Sven Dummer

David Wiesner, Julian Suk, Sven Dummer et al.

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 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.

David Wiesner, Julian Suk, Sven Dummer et al.

Methods allowing the synthesis of realistic cell shapes could help generate training data sets to improve cell tracking and segmentation in biomedical images. Deep generative models for cell shape synthesis require a light-weight and flexible representation of the cell shape. However, commonly used voxel-based representations are unsuitable for high-resolution shape synthesis, and polygon meshes have limitations when modeling topology changes such as cell growth or mitosis. In this work, we propose to use level sets of signed distance functions (SDFs) to represent cell shapes. We optimize a neural network as an implicit neural representation of the SDF value at any point in a 3D+time domain. The model is conditioned on a latent code, thus allowing the synthesis of new and unseen shape sequences. We validate our approach quantitatively and qualitatively on C. elegans cells that grow and divide, and lung cancer cells with growing complex filopodial protrusions. Our results show that shape descriptors of synthetic cells resemble those of real cells, and that our model is able to generate topologically plausible sequences of complex cell shapes in 3D+time.

Simone Garzia, Patryk Rygiel, Sven Dummer et al.

Time-resolved three-dimensional flow MRI (4D flow MRI) provides a unique non-invasive solution to visualize and quantify hemodynamics in blood vessels such as the aortic arch. However, most current analysis methods for arterial 4D flow MRI use static artery walls because of the difficulty in obtaining a full cycle segmentation. To overcome this limitation, we propose a neural fields-based method that directly estimates continuous periodic wall deformations throughout the cardiac cycle. For a 3D + time imaging dataset, we optimize an implicit neural representation (INR) that represents a time-dependent velocity vector field (VVF). An ODE solver is used to integrate the VVF into a deformation vector field (DVF), that can deform images, segmentation masks, or meshes over time, thereby visualizing and quantifying local wall motion patterns. To properly reflect the periodic nature of 3D + time cardiovascular data, we impose periodicity in two ways. First, by periodically encoding the time input to the INR, and hence VVF. Second, by regularizing the DVF. We demonstrate the effectiveness of this approach on synthetic data with different periodic patterns, ECG-gated CT, and 4D flow MRI data. The obtained method could be used to improve 4D flow MRI analysis.

Ioana Mazilu, Shunxin Wang, Sven Dummer et al.

Though modern microscopes have an autofocusing system to ensure optimal focus, out-of-focus images can still occur when cells within the medium are not all in the same focal plane, affecting the image quality for medical diagnosis and analysis of diseases. We propose a method that can deblur images as well as synthesize defocus blur. We train autoencoders with implicit and explicit regularization techniques to enforce linearity relations among the representations of different blur levels in the latent space. This allows for the exploration of different blur levels of an object by linearly interpolating/extrapolating the latent representations of images taken at different focal planes. Compared to existing works, we use a simple architecture to synthesize images with flexible blur levels, leveraging the linear latent space. Our regularized autoencoders can effectively mimic blur and deblur, increasing data variety as a data augmentation technique and improving the quality of microscopic images, which would be beneficial for further processing and analysis.

Sven Dummer, Dongwei Ye, Christoph Brune

Time-dependent partial differential equations are ubiquitous in physics-based modeling, but they remain computationally intensive in many-query scenarios, such as real-time forecasting, optimal control, and uncertainty quantification. Reduced-order modeling (ROM) addresses these challenges by constructing a low-dimensional surrogate model but relies on a fixed discretization, which limits flexibility across varying meshes during evaluation. Operator learning approaches, such as neural operators, offer an alternative by parameterizing mappings between infinite-dimensional function spaces, enabling adaptation to data across different resolutions. Whereas ROM provides rigorous numerical error estimates, neural operator learning largely focuses on discretization convergence and invariance without quantifying the error between the infinite-dimensional and the discretized operators. This work introduces the reduced-order neural operator modeling (RONOM) framework, which bridges concepts from ROM and operator learning. We establish a discretization error bound analogous to those in ROM, and get insights into RONOM's discretization convergence and discretization robustness. Moreover, two numerical examples are presented that compare RONOM to existing neural operators for solving partial differential equations. The results demonstrate that RONOM using standard vector-to-vector neural networks achieves comparable performance in input generalization and superior performance in both spatial super-resolution and discretization robustness, while also offering novel insights into temporal super-resolution scenarios.

Sven Dummer, Puru Vaish, Christoph Brune

Dynamic imaging is critical for understanding and visualizing dynamic biological processes in medicine and cell biology. These applications often encounter the challenge of a limited amount of time series data and time points, which hinders learning meaningful patterns. Regularization methods provide valuable prior knowledge to address this challenge, enabling the extraction of relevant information despite the scarcity of time-series data and time points. In particular, low-dimensionality assumptions on the image manifold address sample scarcity, while time progression models, such as optimal transport (OT), provide priors on image development to mitigate the lack of time points. Existing approaches using low-dimensionality assumptions disregard a temporal prior but leverage information from multiple time series. OT-prior methods, however, incorporate the temporal prior but regularize only individual time series, ignoring information from other time series of the same image modality. In this work, we investigate the effect of integrating a low-dimensionality assumption of the underlying image manifold with an OT regularizer for time-evolving images. In particular, we propose a latent model representation of the underlying image manifold and promote consistency between this representation, the time series data, and the OT prior on the time-evolving images. We discuss the advantages of enriching OT interpolations with latent models and integrating OT priors into latent models.

Sven Dummer, Tjeerd Jan Heeringa, José A. Iglesias

Recently, there has been growing interest in characterizing the function spaces underlying neural networks. While shallow and deep scalar-valued neural networks have been linked to scalar-valued reproducing kernel Banach spaces (RKBS), $\mathbb{R}^d$-valued neural networks and neural operator models remain less understood in the RKBS setting. To address this gap, we develop a general definition of vector-valued RKBS (vv-RKBS), which inherently includes the associated reproducing kernel. Our construction extends existing definitions by avoiding restrictive assumptions such as symmetric kernel domains, finite-dimensional output spaces, reflexivity, or separability, while still recovering familiar properties of vector-valued reproducing kernel Hilbert spaces (vv-RKHS). We then show that shallow $\mathbb{R}^d$-valued neural networks are elements of a specific vv-RKBS, namely an instance of the integral and neural vv-RKBS. To also explore the functional structure of neural operators, we analyze the DeepONet and Hypernetwork architectures and demonstrate that they too belong to an integral and neural vv-RKBS. In all cases, we establish a Representer Theorem, showing that optimization over these function spaces recovers the corresponding neural architectures.

Sven Dummer, Nicola Strisciuglio, Christoph Brune

Diffeomorphic registration frameworks such as Large Deformation Diffeomorphic Metric Mapping (LDDMM) are used in computer graphics and the medical domain for atlas building, statistical latent modeling, and pairwise and groupwise registration. In recent years, researchers have developed neural network-based approaches regarding diffeomorphic registration to improve the accuracy and computational efficiency of traditional methods. In this work, we focus on a limitation of neural network-based atlas building and statistical latent modeling methods, namely that they either are (i) resolution dependent or (ii) disregard any data- or problem-specific geometry needed for proper mean-variance analysis. In particular, we overcome this limitation by designing a novel encoder based on resolution-independent implicit neural representations. The encoder achieves resolution invariance for LDDMM-based statistical latent modeling. Additionally, the encoder adds LDDMM Riemannian geometry to resolution-independent deep learning models for statistical latent modeling. We investigate how the Riemannian geometry improves latent modeling and is required for a proper mean-variance analysis. To highlight the benefit of resolution independence for LDDMM-based data variability modeling, we show that our approach outperforms current neural network-based LDDMM latent code models. Our work paves the way for more research into how Riemannian geometry, shape respectively image analysis, and deep learning can be combined.