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High-Resolution MRI of Viral Gene Expression in the CNS

$49,928F32FY2005EBNIH

Carnegie-Mellon University, Pittsburgh PA

Investigators

Abstract

DESCRIPTION (provided by applicant): A robust method for real-time, in vivo imaging of gene expression could significantly impact the fields of biomedical research and medicine. The scope of this study is to establish an integrative model of noninvasive molecular imaging derived from the fields of high-resolution magnetic resonance imaging (MRI) and molecular biology. The hypothesis is that in vivo up-regulation of genetically encoded MRI reporter molecules will induce a significant NMR solvent-relaxation in the vicinity of reporter-expressing cells. If the reporter molecules are sufficiently present, they will collectively produce a potent contrast in T2-weighted MR images. We propose to test these hypotheses by over-expressing MRI-sensitive reporters via recombinant viral vectors, in vitro and in vivo, followed by analysis and comparison of transgene expression by using chemical, biochemical, and biophysical methods followed by high-resolution MR imaging. By appropriately expressing MRI-sensitive gene products within the central nervous system of test animals, we will attempt to spatially and temporally image gene activity deep within tissues of living animals over long periods of time.

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