Integrating along-tract profiling with fixel-based analysis for tract-specific characterization of white matter

A fixel-based analysis (FBA) applied to diffusion MRI data can yield biologically specific and interpretable metrics reflecting the microstructural properties of the brain's white matter fibers. At present, the anatomical interpretation of these metrics is tied to individual fixels, which limits the technique's use for the fine-grained evaluation of along-tract white matter changes, for example as a consequence of neurodegeneration. We present a methodological extension of FBA: along-tract profiling. Our method projects fixel-based metrics onto tractography-defined core streamlines, creating continuous, anatomically aligned profiles along any white matter tract of interest. These tract profiles visualize and quantify microstructural white matter properties of a complete tract at a glance, and can also be used to detect changes therein. We demonstrate the utility of our along-tract profiling by applying it to two cohorts with visual conditions and distinct patterns of visual pathway degeneration: glaucoma and homonymous hemianopia. In both cohorts, the results showed the characteristic signs of degeneration, namely progressive degeneration in glaucoma and local degeneration with distal spread in hemianopia. By anchoring fixel-based metrics to the underlying structure of the tract of interest, the resulting along-tract profiles facilitate and enhance the visualization and interpretability of FBA results. While we demonstrated the use of our approach in the primary visual pathway, along-tract profiling can be applied to any white matter tract of interest and may thus find use in a wide variety of fundamental, translational and clinical studies.