Morphological changes in axons, such as axonal varicosities or beadings, are observed in neurological disorders, as well as in development and aging. Here, we reveal the sensitivity of time-dependent diffusion MRI (dMRI) to the structurally disordered axonal morphology at the micrometer scale. Scattering theory uncovers the two parameters that determine the diffusive dynamics of water along axons: the average reciprocal cross-section and the variance of long-range cross-sectional fluctuations. This theoretical development enables us to predict dMRI metrics sensitive to axonal alterations over tens of thousands of axons in seconds, rather than months of simulation, in a rat model of traumatic brain injury, and is corroborated by ex vivo dMRI. [1] A. Abdollahzadeh, R. Coronado-Leija, H-H Lee, A. Sierra, E. Fieremans, D. S. Novikov, Scattering approach to diffusion quantifies axonal damage in brain injury, arXiv:2501.18167 (2025). [2] A. Abdollahzadeh, I. Belevich, E. Jokitalo, A. Sierra, J. Tohka, DeepACSON automated segmentation of white matter in 3D electron microscopy, Communications Biology 4, 179 (2021). [3] D. S. Novikov, J. H. Jensen, J. A. Helpern, and E. Fieremans, Revealing mesoscopic structural universality with diffusion, PNAS 111, 5088 (2014).

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