Spinverse: Differentiable Physics for Permeability-Aware Microstructure Reconstruction from Diffusion MRI

Diffusion MRI microstructure fitting is nonconvex and often performed voxelwise, which limits fiber peak recovery in narrow crossings. This work introduces PRISM, a differentiable analysis-by-synthesis framework that fits an explicit multi-compartment forward model end-to-end over spatial patches. The model combines cerebrospinal fluid (CSF), gray matter, up to K white-matter fiber compartments (stick-and-zeppelin), and a restricted compartment, with explicit fiber directions and soft model selection via repulsion and sparsity priors. PRISM supports a fast MSE objective and a Rician negative log-likelihood (NLL) that jointly learns sigma without oracle information. A lightweight nuisance calibration module (smooth bias field and per-measurement scale/offset) is included for robustness and regularized to identity in clean-data tests. On synthetic crossing-fiber data (SNR=30; five methods, 16 crossing angles), PRISM achieves 3.5 degrees best-match angular error with 95% recall, which is 1.9x lower than the best baseline (MSMT-CSD, 6.8 degrees, 83% recall); in NLL mode with learned sigma, error drops to 2.3 degrees with 99% recall, resolving crossings down to 20 degrees. On the DiSCo1 phantom (NLL mode), PRISM improves connectivity correlation over CSD baselines at all four tracking angles (best r=.934 at 25 degrees vs. .920 for MSMT-CSD). Whole-brain HCP fitting (~741k voxels, MSE mode) completes in ~12 min on a single GPU with near-identical results across random seeds.

Diffusion MRI (dMRI) probes water diffusion within the brain, providing unique information about tissue microstructure and white matter connectivity. High-quality dMRI enables advanced and accurate analyses but demands dense acquisitions, resulting in long scan times and hardware constraints that are often infeasible. Further, dMRI requires dedicated computational methods to support diverse analysis tasks (e.g., parcellation, registration, and synthesis) for both neuroscientific and clinical applications. Here, we present dMRI-F, a foundation model that unifies dMRI data enhancement and downstream tasks across diverse acquisitions and populations, while requiring only minimal acquisition input. dMRI-F is pre-trained with a q-space masked reconstruction task: predicting densely sampled multi-shell data from only six volumes. It learns generalizable latent feature representations of dMRI data, which serve as a core foundation for adapting to diverse downstream tasks, including brain parcellation, brain registration, and cross-modal synthesis. Across nine independently acquired datasets, we demonstrate that dMRI-F outperforms state-of-the-art methods with robust generalization across acquisitions, populations, and tasks. Our results demonstrate dMRI-F's versatility as a general-purpose framework that enables diverse dMRI applications from low-cost, 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.