# Causality-inspired Single-source Domain Generalization for Medical Image Segmentation

arXiv: https://arxiv.org/abs/2111.12525 · HTML: https://mlsanity.com/paper/2111.12525/

## Key facts

- Cited by 119 papers in the map (data through 14 Oct 2026).
- Builds on 60 of its 76 references that are in the map.
- First posted on arXiv 24 Nov 2021.

## Builds on (most cited first, 30 of 60)

- [Adam: A Method for Stochastic Optimization](https://mlsanity.com/paper/1412.6980/) (2014)
- [U-Net: Convolutional Networks for Biomedical Image Segmentation](https://mlsanity.com/paper/1505.04597/) (2015)
- [EfficientNet: Rethinking Model Scaling for Convolutional Neural Networks](https://mlsanity.com/paper/1905.11946/) (2019)
- [mixup: Beyond Empirical Risk Minimization](https://mlsanity.com/paper/1710.09412/) (2017)
- [Model-Agnostic Meta-Learning for Fast Adaptation of Deep Networks](https://mlsanity.com/paper/1703.03400/) (2017)
- [Supervised Contrastive Learning](https://mlsanity.com/paper/2004.11362/) (2020)
- [Arbitrary Style Transfer in Real-time with Adaptive Instance Normalization](https://mlsanity.com/paper/1703.06868/) (2017)
- [Shortcut Learning in Deep Neural Networks](https://mlsanity.com/paper/2004.07780/) (2020)
- [Unsupervised Domain Adaptation by Backpropagation](https://mlsanity.com/paper/1409.7495/) (2014)
- [Invariant Risk Minimization](https://mlsanity.com/paper/1907.02893/) (2019)
- [Improved Regularization of Convolutional Neural Networks with Cutout](https://mlsanity.com/paper/1708.04552/) (2017)
- [UNet++: A Nested U-Net Architecture for Medical Image Segmentation](https://mlsanity.com/paper/1807.10165/) (2018)
- [Attention U-Net: Learning Where to Look for the Pancreas](https://mlsanity.com/paper/1804.03999/) (2018)
- [Learning deep representations by mutual information estimation and maximization](https://mlsanity.com/paper/1808.06670/) (2018)
- [Virtual Adversarial Training: A Regularization Method for Supervised and Semi-Supervised Learning](https://mlsanity.com/paper/1704.03976/) (2017)
- [AugMix: A Simple Data Processing Method to Improve Robustness and Uncertainty](https://mlsanity.com/paper/1912.02781/) (2019)
- [The Medical Segmentation Decathlon](https://mlsanity.com/paper/2106.05735/) (2021)
- [Domain Generalization via Invariant Feature Representation](https://mlsanity.com/paper/1301.2115/) (2013)
- [Deep Domain Confusion: Maximizing for Domain Invariance](https://mlsanity.com/paper/1412.3474/) (2014)
- [Domain Generalization with MixStyle](https://mlsanity.com/paper/2104.02008/) (2021)
- [Generalizing to Unseen Domains via Adversarial Data Augmentation](https://mlsanity.com/paper/1805.12018/) (2018)
- [Domain Generalization by Solving Jigsaw Puzzles](https://mlsanity.com/paper/1903.06864/) (2019)
- [Regularization With Stochastic Transformations and Perturbations for Deep Semi-Supervised Learning](https://mlsanity.com/paper/1606.04586/) (2016)
- [Self-Challenging Improves Cross-Domain Generalization](https://mlsanity.com/paper/2007.02454/) (2020)
- [Domain Generalization via Model-Agnostic Learning of Semantic Features](https://mlsanity.com/paper/1910.13580/) (2019)
- [Deep Learning for Medical Image Analysis](https://mlsanity.com/paper/1708.08987/) (2017)
- [Confounding variables can degrade generalization performance of radiological deep learning models](https://mlsanity.com/paper/1807.00431/) (2018)
- [CHAOS Challenge -- Combined (CT-MR) Healthy Abdominal Organ Segmentation](https://mlsanity.com/paper/2001.06535/) (2020)
- [Learning to Learn Single Domain Generalization](https://mlsanity.com/paper/2003.13216/) (2020)
- [nnU-Net: Self-adapting Framework for U-Net-Based Medical Image Segmentation](https://mlsanity.com/paper/1809.10486/) (2018)

## Built on by (most cited first, 30 of 119)

- [Trustworthy clinical AI solutions: a unified review of uncertainty quantification in deep learning models for medical image analysis](https://mlsanity.com/paper/2210.03736/) (2022)
- [Rethinking Data Augmentation for Single-source Domain Generalization in Medical Image Segmentation](https://mlsanity.com/paper/2211.14805/) (2022)
- [BayeSeg: Bayesian Modeling for Medical Image Segmentation with Interpretable Generalizability](https://mlsanity.com/paper/2303.01710/) (2023)
- [Anomaly Detection under Distribution Shift](https://mlsanity.com/paper/2303.13845/) (2023)
- [On-the-Fly Test-time Adaptation for Medical Image Segmentation](https://mlsanity.com/paper/2203.05574/) (2022)
- [Devil is in Channels: Contrastive Single Domain Generalization for Medical Image Segmentation](https://mlsanity.com/paper/2306.05254/) (2023)
- [Unbiased Faster R-CNN for Single-source Domain Generalized Object Detection](https://mlsanity.com/paper/2405.15225/) (2024)
- [DeSAM: Decoupled Segment Anything Model for Generalizable Medical Image Segmentation](https://mlsanity.com/paper/2306.00499/) (2023)
- [Deep learning for unsupervised domain adaptation in medical imaging: Recent advancements and future perspectives](https://mlsanity.com/paper/2308.01265/) (2023)
- [Adversarial Consistency for Single Domain Generalization in Medical Image Segmentation](https://mlsanity.com/paper/2206.13737/) (2022)
- [Frequency-mixed Single-source Domain Generalization for Medical Image Segmentation](https://mlsanity.com/paper/2307.09005/) (2023)
- [FairDomain: Achieving Fairness in Cross-Domain Medical Image Segmentation and Classification](https://mlsanity.com/paper/2407.08813/) (2024)
- [CheXWorld: Exploring Image World Modeling for Radiograph Representation Learning](https://mlsanity.com/paper/2504.13820/) (2025)
- [A Review of Causality for Learning Algorithms in Medical Image Analysis](https://mlsanity.com/paper/2206.05498/) (2022)
- [Not Just Pretty Pictures: Toward Interventional Data Augmentation Using Text-to-Image Generators](https://mlsanity.com/paper/2212.11237/) (2022)
- [CaRTS: Causality-driven Robot Tool Segmentation from Vision and Kinematics Data](https://mlsanity.com/paper/2203.09475/) (2022)
- [Domain Generalization -- A Causal Perspective](https://mlsanity.com/paper/2209.15177/) (2022)
- [Causal reasoning in typical computer vision tasks](https://mlsanity.com/paper/2307.13992/) (2023)
- [De-LightSAM: Modality-Decoupled Lightweight SAM for Generalizable Medical Segmentation](https://mlsanity.com/paper/2407.14153/) (2024)
- [Domain generalization in deep learning-based mass detection in mammography: A large-scale multi-center study](https://mlsanity.com/paper/2201.11620/) (2022)
- [MoreStyle: Relax Low-frequency Constraint of Fourier-based Image Reconstruction in Generalizable Medical Image Segmentation](https://mlsanity.com/paper/2403.11689/) (2024)
- [Prompting Segment Anything Model with Domain-Adaptive Prototype for Generalizable Medical Image Segmentation](https://mlsanity.com/paper/2409.12522/) (2024)
- [Bridging Domain Generalization to Multimodal Domain Generalization via Unified Representations](https://mlsanity.com/paper/2507.03304/) (2025)
- [Intra- & Extra-Source Exemplar-Based Style Synthesis for Improved Domain Generalization](https://mlsanity.com/paper/2307.00648/) (2023)
- [WeakMedSAM: Weakly-Supervised Medical Image Segmentation via SAM with Sub-Class Exploration and Prompt Affinity Mining](https://mlsanity.com/paper/2503.04106/) (2025)
- [Domain shifts in dermoscopic skin cancer datasets: Evaluation of essential limitations for clinical translation](https://mlsanity.com/paper/2304.06968/) (2023)
- [Comprehensive analysis of synthetic learning applied to neonatal brain MRI segmentation](https://mlsanity.com/paper/2309.05306/) (2023)
- [Cooperative Classification and Rationalization for Graph Generalization](https://mlsanity.com/paper/2403.06239/) (2024)
- [Improving cross-domain brain tissue segmentation in fetal MRI with synthetic data](https://mlsanity.com/paper/2403.15103/) (2024)
- [Medical Image Segmentation via Single-Source Domain Generalization with Random Amplitude Spectrum Synthesis](https://mlsanity.com/paper/2409.04768/) (2024)

## Abstract (arXiv)

Deep learning models usually suffer from domain shift issues, where models trained on one source domain do not generalize well to other unseen domains. In this work, we investigate the single-source domain generalization problem: training a deep network that is robust to unseen domains, under the condition that training data is only available from one source domain, which is common in medical imaging applications. We tackle this problem in the context of cross-domain medical image segmentation. Under this scenario, domain shifts are mainly caused by different acquisition processes. We propose a simple causality-inspired data augmentation approach to expose a segmentation model to synthesized domain-shifted training examples. Specifically, 1) to make the deep model robust to discrepancies in image intensities and textures, we employ a family of randomly-weighted shallow networks. They augment training images using diverse appearance transformations. 2) Further we show that spurious correlations among objects in an image are detrimental to domain robustness. These correlations might be taken by the network as domain-specific clues for making predictions, and they may break on unseen domains. We remove these spurious correlations via causal intervention. This is achieved by resampling the appearances of potentially correlated objects independently. The proposed approach is validated on three cross-domain segmentation tasks: cross-modality (CT-MRI) abdominal image segmentation, cross-sequence (bSSFP-LGE) cardiac MRI segmentation, and cross-center prostate MRI segmentation. The proposed approach yields consistent performance gains compared with competitive methods when tested on unseen domains.