Daniel H. Turnbull
Professor, Skirball Institute of Biomolecular Medicine, Structural Biology. Departments of Radiology (CBI) and Pathology. Dir Biomedical Imaging Grad Program
Ph.D., 1991 University of Toronto
MRI; Ultrasound; Mouse Embryo; Neonate; MRI Reporters
Skirball Institute of Biomolecular Medicine
540 First Avenue 5th floor, Lab 6-7
New York, N.Y. 10016
Office Tel: (212) 263-7262
Lab Tel: (212) 263-7261
Fax: (212) 263-8214
Tel: (212) 263-3261
In Vivo Micro-Imaging of Mouse Brain and Cardiovascular Development
Extensive genetic information and the availability of techniques to manipulate the genome of the mouse have led to its widespread use in studies of development and to model human diseases. In this rapid proliferation of methods to genetically engineer mice, in vivo technologies to analyze structural and functional phenotypes in mutant mouse are critical. Noninvasive imaging methods such as ultrasound and magnetic resonance imaging (MRI) are essential clinical tools for assessing fetal health, and for diagnosing and staging many human diseases including cancer, heart disease and many neuro-degenerative disorders. We are developing a combination of ultrasound and MRI microimaging approaches with sufficient resolution and sensitivity to provide noninvasive structural, functional and molecular data on developmental and disease processes in normal and genetically-engineered mice.
Our laboratory pioneered ultrasound imaging and Doppler blood flow approaches for in vivo analysis of mouse cardiovascular development from the earliest embryonic stages of cardiac function. Recently, we have explored the use of intravascular contrast agents to produce high-resolution, 3D vascular images with both ultrasound and MRI. These approaches are currently being extended to enable cell-specific vascular imaging, using contrast agents targeted to membrane proteins expressed in endothelial cells of transgenic mouse embryos. Taken together, these methods are providing in vivo approaches for analyzing cardiovascular development in the mouse, from structure and function at the whole organism level, to the cellular and molecular levels through targeted contrast-enhanced imaging.
In the mouse nervous system, we have developed a unique set of in vivo analytic tools based on MRI and ultrasound imaging technologies. Ultrasound has been developed as a tool for in utero imaging and image-guided injection, enabling cell transplantation and genetic gain-of-function studies with retroviruses. MRI provides a wealth of 3D anatomical and functional data from the fetal to adult mouse brain, allowing longitudinal analysis of the progression of brain cancer, neuro-degenerative disease models, and in vivo phenotype analysis of a wide range of neurological mouse mutants. In addition to anatomical studies, we have developed functional MRI methods, including manganese-enhanced MRI for neural activity mapping in the mouse brain from early postnatal stages. Currently, we are developing several MRI methods for stem cell labeling and tracking, including iron-oxide nano and micro-particles for in vivo cell tagging, and transgenic expression of proteins involved in metal internalization and storage as an MRI reporter system for cellular imaging in the developing mouse brain.
- Szulc KU, Lerch JP, Nieman BJ, Bartelle BB, Friedel M, Suero-Abreu GA, Watson C, Joyner AL, Turnbull DH (2015). 4D MEMRI atlas of neonatal FVB/N mouse brain development. NeuroImage 118: 49-62. PMID: 26037053
- Deans AE, Wadghiri YZ, Aristizábal O, Turnbull DH (2015). 3D mapping of neuronal migration in the embryonic mouse brain with magnetic resonance microimaging. NeuroImage 114: 303-10. PMID: 25869862
- Suero-Abreu GA, Raju GP, Aristizábal O, Volkova E, Wojcinski A, Houston EJ, Pham D, Szulc KU, Colon D, Joyner AL, Turnbull DH (2014). In vivo Mn-enhanced MRI for early tumor detection and growth rate analysis in a mouse medulloblastoma model. Neoplasia 16: 993-1006. PMID: 25499213
- Bartelle BB, Szulc KU, Suero-Abreu GA, Rodriguez JJ, Turnbull DH (2013). Divalent metal transporter, DMT1: A novel MRI reporter protein. Magn Reson Med 70: 842-50. PMID: 23065715
- Bartelle BB, Berrios-Otero CA, Rodriguez JJ, Friedland AE, Aristizábal O, Turnbull DH (2012). Novel genetic approach for in vivo vascular imaging in mice. Circ Res 110: 938-47. PMID: 22374133