Non-invasive imaging using reporter genes altering cellular water permeability

Non-invasive imaging of gene expression in live, optically opaque animals is important for multiple applications, including monitoring of genetic circuits and tracking of cell-based therapeutics. Magnetic resonance imaging (MRI) could enable such monitoring with high spatiotemporal resolution. Howev...

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Published inNature communications Vol. 7; no. 1; p. 13891
Main Authors Mukherjee, Arnab, Wu, Di, Davis, Hunter C, Shapiro, Mikhail G
Format Journal Article
LanguageEnglish
Published England Nature Publishing Group 23.12.2016
Nature Portfolio
Subjects
Animals
Aquaporins
Aquaporins - genetics
Aquaporins - metabolism
Brain Neoplasms - genetics
Brain Neoplasms - metabolism
Brain Neoplasms - pathology
Cell Line, Tumor
CHO Cells
Cricetulus
Cytomegalovirus
Diffusion Magnetic Resonance Imaging - methods
Gene Expression
Green Fluorescent Proteins - genetics
Green Fluorescent Proteins - metabolism
HEK293 Cells
Humans
Magnetic resonance imaging
Metals
Mice, SCID
Neuroblastoma
Permeability
Proteins
Transplantation, Heterologous
Tumors
Water - metabolism
United States > US
California
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Summary:Non-invasive imaging of gene expression in live, optically opaque animals is important for multiple applications, including monitoring of genetic circuits and tracking of cell-based therapeutics. Magnetic resonance imaging (MRI) could enable such monitoring with high spatiotemporal resolution. However, existing MRI reporter genes based on metalloproteins or chemical exchange probes are limited by their reliance on metals or relatively low sensitivity. Here we introduce a new class of MRI reporters based on the human water channel aquaporin 1. We show that aquaporin overexpression produces contrast in diffusion-weighted MRI by increasing tissue water diffusivity without affecting viability. Low aquaporin levels or mixed populations comprising as few as 10% aquaporin-expressing cells are sufficient to produce MRI contrast. We characterize this new contrast mechanism through experiments and simulations, and demonstrate its utility in vivo by imaging gene expression in tumours. Our results establish an alternative class of sensitive, metal-free reporter genes for non-invasive imaging.
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These authors contributed equally to this work
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms13891