The main purpose of this study was to express human myoglobin in mouse brain neurons and investigate the effects of this expression on metabolism and blood flow using phosphorous (31P) NMR spectroscopy and NMR perfusion imaging. Transgenic mice expressing brain myoglobin were created using a cDNA sequence for human myoglobin placed under the transcriptional control of either a human platelet-drived grown factor polypeptide B (PDGF-B) promoter sequence or a rat neuron-specific enolase (NSE) promoter sequence. The presence of myoglobin having a functional, reduced-state, heme group was demonstrated by protein analysis and immunocytochemistry. Expression levels were highest in the hippocampus, cerebellum, and cerebral cortex. No gross morphological adaptations of neural tissue resulting from the expression were observed and no statistically significant differences in the energetic state, as measured by 31P NMR, or baseline cortical perfusion, as measured by an NMR perfusion imaging technique, were found.
"Transfected mouse fibroblasts and HEK cells grown in culture  Myoglobin Heme protein and T 2 -based oxygen sensor naturally expressed at high levels in myocytes No statistically significant contrast with ectopic expression (4.7 T) Transgenic mouse  Hemoglobin Heme protein that acts as an innate T 2 -based oxygen sensor in erythrocytes BOLD contrast: T 2 changes from 50 to 4 ms with 100% modulation of blood oxygenation at 7 T "
[Show abstract][Hide abstract] ABSTRACT: Application of MRI contrast agents to neural systems research is complicated by the need to deliver agents past the blood-brain barrier or into cells, and the difficulty of targeting agents to specific brain structures or cell types. In the future, these barriers may be wholly or partially overcome using genetic methods for producing and directing MRI contrast. Here we review MRI contrast mechanisms that have used gene expression to manipulate MRI signal in cultured cells or in living animals. We discuss both fully genetic systems involving endogenous biosynthesis of contrast agents, and semi-genetic systems in which expressed proteins influence the localization or activity of exogenous contrast agents. We close by considering which contrast-generating mechanisms might be most suitable for applications in neuroscience, and we ask how genetic control machinery could be productively combined with existing molecular agents to enable next-generation neuroimaging experiments.
Magnetic Resonance Imaging 08/2007; 25(6):1004-10. DOI:10.1016/j.mri.2006.11.027 · 2.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Metalloproteins have long been recognized as key determinants of endogenous contrast in magnetic resonance imaging (MRI) of biological subjects. More recently, both natural and engineered metalloproteins have been harnessed as biotechnological tools to probe gene expression, enzyme activity, and analyte concentrations by MRI. Metalloprotein MRI probes are paramagnetic and function by analogous mechanisms to conventional gadolinium or iron oxide-based MRI contrast agents. Compared with synthetic agents, metalloproteins typically offer worse sensitivity, but the possibilities of using protein engineering and targeted gene expression approaches in conjunction with metalloprotein contrast agents are powerful and sometimes definitive strengths. This review summarizes theoretical and practical aspects of metalloprotein-based contrast agents, and discusses progress in the exploitation of these proteins for molecular imaging applications.
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