# CLIMB: Controllable Longitudinal Brain Image Generation using Mamba-based Latent Diffusion Model and Gaussian-aligned Autoencoder

arXiv: https://arxiv.org/abs/2604.15611 · HTML: https://mlsanity.com/paper/2604.15611/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Placed in Medical imaging and segmentation, one of 14 directions in Diffusion models.
- Builds on 24 of its 39 references that are in the map.
- First posted on arXiv 17 Apr 2026.

## Placed in

- Diffusion models / [Medical imaging and segmentation](https://mlsanity.com/diffusion/medical-imaging-and-segmentation/)
- State-space sequence models (S4, Mamba) / [Mamba for medical image analysis](https://mlsanity.com/ssm/mamba-for-medical-image-analysis/)

## Builds on (most cited first, 24 of 24)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [Adam: A Method for Stochastic Optimization](https://mlsanity.com/paper/1412.6980/) (2014)
- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
- [The Unreasonable Effectiveness of Deep Features as a Perceptual Metric](https://mlsanity.com/paper/1801.03924/) (2018)
- [Denoising Diffusion Implicit Models](https://mlsanity.com/paper/2010.02502/) (2020)
- [Scalable Diffusion Models with Transformers](https://mlsanity.com/paper/2212.09748/) (2022)
- [Adding Conditional Control to Text-to-Image Diffusion Models](https://mlsanity.com/paper/2302.05543/) (2023)
- [Mamba: Linear-Time Sequence Modeling with Selective State Spaces](https://mlsanity.com/paper/2312.00752/) (2023)
- [Hungry Hungry Hippos: Towards Language Modeling with State Space Models](https://mlsanity.com/paper/2212.14052/) (2022)
- [DragDiffusion: Harnessing Diffusion Models for Interactive Point-based Image Editing](https://mlsanity.com/paper/2306.14435/) (2023)
- [Brain Imaging Generation with Latent Diffusion Models](https://mlsanity.com/paper/2209.07162/) (2022)
- [SynthSeg: Segmentation of brain MRI scans of any contrast and resolution without retraining](https://mlsanity.com/paper/2107.09559/) (2021)
- [Unsupervised Medical Image Translation with Adversarial Diffusion Models](https://mlsanity.com/paper/2207.08208/) (2022)
- [MedSegDiff: Medical Image Segmentation with Diffusion Probabilistic Model](https://mlsanity.com/paper/2211.00611/) (2022)
- [SynthStrip: Skull-Stripping for Any Brain Image](https://mlsanity.com/paper/2203.09974/) (2022)
- [Ambiguous Medical Image Segmentation using Diffusion Models](https://mlsanity.com/paper/2304.04745/) (2023)
- [ZigMa: A DiT-style Zigzag Mamba Diffusion Model](https://mlsanity.com/paper/2403.13802/) (2024)
- [Patch-Based Image Inpainting with Generative Adversarial Networks](https://mlsanity.com/paper/1803.07422/) (2018)
- [CoLa-Diff: Conditional Latent Diffusion Model for Multi-Modal MRI Synthesis](https://mlsanity.com/paper/2303.14081/) (2023)
- [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)
- [Enhancing Spatiotemporal Disease Progression Models via Latent Diffusion and Prior Knowledge](https://mlsanity.com/paper/2405.03328/) (2024)
- [I2I-Mamba: Multi-modal medical image synthesis via selective state space modeling](https://mlsanity.com/paper/2405.14022/) (2024)
- [Artifact Restoration in Histology Images with Diffusion Probabilistic Models](https://mlsanity.com/paper/2307.14262/) (2023)

## Abstract (arXiv)

Latent diffusion models have emerged as powerful generative models in medical imaging, enabling the synthesis of high quality brain magnetic resonance imaging scans. In particular, predicting the evolution of a patients brain can aid in early intervention, prognosis, and treatment planning. In this study, we introduce CLIMB, Controllable Longitudinal brain Image generation via state space based latent diffusion model, an advanced framework for modeling temporal changes in brain structure. CLIMB is designed to model the structural evolution of the brain structure over time, utilizing a baseline MRI scan and its acquisition age as foundational inputs. Additionally, multiple conditional variables, including projected age, gender, disease status, genetic information, and brain structure volumes, are incorporated to enhance the temporal modeling of anatomical changes. Unlike existing LDM methods that rely on self attention modules, which effectively capture contextual information from input images but are computationally expensive, our approach leverages state space, a state space model architecture that substantially reduces computational overhead while preserving high-quality image synthesis. Furthermore, we introduce a Gaussian-aligned autoencoder that extracts latent representations conforming to prior distributions without the sampling noise inherent in conventional variational autoencoders. We train and evaluate our proposed model on the Alzheimers Disease Neuroimaging Initiative dataset, consisting of 6,306 MRI scans from 1,390 participants. By comparing generated images with real MRI scans, CLIMB achieves a structural similarity index of 0.9433, demonstrating notable improvements over existing methods.