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Walter de Back

Publications and source records attributed to Walter de Back.

4 recordsLinked to original sources

Structure-Preserving Multi-Domain Stain Color Augmentation using Style-Transfer with Disentangled Representations

In digital pathology, different staining procedures and scanners cause substantial color variations in whole-slide images (WSIs), especially across different laboratories. These color shifts result in a poor generalization of deep learning-based methods from the training domain to external pathology data. To increase test performance, stain normalization techniques are used to reduce the variance between training and test domain. Alternatively, color augmentation can be applied during training leading to a more robust model without the extra step of color normalization at test time. We propose a novel color augmentation technique, HistAuGAN, that can simulate a wide variety of realistic histology stain colors, thus making neural networks stain-invariant when applied during training. Based on a generative adversarial network (GAN) for image-to-image translation, our model disentangles the content of the image, i.e., the morphological tissue structure, from the stain color attributes. It can be trained on multiple domains and, therefore, learns to cover different stain colors as well as other domain-specific variations introduced in the slide preparation and imaging process. We demonstrate that HistAuGAN outperforms conventional color augmentation techniques on a classification task on the publicly available dataset Camelyon17 and show that it is able to mitigate present batch effects.

eess.IV

An interpretable automated detection system for FISH-based HER2 oncogene amplification testing in histo-pathological routine images of breast and gastric cancer diagnostics

Histo-pathological diagnostics are an inherent part of the everyday work but are particularly laborious and associated with time-consuming manual analysis of image data. In order to cope with the increasing diagnostic case numbers due to the current growth and demographic change of the global population and the progress in personalized medicine, pathologists ask for assistance. Profiting from digital pathology and the use of artificial intelligence, individual solutions can be offered (e.g. detect labeled cancer tissue sections). The testing of the human epidermal growth factor receptor 2 (HER2) oncogene amplification status via fluorescence in situ hybridization (FISH) is recommended for breast and gastric cancer diagnostics and is regularly performed at clinics. Here, we develop an interpretable, deep learning (DL)-based pipeline which automates the evaluation of FISH images with respect to HER2 gene amplification testing. It mimics the pathological assessment and relies on the detection and localization of interphase nuclei based on instance segmentation networks. Furthermore, it localizes and classifies fluorescence signals within each nucleus with the help of image classification and object detection convolutional neural networks (CNNs). Finally, the pipeline classifies the whole image regarding its HER2 amplification status. The visualization of pixels on which the networks' decision occurs, complements an essential part to enable interpretability by pathologists.

eess.IV

Quantification of Nematic Cell Polarity in Three-dimensional Tissues

How epithelial cells coordinate their polarity to form functional tissues is an open question in cell biology. Here, we characterize a unique type of polarity found in liver tissue, nematic cell polarity, which is different from vectorial cell polarity in simple, sheet-like epithelia. We propose a conceptual and algorithmic framework to characterize complex patterns of polarity proteins on the surface of a cell in terms of a multipole expansion. To rigorously quantify previously observed tissue-level patterns of nematic cell polarity (Morales-Navarette et al., eLife 8:e44860, 2019), we introduce the concept of co-orientational order parameters, which generalize the known biaxial order parameters of the theory of liquid crystals. Applying these concepts to three-dimensional reconstructions of single cells from high-resolution imaging data of mouse liver tissue, we show that the axes of nematic cell polarity of hepatocytes exhibit local coordination and are aligned with the biaxially anisotropic sinusoidal network for blood transport. Our study characterizes liver tissue as a biological example of a biaxial liquid crystal. The general methodology developed here could be applied to other tissues or in-vitro organoids.

q-bio.TO

Statistical and mathematical modeling of spatiotemporal dynamics of stem cells

Statistical and mathematical modeling are crucial to describe, interpret, compare and predict the behavior of complex biological systems including the organization of hematopoietic stem and progenitor cells in the bone marrow environment. The current prominence of high-resolution and live-cell imaging data provides an unprecedented opportunity to study the spatiotemporal dynamics of these cells within their stem cell niche and learn more about aberrant, but also unperturbed, normal hematopoiesis. However, this requires careful quantitative statistical analysis of the spatial and temporal behavior of cells and the interaction with their microenvironment. Moreover, such quantification is a prerequisite for the construction of hypothesis-driven mathematical models that can provide mechanistic explanations by generating spatiotemporal dynamics that can be directly compared to experimental observations. Here, we provide a brief overview of statistical methods in analyzing spatial distribution of cells, cell motility, cell shapes and cellular genealogies. We also describe cell- based modeling formalisms that allow researchers to simulate emergent behavior in a multicellular system based on a set of hypothesized mechanisms. Together, these methods provide a quantitative workflow for the analytic and synthetic study of the spatiotemporal behavior of hematopoietic stem and progenitor cells.

q-bio.QM