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Cellpose-SAM: superhuman generalization for cellular segmentation

Marius PachitariuiD, Michael RarideniD, Carsen StringeriD

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In-depth summary

Claude Opus 5.5 · xhigh effort · 17 Oct 2026 · from the full text of version 1 (1 May 2025) · CC BY-NC 4.0

Cellpose's flow-field output on SAM's pretrained encoder yields one segmenter that errs less than a second human annotator on out-of-distribution images (0.163 vs 0.257 error rate).

Generalist cell segmenters are usually judged against inter-annotator agreement, which the paper argues is not a ceiling because a consensus annotation would have roughly half the errors, and SAM-based biological adaptations have not clearly beaten Cellpose. Here SAM's pretrained ViT-L encoder is kept but its prompt-driven decoders are replaced by direct Cellpose flow-field prediction, giving a single model that also tolerates shuffled channels, varied cell sizes and common image degradations.

Key results

  1. ShownOn the Cellpose test set, chosen because its test images differ most from the training images, Cellpose-SAM makes fewer errors than a second human annotator and than earlier models, approaching the estimated human-consensus bound.

    Error rate at IoU 0.5 on the Cellpose test set: Cellpose-SAM 0.163, Cellpose3 0.292, CellSAM 0.328; Annotator2 (scored against Annotator1) 0.257; consensus estimate 0.128, half that rate. Training used Annotator1 labels only. On the more homogeneous TissueNet, LiveCell, Omnipose, DeepBacs and MoNuSeg test sets it matched or beat other models, typically by smaller margins (values not in this text). · Model validation; Human-consensus bound; Segmentation benchmarks

  2. ShownA single model copes with arbitrary channel order, a wide range of cell sizes without rescaling, and noisy, blurred or downsampled images without a separate restoration step.

    Channel permutation in training (RGB, BRG, GBR and random orders tested) cost no accuracy; trained on diameters 7.5 to 120 pixels and tested at 10 to 90, with a small loss only for small cells; under Poisson noise, blur and (anisotropic) downsampling it matched the authors' best earlier restoration models, each trained for one degradation. Scores are not in this text. · Invariance and robustness; Color and size invariance; Robustness to image degradation as

  3. ShownAs an initialisation for fine-tuning on data unseen in training, Cellpose-SAM outperforms cyto3 in 2D and 3D, with the advantage largest when few labelled images are available.

    On BlastoSPIM mouse embryo volumes and PlantSeg lateral root and ovule volumes, using 1 to 512 training images or the full set, Cellpose-SAM started higher and improved equally fast or faster than cyto3; the gap generally narrowed with more data but sometimes persisted. Fine-tuning used batch size 1, which the authors say is always feasible even on 8-12 GB GPUs. Exact scores are not in this text. · Finetuning Cellpose-SAM in 2D and 3D and for…; Fine-tuning and evaluation; Fine-tuning datasets

  4. ShownDespite about 50 times more parameters than Cellpose, Cellpose-SAM was the fastest per image among the compared models.

    Speed is attributed to GPU tensor cores accelerating transformer layers, post-processing taking a large share of runtime, and dropping the separate size-estimation pass that Cellpose 1/2/3 need; inputs were reduced from 1024×1024 to 256×256 with 8×8 patches. Timing values are not in this text. · Model design; Model validation

  5. ShownRetrained with extra class-output maps, a Cellpose-SAM-based model jointly segments and classifies nuclei and beat the MoNuSAC 2020 challenge winners on nearly every class.

    Four H&E nucleus classes (epithelial, lymphocyte, macrophage, neutrophil); compared against predictions shared by winners PL1, PL2, PL3 and L2 (the L1 link did not work), it was better on nearly all cell types and raised overall classification accuracy substantially. Per-class error rate and average precision values are not in this text. · Finetuning Cellpose-SAM in 2D and 3D and for…; Semantic segmentation training and evaluation

Methods, data and reproducibility

SAM's ViT-L image encoder (305M of 312M parameters), adapted to 256×256 inputs, 8×8 patches and global attention, directly predicts Cellpose cell-probability and XY flow maps; it was trained on 22,826 images (3,341,254 ROIs) pooled from public cell and nucleus datasets with channel, size and degradation augmentations, then compared with cyto3, CellSAM, SAMCell, MicroSAM and PathoSAM.

  • Combined training set from 18 public cell and nucleus datasets (including Cellpose, TissueNet, LiveCell, Omnipose, DeepBacs, YeaZ, CoNIC, PanNuke) · multiple (human, mouse, yeast, bacteria) · n = 22,826 training images; 3,341,254 ROIs
  • Updated Cellpose test set, relabelled by a second annotator to measure inter-annotator error · n = 67 test images
  • In-domain test sets: TissueNet, LiveCell, Omnipose, DeepBacs, MoNuSeg · n = 1249, 1516, 75+148, 35 and 14 test images respectively
  • PlantSeg lateral root and ovule 3D volumes for fine-tuning (not used in training) · Arabidopsis thaliana · n = 27 and 31 volumes
  • BlastoSPIM 3D volumes of early- and late-stage embryos for fine-tuning (not used in training) · mouse · n = 231 early-stage volumes from 55 embryos; 80 late-stage volumes
  • MoNuSAC H&E images with four nucleus classes (panoptic segmentation task) · n = 209 training and 85 test images
Methods & tools
Cellpose-SAM, Segment Anything Model (SAM, ViT-L encoder), Cellpose cyto3, CellSAM, SAMCell, MicroSAM, PathoSAM, PyTorch, AdamW optimizer
Reagents & environment
Python 3 with PyTorch, NumPy, SciPy, OpenCV, tifffile, imagecodecs, fastremap and tqdm; the GUI adds PyQt, pyqtgraph and superqt. No package versions or container are given.
Assay conditions & compute
Training: batch size 256 split over eight H200 GPUs, 2,000 epochs in about 20 hours. Fine-tuning used batch size 1, which the authors say is always feasible even on GPUs with 8-12 GB VRAM.
Reproducibility gaps
Code/GUI and cyto2 data statements lost their URLs in this text, and the LiveCell link is printed broken (with stray spaces); a Hugging Face version is mentioned without a link; figure-recreation scripts and the combined dataset with train/test splits are promised for later release.
Limitations (5)
  • The human-consensus bound relies on approximations (rare shared annotator errors, consistent matching at IoU 0.5) and may never be reached exactly. · stated by the authors
  • Accuracy dips slightly for very small cells, where downsampling discards information. · stated by the authors
  • Gains are smaller on homogeneous in-domain datasets, and the fine-tuning advantage over cyto3 shrinks as more labelled data become available. · stated by the authors
  • Inputs are fixed at three channels; images with more stains need the input layer replaced and the model retrained. · stated by the authors
  • The headline out-of-distribution and better-than-human claims rest on one 67-image test set from the authors' own Cellpose dataset, with a single additional annotator. · noted in this summary

Read this if you segment cells or nuclei in microscopy from new stains, tissues or microscopes and want one pretrained model that needs no channel or diameter settings and fine-tunes from few labels.

Citations
257

Abstract

Modern algorithms for biological segmentation can match inter-human agreement in annotation quality. This however is not a performance bound: a hypothetical human-consensus segmentation could reduce error rates in half. To obtain a model that generalizes better we adapted the pretrained transformer backbone of a foundation model (SAM) to the Cellpose framework. The resulting Cellpose-SAM model substantially outperforms inter-human agreement and approaches the human-consensus bound. We increase generalization performance further by making the model robust to channel shuffling, cell size, shot noise, downsampling, isotropic and anisotropic blur. The new model can be readily adopted into the Cellpose ecosystem which includes finetuning, human-in-the-loop training, image restoration and 3D segmentation approaches. These properties establish Cellpose-SAM as a foundation model for biological segmentation.

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