Realistic noise synthesis reduces bias and improves tissue microstructure estimation with supervised machine learning

Diffusion MRI enables non-invasive probing of tissue microstructure, but accurate parameter estimation is challenged by noise-related effects. In supervised machine learning frameworks trained on simulated data, discrepancies between the noise characteristics of simulated and acquired signals introduce a form of covariate shift, whereby the input signal distribution differs between training and inference. We investigated the impact of this mismatch on microstructure parameter estimation and propose a realistic noise synthesis (RNS) framework to mitigate it. RNS incorporates both the Rician expectation and the effective post-processing noise variance into simulated training signals. The Rician expectation was modelled using a noise standard deviation estimated with MPPCA, while the effective standard deviation was derived from spherical harmonic residuals of preprocessed data. The method was evaluated using the cylinder-zeppelin and the SANDI models on simulated datasets across multiple SNR levels and on in vivo diffusion data with repeated acquisitions. Sensitivity to noise misestimation was also assessed. Ignoring magnitude-induced noise effects during training produced systematic, SNR-dependent parameter bias, particularly at low SNR. Incorporating the Rician expectation substantially reduced bias to the level of noise-aware nonlinear least-squares fitting. Modelling the effective standard deviation further improved precision. Performance was largely independent of regression architecture but sensitive to accurate noise estimation. These findings demonstrate that realistic noise modelling in simulated training data mitigates signal-domain covariate shift and is essential for unbiased supervised microstructure estimation, particularly in low-SNR regimes associated with high b-values or high spatial resolution.

DMD-augmented Unpaired Neural Schrödinger Bridge for Ultra-Low Field MRI Enhancement

Ultra Low Field (64 mT) brain MRI improves accessibility but suffers from reduced image quality compared to 3 T. As paired 64 mT - 3 T scans are scarce, we propose an unpaired 64 mT $\rightarrow$ 3 T translation framework that enhances realism while preserving anatomy. Our method builds upon the Unpaired Neural Schrödinge Bridge (UNSB) with multi-step refinement. To strengthen target distribution alignment, we augment the adversarial objective with DMD2-style diffusion-guided distribution matching using a frozen 3T diffusion teacher. To explicitly constrain global structure beyond patch-level correspondence, we combine PatchNCE with an Anatomical Structure Preservation (ASP) regularizer that enforces soft foreground background consistency and boundary aware constraints. Evaluated on two disjoint cohorts, the proposed framework achieves an improved realism structure trade-off, enhancing distribution level realism on unpaired benchmarks while increasing structural fidelity on the paired cohort compared to unpaired baselines.