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Type: Journal article
Title: Synchrotron phase-contrast X-ray imaging reveals fluid dosing dynamics for gene transfer into mouse airways
Author: Donnelley, M.
Siu, K.
Jamison, R.
Parsons, D.
Citation: Gene Therapy, 2012; 19(1):8-14
Publisher: Nature Publishing Group
Issue Date: 2012
ISSN: 0969-7128
Statement of
M Donnelley, KKW Siu, RA Jamison and DW Parsons
Abstract: Although airway gene transfer research in mouse models relies on bolus fluid dosing into the nose or trachea, the dynamics and immediate fate of delivered gene transfer agents are poorly understood. In particular, this is because there are no in vivo methods able to accurately visualize the movement of fluid in small airways of intact animals. Using synchrotron phase-contrast X-ray imaging, we show that the fate of surrogate fluid doses delivered into live mouse airways can now be accurately and non-invasively monitored with high spatial and temporal resolution. This new imaging approach can help explain the non-homogenous distributions of gene expression observed in nasal airway gene transfer studies, suggests that substantial dose losses may occur at deliver into mouse trachea via immediate retrograde fluid motion and shows the influence of the speed of bolus delivery on the relative targeting of conducting and deeper lung airways. These findings provide insight into some of the factors that can influence gene expression in vivo, and this method provides a new approach to documenting and analyzing dose delivery in small-animal models.
Keywords: X-ray imaging; high resolution; mouse; airways; instillation; gene transfer
Rights: © 2012 Macmillan Publishers Limited. All rights reserved.
RMID: 0020116008
DOI: 10.1038/gt.2011.80
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Appears in Collections:Paediatrics publications

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