Title: Diffusion time dependence of microstructural parameters in fixed spinal cord,
Abstract: Biophysical modelling of diffusion MRI is necessary to provide specific
microstructural tissue properties. However, estimating model parameters from
data with limited diffusion gradient strength, such as clinical scanners, has
proven unreliable due to a shallow optimization landscape. On the other hand,
estimation of diffusion kurtosis (DKI) parameters is more robust as the
clinical acquisitions typically probe a regime in which the associated 4th
order cumulant expansion is adequate; however, its parameters are not
microstructurally specific a priori. Given an appropriate biophysical model,
its parameters may be connected to DKI parameters, but it was previously shown
that at the DKI level, it still does not provide sufficient information to
uniquely determine all model parameters. Earlier work has shown that by
neglecting axonal dispersion, this parameter degeneracy reduces to the question
of whether intra-axonal diffusivity is larger than or smaller than extra-axonal
diffusivity. Here we develop a model of diffusion in spinal cord white matter
including axonal dispersion and demonstrate stable estimation of all model
parameters from DKI. By employing the recently developed fast axisymmetric DKI,
we use stimulated echo acquisition mode to collect data over an unprecedented
diffusion time range with very narrow diffusion gradient pulses, enabling
finely resolved measurements of diffusion time dependence of both net diffusion
and kurtosis metrics, as well as model intra- and extra-axonal diffusivities,
and axonal dispersion. Our results demonstrate substantial time dependence of
all parameters except volume fractions, and the additional time dimension
provides support for intra-axonal diffusivity to be larger than extra-axonal
diffusivity in spinal cord white matter, although not unambiguously. We compare
our findings to predictions from effective medium theory.