On the construction of a ground truth framework for evaluating voxel-based diffusion tensor MRI analysis methods.

Although many studies are starting to use voxel-based analysis (VBA) methods to compare diffusion tensor images between healthy and diseased subjects, it has been demonstrated that VBA results depend heavily on parameter settings and implementation strategies, such as the applied coregistration technique, smoothing kernel width, statistical analysis, etc. In order to investigate the effect of different parameter settings and implementations on the accuracy and precision of the VBA results quantitatively, ground truth knowledge regarding the underlying microstructural alterations is required. To address the lack of such a gold standard, simulated diffusion tensor data sets are developed, which can model an array of anomalies in the diffusion properties of a predefined location. These data sets can be employed to evaluate the numerous parameters that characterize the pipeline of a VBA algorithm and to compare the accuracy, precision, and reproducibility of different post-processing approaches quantitatively. We are convinced that the use of these simulated data sets can improve the understanding of how different diffusion tensor image post-processing techniques affect the outcome of VBA. In turn, this may possibly lead to a more standardized and reliable evaluation of diffusion tensor data sets of large study groups with a wide range of white matter altering pathologies. The simulated DTI data sets will be made available online (http://www.dti.ua.ac.be).