Peter A. Fasching

Mathias Öttl, Frauke Wilm, Jana Steenpass et al.

Deep learning-based image generation has seen significant advancements with diffusion models, notably improving the quality of generated images. Despite these developments, generating images with unseen characteristics beneficial for downstream tasks has received limited attention. To bridge this gap, we propose Style-Extracting Diffusion Models, featuring two conditioning mechanisms. Specifically, we utilize 1) a style conditioning mechanism which allows to inject style information of previously unseen images during image generation and 2) a content conditioning which can be targeted to a downstream task, e.g., layout for segmentation. We introduce a trainable style encoder to extract style information from images, and an aggregation block that merges style information from multiple style inputs. This architecture enables the generation of images with unseen styles in a zero-shot manner, by leveraging styles from unseen images, resulting in more diverse generations. In this work, we use the image layout as target condition and first show the capability of our method on a natural image dataset as a proof-of-concept. We further demonstrate its versatility in histopathology, where we combine prior knowledge about tissue composition and unannotated data to create diverse synthetic images with known layouts. This allows us to generate additional synthetic data to train a segmentation network in a semi-supervised fashion. We verify the added value of the generated images by showing improved segmentation results and lower performance variability between patients when synthetic images are included during segmentation training. Our code will be made publicly available at [LINK].

Mathias Öttl, Siyuan Mei, Frauke Wilm et al.

Denoising Diffusion Probabilistic models have become increasingly popular due to their ability to offer probabilistic modeling and generate diverse outputs. This versatility inspired their adaptation for image segmentation, where multiple predictions of the model can produce segmentation results that not only achieve high quality but also capture the uncertainty inherent in the model. Here, powerful architectures were proposed for improving diffusion segmentation performance. However, there is a notable lack of analysis and discussions on the differences between diffusion segmentation and image generation, and thorough evaluations are missing that distinguish the improvements these architectures provide for segmentation in general from their benefit for diffusion segmentation specifically. In this work, we critically analyse and discuss how diffusion segmentation for medical images differs from diffusion image generation, with a particular focus on the training behavior. Furthermore, we conduct an assessment how proposed diffusion segmentation architectures perform when trained directly for segmentation. Lastly, we explore how different medical segmentation tasks influence the diffusion segmentation behavior and the diffusion process could be adapted accordingly. With these analyses, we aim to provide in-depth insights into the behavior of diffusion segmentation that allow for a better design and evaluation of diffusion segmentation methods in the future.

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.

Yinchong Yang, Zhiliang Wu, Volker Tresp et al.

Electronic Health Records often suffer from missing data, which poses a major problem in clinical practice and clinical studies. A novel approach for dealing with missing data are Generative Adversarial Nets (GANs), which have been generating huge research interest in image generation and transformation. Recently, researchers have attempted to apply GANs to missing data generation and imputation for EHR data: a major challenge here is the categorical nature of the data. State-of-the-art solutions to the GAN-based generation of categorical data involve either reinforcement learning, or learning a bidirectional mapping between the categorical and the real latent feature space, so that the GANs only need to generate real-valued features. However, these methods are designed to generate complete feature vectors instead of imputing only the subsets of missing features. In this paper we propose a simple and yet effective approach that is based on previous work on GANs for data imputation. We first motivate our solution by discussing the reason why adversarial training often fails in case of categorical features. Then we derive a novel way to re-code the categorical features to stabilize the adversarial training. Based on experiments on two real-world EHR data with multiple settings, we show that our imputation approach largely improves the prediction accuracy, compared to more traditional data imputation approaches.

Zhiliang Wu, Yinchong Yang, Peter A. Fasching et al.

Recurrent neural network based solutions are increasingly being used in the analysis of longitudinal Electronic Health Record data. However, most works focus on prediction accuracy and neglect prediction uncertainty. We propose Deep Kernel Accelerated Failure Time models for the time-to-event prediction task, enabling uncertainty-awareness of the prediction by a pipeline of a recurrent neural network and a sparse Gaussian Process. Furthermore, a deep metric learning based pre-training step is adapted to enhance the proposed model. Our model shows better point estimate performance than recurrent neural network based baselines in experiments on two real-world datasets. More importantly, the predictive variance from our model can be used to quantify the uncertainty estimates of the time-to-event prediction: Our model delivers better performance when it is more confident in its prediction. Compared to related methods, such as Monte Carlo Dropout, our model offers better uncertainty estimates by leveraging an analytical solution and is more computationally efficient.

Yinchong Yang, Peter A. Fasching, Markus Wallwiener et al.

With the introduction of the Electric Health Records, large amounts of digital data become available for analysis and decision support. When physicians are prescribing treatments to a patient, they need to consider a large range of data variety and volume, making decisions increasingly complex. Machine learning based Clinical Decision Support systems can be a solution to the data challenges. In this work we focus on a class of decision support in which the physicians' decision is directly predicted. Concretely, the model would assign higher probabilities to decisions that it presumes the physician are more likely to make. Thus the CDS system can provide physicians with rational recommendations. We also address the problem of correlation in target features: Often a physician is required to make multiple (sub-)decisions in a block, and that these decisions are mutually dependent. We propose a solution to the target correlation problem using a tensor factorization model. In order to handle the patients' historical information as sequential data, we apply the so-called Encoder-Decoder-Framework which is based on Recurrent Neural Networks (RNN) as encoders and a tensor factorization model as a decoder, a combination which is novel in machine learning. With experiments with real-world datasets we show that the proposed model does achieve better prediction performances.

Volker Tresp, Sonja Zillner, Maria J. Costa et al.

In this paper we define Clinical Data Intelligence as the analysis of data generated in the clinical routine with the goal of improving patient care. We define a science of a Clinical Data Intelligence as a data analysis that permits the derivation of scientific, i.e., generalizable and reliable results. We argue that a science of a Clinical Data Intelligence is sensible in the context of a Big Data analysis, i.e., with data from many patients and with complete patient information. We discuss that Clinical Data Intelligence requires the joint efforts of knowledge engineering, information extraction (from textual and other unstructured data), and statistics and statistical machine learning. We describe some of our main results as conjectures and relate them to a recently funded research project involving two major German university hospitals.