This article presents the potential problems arising from the use of "axial" and "radial" diffusivities, derived from the eigenvalues of the diffusion tensor, and their interpretation in terms of the underlying biophysical properties, such as myelin and axonal density. Simulated and in vivo data are shown. The simulations demonstrate that a change in "radial" diffusivity can cause a fictitious change in "axial" diffusivity and vice versa in voxels characterized by crossing fibers. The in vivo data compare the direction of the principle eigenvector in four different subjects, two healthy and two affected by multiple sclerosis, and show that the angle, alpha, between the principal eigenvectors of corresponding voxels of registered datasets is greater than 45 degrees in areas of low anisotropy, severe pathology, and partial volume. Also, there are areas of white matter pathology where the "radial" diffusivity is 10% greater than that of the corresponding normal tissue and where the direction of the principal eigenvector is altered by more than 45 degrees compared to the healthy case. This should strongly discourage researchers from interpreting changes of the "axial" and "radial" diffusivities on the basis of the underlying tissue structure, unless accompanied by a thorough investigation of their mathematical and geometrical properties in each dataset studied.
(c) 2009 Wiley-Liss, Inc.