Recent advances in generative machine learning models have significantly improved medical imaging, offering promising solutions for data augmentation, privacy preservation, and improved model generalization. However, synthesizing high-quality structural MRI data for Alzheimer's Disease (AD) remains challenging due to the subtle, region-specific, and progressive anatomical changes associated with neurodegeneration. In this paper, we extend the Med-DDPM conditional diffusion model -- originally designed for brain tumor synthesis -- to generate 3D structural MRIs specifically tailored to AD. We adopted Med-DDPM due to its established stability and structural fidelity compared to other generative models, which makes it particularly suitable for capturing the subtle anatomical changes characteristic of AD. Our approach conditions the diffusion process on anatomical segmentation masks derived from the ADNI dataset, incorporating key AD-relevant brain structures into the generation process. We systematically evaluate the quality and utility of the synthetic images by training segmentation models on real, synthetic, and hybrid (mixed) datasets. Experimental results demonstrate that segmentation models trained exclusively on synthetic data achieve comparable Dice scores (0.6532) to those trained on real data (0.6513), while exhibiting significantly enhanced recall. Notably, models trained on hybrid datasets (mixing real and synthetic images) outperform both real and synthetic-only baselines, achieving a Dice score of 0.7244. These findings underscore the successful use of conditional diffusion models for generating anatomically accurate, AD-specific synthetic MRIs, and highlight their potential for enhancing training data availability, improving diagnostic accuracy, and promoting research reproducibility in neuroimaging studies.
Accurate classification of diffuse gliomas is often hindered by domain shifts across centers and a lack of large, annotated datasets. We propose the Anatomically-conditioned Latent Diffusion Model (ALDM), a novel framework for data-efficient, few-shot 3D volumetric MRI synthesis. ALDM utilizes a two-stage approach: a 3D variational autoencoder learns anatomical priors from a data-rich source domain, while a conditional latent diffusion model, guided by tumor masks via a ControlNet, generates structurally coherent volumes for a data-scarce target domain. Evaluated in an extreme few-shot setting with only 16 target images, ALDM outperformed GAN and hybrid baselines, achieving a superior Frechet Inception Distance (FID) of 85.40 and a downstream classification AUC of 0.987. Qualitative results confirm that the model preserves sharp pathology boundaries and cross-modal consistency, with visual fidelity improving progressively during training. By capturing essential diagnostic features, ALDM provides a robust tool for clinical data augmentation in low-resource settings. Our implementation is available at https://github.com/Analytics-Everywhere-Lab/anatomically-conditioned-LDM.
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.
3D FLAIR MRI is widely recommended as one of the standard MRI sequences for brain imaging in multiple sclerosis (MS), but publicly available MS datasets remain relatively small and vary across scanners, acquisition protocols, and lesion patterns. This scarcity and variability hinder the development of robust neuroimaging machine learning models and are particularly challenging for generative models that aim to synthesize images while preserving small, sparse lesions. We propose Lesion-DDPM, a 3D conditional diffusion framework for lesion-aware FLAIR synthesis that incorporates multi-level anatomical mask injection together with a lesion-weighted reconstruction loss to emphasize lesion voxels while maintaining global brain structure. Using a curated subset of the MSLesSeg dataset, we compare Lesion-DDPM with representative state-of-the-art GAN- and diffusion-based models, assessing both image-generation metrics and downstream 3D U-Net segmentation. In our experiments, Lesion-DDPM achieved the lowest lesion-region reconstruction error among all methods. In a downstream 3D U-Net lesion segmentation task, a model trained only on Lesion-DDPM-generated scans and evaluated on real MRIs reached a Dice score of 0.616 compared with 0.569 for the best competing synthetic dataset. When Lesion-DDPM images were added to the real training set, the Dice score further increased to 0.685.