Organizations: School of Computer Science, University of Nottingham, UK · School of Computer Science, University of Nottingham Ningbo China, China · School of Engineering and Physical Science, University of Lincoln, UK · Department of Computer Science, University of Rochester, USA · Department of Data Science and Artificial Intelligence, The Hong Kong Polytechnic University, Hong Kong SAR
Cell segmentation is critical for computational pathology and biomedical discovery. While recent Vision Foundation Models (VFMs) have demonstrated remarkable universal feature representations, unlocking their full potential for cellular imaging is currently bottlenecked by resource-intensive adaptation paradigms. Existing methods typically rely on fine-tuning heavy visual encoders, leading to extensive computational overhead and a dependency on large-scale annotations. To address this, we propose the EffiCell-Seg framework for highly efficient cell segmentation without re-training the visual encoder. Our core insight is that pretrained VFMs intrinsically encode complementary structural priors: global saliency for localizing potential cells, and local morphological patterns for delineating cellular structures. To harness these priors, we devise a Cell Structure Prompt Encoder (CSP-Encoder) that synthesizes semantic-aware saliency and principal morphological features from frozen VFM representations into explicit structural prior maps. Moreover, we propose a Synergistic Mask Decoder (SM-Decoder) that enforces contextual consistency by jointly predicting geometric distance fields and semantic maps via mutual cross-guidance. Extensive experiments demonstrate that EffiCell-Seg outperforms state-of-the-art methods across diverse cell imaging modalities while requiring only ~5M trainable parameters, over 130x fewer than fully fine-tuned VFM counterparts. The code is available at https://github.com/xq141839/EffiCell-Seg.
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 (μSAM, 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.
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 \textbf{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 \textbf{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/
Cell-level dense prediction is central to computational pathology, but remains challenging due to fine-grained histological structures, strong domain shifts, and costly dense annotations. Existing ViT-based pathology foundation models rely on patch tokenization, which can disrupt spatial continuity and weaken local morphological details needed for cell-level prediction. To address this, we propose Masked-Diffusion Convolutional Foundation Models, termed ConvNeXt Masked-Diffusion (CMD), a self-supervised convolutional generative pretraining framework for dense pathology representation learning. CMD uses a fully convolutional ConvNeXt-UNet backbone, performs masked-diffusion pretraining in pixel space, and incorporates frozen pathology foundation model features through adaptive normalization. Experimental results demonstrate that CMD consistently outperforms existing ViT-based pathology foundation models and even surpasses state-of-the-art end-to-end segmentation methods while fine-tuning only a small number of task-specific parameters across multiple pathology dense prediction tasks. The advantage is particularly pronounced under limited annotation settings, where CMD exhibits stronger robustness and generalization ability. Our findings suggest that purely convolutional architectures can also serve as competitive pathology foundation models for cell-level dense prediction, achieving leading performance within the current ViT-dominated paradigm and providing a scalable, high-performance solution that better preserves histological structural priors for fine-grained pathology understanding.