Revisiting foundation models for cell instance segmentation

Accurate delineation of individual cells in microscopy videos is essential for studying cellular dynamics, yet separating touching or overlapping instances remains a persistent challenge. Although foundation-model for segmentation such as SAM have broadened the accessibility of image segmentation, they still struggle to separate nearby cell instances in dense microscopy scenes without extensive prompting. We propose a prompt-free, boundary-aware instance segmentation framework that predicts signed distance functions (SDFs) instead of binary masks, enabling smooth and geometry-consistent modeling of cell contours. A learned sigmoid mapping converts SDFs into probability maps, yielding sharp boundary localization and robust separation of adjacent instances. Training is guided by a unified Modified Hausdorff Distance (MHD) loss that integrates region- and boundary-based terms. Evaluations on both public and private high-throughput microscopy datasets demonstrate improved boundary accuracy and instance-level performance compared to recent SAM-based and foundation-model approaches. Source code is available at: https://github.com/ThomasMendelson/BAISeg.git

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/

Deep learning underlies most modern approaches and tools in computer vision, including biomedical imaging. However, for interactive semantic segmentation (often called pixel classification in this context) and interactive object-level classification (object classification), feature-based shallow learning remains widely used. This is due to the diversity of data in this domain, the lack of large pretraining datasets, and the need for computational and label efficiency. In contrast, state-of-the-art tools for many other vision tasks in microscopy - most notably cellular instance segmentation - already rely on deep learning and have recently benefited substantially from vision foundation models (VFMs), particularly SAM. Here, we investigate whether VFMs can also improve pixel and object classification compared to current approaches. To this end, we evaluate several VFMs, including general-purpose models (SAM, SAM2, SAM3, DINOv3) and domain-specific ones ($μ$SAM, PathoSAM, KRONOS), in combination with shallow learning and attentive probing on five diverse and challenging datasets. Our results demonstrate consistent improvements over hand-crafted features and provide a clear pathway toward practical improvements. Furthermore, our study establishes a benchmark for VFMs in microscopy and informs future developments in this area.