Jan 25, 2016

A Genetically Encoded Reporter for Diffusion Weighted Magnetic Resonance Imaging

BioRxiv : the Preprint Server for Biology
Arnab MukherjeeMikhail G. Shapiro

Abstract

The ability to monitor gene expression in intact, optically opaque animals is important for a multitude of applications including longitudinal imaging of transgene expression and long term tracking of cell based therapeutics. Magnetic resonance imaging (MRI) could enable such monitoring with high spatial and temporal resolution. However, existing MRI reporter genes, based primarily on metal-binding proteins or chemical exchange saturation transfer probes, are limited by their reliance on metal ions or relatively low sensitivity. In this work, we introduce a new class of genetically encoded reporters for MRI that work by altering water diffusivity. We show that overexpression of the human water channel aquaporin 1 (AQP1) produces robust contrast in diffusion weighted MRI by increasing effective water diffusivity in tissues by over 100% without affecting cell viability or morphology. Low levels of AQP1 expression (~1 μM), or mixed populations comprising as few as 10% AQP1-expressing cells, produce sufficient contrast to be observed by MRI. We demonstrate the utility of AQP1 in vivo by imaging gene expression in intracranial tumor xenografts. Overall, our results establish AQP1 as a new, metal-free, nontoxic and sensitive genetica...Continue Reading

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Mentioned in this Paper

In Vivo
Magnetic Resonance Imaging
Diffusion Weighted Imaging
Science of Morphology
Spatial Distribution
Diffusion Magnetic Resonance Imaging
Ions
Metals
Gene Expression
Water channel

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