# SMART: A Flexible, Interpretable, and Scalable Spatio-temporal Brain Atlas from High-Resolution Imaging Data

arXiv: https://arxiv.org/abs/2606.18753 · HTML: https://mlsanity.com/paper/2606.18753/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 12 of its 40 references that are in the map.
- First posted on arXiv 17 Jun 2026.

## Builds on (most cited first, 12 of 12)

- [Neural Ordinary Differential Equations](https://mlsanity.com/paper/1806.07366/) (2018)
- [VoxelMorph: A Learning Framework for Deformable Medical Image Registration](https://mlsanity.com/paper/1809.05231/) (2018)
- [SynthSeg: Segmentation of brain MRI scans of any contrast and resolution without retraining](https://mlsanity.com/paper/2107.09559/) (2021)
- [SynthStrip: Skull-Stripping for Any Brain Image](https://mlsanity.com/paper/2203.09974/) (2022)
- [Learning Conditional Deformable Templates with Convolutional Networks](https://mlsanity.com/paper/1908.02738/) (2019)
- [SADM: Sequence-Aware Diffusion Model for Longitudinal Medical Image Generation](https://mlsanity.com/paper/2212.08228/) (2022)
- [Equitable modelling of brain imaging by counterfactual augmentation with morphologically constrained 3D deep generative models](https://mlsanity.com/paper/2111.14923/) (2021)
- [Med-NCA: Robust and Lightweight Segmentation with Neural Cellular Automata](https://mlsanity.com/paper/2302.03473/) (2023)
- [Learning Spatio-Temporal Model of Disease Progression with NeuralODEs from Longitudinal Volumetric Data](https://mlsanity.com/paper/2211.04234/) (2022)
- [M3D-NCA: Robust 3D Segmentation with Built-in Quality Control](https://mlsanity.com/paper/2309.02954/) (2023)
- [NCA-Morph: Medical Image Registration with Neural Cellular Automata](https://mlsanity.com/paper/2410.22265/) (2024)
- [TimeFlow: Temporal Conditioning for Longitudinal Brain MRI Registration and Aging Analysis](https://mlsanity.com/paper/2501.08667/) (2025)

## Abstract (arXiv)

We introduce SMART, a framework for learning a flexible, interpretable, and scalable spatio-temporal brain atlas from longitudinal high-resolution 3D medical images. Existing approaches to spatio-temporal atlas construction rely on black-box generative models that lack flexibility, limit interpretability, and struggle to scale to high-dimensional data. SMART addresses these challenges by learning a continuous disease-time atlas that decouples global group-wise disease dynamics from their patient-specific anatomical manifestation. Guided by anatomically inspired priors, SMART models interpretable global trajectories of regional progression along a shared disease timeline through region-specific differential equations. Global trajectories are further personalized to individual anatomies via dense diffeomorphic displacements parameterized by a flexible and scalable multi-scale Neural Cellular Automata. Evaluated on five longitudinal MRI datasets in Alzheimer's disease (ADNI-1/GO/2, OASIS-3, AIBL; > 1,300 subjects), SMART produces anatomically meaningful predictions of disease progression and achieves state-of-the-art forecasting accuracy and improved temporal consistency over adversarial and diffusion baselines. Our approach establishes a new paradigm for flexible, interpretable, and scalable modeling of spatio-temporal change in high-dimensional medical image time-series.