# Few-Shot Distribution-Aligned Flow Matching for Data Synthesis in Medical Image Segmentation

arXiv: https://arxiv.org/abs/2604.02868 · HTML: https://mlsanity.com/paper/2604.02868/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Placed in Medical imaging and segmentation, one of 14 directions in Diffusion models.
- Builds on 33 of its 45 references that are in the map.
- First posted on arXiv 3 Apr 2026.

## Placed in

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

## Builds on (most cited first, 30 of 33)

- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
- [U-Net: Convolutional Networks for Biomedical Image Segmentation](https://mlsanity.com/paper/1505.04597/) (2015)
- [High-Resolution Image Synthesis with Latent Diffusion Models](https://mlsanity.com/paper/2112.10752/) (2021)
- [The Unreasonable Effectiveness of Deep Features as a Perceptual Metric](https://mlsanity.com/paper/1801.03924/) (2018)
- [Denoising Diffusion Implicit Models](https://mlsanity.com/paper/2010.02502/) (2020)
- [Score-Based Generative Modeling through Stochastic Differential Equations](https://mlsanity.com/paper/2011.13456/) (2020)
- [Flow Matching for Generative Modeling](https://mlsanity.com/paper/2210.02747/) (2022)
- [Adding Conditional Control to Text-to-Image Diffusion Models](https://mlsanity.com/paper/2302.05543/) (2023)
- [mixup: Beyond Empirical Risk Minimization](https://mlsanity.com/paper/1710.09412/) (2017)
- [Scaling Rectified Flow Transformers for High-Resolution Image Synthesis](https://mlsanity.com/paper/2403.03206/) (2024)
- [Flow Straight and Fast: Learning to Generate and Transfer Data with Rectified Flow](https://mlsanity.com/paper/2209.03003/) (2022)
- [Elucidating the Design Space of Diffusion-Based Generative Models](https://mlsanity.com/paper/2206.00364/) (2022)
- [SegFormer: Simple and Efficient Design for Semantic Segmentation with Transformers](https://mlsanity.com/paper/2105.15203/) (2021)
- [CutMix: Regularization Strategy to Train Strong Classifiers with Localizable Features](https://mlsanity.com/paper/1905.04899/) (2019)
- [T2I-Adapter: Learning Adapters to Dig out More Controllable Ability for Text-to-Image Diffusion Models](https://mlsanity.com/paper/2302.08453/) (2023)
- [Demystifying MMD GANs](https://mlsanity.com/paper/1801.01401/) (2018)
- [Random Erasing Data Augmentation](https://mlsanity.com/paper/1708.04896/) (2017)
- [ImageReward: Learning and Evaluating Human Preferences for Text-to-Image Generation](https://mlsanity.com/paper/2304.05977/) (2023)
- [Training Diffusion Models with Reinforcement Learning](https://mlsanity.com/paper/2305.13301/) (2023)
- [Flow-GRPO: Training Flow Matching Models via Online RL](https://mlsanity.com/paper/2505.05470/) (2025)
- [Simple Copy-Paste is a Strong Data Augmentation Method for Instance Segmentation](https://mlsanity.com/paper/2012.07177/) (2020)
- [Kvasir-SEG: A Segmented Polyp Dataset](https://mlsanity.com/paper/1911.07069/) (2019)
- [Directly Fine-Tuning Diffusion Models on Differentiable Rewards](https://mlsanity.com/paper/2309.17400/) (2023)
- [Aligning Text-to-Image Diffusion Models with Reward Backpropagation](https://mlsanity.com/paper/2310.03739/) (2023)
- [Adjoint Matching: Fine-tuning Flow and Diffusion Generative Models with Memoryless Stochastic Optimal Control](https://mlsanity.com/paper/2409.08861/) (2024)
- [Video Diffusion Alignment via Reward Gradients](https://mlsanity.com/paper/2407.08737/) (2024)
- [Medical Image Synthesis with Context-Aware Generative Adversarial Networks](https://mlsanity.com/paper/1612.05362/) (2016)
- [MedSyn: Text-guided Anatomy-aware Synthesis of High-Fidelity 3D CT Images](https://mlsanity.com/paper/2310.03559/) (2023)
- [REFUGE2 Challenge: A Treasure Trove for Multi-Dimension Analysis and Evaluation in Glaucoma Screening](https://mlsanity.com/paper/2202.08994/) (2022)
- [3D MedDiffusion: A 3D Medical Latent Diffusion Model for Controllable and High-quality Medical Image Generation](https://mlsanity.com/paper/2412.13059/) (2024)

## Abstract (arXiv)

Data heterogeneity hinders clinical deployment of medical image analysis models, and generative data augmentation helps mitigate this issue. However, recent diffusion-based methods that synthesize image-mask pairs often ignore distribution shifts between generated and real images across scenarios, and such mismatches can markedly degrade downstream performance. To address this issue, we propose AlignFlow, a flow matching model that aligns with the target reference image distribution via differentiable reward fine-tuning, and remains effective even when only a small number of reference images are provided. Specifically, we divide the training of the flow matching model into two stages: in the first stage, the model fits the training data to generate plausible images; Then, we introduce a distribution alignment mechanism and employ differentiable reward to steer the generated images toward the distribution of the given samples from the target domain. In addition, to enhance the diversity of generated masks, we also design a flow matching based mask generation to complement the diversity in regions of interest. Extensive experiments demonstrate the effectiveness of our approach, i.e., performance improvement by 3.5-4.0% in mDice and 3.5-5.6% in mIoU across a variety of datasets and scenarios.