Two-axon population (TAP) modelling for large axon diffusion imaging in the peripheral nervous system

Motivation: The stick (zero-radius cylinder), a standard diffusion MRI model for the intra-axonal brain white matter signal, may not be suitable in the peripheral nervous system (PNS), due to co-existence of small and large axons. Goal(s): To test the feasibility of replacing the stick model with a two-axon population (TAP) approach, accounting for large axons, in the PNS. Approach: We compared TAP versus standard stick modelling in simulations, and derived TAP metrics in the sciatic nerve in vivo. Results: TAP enables more accurate parameter fitting than stick modelling, and is shown to be feasible in vivo in healthy controls and multiple sclerosis patients. Impact: We propose two-axon population (TAP) diffusion-weighted MRI, a method tailored for imaging of the peripheral nervous system, characterised by co-existence of small and large axons. TAP may enable more accurate microstructural imaging than standard approaches, providing non-invasive markers of neurophysiology.