# SADM: Sequence-Aware Diffusion Model for Longitudinal Medical Image Generation

arXiv: https://arxiv.org/abs/2212.08228 · HTML: https://mlsanity.com/paper/2212.08228/

## Key facts

- Cited by 56 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 22 references that are in the map.
- First posted on arXiv 16 Dec 2022.

## 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)
- [Diffusion Models Beat GANs on Image Synthesis](https://mlsanity.com/paper/2105.05233/) (2021)
- [Classifier-Free Diffusion Guidance](https://mlsanity.com/paper/2207.12598/) (2022)
- [Improved Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2102.09672/) (2021)
- [Imagen Video: High Definition Video Generation with Diffusion Models](https://mlsanity.com/paper/2210.02303/) (2022)
- [ViViT: A Video Vision Transformer](https://mlsanity.com/paper/2103.15691/) (2021)
- [Variational Diffusion Models](https://mlsanity.com/paper/2107.00630/) (2021)
- [VoxelMorph: A Learning Framework for Deformable Medical Image Registration](https://mlsanity.com/paper/1809.05231/) (2018)
- [Flexible Diffusion Modeling of Long Videos](https://mlsanity.com/paper/2205.11495/) (2022)
- [Brain Imaging Generation with Latent Diffusion Models](https://mlsanity.com/paper/2209.07162/) (2022)
- [Generative Adversarial Network in Medical Imaging: A Review](https://mlsanity.com/paper/1809.07294/) (2018)
- [Causal Machine Learning: A Survey and Open Problems](https://mlsanity.com/paper/2206.15475/) (2022)
- [Diffusion Deformable Model for 4D Temporal Medical Image Generation](https://mlsanity.com/paper/2206.13295/) (2022)
- [Sequence-Aware Recommender Systems](https://mlsanity.com/paper/1802.08452/) (2018)
- [DiffuseMorph: Unsupervised Deformable Image Registration Using Diffusion Model](https://mlsanity.com/paper/2112.05149/) (2021)
- [Learn-Explain-Reinforce: Counterfactual Reasoning and Its Guidance to Reinforce an Alzheimer's Disease Diagnosis Model](https://mlsanity.com/paper/2108.09451/) (2021)

## Built on by (most cited first, 30 of 56)

- [MedSyn: Text-guided Anatomy-aware Synthesis of High-Fidelity 3D CT Images](https://mlsanity.com/paper/2310.03559/) (2023)
- [Enhancing Spatiotemporal Disease Progression Models via Latent Diffusion and Prior Knowledge](https://mlsanity.com/paper/2405.03328/) (2024)
- [Rethinking Diffusion Model for Multi-Contrast MRI Super-Resolution](https://mlsanity.com/paper/2404.04785/) (2024)
- [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)
- [Deep Generative Models for 3D Medical Image Synthesis](https://mlsanity.com/paper/2410.17664/) (2024)
- [Elucidating Optimal Reward-Diversity Tradeoffs in Text-to-Image Diffusion Models](https://mlsanity.com/paper/2409.06493/) (2024)
- [Latent Drifting in Diffusion Models for Counterfactual Medical Image Synthesis](https://mlsanity.com/paper/2412.20651/) (2024)
- [Generative AI-Driven Human Digital Twin in IoT-Healthcare: A Comprehensive Survey](https://mlsanity.com/paper/2401.13699/) (2024)
- [A Survey of Emerging Applications of Diffusion Probabilistic Models in MRI](https://mlsanity.com/paper/2311.11383/) (2023)
- [Synthesizing Individualized Aging Brains in Health and Disease with Generative Models and Parallel Transport](https://mlsanity.com/paper/2502.21049/) (2025)
- [Generative Artificial Intelligence in Medical Imaging: Foundations, Progress, and Clinical Translation](https://mlsanity.com/paper/2508.09177/) (2025)
- [Learning Patient-Specific Disease Dynamics with Latent Flow Matching for Longitudinal Imaging Generation](https://mlsanity.com/paper/2512.09185/) (2025)
- [Individualized multi-horizon MRI trajectory prediction for Alzheimer's Disease](https://mlsanity.com/paper/2408.02018/) (2024)
- [LoCI-DiffCom: Longitudinal Consistency-Informed Diffusion Model for 3D Infant Brain Image Completion](https://mlsanity.com/paper/2405.10691/) (2024)
- [NODER: Image Sequence Regression Based on Neural Ordinary Differential Equations](https://mlsanity.com/paper/2407.13241/) (2024)
- [Temporal Flow Matching for Learning Spatio-Temporal Trajectories in 4D Longitudinal Medical Imaging](https://mlsanity.com/paper/2508.21580/) (2025)
- [Improving Robustness and Reliability in Medical Image Classification with Latent-Guided Diffusion and Nested-Ensembles](https://mlsanity.com/paper/2310.15952/) (2023)
- [BrainMRDiff: A Diffusion Model for Anatomically Consistent Brain MRI Synthesis](https://mlsanity.com/paper/2504.04532/) (2025)
- [Latent Diffusion Autoencoders: Toward Efficient and Meaningful Unsupervised Representation Learning in Medical Imaging](https://mlsanity.com/paper/2504.08635/) (2025)
- [Devil is in Details: Locality-Aware 3D Abdominal CT Volume Generation for Self-Supervised Organ Segmentation](https://mlsanity.com/paper/2409.20332/) (2024)
- [TimeFlow: Temporal Conditioning for Longitudinal Brain MRI Registration and Aging Analysis](https://mlsanity.com/paper/2501.08667/) (2025)
- [MedLoRD: A Medical Low-Resource Diffusion Model for High-Resolution 3D CT Image Synthesis](https://mlsanity.com/paper/2503.13211/) (2025)
- [Temporally-Aware Diffusion Model for Brain Progression Modelling with Bidirectional Temporal Regularisation](https://mlsanity.com/paper/2509.03141/) (2025)
- [Diff-DTI: Fast Diffusion Tensor Imaging Using A Feature-Enhanced Joint Diffusion Model](https://mlsanity.com/paper/2405.15830/) (2024)
- [Neural Autoregressive Modeling of Brain Aging](https://mlsanity.com/paper/2507.22954/) (2025)
- [Anatomically Guided Latent Diffusion for Brain MRI Progression Modeling](https://mlsanity.com/paper/2601.14584/) (2026)
- [Extrapolating Prospective Glaucoma Fundus Images through Diffusion Model in Irregular Longitudinal Sequences](https://mlsanity.com/paper/2410.21130/) (2024)
- [Identity Preserving Latent Diffusion for Brain Aging Modeling](https://mlsanity.com/paper/2503.09634/) (2025)

## Abstract (arXiv)

Human organs constantly undergo anatomical changes due to a complex mix of short-term (e.g., heartbeat) and long-term (e.g., aging) factors. Evidently, prior knowledge of these factors will be beneficial when modeling their future state, i.e., via image generation. However, most of the medical image generation tasks only rely on the input from a single image, thus ignoring the sequential dependency even when longitudinal data is available. Sequence-aware deep generative models, where model input is a sequence of ordered and timestamped images, are still underexplored in the medical imaging domain that is featured by several unique challenges: 1) Sequences with various lengths; 2) Missing data or frame, and 3) High dimensionality. To this end, we propose a sequence-aware diffusion model (SADM) for the generation of longitudinal medical images. Recently, diffusion models have shown promising results in high-fidelity image generation. Our method extends this new technique by introducing a sequence-aware transformer as the conditional module in a diffusion model. The novel design enables learning longitudinal dependency even with missing data during training and allows autoregressive generation of a sequence of images during inference. Our extensive experiments on 3D longitudinal medical images demonstrate the effectiveness of SADM compared with baselines and alternative methods. The code is available at https://github.com/ubc-tea/SADM-Longitudinal-Medical-Image-Generation.