Quantitative metrics commonly derived from diffusion tractography covary with streamline length: a characterization and method of adjustment

Tractography algorithms are used extensively to delineate white matter structures, by operating on the voxel-wise information generated through the application of diffusion tensor imaging (DTI) or other models to diffusion weighted (DW) magnetic resonance imaging (MRI) data. Through statistical modelling, we demonstrate that these methods commonly yield substantial and systematic associations between streamline length and several tractography derived quantitative metrics, such as fractional anisotropy (FA). These associations may be described as piecewise linear. For streamlines shorter than an inflection point (determined for a group of tracts delineated for each individual brain), estimates of FA exhibit a positive linear relation with streamline length. For streamlines longer than the point of inflection, the association is weaker, with the slope of the relationship between streamline length and FA differing only marginally from zero. As the association is most pronounced for a range of streamline lengths encountered typically in DW imaging of the human brain (less than ~ 100 mm), our results suggest that some quantitative metrics derived from diffusion tractography have the potential to mislead, if variations in streamline length are not considered. A method is described, whereby an Akaike information weighted average of linear, Blackman and piecewise linear model predictions, may be used to compensate effectively for the association of FA (and other quantitative metrics) with streamline length, across the entire range of streamline lengths present in each specimen.