Enhanced delineation of white matter structures of the fixed mouse brain using Gd-DTPA in microscopic MRI.

The purpose of this study was to investigate the effect of gadolinium (III) diethyltriaminepenta-acetic acid (Gd-DTPA) mixed with a fixative on the image contrast between the white and gray matter of the perfusion-fixed mouse brain. A series of microscopic MRI (microMRI) studies using different concentrations of Gd-DTPA were performed at multiple time points to determine the optimal Gd-DTPA concentration and fixation time necessary to maximize the contrast-to-noise ratio between the white and gray matter with relatively short scan time using a three-dimensional gradient-echo pulse sequence. On the basis of the experimental results, high-resolution (39 microm isotropic) images with excellent contrast-to-noise ratio ( approximately 50) were acquired in less than 2 h of scan time after the specimen had been soaked in 10 mM Gd-DTPA for 4 days. Excellent correlation was noted between microMRI and histology in that the microMRI clearly depicted brain regions that were also observed by the Kluver-Barrera stain. The enhanced contrast between the white and gray matter obtained by the proposed microMRI method may facilitate the development of microMRI-based morphological phenotyping methods for mouse models of neurological disorders.