Large axon diffusion MRI modelling in the sciatic nerve in vivo

Motivation: The "stick", a standard zero-radius diffusion model, can bias intra-axonal fraction (fa) estimation when large axons (e.g., radii ≥ 4 μm) are present, as in the peripheral nervous system (PNS). Goal(s): To compare signal models for in vivo fa characterization in the PNS: Ball-and-Stick (BS), Two-Axon Population (TAP) and general Gamma Distribution Axon Population (GDAP). Approach: Maps of fa and other diffusion properties were compared in healthy and diseased (Multiple Sclerosis) sciatic nerves in vivo through BS, TAP and GDAP. Results: TAP and GDAP models provided higher estimates of fa than BS and may thus offer promising new PNS biomarkers. Impact: We demonstrate that diffusion MRI can accurately resolve axon diameter information in the sciatic nerve in vivo using Two-Axon Population (TAP) and Gamma Distribution Axon Population (GDAP) imaging. These methods provide higher intra-axonal signal fraction estimates than the Ball-and-Stick model