Personalized Cell Segmentation: Benchmark and Framework for Reference-Guided Cell Type Segmentation

Instance segmentation enables the analysis of spatial and temporal properties of cells in microscopy images by identifying the pixels belonging to each cell. However, progress is constrained by the scarcity of high-quality labeled microscopy datasets. Many recent approaches address this challenge by initializing models with segmentation-pretrained weights from large-scale natural-image models such as Segment Anything Model (SAM). However, representations learned from natural images often encode objectness and texture priors that are poorly aligned with microscopy data, leading to degraded performance under domain shift. We propose DINOCell, a self-supervised framework for cell instance segmentation that leverages representations from DINOv2 and adapts them to microscopy through continued self-supervised training on unlabeled cell images prior to supervised fine-tuning. On the LIVECell benchmark, DINOCell achieves a SEG score of 0.784, improving by 10.42% over leading SAM-based models, and demonstrates strong zero-shot performance on three out-of-distribution microscopy datasets. These results highlight the benefits of domain-adapted self-supervised pretraining for robust cell segmentation.

Cell instance segmentation models trained on cell-specific datasets suffer severe performance drops on out-of-distribution cell types, while interactive foundation models overcome this through per-instance prompting at a cost that is prohibitively expensive for histopathology images containing hundreds to thousands of densely packed instances. We introduce Group Prompting, a new paradigm that shifts interactive segmentation from per-instance $O(N)$ to per-type $O(T)$, where a single click per cell type suffices to segment all instances of that type. Our key observation is that the frozen image encoder of the Segment Anything Model (SAM) already clusters same-type cells in its feature space before any prompt is given, and that this clustering holds across staining modalities without any training. Exploiting this property, we propose Chain-of-Prompts (CoP), a training-free framework that recursively expands a single user click by (1) identifying reliable same-type locations through non-parametric gating of multi-scale encoder features, and (2) selecting the most spatially distant reliable point as the next prompt to maximize coverage. On eleven benchmarks, CoP generalizes to both unseen cell types and unseen imaging modalities without any adaptation: with one click per type it retains over 90% of per-instance performance on three cell-type-annotated datasets while surpassing fully-supervised methods, and with one click per image it retains over 95% on eight datasets spanning both H&E and non-H&E imaging. Project Page: https://shjo-april.github.io/Chain-of-Prompts/

Existing cell instance segmentation pipelines typically combine deterministic predictions with post-processing, which imposes limited explicit constraints on the global structure of instance masks. In this work, we propose a multi-task image-to-image Schrödinger Bridge framework that formulates instance segmentation as a distribution-based image-to-image generation problem. Boundary-aware supervision is integrated through a reverse distance map, and deterministic inference is employed to produce stable predictions. Experimental results on the PanNuke dataset demonstrate that the proposed method achieves competitive or superior performance without relying on SAM pre-training or additional post-processing. Additional results on the MoNuSeg dataset show robustness under limited training data. These findings indicate that Schrödinger Bridge-based image-to-image generation provides an effective framework for cell instance segmentation.