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The development of effective strategies for gene therapy has been hampered by difficulties verifying transgene delivery in vivo and quantifying gene expression non-invasively. Magnetic resonance imaging (MRI) offers high spatial resolution and three-dimensional views, without tissue depth limitations. The iron-storage protein ferritin is a prototype MRI gene reporter. Ferritin forms a paramagnetic ferrihydrite core that can be detected by MRI via its effect on the local magnetic field experienced by water protons. In an effort to better characterize the ferritin reporter for central nervous system applications, we expressed ferritin in the mouse brain in vivo using a neurotropic herpes simplex virus type 1 (HSV-1). We computed three-dimensional maps of MRI transverse relaxation rates in the mouse brain with ascending doses of ferritin-expressing HSV-1. We established that the transverse relaxation rates correlate significantly to the number of inoculated infectious particles. Our results are potentially useful for quantitatively assessing limitations of ferritin reporters for gene therapy applications.

Quantification of HSV-1-mediated expression of the ferritin MRI reporter in the mouse brain