SFL-Net: Source-Factorized Latent Representation Learning for Multi-Contrast MRI to Tau-PET Synthesis

arXiv:2602.22545v3 Announce Type: replace Abstract: Tau positron emission tomography supports Alzheimer's disease staging but is difficult to scale because of tracer, scanner, and radiation constraints. Synthesis from structural MRI is therefore attractive, but it is a particularly difficult setting. T1-weighted and FLAIR MRI provide anatomy and disease correlated morphology, but they do not directly measure Tau-PET relevant signal. We introduce SFL-Net, a multi-input synthesis framework that predicts Tau-PET from T1-weighted and FLAIR MRI. SFL-Net factorizes the latent representation into shared, T1-specific, FLAIR-specific, and complementary pathways and preserves anatomical detail through latent structural conditioning rather than direct encoder-decoder connections. We evaluated SFL-Net and baseline models using 605 training and 83 validation subjects from ADNI-3 and OASIS-3 datasets. Evaluation included raw image fidelity, standardized uptake value ratio agreement, high uptake overlap, regional Bland-Altman bias, braak derived stage agreement, non-inferiority sensitivity analysis, and latent component Shapley attribution. SFL-Net performed competitively on both clinically relevant and reconstruction metrics, while also delivering explicit source level auditability that conventional UNet derived models lack.