Microscopic diffusion tensor atlas of the mouse brain.

Eight diffusion tensor imaging (DTI) datasets of normal adult C57BL/6J mouse brains were acquired with an isotropic Nyquist limited resolution of 43 μm (voxel volume ~80 pl). Each specimen was scanned with a b0 image and 6 diffusion-weighted images. T1- and T2*-weighted data were acquired with each specimen to aid nonlinear registration of the data to a common reference space (called "Waxholm Space"). We identified 80 different discrete landmarks in Waxholm Space to provide the gold standard for measuring the registration quality. The accuracy of the registration was established by measuring displacement of the 80 landmarks in each registered brain from the same landmarks in the reference brain. The accuracy was better than 130 μm for 95% of the landmarks (overall landmark displacement is 65±40 μm, n=640). Mean and coefficient of variation atlases of DTI indices were generated with potential application for both voxel-based and region of interest-based analysis. To examine consistency of DTI data among individual subjects in this study and difference in diffusion indices between separate brain structures within each subject, averaged values of DTI indices (axial diffusivity, radial diffusivity, fractional anisotropy, and angular deviation of the primary eigenvector) were computed in 9 white matter structures in each brain. The variation of the DTI indices across the population was very small, e.g., ~5% for axial diffusivity for each white matter structure, enabling confident differentiation of differences in these structures within each subject. ANOVA tests indicated that the current protocol is able to provide consistent DTI data of individual brains (p>0.25), and distinguish difference of diffusion indices between white matter structures (p<0.001). Power analysis was also performed to provide an estimate of the number of specimens required to detect a 10% change of the DTI indices in each white matter structure. The data provide a critical addition to Waxholm Space, the International Neuroinformatics Coordinating Facility (www.incf.org) online comprehensive atlas of the mouse brain.