Bridging Modalities on the Cortex: Surface-based MRI to PET Translation with a Diffusion Bridge

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.

Tau positron emission tomography (PET) is widely used for the in vivo characterization of disease stage and progression in Alzheimer's disease (AD). With the adoption of multiple tau PET tracers including AV-1451, PI-2620, MK-6240 with different binding behaviors in various large-scale studies, there is a great need of effective harmonization methods to enable the cross-tracer integration of tau PET datasets. While previous methods such as CenTauR were proposed to standardize scalar tau PET measures, they are limited in accounting for the heterogeneity of tau pathology. In this work, we propose Feynman-Kac Reweighted Schrödinger Bridge Matching (FKRSBM), a surface-based framework for cross-tracer tau PET harmonization. FKRSBM learns a direct stochastic transport between tracer domains using Schrödinger Bridge matching, avoiding the Gaussian-prior routing used in diffusion-based translation. To promote biologically consistent transport, FKRSBM introduces an endpoint penalty favoring bridge pairings with matched tau-pathology status and implements it through a Feynman-Kac reweighted endpoint proposal. To preserve cortical organization, FKRSBM uses a spherical convolutional network for vertex-level harmonization on cortical surface meshes. In our experiments, we demonstrate our method by harmonizing Tau PET images acquired with the AV-1451 (n=1480) and PI-2620 (n=2458) tracers from two large-scale datasets. Compared to previous methods including ComBat, CycleGAN, Diffusion Model(DF), and unregularized Schrödinger Bridge Model(DSBM), the proposed FKRSBM method outperforms these baselines in subgroup-level alignment, tau-positivity consistency, and diagnostic classification while preserving subject-specific cortical topography of tau pathology. The code is available at: https://github.com/jianweizhang17/FKRSBM.

While longitudinal brain PET imaging is the gold standard for quantifying the spatiotemporal accumulation of Beta-amyloid, its widespread clinical utility is constrained by high operational costs and cumulative radiation risks. Recent deep generative models show promise in longitudinal image synthesis; however, they often fail to capture subtle pathological progression due to identity drift and a persistent bias toward trivially replicating baseline signal intensities rather than modeling temporal transition. To this end, we propose Delta-Diffusion, a novel progression-aware framework that redefines longitudinal PET synthesis as a conditional Poisson Diffusion Bridge (PDB) process. Unlike standard diffusion models that start from Gaussian noise, our PDB formulation is mathematically anchored to the subject's baseline PET, effectively transforming the generative task into a conditional distribution transition of the amyloid trajectory. To handle heteroscedastic nature of PET imaging, we introduce a physically-grounded Poisson perturbation within a Diffusion Transformer (DiT). This architecture uses adaptive scale-shift modulation to precisely calibrate the synthesis with the elapsed clinical interval and structural MRI context. A volume-of-interest balanced objective is designed to emphasize sparse, high-risk regions of amyloid accumulation. Validated on two cohorts with 542 subjects, Delta-Diffusion demonstrates superior performance in capturing longitudinal variations in amyloid deposition compared to state-of-the-art methods, offering a robust computational framework for tracking disease progression.