Local Label-Informed Feature Transfer for Generating Ground-Truth Medical Images: A Comparison of GAN- and Diffusion-Based Approaches

Generative data augmentation with latent diffusion models is a promising strategy for addressing class imbalance in medical imaging, yet current approaches focus on perceptual fidelity and domain-specific autoencoder fine-tuning while neglecting a more fundamental bottleneck. We identify and formalize the learnability gap: large-scale pretrained autoencoders faithfully encode discriminative features for medical classification, as evidenced by near-lossless performance in reconstruction space, yet their latent representations are structured in ways that are difficult for classifiers to learn from. Across five autoencoder families and four medical benchmarks spanning chest radiography, dermatoscopy, computed tomography, and echocardiography, we show that this gap persists regardless of architecture, initialization strategy, or hyperparameter tuning, and that medical-domain fine-tuning of the autoencoder does not close it. To probe and partially narrow the gap, we develop noise-conditioned latent classifiers with FiLM layers and image-space distillation that offer 64x throughput and 120x memory gains over image-space models while serving as diagnostic tools for latent space quality. Our analysis provides a new framework for evaluating autoencoder latent spaces and identifies their structure, rather than their fidelity or domain specificity, as the primary obstacle to closing the performance gap between real and synthetic medical training data.

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.

Medical image-to-image (I2I) translation enables virtual scanning, i.e. the synthesis of a target imaging modality from a source one without additional acquisitions. Despite growing interest, most proposed methods operate on 2D slices, are evaluated on isolated tasks with different experimental set-ups and lack clinical validation. The primary contribution of this work is a reproducible, standardized comparative evaluation of 3D I2I translation methods in oncological imaging, designed to standardize preprocessing, splitting, inference, and multi-level evaluation across heterogeneous clinical tasks. Within this framework, we compare seven generative models, three Generative Adversarial Networks (GANs: Pix2Pix, CycleGAN, SRGAN) and four latent generative models (Latent Diffusion Model, Latent Diffusion Model+ControlNet, Brownian Bridge, Flow Matching), across eleven datasets spanning three anatomical regions (head/neck, lung, pelvis) and four translation directions (cone-beam CT to CT, MRI to CT, CT to PET, MRI T2-weighted to T2-FLAIR), for a total of 77 experiments under uniform training, inference, and evaluation conditions. The results show that GANs outperform latent generative models across all tasks, with SRGAN achieving statistically significant superiority. Our lesion-level analysis reveals that all models struggle with small lesions and that, in CT to PET synthesis, models reproduce lesion shape more reliably than absolute uptake-related intensity. We also performed a Visual Turing test administered to 17 physicians, including 15 radiologists, which shows near-chance classification accuracy (56.7%), confirming that synthetic volumes are largely indistinguishable from real acquisitions, while exposing a dissociation between quantitative metrics and clinical preference.