The availability of transgenic and gene targeting methods, and the large number of spontaneous and induced mutant mice with altered neural development, have led to significant progress in dissecting the genetic pathways involved in patterning and cell specification in the mouse nervous system, and in producing many mouse models of human neurodegenerative diseases. Despite these advances, little is known currently about the relationship between genetic changes and altered brain function, in part because of the lack of readily available and efficient quantitative methods to analyze functional changes in the mouse brain. We have developed both ultrasound biomicroscopy (UBM) and magnetic resonance micro-imaging (muMRI) approaches to analyze anatomical and functional neural development and disease in the mouse from early embryonic to adult stages. UBM-guided injections have also provided the means to perform rapid, direct gain-of-function genetic studies in the embryonic mouse CNS. The combination of UBM and muMRI approaches being developed can provide in vivo assessment of brain function in normal and disease model mice. The broad goals of this project are to develop in vivo micro-imaging approaches enabling analysis of normal and abnormal function in the developing mouse brain, and the relationships between genetic changes and altered brain function from embryonic to adult stages.
The specific aims are: 1) To develop and test two new direct methods for gain-of-function studies in the embryonic mouse CNS. 2) To test whether transgenic, CNS-specific over-expression of iron transport and storage proteins can be used for in vivo imaging of gene expression with gMRI. 3) To develop UBM and pMRI methods to quantify blood volume and flow in the developing mouse brain. 4) To quantify changes in manganese-enhanced MRI resulting from stimulation of neuronal activity in the early postnatal to adult mouse brain. The combination of genetic engineering approaches in the mouse with advanced ultrasound and magnetic resonance micro-imaging technology will provide powerful new tools for analyzing mouse developmental neurobiology, and leading to new insights into mammalian brain development and neurodegenerative diseases.
| Qiu, Lily R; Fernandes, Darren J; Szulc-Lerch, Kamila U et al. (2018) Mouse MRI shows brain areas relatively larger in males emerge before those larger in females. Nat Commun 9:2615 |
| Zhang, Jiangyang; Wu, Dan; Turnbull, Daniel H (2018) In Utero MRI of Mouse Embryos. Methods Mol Biol 1718:285-296 |
| Leffler, Shoshana R; Legué, Emilie; Aristizábal, Orlando et al. (2016) A Mathematical Model of Granule Cell Generation During Mouse Cerebellum Development. Bull Math Biol 78:859-78 |
| Phoon, Colin K L; Turnbull, Daniel H (2016) Cardiovascular Imaging in Mice. Curr Protoc Mouse Biol 6:15-38 |
| Deans, Abby E; Wadghiri, Youssef Zaim; Aristizábal, Orlando et al. (2015) 3D mapping of neuronal migration in the embryonic mouse brain with magnetic resonance microimaging. Neuroimage 114:303-10 |
| Szulc, Kamila U; Lerch, Jason P; Nieman, Brian J et al. (2015) 4D MEMRI atlas of neonatal FVB/N mouse brain development. Neuroimage 118:49-62 |
| Bartelle, Benjamin B; Mana, Miyeko D; Suero-Abreu, Giselle A et al. (2015) Engineering an effective Mn-binding MRI reporter protein by subcellular targeting. Magn Reson Med 74:1750-7 |
| Steadman, Patrick E; Ellegood, Jacob; Szulc, Kamila U et al. (2014) Genetic effects on cerebellar structure across mouse models of autism using a magnetic resonance imaging atlas. Autism Res 7:124-37 |
| Suero-Abreu, Giselle A; Praveen Raju, G; Aristizábal, Orlando et al. (2014) In vivo Mn-enhanced MRI for early tumor detection and growth rate analysis in a mouse medulloblastoma model. Neoplasia 16:993-1006 |
| Bartelle, Benjamin B; Szulc, Kamila U; Suero-Abreu, Giselle A et al. (2013) Divalent metal transporter, DMT1: a novel MRI reporter protein. Magn Reson Med 70:842-50 |
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