Abstract
PURPOSE: To introduce synchrotron X-ray microcomputed tomography (microCT) and demonstrate its use as a natively isotropic, nondestructive, 3D validation modality for diffusion MRI in whole, fixed mouse brain. METHODS: Postmortem diffusion MRI and microCT data were acquired of the same whole mouse brain. Diffusion data were processed using constrained spherical deconvolution. Synchrotron data were acquired at an isotropic voxel size of 1.17 μm. Structure tensor analysis was used to calculate fiber orientation distribution functions from the microCT data. A pipeline was developed to spatially register the 2 datasets in order to perform qualitative comparisons of fiber geometries represented by fiber orientation distribution functions. Fiber orientations from both modalities were used to perform whole-brain deterministic tractography to demonstrate validation of long-range white matter pathways. RESULTS: Fiber orientation distribution functions were able to be extracted throughout the entire microCT dataset, with spatial registration to diffusion MRI simplified due to the whole brain extent of the microCT data. Fiber orientations and tract pathways showed good agreement between modalities. CONCLUSION: Synchrotron microCT is a potentially valuable new tool for future multi-scale diffusion MRI validation studies, providing comparable value to optical histology validation methods while addressing some key limitations in data acquisition and ease of processing.