Scattering approach to diffusion quantifies axonal damage in brain injury

TL;DR

This paper introduces a scattering theory-based approach to diffusion MRI that detects early axonal damage at the cellular level, providing rapid, quantitative biomarkers for neurological disorders.

Contribution

It develops a theoretical framework linking axonal microstructure to diffusion MRI signals, enabling fast prediction of axonal damage markers in brain injury.

Findings

The theory predicts MRI metrics sensitive to axonal changes.

Validation with ex vivo MRI confirms the model's accuracy.

Method allows rapid assessment of axonal damage in models.

Abstract

Early diagnosis and noninvasive monitoring of neurological disorders require sensitivity to elusive cellular-level alterations that occur much earlier than volumetric changes observable with the millimeter-resolution of medical imaging modalities. 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 allows us to predict dMRI metrics sensitive to axonal alterations over tens of thousands of axons in seconds rather than months of simulations in a rat model of traumatic brain injury, and is corroborated with ex vivo dMRI. Our approach bridges the gap between micrometers and millimeters in resolution, offering quantitative and objective biomarkers applicable to a broad spectrum of neurological disorders.