Prevalence of white matter pathways coming into a single white matter voxel orientation: The bottleneck issue in tractography

Characterizing and understanding the limitations of diffusion MRI fiber tractography\udis a prerequisite for methodological advances and innovations which will allow these\udtechniques to accurately map the connections of the human brain. The so-called\ud“crossing fiber problem” has received tremendous attention and has continuously\udtriggered the community to develop novel approaches for disentangling distinctly oriented fiber populations. Perhaps an even greater challenge occurs when multiple\udwhite matter bundles converge within a single voxel, or throughout a single brain\udregion, and share the same parallel orientation, before diverging and continuing\udtowards their final cortical or sub-cortical terminations. These so-called “bottleneck”\udregions contribute to the ill-posed nature of the tractography process, and lead to\udboth false positive and false negative estimated connections. Yet, as opposed to the\udextent of crossing fibers, a thorough characterization of bottleneck regions has not\udbeen performed. The aim of this study is to quantify the prevalence of bottleneck\udregions. To do this, we use diffusion tractography to segment known white matter\udbundles of the brain, and assign each bundle to voxels they pass through and to specific orientations within those voxels (i.e. fixels). We demonstrate that bottlenecks\udoccur in greater than 50-70% of fixels in the white matter of the human brain. We find that all projection, association, and commissural fibers contribute to, and are\udaffected by, this phenomenon, and show that even regions traditionally considered\ud“single fiber voxels” often contain multiple fiber populations. Together, this study\udshows that a majority of white matter presents bottlenecks for tractography which\udmay lead to incorrect or erroneous estimates of brain connectivity or quantitative\udtractography (i.e., tractometry), and underscores the need for a paradigm shift in the\udprocess of tractography and bundle segmentation for studying the fiber pathways of\udthe human brain.