Scattering approach to diffusion quantifies axonal damage in brain injury

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).