A major challenge in the analysis of tissue imaging data is cell segmentation, the task of identifying the precise boundary of every cell in an image. To address this problem we constructed TissueNet, a dataset for training segmentation models that contains more than 1 million manually labeled cells, an order of magnitude more than all previously published segmentation training datasets. We used TissueNet to train Mesmer, a deep learning-enabled segmentation algorithm. We demonstrated that Mesmer is more accurate than previous methods, generalizes to the full diversity of tissue types and imaging platforms in TissueNet, and achieves human-level performance. Mesmer enabled the automated extraction of key cellular features, such as subcellular localization of protein signal, which was challenging with previous approaches. We then adapted Mesmer to harness cell lineage information in highly multiplexed datasets and used this enhanced version to quantify cell morphology changes during human gestation. All code, data, and models are released as a community resource.

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Understanding the spatial organization of tissues is of critical importance for both basic and translational research. While recent advances in tissue imaging are opening an exciting new window into the biology of human tissues, interpreting the data that they create is a significant computational challenge. Cell segmentation, the task of uniquely identifying each cell in an image, remains a substantial barrier for tissue imaging, as existing approaches are inaccurate or require a substantial amount of manual curation to yield useful results. Here, we addressed the problem of cell segmentation in tissue imaging data through large-scale data annotation and deep learning. We constructed TissueNet, an image dataset containing >1 million paired whole-cell and nuclear annotations for tissue images from nine organs and six imaging platforms. We created Mesmer, a deep learning-enabled segmentation algorithm trained on TissueNet that performs nuclear and whole-cell segmentation in tissue imaging data. We demonstrated that Mesmer has better speed and accuracy than previous methods, generalizes to the full diversity of tissue types and imaging platforms in TissueNet, and achieves human-level performance for whole-cell segmentation. Mesmer enabled the automated extraction of key cellular features, such as subcellular localization of protein signal, which was challenging with previous approaches. We further showed that Mesmer could be adapted to harness cell lineage information present in highly multiplexed datasets. We used this enhanced version to quantify cell morphology changes during human gestation. All underlying code and models are released with permissive licenses as a community resource.

Recent advances in text-to-image generation with diffusion models present transformative capabilities in image quality. However, user controllability of the generated image, and fast adaptation to new tasks still remains an open challenge, currently mostly addressed by costly and long retraining and fine-tuning or ad-hoc adaptations to specific image generation tasks. In this work, we present MultiDiffusion, a unified framework that enables versatile and controllable image generation, using a pre-trained text-to-image diffusion model, without any further training or finetuning. At the center of our approach is a new generation process, based on an optimization task that binds together multiple diffusion generation processes with a shared set of parameters or constraints. We show that MultiDiffusion can be readily applied to generate high quality and diverse images that adhere to user-provided controls, such as desired aspect ratio (e.g., panorama), and spatial guiding signals, ranging from tight segmentation masks to bounding boxes.Project page is available at https://multidiffusion. github.io.

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