Bridging the microstructural gap in human connectomics using hierarchical phase-contrast tomography as a reference...

Area of Science:

• Neuroimaging
• Biophysics
• Materials Science

Background:

• Diffusion MRI (dMRI) non-invasively images the human connectome but struggles with micrometer-scale axonal geometries due to water diffusion limitations.
• Invasive histology methods are destructive and limited to small volumes, highlighting a need for non-destructive 3D microscopic imaging of white matter fiber orientations.

Purpose of the Study:

• To utilize Hierarchical Phase-Contrast Tomography (HiP-CT) for characterizing white matter architecture at the microscale.
• To compare HiP-CT derived fiber architecture with dMRI data and assess its potential as a reference modality.

Main Methods:

• Applied structure-tensor analysis to HiP-CT data to compute fiber Orientation Distribution Functions.
• Performed tractography analogous to dMRI using HiP-CT derived orientation data.
• Evaluated the impact of vascular structures on HiP-CT orientation estimates.

Main Results:

• HiP-CT data revealed substantially greater microstructural complexity in white matter fiber architecture compared to dMRI.
• Strong correspondence was observed between fiber architecture derived from HiP-CT and dMRI across multiple brain regions.
• Vascular structures were found to minimally confound HiP-CT orientation estimates despite its label-free nature.

Conclusions:

• HiP-CT is established as a valuable non-destructive reference modality for imaging microscopic white matter architecture.
• HiP-CT complements dMRI by providing higher-resolution insights into microstructural complexity.
• This technique facilitates multi-scale studies of white matter organization and the human connectome.