Quantification of voxel-wise total fibre density: Investigating the problems associated with track-count mapping

A biological parameter that would be valuable to be able to extract from diffusion MRI data is the local white matter axonal density. Track-density imaging (TDI) has been used as if it could provide such a measure; however, this has been the subject of controversy, primarily due to the fact that track-count quantitation is highly sensitive to tracking biases and errors. The spherical-deconvolution informed filtering of tractograms (SIFT) post-processing method was recently introduced to minimise tractography biases, and thus provides a more biologically meaningful measure that could be used in track-count mapping (i.e. TDI following SIFT). The TDI intensity following SIFT ideally corresponds to the orientational average of the fibre orientation distribution (FOD), which corresponds to the total Apparent Fibre Density (AFDtotal) within the AFD framework; in fact, AFDtotal provides a direct measure of local fibre density at native resolution that does not rely on fibre-tracking. In this study, we demonstrate problems associated with quantitative TDI investigations, which can be avoided by using SIFT processing or directly by using AFDtotal maps. We also characterise the intra- and inter-subject reproducibility of TDI maps (with and without SIFT pre-processing) and AFDtotal maps. It is shown that SIFT improves the quantitative characteristics of TDI, but is still vastly inferior to the properties of the AFDtotal parameter itself, because the latter does not require tracking. While standard TDI might be preferable in applications when high anatomical contrast is required, particularly when combined with super-resolution, for voxel-wise quantitation of total tract density (i.e. without tract orientation information) at native resolution, the total AFD maps are preferable to TDI or other related track-count maps. Regardless of the track-count measure, it should be noted that all of these voxel-averaged approaches discard important information that is retained in fibre-specific approaches such as AFD.