title: Non-invasive imaging using reporter genes altering cellular water permeability.
abstract: 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.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, MC 210-41, Pasadena, California 91125, USA.
authors.forename: Arnab
authors.initials: A
authors.lastname: Mukherjee
authors.affiliation: Division of Engineering and Applied Sciences, California Institute of Technology, Pasadena, California 91125, USA.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, MC 210-41, Pasadena, California 91125, USA.
authors.forename: Hunter C
authors.initials: HC
authors.lastname: Davis
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, MC 210-41, Pasadena, California 91125, USA.
authors.forename: Mikhail G
authors.identifier: 0000-0002-0291-4215
authors.initials: MG
authors.lastname: Shapiro
mesh_terms: D000818:Animals; D020346:Aquaporins / Q000235:genetics / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016466:CHO Cells; D045744:Cell Line, Tumor; D003412:Cricetulus; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D015870:Gene Expression; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D016513:Mice, SCID; D010539:Permeability; D014183:Transplantation, Heterologous; D014867:Water / Q000378:metabolism*
chemical_list: D020346:Aquaporins; D014867:Water; D049452:Green Fluorescent Proteins