# Reverse Spatio-Temporal Disease Progression Modelling

arXiv: https://arxiv.org/abs/2609.14590 · HTML: https://mlsanity.com/paper/2609.14590/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 15 of its 21 references that are in the map.
- First posted on arXiv 13 Sep 2026.

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

- [Adam: A Method for Stochastic Optimization](https://mlsanity.com/paper/1412.6980/) (2014)
- [High-Resolution Image Synthesis with Latent Diffusion Models](https://mlsanity.com/paper/2112.10752/) (2021)
- [The Unreasonable Effectiveness of Deep Features as a Perceptual Metric](https://mlsanity.com/paper/1801.03924/) (2018)
- [Neural Discrete Representation Learning](https://mlsanity.com/paper/1711.00937/) (2017)
- [Neural Ordinary Differential Equations](https://mlsanity.com/paper/1806.07366/) (2018)
- [Taming Transformers for High-Resolution Image Synthesis](https://mlsanity.com/paper/2012.09841/) (2020)
- [Latent ODEs for Irregularly-Sampled Time Series](https://mlsanity.com/paper/1907.03907/) (2019)
- [Deep Autoencoding Models for Unsupervised Anomaly Segmentation in Brain MR Images](https://mlsanity.com/paper/1804.04488/) (2018)
- [Automated brain extraction of multi-sequence MRI using artificial neural networks](https://mlsanity.com/paper/1901.11341/) (2019)
- [Morpho-MNIST: Quantitative Assessment and Diagnostics for Representation Learning](https://mlsanity.com/paper/1809.10780/) (2018)
- [SADM: Sequence-Aware Diffusion Model for Longitudinal Medical Image Generation](https://mlsanity.com/paper/2212.08228/) (2022)
- [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)
- [Patch-based Brain Age Estimation from MR Images](https://mlsanity.com/paper/2008.12965/) (2020)
- [4D VQ-GAN: Synthesising Medical Scans at Any Time Point for Personalised Disease Progression Modelling of Idiopathic Pulmonary Fibrosis](https://mlsanity.com/paper/2502.05713/) (2025)

## Abstract (arXiv)

Deep learning-based spatio-temporal disease progression models commonly overlook the incubation period of progressive diseases, limiting the use of those models in early interventions, which are vital for not easily reversible diseases such as Alzheimer's. This is because, the existing deep learning based longitudinal disease-progression models are almost always run forward: from an observed baseline they predict future decline. In many clinical settings, however, imaging begins only after pathology is suspected or already visible, the earlier, healthier patient-specific reference was never acquired. To address this, we propose to study reverse disease progression prediction: given later diseased anatomy, reconstruct the unobserved healthier anatomy that preceded it. We use a two-stage model in which a frozen 3D vector-quantised autoencoder defines a compact discrete latent space, while a Neural Ordinary Differential Equation (ODE) learns continuous-time dynamics in that space. A recurrent encoder reads late observations in reverse temporal order, initialises the latent state, and the ODE is integrated backwards across the trajectory. On a controlled Morpho-MNIST benchmark with a sinusoidal perturbation, our model successfully recovered the unseen previous states from later observations of the non-monotonic trajectory. On longitudinal brain MRIs from Alzheimer's Disease Neuroimaging Initiative, at the task to recover the previous unseen trajectory towards healthy states of the patients from observed later diseased states, our model outperforms the baselines that uses copy-nearest and mean-observed, with positive disease-reversal scores in every diagnostic stratum. We hope that our work can provide insights and tools towards discovering the incubation periods from single-shot scans, and developing early interventions of diseases based on imaging.