Using the biophysical CHARMED model to elucidate the underpinnings of contrast in diffusional kurtosis analysis of diffusion-weighted MRI

Object The aim of this work was to understand biophysical substrate underpinning contrast in diffusional kurtosis imaging (DKI) in white matter, using the composite hindered and restricted model of diffusion (CHARMED). Materials and methods A theoretical relationship between the kurtosis function K and the CHARMED parameters, i.e., the restricted volume fraction RF and the axonal longitudinal diffusivity D was derived for the propagator used in the CHARMED model. Evidence for a similar correlation between these measures was then investigated in vivo across different WM regions in five healthy young subjects that underwent a CHARMED protocol at 3T. Results Our theoretical treatment shows that K has an increasing trend for both increasing RF values and increasing D. In vivo, a significant positive correlation (P\0.001) was found between the kurtosis orthogonal to the fibre orientation K\ and RF. A multilinear regression showed that K\ values are better explained by a mixed contribution of bothRF and D. Conclusions The CHARMED model was used to understand whether and where DKI contrast can be explained in terms of the underlying axonal geometry. This work demonstrates that the information contained in DKI overlaps with the information extracted by CHARMED in areas of higher intra-voxel directional coherence.