Carol I. Geppert

Mathias Öttl, Jana Mönius, Matthias Rübner et al.

Tumor segmentation in histopathology images is often complicated by its composition of different histological subtypes and class imbalance. Oversampling subtypes with low prevalence features is not a satisfactory solution since it eventually leads to overfitting. We propose to create synthetic images with semantically-conditioned deep generative networks and to combine subtype-balanced synthetic images with the original dataset to achieve better segmentation performance. We show the suitability of Generative Adversarial Networks (GANs) and especially diffusion models to create realistic images based on subtype-conditioning for the use case of HER2-stained histopathology. Additionally, we show the capability of diffusion models to conditionally inpaint HER2 tumor areas with modified subtypes. Combining the original dataset with the same amount of diffusion-generated images increased the tumor Dice score from 0.833 to 0.854 and almost halved the variance between the HER2 subtype recalls. These results create the basis for more reliable automatic HER2 analysis with lower performance variance between individual HER2 subtypes.

Mathias Öttl, Jana Mönius, Christian Marzahl et al.

Supervised deep learning has shown state-of-the-art performance for medical image segmentation across different applications, including histopathology and cancer research; however, the manual annotation of such data is extremely laborious. In this work, we explore the use of superpixel approaches to compute a pre-segmentation of HER2 stained images for breast cancer diagnosis that facilitates faster manual annotation and correction in a second step. Four methods are compared: Standard Simple Linear Iterative Clustering (SLIC) as a baseline, a domain adapted SLIC, and superpixels based on feature embeddings of a pretrained ResNet-50 and a denoising autoencoder. To tackle oversegmentation, we propose to hierarchically merge superpixels, based on their content in the respective feature space. When evaluating the approaches on fully manually annotated images, we observe that the autoencoder-based superpixels achieve a 23% increase in boundary F1 score compared to the baseline SLIC superpixels. Furthermore, the boundary F1 score increases by 73% when hierarchical clustering is applied on the adapted SLIC and the autoencoder-based superpixels. These evaluations show encouraging first results for a pre-segmentation for efficient manual refinement without the need for an initial set of annotated training data.

Frauke Wilm, Michaela Benz, Volker Bruns et al.

Automatic outlining of different tissue types in digitized histological specimen provides a basis for follow-up analyses and can potentially guide subsequent medical decisions. The immense size of whole-slide-images (WSI), however, poses a challenge in terms of computation time. In this regard, the analysis of non-overlapping patches outperforms pixelwise segmentation approaches, but still leaves room for optimization. Furthermore, the division into patches, regardless of the biological structures they contain, is a drawback due to the loss of local dependencies. We propose to subdivide the WSI into coherent regions prior to classification by grouping visually similar adjacent pixels into superpixels. Afterwards, only a random subset of patches per superpixel is classified and patch labels are combined into a superpixel label. We propose a metric for identifying superpixels with an uncertain classification and evaluate two medical applications, namely tumor area and invasive margin estimation and tumor composition analysis. The algorithm has been developed on 159 hand-annotated WSIs of colon resections and its performance is compared to an analysis without prior segmentation. The algorithm shows an average speed-up of 41% and an increase in accuracy from 93.8% to 95.7%. By assigning a rejection label to uncertain superpixels, we further increase the accuracy by 0.4%. Whilst tumor area estimation shows high concordance to the annotated area, the analysis of tumor composition highlights limitations of our approach. By combining superpixel segmentation and patch classification, we designed a fast and accurate framework for whole-slide cartography that is AI-model agnostic and provides the basis for various medical endpoints.