Abstract:Introduction: Generative Adversarial Networks (GANs) are increasingly used to generate synthetic medical images, addressing the critical shortage of annotated data for training Artificial Intelligence (AI) systems. This study introduces a novel memory-efficient GAN architecture, incorporating Conditional Random Fields (CRFs) to generate high-resolution 3D medical images and evaluates its performance against the state-of-the-art hierarchical (HA)-GAN model. Materials and Methods: The CRF-GAN was trained using the open-source lung CT LUNA16 dataset. The architecture was compared to HA-GAN through a quantitative evaluation, using Frechet Inception Distance (FID) and Maximum Mean Discrepancy (MMD) metrics, and a qualitative evaluation, through a two-alternative forced choice (2AFC) test completed by a pool of 12 resident radiologists, in order to assess the realism of the generated images. Results: CRF-GAN outperformed HA-GAN with lower FID (0.047 vs. 0.061) and MMD (0.084 vs. 0.086) scores, indicating better image fidelity. The 2AFC test showed a significant preference for images generated by CRF-Gan over those generated by HA-GAN with a p-value of 1.93e-05. Additionally, CRF-GAN demonstrated 9.34% lower memory usage at 256 resolution and achieved up to 14.6% faster training speeds, offering substantial computational savings. Discussion: CRF-GAN model successfully generates high-resolution 3D medical images with non-inferior quality to conventional models, while being more memory-efficient and faster. Computational power and time saved can be used to improve the spatial resolution and anatomical accuracy of generated images, which is still a critical factor limiting their direct clinical applicability.