# Cortex-Grounded Diffusion Models for Brain Image Generation

arXiv: https://arxiv.org/abs/2601.19498 · HTML: https://mlsanity.com/paper/2601.19498/

## Key facts

- Cited by 1 papers in the map (data through 14 Oct 2026).
- Placed in Medical imaging and segmentation, one of 14 directions in Diffusion models.
- Builds on 38 of its 76 references that are in the map.
- First posted on arXiv 27 Jan 2026.

## Placed in

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

## Builds on (most cited first, 30 of 38)

- [Adam: A Method for Stochastic Optimization](https://mlsanity.com/paper/1412.6980/) (2014)
- [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)
- [Denoising Diffusion Implicit Models](https://mlsanity.com/paper/2010.02502/) (2020)
- [Diffusion Models Beat GANs on Image Synthesis](https://mlsanity.com/paper/2105.05233/) (2021)
- [Deep Unsupervised Learning using Nonequilibrium Thermodynamics](https://mlsanity.com/paper/1503.03585/) (2015)
- [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)
- [High-Resolution Image Synthesis and Semantic Manipulation with Conditional GANs](https://mlsanity.com/paper/1711.11585/) (2017)
- [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)
- [BBDM: Image-to-image Translation with Brownian Bridge Diffusion Models](https://mlsanity.com/paper/2205.07680/) (2022)
- [SynthStrip: Skull-Stripping for Any Brain Image](https://mlsanity.com/paper/2203.09974/) (2022)
- [FastSurfer -- A fast and accurate deep learning based neuroimaging pipeline](https://mlsanity.com/paper/1910.03866/) (2019)
- [MAISI: Medical AI for Synthetic Imaging](https://mlsanity.com/paper/2409.11169/) (2024)
- [Conditional Diffusion Models for Semantic 3D Brain MRI Synthesis](https://mlsanity.com/paper/2305.18453/) (2023)
- [Anatomically-Controllable Medical Image Generation with Segmentation-Guided Diffusion Models](https://mlsanity.com/paper/2402.05210/) (2024)
- [Hierarchical Amortized Training for Memory-efficient High Resolution 3D GAN](https://mlsanity.com/paper/2008.01910/) (2020)
- [Robust machine learning segmentation for large-scale analysis of heterogeneous clinical brain MRI datasets](https://mlsanity.com/paper/2209.02032/) (2022)
- [Detect and Correct Bias in Multi-Site Neuroimaging Datasets](https://mlsanity.com/paper/2002.05049/) (2020)
- [Equitable modelling of brain imaging by counterfactual augmentation with morphologically constrained 3D deep generative models](https://mlsanity.com/paper/2111.14923/) (2021)
- [MedGen3D: A Deep Generative Framework for Paired 3D Image and Mask Generation](https://mlsanity.com/paper/2304.04106/) (2023)
- [Generating Realistic Brain MRIs via a Conditional Diffusion Probabilistic Model](https://mlsanity.com/paper/2212.08034/) (2022)
- [Hallucination Index: An Image Quality Metric for Generative Reconstruction Models](https://mlsanity.com/paper/2407.12780/) (2024)
- [DeepSSM: A Blueprint for Image-to-Shape Deep Learning Models](https://mlsanity.com/paper/2110.07152/) (2021)
- [Synthetically Enhanced: Unveiling Synthetic Data's Potential in Medical Imaging Research](https://mlsanity.com/paper/2311.09402/) (2023)
- [Brain Latent Progression: Individual-based Spatiotemporal Disease Progression on 3D Brain MRIs via Latent Diffusion](https://mlsanity.com/paper/2502.08560/) (2025)
- [Neural deformation fields for template-based reconstruction of cortical surfaces from MRI](https://mlsanity.com/paper/2401.12938/) (2024)
- [Metadata-Conditioned Generative Models to Synthesize Anatomically-Plausible 3D Brain MRIs](https://mlsanity.com/paper/2310.04630/) (2023)

## Built on by (most cited first, 1 of 1)

- [AnaDiffusion: Anatomically CompositionalLatent Diffusion for Controllable 3D Brain MRI Generation](https://mlsanity.com/paper/2608.23014/) (2026)

## Abstract (arXiv)

Synthetic neuroimaging data can mitigate critical limitations of real-world datasets, including the scarcity of rare phenotypes, domain shifts across scanners, and insufficient longitudinal coverage. However, existing generative models largely rely on weak conditioning signals, such as labels or text, which lack anatomical grounding and often produce biologically implausible outputs. To this end, we introduce Cor2Vox, a cortex-grounded generative framework for brain magnetic resonance image (MRI) synthesis that ties image generation to continuous structural priors of the cerebral cortex. It leverages high-resolution cortical surfaces to guide a 3D shape-to-image Brownian bridge diffusion process, enabling topologically faithful synthesis and precise control over underlying anatomies. To support the generation of new, realistic brain shapes, we developed a large-scale statistical shape model of cortical morphology derived from over 33,000 UK Biobank scans. We validated the fidelity of Cor2Vox based on traditional image quality metrics, advanced cortical surface reconstruction, and whole-brain segmentation quality, outperforming many baseline methods. Across three applications, namely (i) anatomically consistent synthesis, (ii) simulation of progressive gray matter atrophy, and (iii) harmonization of in-house frontotemporal dementia scans with public datasets, Cor2Vox preserved fine-grained cortical morphology at the sub-voxel level, exhibiting remarkable robustness to variations in cortical geometry and disease phenotype without retraining.