Insights for in vivo MR axon radius mapping from simulations based on large-scale histology

Motivation: To understand deviations between axon radii from in vivo MR experiments and histology. Goal(s): To assess the sensitivity of the intra-axonal MR signal to the axon radius; to assess the impact of confounders (extra-axonal signal and Rician noise bias); to discuss deviations between in vivo MR experiments and simulations. Approach: We simulated MR signals for axon radii distributions from large-scale histology with and without confounders; we compared radii fitted to in vivo MR experiments and simulations. Results: Large MR radii are inherently underestimated; confounders are expected to further bias MR radii and can potentially explain deviations between in vivo MR experiments and simulations. Impact: We reveal an inherent bias in the MR axon radius model for in vivo measurements. Furthermore, we identified two main confounders that can significantly narrow the dynamic range of MR radius measurements and reduce sensitivity to small-axon radii regions.