# Temporally-Aware Diffusion Model for Brain Progression Modelling with Bidirectional Temporal Regularisation

arXiv: https://arxiv.org/abs/2509.03141 · HTML: https://mlsanity.com/paper/2509.03141/

## Key facts

- Cited by 3 papers in the map (data through 14 Oct 2026).
- Placed in Medical imaging and segmentation, one of 14 directions in Diffusion models.
- Builds on 15 of its 27 references that are in the map.
- First posted on arXiv 3 Sep 2025.

## Placed in

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

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

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
- [SRDiff: Single Image Super-Resolution with Diffusion Probabilistic Models](https://mlsanity.com/paper/2104.14951/) (2021)
- [SynthSeg: Segmentation of brain MRI scans of any contrast and resolution without retraining](https://mlsanity.com/paper/2107.09559/) (2021)
- [Diffusion Deformable Model for 4D Temporal Medical Image Generation](https://mlsanity.com/paper/2206.13295/) (2022)
- [DiffuseMorph: Unsupervised Deformable Image Registration Using Diffusion Model](https://mlsanity.com/paper/2112.05149/) (2021)
- [SADM: Sequence-Aware Diffusion Model for Longitudinal Medical Image Generation](https://mlsanity.com/paper/2212.08228/) (2022)
- [Learning to synthesise the ageing brain without longitudinal data](https://mlsanity.com/paper/1912.02620/) (2019)
- [Equitable modelling of brain imaging by counterfactual augmentation with morphologically constrained 3D deep generative models](https://mlsanity.com/paper/2111.14923/) (2021)
- [Enhancing Spatiotemporal Disease Progression Models via Latent Diffusion and Prior Knowledge](https://mlsanity.com/paper/2405.03328/) (2024)
- [Degenerative Adversarial NeuroImage Nets for Brain Scan Simulations: Application in Ageing and Dementia](https://mlsanity.com/paper/1912.01526/) (2019)
- [Degenerative Adversarial NeuroImage Nets: Generating Images that Mimic Disease Progression](https://mlsanity.com/paper/1907.02787/) (2019)
- [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)
- [Individualized multi-horizon MRI trajectory prediction for Alzheimer's Disease](https://mlsanity.com/paper/2408.02018/) (2024)

## Built on by (most cited first, 3 of 3)

- [Anatomically Guided Latent Diffusion for Brain MRI Progression Modeling](https://mlsanity.com/paper/2601.14584/) (2026)
- [MUMINS: Metadata-conditioned Uncertainty-aware Medical Image Next-state Synthesis](https://mlsanity.com/paper/2609.17169/) (2026)
- [Is your uncertainty map wrong, or is its target? Exact diagnostics for the Tweedie diagonal, and a gradient-free alternative](https://mlsanity.com/paper/2609.33786/) (2026)

## Abstract (arXiv)

Generating realistic MRIs to accurately predict future changes in the structure of brain is an invaluable tool for clinicians in assessing clinical outcomes and analysing the disease progression at the patient level. However, current existing methods present some limitations: (i) some approaches fail to explicitly capture the relationship between structural changes and time intervals, especially when trained on age-imbalanced datasets; (ii) others rely only on scan interpolation, which lack clinical utility, as they generate intermediate images between timepoints rather than future pathological progression; and (iii) most approaches rely on 2D slice-based architectures, thereby disregarding full 3D anatomical context, which is essential for accurate longitudinal predictions. We propose a 3D Temporally-Aware Diffusion Model (TADM-3D), which accurately predicts brain progression on MRI volumes. To better model the relationship between time interval and brain changes, TADM-3D uses a pre-trained Brain-Age Estimator (BAE) that guides the diffusion model in the generation of MRIs that accurately reflect the expected age difference between baseline and generated follow-up scans. Additionally, to further improve the temporal awareness of TADM-3D, we propose the Back-In-Time Regularisation (BITR), by training TADM-3D to predict bidirectionally from the baseline to follow-up (forward), as well as from the follow-up to baseline (backward). Although predicting past scans has limited clinical applications, this regularisation helps the model generate temporally more accurate scans. We train and evaluate TADM-3D on the OASIS-3 dataset, and we validate the generalisation performance on an external test set from the NACC dataset. The code will be available upon acceptance.