Manganese-enhanced magnetic resonance imaging (MEMRI) of mouse brain development

Given the importance of genetically modified mice in studies of mammalian brain development and human congenital brain diseases. MRI has the potential to provide ail efficient in vivo approach for analyzing mutant phenotypes in the early postnatal mouse brain. The combination of reduced tissue contrast at the high magnetic fields required for mice. and the changing cellular composition of the developing mouse brain make it difficult to optimize MRI contrast in neonatal mouse imaging. We have explored ail easily implemented approach for contrast-enhanced imaging, using systemically administered manganese (Mn) to reveal fine anatomical detail in T-1-weighted MR images of neonatal mouse brains. In particular. We demonstrate the utility of this Mn-enhanced MRI (MEMRI) method for analyzing early postnatal patterning of (he mouse cerebellum. Through comparisons with matched histological sections. we further show that MEMRI enhancement correlates qualitatively with granule cell density in the developing cerebellum. suggesting that the cerebellar enhancement is due to uptake of Mn in the granule neurons. Finally, variable cerebellar defects in mice with a conditional mutation in the Gbx2 gene were analyzed with MEMRI to demonstrate the utility of this method for mutant mouse phenotyping. Taken to,ether. our results indicate that MEMRI provides ail efficient and powerful in vivo method for analyzing neonatal brain development in normal and genetically engineered mice. Copyright (C) 2004 John Wiley LP, Sons. Ltd.