Differential Tractography as a Track-Based Biomarker for Neurodegeneration

Diffusion MRI tractography has been used to map the axonal structure of human brain, but its ability to detect neurodegeneration is yet to be explored. Here we report differential tractography, a new type of tractography that utilizes a novel tracking strategy to map the exact segment of fiber pathways with neurodegeneration. It utilizes voxel-wise differences from repeat scans and aggregates them as track-based biomarkers for neurodegeneration. We examined differential tractography on multiple sclerosis, Huntington disease, amyotrophic lateral sclerosis, and epileptic patients. The results showed that the affected pathways shown by differential tractography matched well with the unique clinical symptoms of the patients, and the false discovery rate of the findings could be estimated using a sham setting to provide a reliability measurement. This novel approach enables a quantitative and objective method to monitor neurodegeneration in individuals, allowing for diagnostic and prognostic evaluation of brain diseases.