# MRExtrap: Longitudinal Aging of Brain MRIs using Linear Modeling in Latent Space

arXiv: https://arxiv.org/abs/2508.19482 · HTML: https://mlsanity.com/paper/2508.19482/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 22 of its 37 references that are in the map.
- First posted on arXiv 26 Aug 2025.

## Builds on (most cited first, 22 of 22)

- [An Image is Worth 16x16 Words: Transformers for Image Recognition at Scale](https://mlsanity.com/paper/2010.11929/) (2020)
- [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)
- [The Unreasonable Effectiveness of Deep Features as a Perceptual Metric](https://mlsanity.com/paper/1801.03924/) (2018)
- [Diffusion Models Beat GANs on Image Synthesis](https://mlsanity.com/paper/2105.05233/) (2021)
- [Adding Conditional Control to Text-to-Image Diffusion Models](https://mlsanity.com/paper/2302.05543/) (2023)
- [Neural Discrete Representation Learning](https://mlsanity.com/paper/1711.00937/) (2017)
- [Image-to-Image Translation with Conditional Adversarial Networks](https://mlsanity.com/paper/1611.07004/) (2016)
- [Generalised Dice overlap as a deep learning loss function for highly unbalanced segmentations](https://mlsanity.com/paper/1707.03237/) (2017)
- [Brain Imaging Generation with Latent Diffusion Models](https://mlsanity.com/paper/2209.07162/) (2022)
- [Generation of 3D Brain MRI Using Auto-Encoding Generative Adversarial Networks](https://mlsanity.com/paper/1908.02498/) (2019)
- [SADM: Sequence-Aware Diffusion Model for Longitudinal Medical Image Generation](https://mlsanity.com/paper/2212.08228/) (2022)
- [Robust machine learning segmentation for large-scale analysis of heterogeneous clinical brain MRI datasets](https://mlsanity.com/paper/2209.02032/) (2022)
- [Visual Feature Attribution using Wasserstein GANs](https://mlsanity.com/paper/1711.08998/) (2017)
- [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)
- [Variational AutoEncoder For Regression: Application to Brain Aging Analysis](https://mlsanity.com/paper/1904.05948/) (2019)
- [ICAM-reg: Interpretable Classification and Regression with Feature Attribution for Mapping Neurological Phenotypes in Individual Scans](https://mlsanity.com/paper/2103.02561/) (2021)
- [Morphology-preserving Autoregressive 3D Generative Modelling of the Brain](https://mlsanity.com/paper/2209.03177/) (2022)
- [Multiscale Metamorphic VAE for 3D Brain MRI Synthesis](https://mlsanity.com/paper/2301.03588/) (2023)
- [Prediction of the progression of subcortical brain structures in Alzheimer's disease from baseline](https://mlsanity.com/paper/1711.08716/) (2017)

## Abstract (arXiv)

Simulating aging in 3D brain MRI scans can reveal disease progression patterns in neurological disorders such as Alzheimer's disease. Current deep learning-based generative models typically approach this problem by predicting future scans from a single observed scan. We investigate modeling brain aging via linear models in the latent space of convolutional autoencoders (MRExtrap). Our approach, MRExtrap, is based on our observation that autoencoders trained on brain MRIs create latent spaces where aging trajectories appear approximately linear. We train autoencoders on brain MRIs to create latent spaces, and investigate how these latent spaces allow predicting future MRIs through linear extrapolation based on age, using an estimated latent progression rate boldsymbolβ. For single-scan prediction, we propose using population-averaged and subject-specific priors on linear progression rates. We also demonstrate that predictions in the presence of additional scans can be flexibly updated using Bayesian posterior sampling, providing a mechanism for subject-specific refinement. On the ADNI dataset, MRExtrap predicts aging patterns accurately and beats a GAN-based baseline for single-volume prediction of brain aging. We also demonstrate and analyze multi-scan conditioning to incorporate subject-specific progression rates. Finally, we show that the latent progression rates in MRExtrap's linear framework correlate with disease and age-based aging patterns from previously studied structural atrophy rates. MRExtrap offers a simple and robust method for the age-based generation of 3D brain MRIs, particularly valuable in scenarios with multiple longitudinal observations.