# Diffusion Deformable Model for 4D Temporal Medical Image Generation

arXiv: https://arxiv.org/abs/2206.13295 · HTML: https://mlsanity.com/paper/2206.13295/

## Key facts

- Cited by 65 papers in the map (data through 14 Oct 2026).
- Builds on 15 of its 20 references that are in the map.
- First posted on arXiv 27 Jun 2022.

## Builds on (most cited first, 15 of 15)

- [Adam: A Method for Stochastic Optimization](https://mlsanity.com/paper/1412.6980/) (2014)
- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
- [Denoising Diffusion Implicit Models](https://mlsanity.com/paper/2010.02502/) (2020)
- [Deep Unsupervised Learning using Nonequilibrium Thermodynamics](https://mlsanity.com/paper/1503.03585/) (2015)
- [Image Super-Resolution via Iterative Refinement](https://mlsanity.com/paper/2104.07636/) (2021)
- [Spatial Transformer Networks](https://mlsanity.com/paper/1506.02025/) (2015)
- [VoxelMorph: A Learning Framework for Deformable Medical Image Registration](https://mlsanity.com/paper/1809.05231/) (2018)
- [ILVR: Conditioning Method for Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2108.02938/) (2021)
- [An Unsupervised Learning Model for Deformable Medical Image Registration](https://mlsanity.com/paper/1802.02604/) (2018)
- [Unsupervised Learning for Fast Probabilistic Diffeomorphic Registration](https://mlsanity.com/paper/1805.04605/) (2018)
- [Medical Image Synthesis with Context-Aware Generative Adversarial Networks](https://mlsanity.com/paper/1612.05362/) (2016)
- [CycleMorph: Cycle Consistent Unsupervised Deformable Image Registration](https://mlsanity.com/paper/2008.05772/) (2020)
- [Learning Conditional Deformable Templates with Convolutional Networks](https://mlsanity.com/paper/1908.02738/) (2019)
- [Unpaired Brain MR-to-CT Synthesis using a Structure-Constrained CycleGAN](https://mlsanity.com/paper/1809.04536/) (2018)
- [Generative Adversarial Registration for Improved Conditional Deformable Templates](https://mlsanity.com/paper/2105.04349/) (2021)

## Built on by (most cited first, 30 of 65)

- [Diffusion Models for Medical Image Analysis: A Comprehensive Survey](https://mlsanity.com/paper/2211.07804/) (2022)
- [3D and 4D World Modeling: A Survey](https://mlsanity.com/paper/2509.07996/) (2025)
- [SADM: Sequence-Aware Diffusion Model for Longitudinal Medical Image Generation](https://mlsanity.com/paper/2212.08228/) (2022)
- [Medical Diffusion: Denoising Diffusion Probabilistic Models for 3D Medical Image Generation](https://mlsanity.com/paper/2211.03364/) (2022)
- [Deep Learning Approaches for Data Augmentation in Medical Imaging: A Review](https://mlsanity.com/paper/2307.13125/) (2023)
- [Make-A-Volume: Leveraging Latent Diffusion Models for Cross-Modality 3D Brain MRI Synthesis](https://mlsanity.com/paper/2307.10094/) (2023)
- [High-Frequency Space Diffusion Models for Accelerated MRI](https://mlsanity.com/paper/2208.05481/) (2022)
- [ArSDM: Colonoscopy Images Synthesis with Adaptive Refinement Semantic Diffusion Models](https://mlsanity.com/paper/2309.01111/) (2023)
- [Recent Trends in 3D Reconstruction of General Non-Rigid Scenes](https://mlsanity.com/paper/2403.15064/) (2024)
- [A Diffusion Model Predicts 3D Shapes from 2D Microscopy Images](https://mlsanity.com/paper/2208.14125/) (2022)
- [Medical diffusion on a budget: Textual Inversion for medical image generation](https://mlsanity.com/paper/2303.13430/) (2023)
- [Treatment-aware Diffusion Probabilistic Model for Longitudinal MRI Generation and Diffuse Glioma Growth Prediction](https://mlsanity.com/paper/2309.05406/) (2023)
- [TADM: Temporally-Aware Diffusion Model for Neurodegenerative Progression on Brain MRI](https://mlsanity.com/paper/2406.12411/) (2024)
- [Brain Latent Progression: Individual-based Spatiotemporal Disease Progression on 3D Brain MRIs via Latent Diffusion](https://mlsanity.com/paper/2502.08560/) (2025)
- [Data-Efficient Unsupervised Interpolation Without Any Intermediate Frame for 4D Medical Images](https://mlsanity.com/paper/2404.01464/) (2024)
- [Generative Enhancement for 3D Medical Images](https://mlsanity.com/paper/2403.12852/) (2024)
- [DiffDP: Radiotherapy Dose Prediction via a Diffusion Model](https://mlsanity.com/paper/2307.09794/) (2023)
- [Enhancing Label-efficient Medical Image Segmentation with Text-guided Diffusion Models](https://mlsanity.com/paper/2407.05323/) (2024)
- [M3Dsynth: A dataset of medical 3D images with AI-generated local manipulations](https://mlsanity.com/paper/2309.07973/) (2023)
- [DiffuseIR:Diffusion Models For Isotropic Reconstruction of 3D Microscopic Images](https://mlsanity.com/paper/2306.12109/) (2023)
- [A Survey of Emerging Applications of Diffusion Probabilistic Models in MRI](https://mlsanity.com/paper/2311.11383/) (2023)
- [Trade-offs in Fine-tuned Diffusion Models Between Accuracy and Interpretability](https://mlsanity.com/paper/2303.17908/) (2023)
- [Diff-Def: Diffusion-Generated Deformation Fields for Conditional Atlases](https://mlsanity.com/paper/2403.16776/) (2024)
- [Interactive Generation of Laparoscopic Videos with Diffusion Models](https://mlsanity.com/paper/2406.06537/) (2024)
- [SimuScope: Realistic Endoscopic Synthetic Dataset Generation through Surgical Simulation and Diffusion Models](https://mlsanity.com/paper/2412.02332/) (2024)
- [Generative Artificial Intelligence in Medical Imaging: Foundations, Progress, and Clinical Translation](https://mlsanity.com/paper/2508.09177/) (2025)
- [Bi-parametric prostate MR image synthesis using pathology and sequence-conditioned stable diffusion](https://mlsanity.com/paper/2303.02094/) (2023)
- [Deformation-Recovery Diffusion Model (DRDM): Instance Deformation for Image Manipulation and Synthesis](https://mlsanity.com/paper/2407.07295/) (2024)
- [LoCI-DiffCom: Longitudinal Consistency-Informed Diffusion Model for 3D Infant Brain Image Completion](https://mlsanity.com/paper/2405.10691/) (2024)
- [Diffuse-UDA: Addressing Unsupervised Domain Adaptation in Medical Image Segmentation with Appearance and Structure Aligned Diffusion Models](https://mlsanity.com/paper/2408.05985/) (2024)

## Abstract (arXiv)

Temporal volume images with 3D+t (4D) information are often used in medical imaging to statistically analyze temporal dynamics or capture disease progression. Although deep-learning-based generative models for natural images have been extensively studied, approaches for temporal medical image generation such as 4D cardiac volume data are limited. In this work, we present a novel deep learning model that generates intermediate temporal volumes between source and target volumes. Specifically, we propose a diffusion deformable model (DDM) by adapting the denoising diffusion probabilistic model that has recently been widely investigated for realistic image generation. Our proposed DDM is composed of the diffusion and the deformation modules so that DDM can learn spatial deformation information between the source and target volumes and provide a latent code for generating intermediate frames along a geodesic path. Once our model is trained, the latent code estimated from the diffusion module is simply interpolated and fed into the deformation module, which enables DDM to generate temporal frames along the continuous trajectory while preserving the topology of the source image. We demonstrate the proposed method with the 4D cardiac MR image generation between the diastolic and systolic phases for each subject. Compared to the existing deformation methods, our DDM achieves high performance on temporal volume generation.