3D Latent Diffusion Model

Accurate longitudinal analysis of brain MRI is often hindered by evolving lesions, which bias automated neuroimaging pipelines. While deep generative models have shown promise in inpainting these lesions, most existing methods operate cross-sectionally or lack 3D anatomical continuity. We present a novel pseudo-3D longitudinal inpainting framework based on Denoising Diffusion Probabilistic Models (DDPM). Our approach utilizes multi-channel conditioning to incorporate longitudinal context from distinct visits (t_1, t_2) and extends Region-Aware Diffusion (RAD) to the medical domain, focusing the generative process on pathological regions without altering surrounding healthy tissue. We evaluated our model against state-of-the-art baselines on longitudinal brain MRI from 93 patients. Our model significantly outperforms the leading baseline (FastSurfer-LIT) in terms of perceptual fidelity, reducing the Learned Perceptual Image Patch Similarity (LPIPS) distance from 0.07 to 0.03 while effectively eliminating inter-slice discontinuities. Furthermore, our model demonstrates high longitudinal stability with a Temporal Fidelity Index of 1.024, closely approaching the ideal value of 1.0 and substantially narrowing the gap compared to LIT's TFI of 1.22. Notably, the RAD mechanism provides a substantial gain in efficiency; our framework achieves an average processing time of 2.53 min per volume, representing approximately 10x speedup over the 24.30 min required by LIT. By leveraging longitudinal priors and region-specific denoising, our framework provides a highly reliable and efficient preprocessing step for the study of progressive neurodegenerative diseases. A derivative dataset consisting of 93 pre-processed scans used for testing will be available upon request after acceptance. Code will be released upon acceptance.

Ambiguous 3D medical image segmentation often involves boundaries where different expert delineations are non-identical yet clinically plausible. Modeling such inter-observer variability requires a careful balance between diversity and anatomical fidelity: deterministic models preserve coherent volumetric structures but collapse expert disagreement into a single mask, while stochastic generative models can produce diverse samples but may introduce disconnected components or slice-to-slice inconsistency when generating full 3D masks from unstructured noise. We propose Volumetric Directional Diffusion (VDD), a prior-anchored diffusion framework that shifts stochastic generation from full-mask synthesis to residual boundary exploration. VDD uses a coarse consensus prediction as an anatomical anchor and learns a directional diffusion process to generate plausible boundary variations around ambiguous regions while preserving stable volumetric topology. Experiments on three multi-rater datasets, including LIDC-IDRI, KiTS21, and ISBI 2015, show that VDD improves uncertainty distribution alignment while maintaining competitive segmentation accuracy and 3D structural consistency. These results suggest that prior-anchored residual diffusion can model clinically plausible expert disagreement without sacrificing anatomical fidelity.

Self-supervised learning (SSL) and diffusion models have respectively advanced representation learning and generative modeling for high-dimensional 3D visual data, yet they are often developed as separate paradigms. Their unification remains challenging under multi-source heterogeneity, as anatomical content must be preserved for analysis while acquisition-related style varies across centers and affects synthesis. In this paper, we propose MeDUET, a 3D Medical image Disentangled UnifiEd PreTraining framework in the variational autoencoder latent space. MeDUET formulates unified pretraining as an empirical factor identifiability problem, aiming to learn domain-invariant content factors for anatomy and domain-specific style factors for appearance. To improve factor separation, MeDUET first uses token demixing with a standard adversarial domain regularizer to establish basic content-style specialization, and further introduces Mixed Factor Token Distillation and Swap-invariance Quadruplet Contrast to reduce mixed-region factor leakage and organize factor spaces with factor-wise invariance and discriminability. With these learned factors, MeDUET transfers effectively to both synthesis and analysis, yielding higher fidelity, faster convergence, and better controllability for synthesis, while achieving competitive or superior domain generalization and label efficiency on diverse datasets, tasks, and modalities. Overall, MeDUET shows that multi-source heterogeneity can serve as useful supervision, with disentanglement providing an effective interface for unifying 3D medical image synthesis and analysis. Our code is available at https://github.com/JK-Liu7/MeDUET.

Ultra-high resolution 7 tesla (7T) magnetic resonance imaging (MRI) provides detailed anatomical views, offering better signal-to-noise ratio, resolution and tissue contrast than 3T MRI, though at the cost of accessibility. We present an advanced deep learning model for synthesizing 7T brain MRI from 3T brain MRI. Paired 7T and 3T T1-weighted images were acquired from 172 participants (124 cognitively unimpaired, 48 impaired) from the Swedish BioFINDER-2 study. To synthesize 7T MRI from 3T images, we trained two models: a specialized U-Net, and a U-Net integrated with a generative adversarial network (GAN U-Net). Our models outperformed two previous state-of-the-art 3T-to-7T models in image-based evaluation metrics. Four blinded MRI professionals judged our synthetic 7T images as comparable in detail to real 7T images, and superior in subjective visual quality to 7T images, due to the reduction of artifacts. Using both SynthSeg and NextBrain, automated segmentations of the synthetic 7T images were more similar to real 7T segmentations than automated segmentations from the 3T images that were used to synthesize the 7T images. Finally, synthetic 7T images showed similar performance to real 3T images in downstream prediction of cognitive status using MRI derivatives (n=3,168). In all, we show that synthetic T1-weighted brain images approaching 7T quality can be generated from 3T images, which may improve image quality and segmentation, without compromising performance in downstream tasks. Future directions, possible clinical use cases, and limitations are discussed.

Generating semantically controllable 3D CT volumes from radiology reports requires more than a rich text encoder, it requires vision-language alignment grounded in volumetric space. Existing Text-to-CT approaches condition generation on encoders pretrained with language only or 2D vision-language objectives, providing conditioning signals that are linguistically expressive but volumetrically blind. We argue this is a structural limitation: the quality of 3D vision-language alignment, not the richness of the text encoder, is the primary bottleneck for semantic controllability in volumetric diffusion models. To address this, we propose a generation-oriented 3D-CLIP encoder trained with structured hard negatives that operate exclusively at the text level. This design increases contrastive difficulty without any additional 3D memory cost, overcoming the small-batch constraints inherent to volumetric encoders. The resulting encoder conditions a fully end-to-end latent diffusion model that operates directly in 3D latent space, eliminating the spatial artifacts and cross-slice inconsistencies introduced by super-resolution pipelines. Through systematic ablations, we establish a clear empirical link between grounding quality and downstream generative controllability. Evaluated on CT-RATE across 18 pathological conditions, our method achieves state-of-the-art performance on both image fidelity and factual correctness, while requiring less inference time and GPU memory than all competing methods. Code is at https://github.com/danielemolino/Text2CT.