# Weak-to-Strong Generalization Enables Fully Automated De Novo Training of Multi-head Mask-RCNN Model for Segmenting Densely Overlapping Cell Nuclei in Multiplex Whole-slice Brain Images

arXiv: https://arxiv.org/abs/2512.11722 · HTML: https://mlsanity.com/paper/2512.11722/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 31 of its 58 references that are in the map.
- First posted on arXiv 12 Dec 2025.

## Builds on (most cited first, 30 of 31)

- [Deep Residual Learning for Image Recognition](https://mlsanity.com/paper/1512.03385/) (2015)
- [Learning Transferable Visual Models From Natural Language Supervision](https://mlsanity.com/paper/2103.00020/) (2021)
- [U-Net: Convolutional Networks for Biomedical Image Segmentation](https://mlsanity.com/paper/1505.04597/) (2015)
- [Segment Anything](https://mlsanity.com/paper/2304.02643/) (2023)
- [Mask R-CNN](https://mlsanity.com/paper/1703.06870/) (2017)
- [Hierarchical Text-Conditional Image Generation with CLIP Latents](https://mlsanity.com/paper/2204.06125/) (2022)
- [mixup: Beyond Empirical Risk Minimization](https://mlsanity.com/paper/1710.09412/) (2017)
- [CutMix: Regularization Strategy to Train Strong Classifiers with Localizable Features](https://mlsanity.com/paper/1905.04899/) (2019)
- [UNet++: A Nested U-Net Architecture for Medical Image Segmentation](https://mlsanity.com/paper/1807.10165/) (2018)
- [Co-teaching: Robust Training of Deep Neural Networks with Extremely Noisy Labels](https://mlsanity.com/paper/1804.06872/) (2018)
- [Panoptic Segmentation](https://mlsanity.com/paper/1801.00868/) (2018)
- [Simple Copy-Paste is a Strong Data Augmentation Method for Instance Segmentation](https://mlsanity.com/paper/2012.07177/) (2020)
- [ECA-Net: Efficient Channel Attention for Deep Convolutional Neural Networks](https://mlsanity.com/paper/1910.03151/) (2019)
- [YOLACT: Real-time Instance Segmentation](https://mlsanity.com/paper/1904.02689/) (2019)
- [How does Disagreement Help Generalization against Label Corruption?](https://mlsanity.com/paper/1901.04215/) (2019)
- [HoVer-Net: Simultaneous Segmentation and Classification of Nuclei in Multi-Tissue Histology Images](https://mlsanity.com/paper/1812.06499/) (2018)
- [Cut, Paste and Learn: Surprisingly Easy Synthesis for Instance Detection](https://mlsanity.com/paper/1708.01642/) (2017)
- [Cell Detection with Star-convex Polygons](https://mlsanity.com/paper/1806.03535/) (2018)
- [Modeling Visual Context is Key to Augmenting Object Detection Datasets](https://mlsanity.com/paper/1807.07428/) (2018)
- [Deep Occlusion-Aware Instance Segmentation with Overlapping BiLayers](https://mlsanity.com/paper/2103.12340/) (2021)
- [InstaBoost: Boosting Instance Segmentation via Probability Map Guided Copy-Pasting](https://mlsanity.com/paper/1908.07801/) (2019)
- [Adaptive Early-Learning Correction for Segmentation from Noisy Annotations](https://mlsanity.com/paper/2110.03740/) (2021)
- [Co-learning: Learning from Noisy Labels with Self-supervision](https://mlsanity.com/paper/2108.04063/) (2021)
- [Theoretical Analysis of Weak-to-Strong Generalization](https://mlsanity.com/paper/2405.16043/) (2024)
- [All-in-SAM: from Weak Annotation to Pixel-wise Nuclei Segmentation with Prompt-based Finetuning](https://mlsanity.com/paper/2307.00290/) (2023)
- [Diffusion-based Data Augmentation for Nuclei Image Segmentation](https://mlsanity.com/paper/2310.14197/) (2023)
- [Mask-RCNN and U-net Ensembled for Nuclei Segmentation](https://mlsanity.com/paper/1901.10170/) (2019)
- [InsMix: Towards Realistic Generative Data Augmentation for Nuclei Instance Segmentation](https://mlsanity.com/paper/2206.15134/) (2022)
- [DoNet: Deep De-overlapping Network for Cytology Instance Segmentation](https://mlsanity.com/paper/2303.14373/) (2023)
- [IRNet: Instance Relation Network for Overlapping Cervical Cell Segmentation](https://mlsanity.com/paper/1908.06623/) (2019)

## Abstract (arXiv)

We present a weak to strong generalization methodology for fully automated training of a multi-head extension of the Mask-RCNN method with efficient channel attention for reliable segmentation of overlapping cell nuclei in multiplex cyclic immunofluorescent (IF) whole-slide images (WSI), and present evidence for pseudo-label correction and coverage expansion, the key phenomena underlying weak to strong generalization. This method can learn to segment de novo a new class of images from a new instrument and/or a new imaging protocol without the need for human annotations. We also present metrics for automated self-diagnosis of segmentation quality in production environments, where human visual proofreading of massive WSI images is unaffordable. Our method was benchmarked against five current widely used methods and showed a significant improvement. The code, sample WSI images, and high-resolution segmentation results are provided in open form for community adoption and adaptation.