FOSCU: Feasibility of Synthetic MRI Generation via Duo-Diffusion Models for Enhancement of 3D U-Nets in Hepatic Segmentation

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.

Acquiring pixel-level annotations for medical image segmentation is a severe bottleneck. Traditional U-Net architectures, while effective, learn local texture patterns and lack awareness of global anatomical structures, leading to boundary delineation failures in low-data regimes. This research paper proposes utilizing unsupervised Denoising Diffusion Probabilistic Models (DDPMs) to extract anatomical features. We train a DDPM on 21 unlabeled abdominal CT scans to learn structural representations, transferring the encoder weights to a downstream segmentation task evaluated on the BTCV multi-organ dataset. Diffusion pretraining significantly improved liver segmentation: Dice increased from $0.75\pm0.36$ to $0.93\pm0.16$ ($p < 5.33\times10^{-26}$, 0.529 Cohen's d), Average Surface Distance (ASD) decreased by 66%, and 95th-percentile Hausdorff Distance (HD95) reduced by 45%. For kidney segmentation, Dice improved from $0.90\pm0.19$ to $0.95\pm0.10$ ($p < 4.01\times10^{-11}$). Multi-organ pooled performance showed a 68% variance reduction and a 74% improvement in boundary precision (Dice $0.95\pm0.07$). Crucially, frozen encoder models retained > 80% of fine-tuned performance without exposure to segmentation labels, proving the existence of learned anatomical priors. In low-data scenarios, diffusion-pretrained models maintained robust performance with only 50% (Dice: 0.92 liver, 0.94 kidney), 25%, and even 10% (Dice: 0.89 liver, 0.71 kidney) of labeled data. Using unlabeled images for diffusion-based pretraining successfully embeds robust anatomical features prior to human supervision, transforming U-Nets into anatomy-aware systems.

Diffusion generative models have demonstrated immense potential for synthetic medical image generation. However, these models often struggle to capture complex morphological characteristics of heterogeneous tumors with irregular boundaries, limiting their utility for downstream clinical tasks such as segmentation. This limitation stems from the standard denoising objective: minimizing a per-pixel error, which smooths high-variance irregular structures characteristic of tumors. To address this, we propose finetuning these generative models with Fréchet Distance loss (FD-loss). FD-loss aligns the first and second order feature statistics of real and generated images in a pretrained encoder space, encouraging the generator to capture complex structural variations characteristic of heterogeneous tumors. We integrate FD-loss across diverse architectural settings, using both natural- and medical-image encoders on multiple liver and brain cancer datasets spanning CT and MRI modalities. Downstream segmentation networks trained on our FD-regularized synthetic data consistently achieve superior performance, improving tumor DSC by >$$5\% over unregularized synthetic augmentation alone. Qualitative analysis suggests these gains are associated with more faithful tumor synthesis and fewer segmentation hallucinations. Our results show FD-loss as an effective regularizer for medical image generative models to improve clinical workflows.