# DiffMix: Diffusion Model-based Data Synthesis for Nuclei Segmentation and Classification in Imbalanced Pathology Image Datasets

arXiv: https://arxiv.org/abs/2306.14132 · HTML: https://mlsanity.com/paper/2306.14132/

## Key facts

- Cited by 28 papers in the map (data through 14 Oct 2026).
- Placed in Medical imaging and segmentation, one of 14 directions in Diffusion models.
- Builds on 16 of its 24 references that are in the map.
- First posted on arXiv 25 Jun 2023.

## Placed in

- Diffusion models / [Medical imaging and segmentation](https://mlsanity.com/diffusion/medical-imaging-and-segmentation/)

## Builds on (most cited first, 16 of 16)

- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
- [Denoising Diffusion Implicit Models](https://mlsanity.com/paper/2010.02502/) (2020)
- [Diffusion Models Beat GANs on Image Synthesis](https://mlsanity.com/paper/2105.05233/) (2021)
- [mixup: Beyond Empirical Risk Minimization](https://mlsanity.com/paper/1710.09412/) (2017)
- [Improved Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2102.09672/) (2021)
- [GLIDE: Towards Photorealistic Image Generation and Editing with Text-Guided Diffusion Models](https://mlsanity.com/paper/2112.10741/) (2021)
- [CutMix: Regularization Strategy to Train Strong Classifiers with Localizable Features](https://mlsanity.com/paper/1905.04899/) (2019)
- [Improved Regularization of Convolutional Neural Networks with Cutout](https://mlsanity.com/paper/1708.04552/) (2017)
- [HoVer-Net: Simultaneous Segmentation and Classification of Nuclei in Multi-Tissue Histology Images](https://mlsanity.com/paper/1812.06499/) (2018)
- [Diffusion Models for Medical Anomaly Detection](https://mlsanity.com/paper/2203.04306/) (2022)
- [Semantic Image Synthesis via Diffusion Models](https://mlsanity.com/paper/2207.00050/) (2022)
- [Micro-Net: A unified model for segmentation of various objects in microscopy images](https://mlsanity.com/paper/1804.08145/) (2018)
- [A Comprehensive Review of Computer-aided Whole-slide Image Analysis: from Datasets to Feature Extraction, Segmentation, Classification, and Detection Approaches](https://mlsanity.com/paper/2102.10553/) (2021)
- [InsMix: Towards Realistic Generative Data Augmentation for Nuclei Instance Segmentation](https://mlsanity.com/paper/2206.15134/) (2022)
- [GradMix for nuclei segmentation and classification in imbalanced pathology image datasets](https://mlsanity.com/paper/2210.12938/) (2022)
- [SIAN: Style-Guided Instance-Adaptive Normalization for Multi-Organ Histopathology Image Synthesis](https://mlsanity.com/paper/2209.02412/) (2022)

## Built on by (most cited first, 28 of 28)

- [TopoCellGen: Generating Histopathology Cell Topology with a Diffusion Model](https://mlsanity.com/paper/2412.06011/) (2024)
- [AI-Generated Images as Data Source: The Dawn of Synthetic Era](https://mlsanity.com/paper/2310.01830/) (2023)
- [A Comprehensive Survey on Imbalanced Data Learning](https://mlsanity.com/paper/2502.08960/) (2025)
- [PathDiff: Histopathology Image Synthesis with Unpaired Text and Mask Conditions](https://mlsanity.com/paper/2506.23440/) (2025)
- [Controllable and Efficient Multi-Class Pathology Nuclei Data Augmentation using Text-Conditioned Diffusion Models](https://mlsanity.com/paper/2407.14426/) (2024)
- [Co-synthesis of Histopathology Nuclei Image-Label Pairs using a Context-Conditioned Joint Diffusion Model](https://mlsanity.com/paper/2407.14434/) (2024)
- [TRACE: Temporally Reliable Anatomically-Conditioned 3D CT Generation with Enhanced Efficiency](https://mlsanity.com/paper/2507.00802/) (2025)
- [GAITGen: Disentangled Motion-Pathology Impaired Gait Generative Model -- Bringing Motion Generation to the Clinical Domain](https://mlsanity.com/paper/2503.22397/) (2025)
- [Content Generation Models in Computational Pathology: A Comprehensive Survey on Methods, Applications, and Challenges](https://mlsanity.com/paper/2505.10993/) (2025)
- [An Organism Starts with a Single Pix-Cell: A Neural Cellular Diffusion for High-Resolution Image Synthesis](https://mlsanity.com/paper/2407.03018/) (2024)
- [Histo-Diffusion: A Diffusion Super-Resolution Method for Digital Pathology with Comprehensive Quality Assessment](https://mlsanity.com/paper/2408.15218/) (2024)
- [DAViD: Modeling Dynamic Affordance of 3D Objects Using Pre-trained Video Diffusion Models](https://mlsanity.com/paper/2501.08333/) (2025)
- [Synthetic Data Augmentation using Pre-trained Diffusion Models for Long-tailed Food Image Classification](https://mlsanity.com/paper/2506.01368/) (2025)
- [An Ordinal Diffusion Model for Generating Medical Images with Different Severity Levels](https://mlsanity.com/paper/2403.00452/) (2024)
- [Mask-guided cross-image attention for zero-shot in-silico histopathologic image generation with a diffusion model](https://mlsanity.com/paper/2407.11664/) (2024)
- [HisynSeg: Weakly-Supervised Histopathological Image Segmentation via Image-Mixing Synthesis and Consistency Regularization](https://mlsanity.com/paper/2412.20924/) (2024)
- [Combining Datasets with Different Label Sets for Improved Nucleus Segmentation and Classification](https://mlsanity.com/paper/2310.03346/) (2023)
- [AdaptDiff: Cross-Modality Domain Adaptation via Weak Conditional Semantic Diffusion for Retinal Vessel Segmentation](https://mlsanity.com/paper/2410.04648/) (2024)
- [Comparative Analysis of Diffusion Generative Models in Computational Pathology](https://mlsanity.com/paper/2411.15719/) (2024)
- [Computationally Efficient Diffusion Models in Medical Imaging: A Comprehensive Review](https://mlsanity.com/paper/2505.07866/) (2025)
- [Zero-shot CT Super-Resolution using Diffusion-based 2D Projection Priors and Signed 3D Gaussians](https://mlsanity.com/paper/2508.15151/) (2025)
- [Geometrically Constrained Stenosis Editing in Coronary Angiography via Entropic Optimal Transport](https://mlsanity.com/paper/2605.08851/) (2026)
- [Contrastive-Adversarial and Diffusion: Exploring pre-training and fine-tuning strategies for sulcal identification](https://mlsanity.com/paper/2405.19204/) (2024)
- [Instance Migration Diffusion for Nuclear Instance Segmentation in Pathology](https://mlsanity.com/paper/2504.01577/) (2025)
- [MSDM: Generating Task-Specific Pathology Images with a Multimodal Conditioned Diffusion Model for Cell and Nuclei Segmentation](https://mlsanity.com/paper/2510.09121/) (2025)
- [Layout-Guided Controllable Pathology Image Generation with In-Context Diffusion Transformers](https://mlsanity.com/paper/2603.13386/) (2026)
- [Central-to-Local Adaptive Generative Diffusion Framework for Improving Gene Expression Prediction in Data-Limited Spatial Transcriptomics](https://mlsanity.com/paper/2603.26827/) (2026)
- [Compositional Reward Models for Conditional Medical Image Generation](https://mlsanity.com/paper/2609.05028/) (2026)

## Abstract (arXiv)

Nuclei segmentation and classification is a significant process in pathology image analysis. Deep learning-based approaches have greatly contributed to the higher accuracy of this task. However, those approaches suffer from the imbalanced nuclei data composition, which shows lower classification performance on the rare nuclei class. In this paper, we propose a realistic data synthesis method using a diffusion model. We generate two types of virtual patches to enlarge the training data distribution, which is for balancing the nuclei class variance and for enlarging the chance to look at various nuclei. After that, we use a semantic-label-conditioned diffusion model to generate realistic and high-quality image samples. We demonstrate the efficacy of our method by experiment results on two imbalanced nuclei datasets, improving the state-of-the-art networks. The experimental results suggest that the proposed method improves the classification performance of the rare type nuclei classification, while showing superior segmentation and classification performance in imbalanced pathology nuclei datasets.