition pipelines. When assessed against the immunohistochemistry-assisted reference standard, all methods resulted in reduced recall scores, but with only minor changes in the order of participants in the ranking.

Fast whole-slide cartography in colon cancer histology using superpixels and CNN classification

Whole-slide-image cartography is the process of automatically detecting and outlining different tissue types in digitized histological specimen. This semantic segmentation provides a basis for many follow-up analyses and can potentially guide subsequent medical decisions. Due to their large size, whole-slide-images typically have to be divided into smaller patches which are then analyzed individually using machine learning-based approaches. Thereby, local dependencies of image regions get lost and since a whole-slide-image comprises many thousands of such patches this process is inherently slow. We propose to subdivide the image into coherent regions prior to classification by grouping visually similar adjacent image pixels into larger segments, i.e. superpixels. Afterwards, only a random subset of patches per superpixel is classified and patch labels are combined into a single superpixel label. The algorithm has been developed and validated on a dataset of 159 hand-annotated whole-slide-images of colon resections and its performance has been compared to a standard patch-based approach. The algorithm shows an average speed-up of 41% on the test data and the overall accuracy is increased from 93.8% to 95.7%. We additionally propose a metric for identifying superpixels with an uncertain classification so they can be excluded from further analysis. Finally, we evaluate two potential medical applications, namely tumor area estimation including tumor invasive margin generation and tumor composition analysis.