# Generating healthy counterfactuals with denoising diffusion bridge models

arXiv: https://arxiv.org/abs/2510.13684 · HTML: https://mlsanity.com/paper/2510.13684/

## 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 17 of its 28 references that are in the map.
- First posted on arXiv 15 Oct 2025.

## Placed in

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

## Builds on (most cited first, 17 of 17)

- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
- [High-Resolution Image Synthesis with Latent Diffusion Models](https://mlsanity.com/paper/2112.10752/) (2021)
- [Score-Based Generative Modeling through Stochastic Differential Equations](https://mlsanity.com/paper/2011.13456/) (2020)
- [On the Variance of the Adaptive Learning Rate and Beyond](https://mlsanity.com/paper/1908.03265/) (2019)
- [SynthSeg: Segmentation of brain MRI scans of any contrast and resolution without retraining](https://mlsanity.com/paper/2107.09559/) (2021)
- [Denoising Diffusion Bridge Models](https://mlsanity.com/paper/2309.16948/) (2023)
- [SynthMorph: learning contrast-invariant registration without acquired images](https://mlsanity.com/paper/2004.10282/) (2020)
- [Denoising diffusion models for out-of-distribution detection](https://mlsanity.com/paper/2211.07740/) (2022)
- [Fast Unsupervised Brain Anomaly Detection and Segmentation with Diffusion Models](https://mlsanity.com/paper/2206.03461/) (2022)
- [Mask, Stitch, and Re-Sample: Enhancing Robustness and Generalizability in Anomaly Detection through Automatic Diffusion Models](https://mlsanity.com/paper/2305.19643/) (2023)
- [Diffusion Bridge Implicit Models](https://mlsanity.com/paper/2405.15885/) (2024)
- [Diffusion Models with Implicit Guidance for Medical Anomaly Detection](https://mlsanity.com/paper/2403.08464/) (2024)
- [Unsupervised 3D out-of-distribution detection with latent diffusion models](https://mlsanity.com/paper/2307.03777/) (2023)
- [Denoising Diffusion Models for Inpainting of Healthy Brain Tissue](https://mlsanity.com/paper/2402.17307/) (2024)
- [The Brain Tumor Segmentation (BraTS) Challenge: Local Synthesis of Healthy Brain Tissue via Inpainting](https://mlsanity.com/paper/2305.08992/) (2023)
- [Conditional diffusion models for guided anomaly detection in brain images using fluid-driven anomaly randomization](https://mlsanity.com/paper/2506.10233/) (2025)
- [Unraveling Normal Anatomy via Fluid-Driven Anomaly Randomization](https://mlsanity.com/paper/2501.13370/) (2025)

## Abstract (arXiv)

Generating healthy counterfactuals from pathological images holds significant promise in medical imaging, e.g., in anomaly detection or for application of analysis tools that are designed for healthy scans. These counterfactuals should represent what a patient's scan would plausibly look like in the absence of pathology, preserving individual anatomical characteristics while modifying only the pathological regions. Denoising diffusion probabilistic models (DDPMs) have become popular methods for generating healthy counterfactuals of pathology data. Typically, this involves training on solely healthy data with the assumption that a partial denoising process will be unable to model disease regions and will instead reconstruct a closely matched healthy counterpart. More recent methods have incorporated synthetic pathological images to better guide the diffusion process. However, it remains challenging to guide the generative process in a way that effectively balances the removal of anomalies with the retention of subject-specific features. To solve this problem, we propose a novel application of denoising diffusion bridge models (DDBMs) - which, unlike DDPMs, condition the diffusion process not only on the initial point (i.e., the healthy image), but also on the final point (i.e., a corresponding synthetically generated pathological image). Treating the pathological image as a structurally informative prior enables us to generate counterfactuals that closely match the patient's anatomy while selectively removing pathology. The results show that our DDBM outperforms previously proposed diffusion models and fully supervised approaches at segmentation and anomaly detection tasks.
