Abstract:The 3D fast silent multi-parametric mapping sequence with zero echo time (MuPa-ZTE) is a novel quantitative MRI (qMRI) acquisition that enables nearly silent scanning by using a 3D phyllotaxis sampling scheme. MuPa-ZTE improves patient comfort and motion robustness, and generates quantitative maps of T1, T2, and proton density using the acquired weighted image series. In this work, we propose a diffusion model-based qMRI mapping method that leverages both a deep generative model and physics-based data consistency to further improve the mapping performance. Furthermore, our method enables additional acquisition acceleration, allowing high-quality qMRI mapping from a fourfold-accelerated MuPa-ZTE scan (approximately 1 minute). Specifically, we trained a denoising diffusion probabilistic model (DDPM) to map MuPa-ZTE image series to qMRI maps, and we incorporated the MuPa-ZTE forward signal model as an explicit data consistency (DC) constraint during inference. We compared our mapping method against a baseline dictionary matching approach and a purely data-driven diffusion model. The diffusion models were trained entirely on synthetic data generated from digital brain phantoms, eliminating the need for large real-scan datasets. We evaluated on synthetic data, a NISM/ISMRM phantom, healthy volunteers, and a patient with brain metastases. The results demonstrated that our method produces 3D qMRI maps with high accuracy, reduced noise and better preservation of structural details. Notably, it generalised well to real scans despite training on synthetic data alone. The combination of the MuPa-ZTE acquisition and our physics-informed diffusion model is termed q3-MuPa, a quick, quiet, and quantitative multi-parametric mapping framework, and our findings highlight its strong clinical potential.