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

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. Magn Reson Med 59:1320–1328, 2008. © 2008 Wiley‐Liss, Inc.

[1]  Luis Puelles,et al.  Atlas of prenatal rat brain development , 1996, Trends in Neurosciences.

[2]  M. Verhoye,et al.  NMR IN BIOMEDICINE NMR Biomed. 2004;17:602–612 Published online in Wiley InterScience (www.interscience.wiley.com). DOI:10.1002/nbm.936 Applications of manganese-enhanced magnetic resonance imaging (MEMRI) to image brain plasticity in song birds , 2022 .

[3]  S. Neubauer,et al.  High‐resolution imaging of normal anatomy, and neural and adrenal malformations in mouse embryos using magnetic resonance microscopy , 2003, Journal of anatomy.

[4]  Yihong Yang,et al.  Cocaine-induced brain activation detected by dynamic manganese-enhanced magnetic resonance imaging (MEMRI) , 2007, Proceedings of the National Academy of Sciences.

[5]  R. Jacobs,et al.  Three-dimensional digital mouse atlas using high-resolution MRI. , 2001, Developmental biology.

[6]  G Allan Johnson,et al.  Effects of breathing and cardiac motion on spatial resolution in the microscopic imaging of rodents , 2005, Magnetic resonance in medicine.

[7]  O. Marín,et al.  Loss of Nkx2.1 homeobox gene function results in a ventral to dorsal molecular respecification within the basal telencephalon: evidence for a transformation of the pallidum into the striatum. , 1999, Development.

[8]  M. Bosma,et al.  Midline serotonergic neurones contribute to widespread synchronized activity in embryonic mouse hindbrain , 2005, The Journal of physiology.

[9]  Stacey P. Memberg,et al.  Dividing neuron precursors express neuron-specific tubulin. , 1995, Journal of neurobiology.

[10]  Matthew H. Kaufman,et al.  The Atlas of Mouse Development , 1992 .

[11]  N. Spitzer,et al.  Development of electrical excitability in embryonic neurons: mechanisms and roles. , 1998, Journal of neurobiology.

[12]  S. Neubauer,et al.  Assessment of motion gating strategies for mouse magnetic resonance at high magnetic fields , 2004, Journal of magnetic resonance imaging : JMRI.

[13]  Ichio Aoki,et al.  Manganese‐enhanced magnetic resonance imaging (MEMRI): methodological and practical considerations , 2004, NMR in biomedicine.

[14]  M. Hanson,et al.  Normal Patterns of Spontaneous Activity Are Required for Correct Motor Axon Guidance and the Expression of Specific Guidance Molecules , 2004, Neuron.

[15]  A. Koretsky,et al.  Manganese ion enhances T1‐weighted MRI during brain activation: An approach to direct imaging of brain function , 1997, Magnetic resonance in medicine.

[16]  Orlando Aristizábal,et al.  Spatial velocity profile in mouse embryonic aorta and Doppler-derived volumetric flow: a preliminary model. , 2002, American journal of physiology. Heart and circulatory physiology.

[17]  J. Domingo,et al.  Effect of day of exposure on the developmental toxicity of manganese in mice. , 1996, Veterinary and human toxicology.

[18]  Hao Huang,et al.  Three-dimensional anatomical characterization of the developing mouse brain by diffusion tensor microimaging , 2003, NeuroImage.

[19]  Xin Yu,et al.  Manganese‐enhanced magnetic resonance imaging (MEMRI) of mouse brain development , 2004, NMR in biomedicine.

[20]  J. Domingo,et al.  Maternal and developmental toxicity of manganese in the mouse. , 1993, Toxicology letters.

[21]  Jens Frahm,et al.  In vivo 3D MRI staining of mouse brain after subcutaneous application of MnCl2 , 2002, Magnetic resonance in medicine.

[22]  D. Spray,et al.  Blood-brain barriers : from ontogeny to artificial interfaces , 2006 .

[23]  Susumu Mori,et al.  MRI in mouse developmental biology , 2007, NMR in biomedicine.

[24]  L W Hedlund,et al.  Time‐course imaging of rat embryos in utero with magnetic resonance microscopy , 1998, Magnetic resonance in medicine.

[25]  R E Poelmann,et al.  Magnetic resonance microscopy of mouse embryos in utero , 2000, The Anatomical record.

[26]  F. Stuart Foster,et al.  In vivo ultrasound biomicroscopy in developmental biology , 2002 .

[27]  Keren Ziv,et al.  MRI detection of transcriptional regulation of gene expression in transgenic mice , 2007, Nature Medicine.

[28]  C H Fox,et al.  The T/ebp null mouse: thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary. , 1996, Genes & development.

[29]  P. Hantson,et al.  Carcinogenicity, mutagenicity and teratogenicity of manganese compounds. , 2002, Critical reviews in oncology/hematology.

[30]  Ichio Aoki,et al.  In vivo detection of neuroarchitecture in the rodent brain using manganese-enhanced MRI , 2004, NeuroImage.

[31]  Alan P. Koretsky,et al.  Tracing Odor-Induced Activation in the Olfactory Bulbs of Mice Using Manganese-Enhanced Magnetic Resonance Imaging , 2002, NeuroImage.

[32]  D. Turnbull,et al.  In vivo auditory brain mapping in mice with Mn-enhanced MRI , 2005, Nature Neuroscience.

[33]  Florence Franconi,et al.  In utero time-course assessment of mouse embryo development using high resolution magnetic resonance imaging , 2002, Anatomy and Embryology.

[34]  Hellmut Merkle,et al.  Manganese‐enhanced magnetic resonance imaging of mouse brain after systemic administration of MnCl2: Dose‐dependent and temporal evolution of T1 contrast , 2005, Magnetic resonance in medicine.