Mn enhancement and respiratory gating for in utero MRI of the embryonic mouse central nervous system

Abstract

The mouse is the preferred model organism for genetic studies of mammalian brain development. MRI has potential for in utero studies of mouse brain development, but has been limited previously by challenges of maximizing image resolution and contrast while minimizing artifacts due to physiological motion. Manganese (Mn)-enhanced MRI (MEMRI) studies have demonstrated central nervous system (CNS) contrast enhancement in mice from the earliest postnatal stages. The purpose of this study was to expand MEMRI to in utero studies of the embryonic CNS in combination with respiratory gating to decrease motion artifacts. We investigated MEMRI-facilitated CNS segmentation and three-dimensional (3D) analysis in wild-type mouse embryos from midgestation, and explored effects of Mn on embryonic survival and image contrast. Motivated by observations that MEMRI provided an effective method for visualization and volumetric analysis of embryonic CNS structures, especially in ventral regions, we used MEMRI to examine Nkx2.1 mutant mice that were previously reported to have ventral forebrain defects. Quantitative MEMRI analysis of Nkx2.1 knockout mice demonstrated volumetric changes in septum (SE) and basal ganglia (BG), as well as alterations in hypothalamic structures. This method may provide an effective means for in utero analysis of CNS phenotypes in a variety of mouse mutants. © 2008 Wiley-Liss, Inc.