Partial volume effect as a hidden covariate in tractography based analyses of fractional anisotropy : Does size matter ?

INTRODUCTION In recent years, diffusion tensor imaging (DTI) has been used extensively to investigate the aging brain, in both young and aging adults. Using fiber tractography (e.g. Basser et al.), it has been shown that fractional anisotropy (FA) of white matter fiber tracts increases during maturation and subsequently decreases with age above the age of approximately 30-40 years. This relation between FA and age has been linked to changes in microstructural organisation: neuronal demyelination, for instance, is thought to result in a lower FA along tracts in elderly people compared to young adults. A well-known influence on accuracy of fiber tractography is the presence of partial volume effects (PVE) in voxels with different tissue organisations. PVE may well have an influence when calculating the FA along a tract, an effect not addressed in the results finding a relationship between age and tract FA. As total brain volume changes with age, and therefore the volume of fiber tract bundles, the relative contribution of PVE will be different between fiber bundles that have a different volume. We hypothesize that there is a correlation between tract volume and FA, through PVE, that could, at least in part, explain the observed age-related FA changes. Preliminary support for our hypothesis can be found in a leftsided co-lateralization of FA with tract volume. In this work, we confirmed our hypothesis using simulations and experiments.