Diffusion-tensor imaging is widely used to characterize diffusion in biological tissue, however, the derived anisotropy information, e.g., the fractional anisotropy, is ambiguous. For instance, low values of the diffusion anisotropy in brain white matter voxels may reflect a reduced axon density, i.e., a loss of fibers, or a lower fiber coherence within the voxel, e.g., more crossing fibers. This ambiguity can be avoided with experiments involving two diffusion-weighting periods applied successively in a single acquisition, so-called double-wave-vector or double-pulsed-field-gradient experiments. For a long mixing time between the two periods such experiments are sensitive to the cells' eccentricity, i.e., the diffusion anisotropy present on a microscopic scale. In this study, it is shown that this microscopic diffusion anisotropy can be detected in white matter in the living human brain, even in a macroscopically isotropic region-of-interest (fractional anisotropy = 0). The underlying signal difference between parallel and orthogonal wave vector orientations does not show up in standard diffusion-weighting experiments but is specific to the double-wave-vector experiment. Furthermore, the modulation amplitude observed is very similar for regions-of-interest with different fractional anisotrpy values. Thus, double-wave-vector experiments may provide a direct and reliable access to white matter integrity independent of the actual fiber orientation distribution within the voxel.
