Diffusion MRI is a non-invasive, in-vivo biomedical imaging method for mapping tissue microstructure. Applications include structural connectivity imaging of the human brain and detecting microstructural neural changes. However, acquiring high signal-to-noise ratio dMRI datasets with high angular and spatial resolution requires prohibitively long scan times, limiting usage in many important clinical settings, especially for children, the elderly, and in acute neurological disorders that may require conscious sedation or general anesthesia. We employ a Swin UNEt Transformers model, trained on augmented Human Connectome Project data and conditioned on registered T1 scans, to perform generalized denoising of dMRI. We also qualitatively demonstrate super-resolution with artificially downsampled HCP data in normal adult volunteers. Remarkably, Swin UNETR can be fine-tuned for an out-of-domain dataset with a single example scan, as we demonstrate on dMRI of children with neurodevelopmental disorders and of adults with acute evolving traumatic brain injury, each cohort scanned on different models of scanners with different imaging protocols at different sites. We exceed current state-of-the-art denoising methods in accuracy and test-retest reliability of rapid diffusion tensor imaging requiring only 90 seconds of scan time. Applied to tissue microstructural modeling of dMRI, Swin UNETR denoising achieves dramatic improvements over the state-of-the-art for test-retest reliability of intracellular volume fraction and free water fraction measurements and can remove heavy-tail noise, improving biophysical modeling fidelity. Swin UNeTR enables rapid diffusion MRI with unprecedented accuracy and reliability, especially for probing biological tissues for scientific and clinical applications. The code and model are publicly available at https://github.com/ucsfncl/dmri-swin.

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