Diffusion tensor imaging (DTI) methods are widely used to reconstruct white matter trajectories and to quantify tissue changes using the average diffusion properties of each brain voxel. Spherical deconvolution (SD) methods have been developed to overcome the limitations of the diffusion tensor model in resolving crossing fibers and to improve tractography reconstructions. However, the use of SD methods to obtain quantitative indices of white matter integrity has not been extensively explored. In this study, we show that the hindrance modulated orientational anisotropy (HMOA) index, defined as the absolute amplitude of each lobe of the fiber orientation distribution, can be used as a compact measure to characterize the diffusion properties along each fiber orientation in white matter regions with complex organization. We demonstrate that the HMOA is highly sensitive to changes in fiber diffusivity (e.g., myelination processes or axonal loss) and to differences in the microstructural organization of white matter like axonal diameter and fiber dispersion. Using simulations to describe diffusivity changes observed in normal brain development and disorders, we observed that the HMOA is able to identify white matter changes that are not detectable with conventional DTI indices. We also show that the HMOA index can be used as an effective threshold for in vivo data to improve tractography reconstructions and to better map white matter complexity inside the brain. In conclusion, the HMOA represents a true tract-specific and sensitive index and provides a compact characterization of white matter diffusion properties with potential for widespread application in normal and clinical populations. Hum Brain Mapp 34:2464–2483, 2013. © 2012 Wiley Periodicals, Inc.