  Purpose: To investigate the effect of realistic microstructural geometry on
the susceptibility-weighted magnetic resonance (MR) signal in white matter
(WM), with application to demyelination.
  Methods: Previous work has modeled susceptibility-weighted signals under the
assumption that axons are cylindrical. In this work, we explore the
implications of this assumption by considering the effect of more realistic
geometries. A three-compartment WM model incorporating relevant properties
based on literature was used to predict the MR signal. Myelinated axons were
modeled with several cross-sectional geometries of increasing realism: nested
circles, warped/elliptical circles and measured axonal geometries from electron
micrographs. Signal simulations from the different microstructural geometries
were compared to measured signals from a Cuprizone mouse model with varying
degrees of demyelination.
  Results: Results from simulation suggest that axonal geometry affects the MR
signal. Predictions with realistic models were significantly different compared
to circular models under the same microstructural tissue properties, for
simulations with and without diffusion.
  Conclusion: The geometry of axons affects the MR signal significantly.
Literature estimates of myelin susceptibility, which are based on fitting
biophysical models to the MR signal, are likely to be biased by the assumed
geometry, as will any derived microstructural properties.
