Generative modeling of living cells with SO-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.

Implicit Neural Representations for Generative Modeling of Living Cell Shapes

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.