Diffusion-Based Synthesis of 3D T1w MPRAGE Images from Multi-Echo GRE with Multi-Parametric MRI Integration

Multi-echo Gradient Echo (mGRE) sequences provide valuable quantitative parametric maps, such as Quantitative Susceptibility Mapping (QSM) and transverse relaxation rate (R2*), sensitive to tissue iron and myelin. However, structural morphometry typically relies on separate T1-weighted MPRAGE acquisitions, prolonging scan times. We propose a deep learning framework to synthesize high-contrast 3D T1w MPRAGE images directly from mGRE data, streamlining neuroimaging protocols. We developed a novel multi-parametric conditional diffusion model based on the Fast-DDPM architecture. Unlike conventional intensity-based synthesis, our approach integrates iron-sensitive QSM and R2* maps as physical priors to address contrast ambiguity in iron-rich deep gray matter. We trained and validated the model on 175 healthy subjects. Performance was evaluated against established U-Net and GAN-based baselines using perceptual metrics and downstream segmentation accuracy. Uniquely, we assessed the biological plausibility of synthesized images by replicating population-level statistical associations with age and sex. The proposed framework significantly outperformed baselines, achieving superior perceptual quality and segmentation accuracy, particularly in subcortical regions like the thalamus and pallidum. Crucially, synthesized images preserved essential biological dependencies: regression analyses showed high concordance in age-related atrophy rates, aging effect sizes, and sexual dimorphism patterns compared to ground truth. By effectively leveraging quantitative MRI priors, our diffusion-based method generates strictly biologically plausible T1w images suitable for reliable clinical morphometric analysis. This approach offers a promising pathway to reduce acquisition time by deriving structural contrasts retrospectively from quantitative mGRE sequences.