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.

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