RelA-Diffusion: Relativistic Adversarial Diffusion for Multi-Tracer PET Synthesis from Multi-Sequence MRI
Minhui Yu, Yongheng Sun, David S. Lalush, Jason P Mihalik, Pew-Thian Yap, Mingxia Liu

TL;DR
RelA-Diffusion is a novel diffusion-based framework that synthesizes multi-tracer PET images from multi-sequence MRI, improving realism and detail through a relativistic adversarial loss and multi-modal inputs.
Contribution
It introduces a relativistic adversarial diffusion model utilizing multi-sequence MRI and a gradient-penalized loss for enhanced PET synthesis accuracy.
Findings
Outperforms existing methods in visual quality and metrics
Demonstrates stable training with relativistic adversarial loss
Effective multi-modal integration improves anatomical detail
Abstract
Multi-tracer positron emission tomography (PET) provides critical insights into diverse neuropathological processes such as tau accumulation, neuroinflammation, and -amyloid deposition in the brain, making it indispensable for comprehensive neurological assessment. However, routine acquisition of multi-tracer PET is limited by high costs, radiation exposure, and restricted tracer availability. Recent efforts have explored deep learning approaches for synthesizing PET images from structural MRI. While some methods rely solely on T1-weighted MRI, others incorporate additional sequences such as T2-FLAIR to improve pathological sensitivity. However, existing methods often struggle to capture fine-grained anatomical and pathological details, resulting in artifacts and unrealistic outputs. To this end, we propose RelA-Diffusion, a Relativistic Adversarial Diffusion framework for…
Peer Reviews
Decision·Submitted to ICLR 2026
The paper is clearly written, well-motivated, and extensively evaluated. They tackle an important problem, synthesizing PET images, which are both costly to obtain and patients often do not want to expose themselves to the radiation involved. As PET images are used for monitoring neurodegenerative disroders, synthetic images may improve the accuracy of predictions of disorder. The authors propose a model that combines the strengths of both diffusion and GAN models to synthesize realistic images
### Clinical Utility While I believe this paper is clearly written and technically sound, I have a hard time justifying the need for such a method. The authors claim that synthesizing PET images can be useful for clinical analysis of neurological disorder. However, I have a hard time believing that clinicians would actually use these types of images to make clinical decisions. While the authors evaluated well that the synthesized images were high quality, I am unconvinced that such a model would
The integration of relativistic adversarial loss into the diffusion framework is a novel way to stabilize adversarial training while improving structural fidelity. The method section provides a clear mathematical formulation for forward/reverse diffusion, adversarial losses, and the hybrid objective. It is easy to follow. Ablation experiments (w/o RA, w/o T1w, w/o T2F) convincingly support each component’s contribution. The method achieves consistent improvements in PSNR, SSIM, and MAE across
The training involves 1000 diffusion steps and adversarial updates. No runtime, training time, or sampling speed comparison is provided against standard diffusion or GAN models. Only 10 subjects for testing in NFL-LONG and 30 ADNI subjects for external validation are relatively small sample sizes, which might limit claims of robustness and clinical readiness.
1. great motivation: PET is expensive and has radiation protection issues, so the generation of MRI-synthesized PET is a practical alternative. 2. clear method coupling: Relative discrimination and gradient penalty are applied to $\hat{x_0}$, forming a hybrid loss function L with the diffuse noise prediction and image L1.
1. The novelty is incremental, the main contribution seems like applying Diffusion-GAN to the generation from MRI to PET. It is suggested to focus on more concrete problem in the generation of PET. 2. It is suggested to add more downstream tasks to verify the performance of generation, like segmentation, classification. 3. In Table 1, CycleGAN outperforms DiffGAN, FICD, MTGD in most metrics across three tasks. Besides, the CycleGAN do not use the diffusion model. I wonder why the CycleGAN ach
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Taxonomy
TopicsMedical Imaging Techniques and Applications · Generative Adversarial Networks and Image Synthesis · Glioma Diagnosis and Treatment
