Synchrotron phase-contrast X-ray imaging reveals fluid dosing dynamics for gene transfer into mouse airways

dc.contributor.authorDonnelley, M.
dc.contributor.authorSiu, K.
dc.contributor.authorJamison, R.
dc.contributor.authorParsons, D.
dc.date.issued2012
dc.description.abstractAlthough 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.
dc.description.statementofresponsibilityM Donnelley, KKW Siu, RA Jamison and DW Parsons
dc.identifier.citationGene Therapy (Basingstoke), 2012; 19(1):8-14
dc.identifier.doi10.1038/gt.2011.80
dc.identifier.issn0969-7128
dc.identifier.issn1476-5462
dc.identifier.orcidDonnelley, M. [0000-0002-5320-7756]
dc.identifier.orcidParsons, D. [0000-0002-8775-3501] [0000-0003-1746-3290]
dc.identifier.urihttp://hdl.handle.net/2440/70264
dc.language.isoen
dc.publisherNature Publishing Group
dc.rights© 2012 Macmillan Publishers Limited. All rights reserved.
dc.source.urihttp://www.nature.com/gt/journal/v19/n1/full/gt201180a.html
dc.subjectX-ray imaging
dc.subjecthigh resolution
dc.subjectmouse
dc.subjectairways
dc.subjectinstillation
dc.subjectgene transfer
dc.titleSynchrotron phase-contrast X-ray imaging reveals fluid dosing dynamics for gene transfer into mouse airways
dc.typeJournal article
pubs.publication-statusPublished

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