Regression is all you need for medical image translation

The acquisition of information-rich images within a limited time budget is crucial in medical imaging. Medical image translation (MIT) can help enhance and supplement existing datasets by generating synthetic images from acquired data. While Generative Adversarial Nets (GANs) and Diffusion Models (DMs) have achieved remarkable success in natural image generation, their benefits - creativity and image realism - do not necessarily transfer to medical applications where highly accurate anatomical information is required. In fact, the imitation of acquisition noise or content hallucination hinder clinical utility. Here, we introduce YODA (You Only Denoise once - or Average), a novel 2.5D diffusion-based framework for volumetric MIT. YODA unites diffusion and regression paradigms to produce realistic or noise-free outputs. Furthermore, we propose Expectation-Approximation (ExpA) DM sampling, which draws inspiration from MRI signal averaging. ExpA-sampling suppresses generated noise and, thus, eliminates noise from biasing the evaluation of image quality. Through extensive experiments on four diverse multi-modal datasets - comprising multi-contrast brain MRI and pelvic MRI-CT - we show that diffusion and regression sampling yield similar results in practice. As such, the computational overhead of diffusion sampling does not provide systematic benefits in medical information translation. Building on these insights, we demonstrate that YODA outperforms several state-of-the-art GAN and DM methods. Notably, YODA-generated images are shown to be interchangeable with, or even superior to, physical acquisitions for several downstream tasks. Our findings challenge the presumed advantages of DMs in MIT and pave the way for the practical application of MIT in medical imaging.