Mathias Öttl

Jingna Qiu, Frauke Wilm, Mathias Öttl et al.

The process of annotating histological gigapixel-sized whole slide images (WSIs) at the pixel level for the purpose of training a supervised segmentation model is time-consuming. Region-based active learning (AL) involves training the model on a limited number of annotated image regions instead of requesting annotations of the entire images. These annotation regions are iteratively selected, with the goal of optimizing model performance while minimizing the annotated area. The standard method for region selection evaluates the informativeness of all square regions of a specified size and then selects a specific quantity of the most informative regions. We find that the efficiency of this method highly depends on the choice of AL step size (i.e., the combination of region size and the number of selected regions per WSI), and a suboptimal AL step size can result in redundant annotation requests or inflated computation costs. This paper introduces a novel technique for selecting annotation regions adaptively, mitigating the reliance on this AL hyperparameter. Specifically, we dynamically determine each region by first identifying an informative area and then detecting its optimal bounding box, as opposed to selecting regions of a uniform predefined shape and size as in the standard method. We evaluate our method using the task of breast cancer metastases segmentation on the public CAMELYON16 dataset and show that it consistently achieves higher sampling efficiency than the standard method across various AL step sizes. With only 2.6\% of tissue area annotated, we achieve full annotation performance and thereby substantially reduce the costs of annotating a WSI dataset. The source code is available at https://github.com/DeepMicroscopy/AdaptiveRegionSelection.

Frauke Wilm, Jonas Ammeling, Mathias Öttl et al.

The U-net architecture has significantly impacted deep learning-based segmentation of medical images. Through the integration of long-range skip connections, it facilitated the preservation of high-resolution features. Out-of-distribution data can, however, substantially impede the performance of neural networks. Previous works showed that the trained network layers differ in their susceptibility to this domain shift, e.g., shallow layers are more affected than deeper layers. In this work, we investigate the implications of this observation of layer sensitivity to domain shifts of U-net-style segmentation networks. By copying features of shallow layers to corresponding decoder blocks, these bear the risk of re-introducing domain-specific information. We used a synthetic dataset to model different levels of data distribution shifts and evaluated the impact on downstream segmentation performance. We quantified the inherent domain susceptibility of each network layer, using the Hellinger distance. These experiments confirmed the higher domain susceptibility of earlier network layers. When gradually removing skip connections, a decrease in domain susceptibility of deeper layers could be observed. For downstream segmentation performance, the original U-net outperformed the variant without any skip connections. The best performance, however, was achieved when removing the uppermost skip connection - not only in the presence of domain shifts but also for in-domain test data. We validated our results on three clinical datasets - two histopathology datasets and one magnetic resonance dataset - with performance increases of up to 10% in-domain and 13% cross-domain when removing the uppermost skip connection.

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.