BundleWarp: Enhancing white matter tractometry and morphometry with precise neuronal mapping using streamline-based nonlinear registration

Tractometry analysis represents a significant advancement in neuroimaging, offering a detailed examination of the brain's white matter at a micro level. Unlike traditional ROI or voxel-based methods, tractometry precisely reconstructs and characterizes white matter tracts. Using advanced diffusion MRI and tractography algorithms, it maps the trajectory, shape, and connectivity patterns of individual white matter bundles. Accurate alignment of these tracts across different groups is crucial for reliable and reproducible results. Nonlinear registration techniques are essential for achieving this alignment, harmonizing bundle shapes, and improving sensitivity to disease-related changes. However, nonlinear registration is complex, especially with tractography data, which digitally represents the brain's white matter anatomy. Potential structural changes in the bundle's shape during registration can lead to artifacts that obscure critical anatomical details needed for disease identification. We introduce BundleWarp, a streamline-based nonlinear deformable registration method designed specifically for white matter tracts. BundleWarp employs a sophisticated approach to align two white matter bundles while preserving their topological and anatomical features. It is formulated as a probability density estimation problem with motion coherence penalties, ensuring coherent movement of points along streamlines and maintaining the anatomical integrity of tracts through displacement field regularization. Additionally, we introduce a tract morphometry framework utilizing the displacement field generated by BundleWarp to analyze white matter tract shape differences. Our results show that BundleWarp effectively quantifies bundle shape differences and enhances structural harmonization in tractometry analysis for diverse subjects, including those with Alzheimer's and Parkinson's disease. Test-retest experiments further demonstrate that BundleWarp substantially improves subject fingerprinting by increasing within-subject reproducibility of both bundle shape and microstructural profiles (FA, MD, RD, AD). It precisely maps the brain's neuronal pathways, offering a robust tractometry framework with enhanced sensitivity for detecting disease-related structural and microstructural changes in white matter tracts associated with Mild Cognitive Impairment (MCI), dementia, and early-stage Alzheimer's biomarkers, including amyloid-beta plaques and tau neurofibrillary tangles.