Dose-aware Diffusion Model for 3D PET Image Denoising: Multi-institutional Validation with Reader Study and Real Low-dose Data

Reducing scan times, radiation dose, and enhancing image quality for lower-performance scanners, are critical in low-dose PET imaging. Deep learning techniques have been investigated for PET image denoising. However, existing models have often resulted in compromised image quality when achieving low-count/low-dose PET and have limited generalizability to different image noise-levels, acquisition protocols, and patient populations. Recently, diffusion models have emerged as the new state-of-the-art generative model to generate high-quality samples and have demonstrated strong potential for medical imaging tasks. However, for low-dose PET imaging, existing diffusion models failed to generate consistent 3D reconstructions, unable to generalize across varying noise-levels, often produced visually-appealing but distorted image details, and produced images with biased tracer uptake. Here, we develop DDPET-3D, a dose-aware diffusion model for 3D low-dose PET imaging to address these challenges. Collected from 4 medical centers globally with different scanners and clinical protocols, we evaluated the proposed model using a total of 9,783 18F-FDG studies with low-dose levels ranging from 1% to 50%. With a cross-center, cross-scanner validation, the proposed DDPET-3D demonstrated its potential to generalize to different low-dose levels, different scanners, and different clinical protocols. As confirmed with reader studies performed by board-certified nuclear medicine physicians, experienced readers judged the images to be similar or superior to the full-dose images and previous DL baselines based on qualitative visual impression. Lesion-level quantitative accuracy was evaluated using a Monte Carlo simulation study and a lesion segmentation network. The presented results show the potential to achieve low-dose PET while maintaining image quality. Real low-dose scans was also included for evaluation.