Eddy-current (EC) and motion effects in diffusion-tensor imaging (DTI) bias the estimation of quantitative diffusion indices, such as the fractional anisotropy. Both effects can be retrospectively corrected by registering the strongly distorted diffusion-weighted images to less-distorted T2-weighted images acquired without diffusion weighting. Two different affine spatial transformations are usually employed for this correction: slicewise and whole-brain transformations. However, a relation between estimated transformation parameters and EC distortions has not been established yet for the latter approach. In this study, a novel diffusion-gradient-direction-independent estimation of the EC field is proposed based solely on affine whole-brain registration parameters. Using this model, it is demonstrated that a more distinct evaluation of the wholebrain EC effects is possible if the through-plane distortion was considered in addition to the well-known in-plane distortions. Moreover, a comparison of different whole-brain registrations relative to a slicewise approach is performed, in terms of the relative tensor error. Our findings suggest that for appropriate intersubject comparison of DTI data, a whole-brain registration containing nine affine parameters provides comparable performance (between 0 and 3%) to slicewise methods and can be performed in a fraction of the time.Magn strong gradients used for diffusion encoding (in the following referred to as "diffusion gradients") create ECs in the conductive parts of the magnet, causing geometric distortions in the DW images that depend on the amplitude and direction of the diffusion gradients (11-14). The EC effects depend on the pulse sequence (15-18), scanner calibration, and scanner design. The EC and motion effects can be retrospectively corrected by registering the strongly distorted DW images to the less distorted images acquired without diffusion weighting (14,19). However, the EC effects cannot be completely corrected by retrospective registration. Thus, after retrospective EC correction residual image artifacts (e.g., image blurring caused by the time-dependent components of the EC field) will remain and reduce the comparability of DTI data. This is particularly important for longitudinal DTI studies, during which the scanner adjustment and, thus, the EC effects might vary.One possibility for assessing the comparability of DTI data is to quantify EC effects by estimating the induced EC field. Rohde et al. (20) presented a new registration approach for EC and motion correction, using a whole-brain transformation. They showed that the EC field induced by one diffusion gradient can be retrospectively estimated from the transformation parameters of a 14-parameter, nonlinear transformation that corrects the distortions of the corresponding DW image. The DTI data, however, consists of at least six DW images, each corresponding to different diffusion directions and containing EC distortions that are corrected by a specific set of EC parameters. Each respective set ...