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

Abstract 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 (µMRI) 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 µm isotropic) images with excellent contrast‐to‐noise ratio (∼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 µMRI and histology in that the µMRI 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 µMRI method may facilitate the development of µMRI‐based morphological phenotyping methods for mouse models of neurological disorders. Copyright © 2008 John Wiley & Sons, Ltd.