dMRI-F: A Foundation Model for Generalizable Diffusion MRI Analysis from Sparse Acquisitions

Diffusion Magnetic Resonance Imaging (dMRI) plays a critical role in studying microstructural changes in the brain. It is, therefore, widely used in clinical practice; yet progress in learning general-purpose representations from dMRI has been limited. A key challenge is that existing deep learning approaches are not well-suited to capture the unique properties of diffusion signals. Brain dMRI is normally composed of several brain volumes, each with different attenuation characteristics dependent on the direction and strength of the diffusion-sensitized gradients. Thus, there is a need to jointly model spatial, diffusion-weighting, and directional dependencies in dMRI. Furthermore, varying acquisition protocols (e.g., differing numbers of directions) further limit traditional models. To address these gaps, we introduce a diffusion space rotatory positional embedding (D-RoPE) plugged into our dMRI transformer to capture both the spatial structure and directional characteristics of diffusion data, enabling robust and transferable representations across diverse acquisition settings and an arbitrary number of diffusion directions. After self-supervised masked autoencoding pretraining, tests on several downstream tasks show that the learned representations and the pretrained model can provide competitive or superior performance compared to several baselines in these downstream tasks (even compared to a fully trained baseline); the finetuned features from our pretrained encoder resulted in a 6% higher accuracy in classifying mild cognitive impairment and a 0.05 increase in the correlation coefficient when predicting cognitive scores. Code is available at: github.com/gustavochau/D-RoPE.

Incomplete field-of-view (FOV) diffusion MRI (dMRI) acquisitions compromise whole-brain white matter analysis by excluding brain regions from tractography and connectivity studies. While deep generative models for dMRI FOV extension have been proposed, their generalizability remains limited by the acquisition-dependent nature of dMRI, where signal intensity varies with b-value, gradient direction, and scanner protocol, and the inherent 4D complexity of the data, making it difficult to train models that transfer across sites or acquisition schemes without retraining. We propose a flow-matching generative model that extends the dMRI FOV in both the superior and inferior directions by predicting apparent diffusion coefficients (ADC) in six directions, conditioned on the two nearest acquired slices and the full-FOV T1w image to enforce both local diffusion continuity and anatomical consistency. The ADC representation decouples the model from acquisition-specific b-values and gradient directions, providing a middle-ground across protocols. The model was trained on 3,103 subjects (5,105 sessions) across five different datasets spanning diverse acquisition schemes (b = 500 and 1000 s/mm$^2$; 21--192 gradient directions), four single-shell (b = 1000) and one multi-shell (b = 500/1000). Evaluated on 299 subjects across five independent datasets spanning b = 750--1500 s/mm$^2$ and 32--90 gradient directions, with single- and multi-shell schemes unseen during training, the proposed method achieves significantly improved bundle Dice score on downstream tractography (p < 0.01).

Understanding the human brain requires access to its microscopic tissue architecture. Diffusion magnetic resonance imaging (MRI) provides the only noninvasive window into whole-brain microstructure in vivo, yet reliable quantitative mapping remains confined to specialized research settings requiring dense sampling and optimized acquisition protocols. To address this gap, we present a physics-informed generative microstructure network (PIGMENT) that learns a universal generative prior of human brain microstructure and adapts it zero-shot to each participant's measured data to recover subject-specific maps. Trained on 11375 scans spanning multiple sites, vendors, and field strengths, PIGMENT enabled reliable quantitative mapping for tensor, kurtosis, and NODDI models across external datasets from five independent centers. It remains effective where conventional fitting becomes unreliable, recovering meaningful maps from extremely sparse acquisitions while supporting downstream tractography and structural connectivity mapping. PIGMENT estimates demonstrated strong biological validity, preserving submillimeter cortical microarchitectural patterns and early-childhood white matter developmental trajectories from 10-fold accelerated scans. Furthermore, PIGMENT enables reliable quantitative tensor mapping on cost-efficient low-field systems and the extraction of tumor-related biomarkers using ultra-fast clinical protocols. Together, these results establish PIGMENT as a physics-informed foundation model that extends quantitative diffusion MRI into regimes traditionally too sparse, heterogeneous, or clinically constrained for reliable analysis.