3D-LLDM: Label-Guided 3D Latent Diffusion Model for Improving High-Resolution Synthetic MR Imaging in Hepatic Structure Segmentation
Authors: Kyeonghun Kim, Jaehyeok Bae, Youngung Han, Joo Young Bae, Seoyoung Ju, Junsu Lim, Gyeongmin Kim, Nam-Joon Kim, +5 more
Organizations: OUTTA, Republic of Korea · Stanford University, USA · Seoul National University, Republic of Korea · Sangmyung University, Republic of Korea · Chung-Ang University, Republic of Korea · Samsung Medical Center, Republic of Korea · NVIDIA, Taiwan · Sungkyunkwan University School of Medicine, Republic of Korea · Samsung Changwon Hospital, Republic of Korea
Deep learning and generative models are advancing rapidly, with synthetic data increasingly being integrated into training pipelines for downstream analysis tasks. However, in medical imaging, their adoption remains constrained by the scarcity of reliable annotated datasets. To address this limitation, we propose 3D-LLDM, a label-guided 3D latent diffusion model that generates high-quality synthetic magnetic resonance (MR) volumes with corresponding anatomical segmentation masks. Our approach uses hepatobiliary phase MR images enhanced with the Gd-EOB-DTPA contrast agent to derive structural masks for the liver, portal vein, hepatic vein, and hepatocellular carcinoma, which then guide volumetric synthesis through a ControlNet-based architecture. Trained on 720 real clinical hepatobiliary phase MR scans from Samsung Medical Center, 3D-LLDM achieves a Fréchet Inception Distance (FID) of 28.31, improving over GANs by 70.9% and over state-of-the-art diffusion baselines by 26.7%. When used for data augmentation, the synthetic volumes improve hepatocellular carcinoma segmentation by up to 11.153% Dice score across five CNN architectures.
Figures & tables
Figure 1: High-Quality synthetic MR volume generated by 3D-LLDM demonstrating anotomical consistency across multi planes: (a) Coronal image, (b) sagittal image, and (c) axial image reformatted from the high-resolution 3D volumetric data shown in (d). Note the tumor highlighted by a red circle, the right hepatic vein indicated by an arrowhead, and the left portal vein marked by an arrow.
Figure 2: Overview of the training and inference pipeline of the proposed 3D-LLDM. The process consists of four steps: (1) training the autoencoder for both label and volume reconstruction, (2) training the latent diffusion model for label and volume synthesis, (3) training the ControlNet to condition the diffusion process on labels, and (4) performing inference using the pretrained latent diffusion models and ControlNet.
Figure 3: Qualitative comparison of synthetic MR volumes of various levels generated by state-of-the-art generative models. The columns correspond to: (1) the label-guided input, (2) the ground truth (GT) MRI scan, (3) the HA-GAN-generated synthetic image, (4) the 3D-DDPM-generated synthetic image, (5) the 3D Latent Diffusion Model (3D LDM) with an autoencoder (AE) backbone, and (6) the proposed 3D-LLDM (Ours)-generated synthetic image.
Method
Ax. FID ↓
Sag. FID ↓
Cor. FID ↓
Avg. FID ↓
HA-GAN
96.32
98.07
97.75
97.38
3D-DDPM
79.53
78.16
76.07
77.92
3D-LDM (w/ VQVAE)
67.17
63.43
62.96
64.52
3D-LDM (w/ VAE)
40.69
37.34
37.83
38.62
3D-LLDM
29.27
27.62
28.04
28.31
Table 1: Comparison of FID scores (↓) among different generative models for medical image synthesis. Lower scores indicate higher image quality. The proposed 3D-LLDM model achieves the lowest FID scores in all views (Axial, Sagittal, and Coronal) as well as the overall average, consistently outperforming conventional generative models.
CNN Model
Segmentation
R
R + S
Improvement
U-Net
Liver-Only
\color blue 0.9650
0.9662
+0.124%
Vein-Only
0.7905
0.8667
+9.640%
HCC-Only
0.7334
0.8152
\color red +11.153%
Multi-Class
0.6968
0.7014
+0.660%
ResUNet
Liver-Only
0.9633
0.9634
+0.010%
Vein-Only
0.7197
0.7902
+9.796%
Table 2: Comparison of segmentation performance using real data only (R) versus real data augmented with synthetic data (R + S) across different CNN architectures and segmentation tasks. The results demonstrate the effectiveness of synthetic data augmentation, with HCC-Only segmentation showing the highest individual improvement (U-Net: +11.153%) and overall improvement (+8.874% average), followed by Vein-Only segmentation (+8.591% average). \color red Best and \color blue 2nd-best results are highlighted.
Figure 4: Qualitative comparison of multi-class segmentation results using U-Net with different training datasets. Each row represents a test sample, while the columns correspond to (1) input MR image, (2) ground truth segmentation, (3) segmentation using only real training data, and (4) segmentation using real+synthetic data from 3D-LLDM. Notably, the 2nd and 4th columns show a more continuous middle hepaticvein, whereas the 3rd column shows a discontinuous appearance.
Medical image segmentation faces fundamental challenges including restricted access, costly annotation, and data shortage to clinical datasets through Picture Archiving and Communication Systems (PACS). These systemic barriers significantly impede the development of robust segmentation algorithms. To address these challenges, we propose FOSCU, which integrates Duo-Diffusion, a 3D latent diffusion model with ControlNet that simultaneously generates high-resolution, anatomically realistic synthetic MRI volumes and corresponding segmentation labels, and an enhanced 3D U-Net training pipeline. Duo-Diffusion employs segmentation-conditioned diffusion to ensure spatial consistency and precise anatomical detail in the generated data. Experimental evaluation on 720 abdominal MRI scans shows that models trained with combined real and synthetic data yield a mean Dice score gain of 0.67% over those using only real data, and achieve a 36.4% reduction in Fréchet Inception Distance (FID), reflecting enhanced image fidelity.
Youngung Han, Kyeonghun Kim, Seoyoung Ju +8
Seoul National University · OUTTA · Sangmyung University +4
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.
Muge Zhang, Muhammad Ali Khaliq, Jamal Alsakran +2
Fairleigh Dickinson University, Vancouver, BC, Canada · University of Colorado at Colorado Springs, Colorado Springs, CO, USA
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.
Salman Shaik, Truong Thanh Hung Nguyen, Hung Cao
Analytics Everywhere Lab, University of New Brunswick, Canada