Globally Optimal Cell Tracking using Integer Programming

We propose a novel approach to automatically tracking cell populations in time-lapse images. To account for cell occlusions and overlaps, we introduce a robust method that generates an over-complete set of competing detection hypotheses. We then perform detection and tracking simultaneously on these hypotheses by solving to optimality an integer program with only one type of flow variables. This eliminates the need for heuristics to handle missed detections due to occlusions and complex morphology. We demonstrate the effectiveness of our approach on a range of challenging sequences consisting of clumped cells and show that it outperforms state-of-the-art techniques.Comment: Engin T\"uretken and Xinchao Wang contributed equally to this wor

Generative modeling of living cells with SO(3)-equivariant implicit neural representations

Data-driven cell tracking and segmentation methods in biomedical imaging require diverse and information-rich training data. In cases where the number of training samples is limited, synthetic computer-generated data sets can be used to improve these methods. This requires the synthesis of cell shapes as well as corresponding microscopy images using generative models. To synthesize realistic living cell shapes, the shape representation used by the generative model should be able to accurately represent fine details and changes in topology, which are common in cells. These requirements are not met by 3D voxel masks, which are restricted in resolution, and polygon meshes, which do not easily model processes like cell growth and mitosis. In this work, we propose to represent living cell shapes as level sets of signed distance functions (SDFs) which are estimated by neural networks. We optimize a fully-connected neural network to provide an implicit representation of the SDF value at any point in a 3D+time domain, conditioned on a learned latent code that is disentangled from the rotation of the cell shape. We demonstrate the effectiveness of this approach on cells that exhibit rapid deformations (Platynereis dumerilii), cells that grow and divide (C. elegans), and cells that have growing and branching filopodial protrusions (A549 human lung carcinoma cells). A quantitative evaluation using shape features, Hausdorff distance, and Dice similarity coefficients of real and synthetic cell shapes shows that our model can generate topologically plausible complex cell shapes in 3D+time with high similarity to real living cell shapes. Finally, we show how microscopy images of living cells that correspond to our generated cell shapes can be synthesized using an image-to-image model.Comment: Medical Image Analysis 2023 (Submitted

Methods for Spatio-Temporal Analysis of Embryo Cleavage In Vitro

Automated or semiautomated time-lapse analysis of early stage embryo images during the cleavage stage can give insight into the timing of mitosis, regularity of both division timing and pattern, as well as cell lineage. Simultaneous monitoring of molecular processes enables the study of connections between genetic expression and cell physiology and development. The study of live embryos poses not only new requirements on the hardware and embryo-holding equipment but also indirectly on analytical software and data analysis as four-dimensional video sequencing of embryos easily creates high quantities of data. The ability to continuously film and automatically analyze growing embryos gives new insights into temporal embryo development by studying morphokinetics as well as morphology. Until recently, this was not possible unless by a tedious manual process. In recent years, several methods have been developed that enable this dynamic monitoring of live embryos. Here we describe three methods with variations in hardware and software analysis and give examples of the outcomes. Together, these methods open a window to new information in developmental embryology, as embryo division pattern and lineage are studied in vivo

Multi-StyleGAN: Towards Image-Based Simulation of Time-Lapse Live-Cell Microscopy

Time-lapse fluorescent microscopy (TLFM) combined with predictive mathematical modelling is a powerful tool to study the inherently dynamic processes of life on the single-cell level. Such experiments are costly, complex and labour intensive. A complimentary approach and a step towards in silico experimentation, is to synthesise the imagery itself. Here, we propose Multi-StyleGAN as a descriptive approach to simulate time-lapse fluorescence microscopy imagery of living cells, based on a past experiment. This novel generative adversarial network synthesises a multi-domain sequence of consecutive timesteps. We showcase Multi-StyleGAN on imagery of multiple live yeast cells in microstructured environments and train on a dataset recorded in our laboratory. The simulation captures underlying biophysical factors and time dependencies, such as cell morphology, growth, physical interactions, as well as the intensity of a fluorescent reporter protein. An immediate application is to generate additional training and validation data for feature extraction algorithms or to aid and expedite development of advanced experimental techniques such as online monitoring or control of cells. Code and dataset is available at https://git.rwth-aachen.de/bcs/projects/tp/multi-stylegan.Comment: revised -- accepted to MICCAI 2021. (Tim Prangemeier and Christoph Reich --- both authors contributed equally