Investigating lung responses with functional hyperpolarized xenon-129 MRI in an ex vivo rat model of asthma

Purpose: Asthma is a disease of increasing worldwide importance that calls for new investigative methods. Ex vivo lung tissue is being increasingly used to study functional respiratory parameters independent of confounding systemic considerations but also to reduce animal numbers and associated rese...

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Main Authors: Lilburn, David M.L., Tatler, Amanda L., Six, Joseph S., Lesbats, Clémentine, Habgood, Antony, Porte, Joanne, Hughes-Riley, Theodore, Shaw, Dominick E., Jenkins, Gisli, Meersmann, Thomas
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Published: Wiley 2015
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Online Access:https://eprints.nottingham.ac.uk/31552/
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author Lilburn, David M.L.
Tatler, Amanda L.
Six, Joseph S.
Lesbats, Clémentine
Habgood, Antony
Porte, Joanne
Hughes-Riley, Theodore
Shaw, Dominick E.
Jenkins, Gisli
Meersmann, Thomas
author_facet Lilburn, David M.L.
Tatler, Amanda L.
Six, Joseph S.
Lesbats, Clémentine
Habgood, Antony
Porte, Joanne
Hughes-Riley, Theodore
Shaw, Dominick E.
Jenkins, Gisli
Meersmann, Thomas
author_sort Lilburn, David M.L.
building Nottingham Research Data Repository
collection Online Access
description Purpose: Asthma is a disease of increasing worldwide importance that calls for new investigative methods. Ex vivo lung tissue is being increasingly used to study functional respiratory parameters independent of confounding systemic considerations but also to reduce animal numbers and associated research costs. In this work a straightforward laboratory method is advanced to probe dynamic changes in gas inhalation patterns by utilizing an ex vivo small animal ovalbumin (OVA) model of human asthma. Methods: Hyperpolarized (hp) 129Xe was actively inhaled by the excised lungs exposed to a constant pressure differential that mimicked negative pleural cavity pressure. The method enabled hp 129Xe MRI of airway responsiveness to intravenous methacholine (MCh) and airway challenge reversal through salbutamol. Results: Significant differences were demonstrated between control and OVA challenged animals on global lung hp 129Xe gas inhalation with p < 0.05 at MCh dosages above 460 μg. Spatial mapping of the regional hp gas distribution revealed an approximately 3 fold increase in heterogeneity for the asthma model organs. Conclusion: The experimental results from this proof of concept work suggest that the ex vivo hp noble gas imaging arrangement and the applied image analysis methodology may be useful as an adjunct to current diagnostic techniques.
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spelling nottingham-315522020-05-04T17:18:36Z https://eprints.nottingham.ac.uk/31552/ Investigating lung responses with functional hyperpolarized xenon-129 MRI in an ex vivo rat model of asthma Lilburn, David M.L. Tatler, Amanda L. Six, Joseph S. Lesbats, Clémentine Habgood, Antony Porte, Joanne Hughes-Riley, Theodore Shaw, Dominick E. Jenkins, Gisli Meersmann, Thomas Purpose: Asthma is a disease of increasing worldwide importance that calls for new investigative methods. Ex vivo lung tissue is being increasingly used to study functional respiratory parameters independent of confounding systemic considerations but also to reduce animal numbers and associated research costs. In this work a straightforward laboratory method is advanced to probe dynamic changes in gas inhalation patterns by utilizing an ex vivo small animal ovalbumin (OVA) model of human asthma. Methods: Hyperpolarized (hp) 129Xe was actively inhaled by the excised lungs exposed to a constant pressure differential that mimicked negative pleural cavity pressure. The method enabled hp 129Xe MRI of airway responsiveness to intravenous methacholine (MCh) and airway challenge reversal through salbutamol. Results: Significant differences were demonstrated between control and OVA challenged animals on global lung hp 129Xe gas inhalation with p < 0.05 at MCh dosages above 460 μg. Spatial mapping of the regional hp gas distribution revealed an approximately 3 fold increase in heterogeneity for the asthma model organs. Conclusion: The experimental results from this proof of concept work suggest that the ex vivo hp noble gas imaging arrangement and the applied image analysis methodology may be useful as an adjunct to current diagnostic techniques. Wiley 2015-10-28 Article PeerReviewed Lilburn, David M.L., Tatler, Amanda L., Six, Joseph S., Lesbats, Clémentine, Habgood, Antony, Porte, Joanne, Hughes-Riley, Theodore, Shaw, Dominick E., Jenkins, Gisli and Meersmann, Thomas (2015) Investigating lung responses with functional hyperpolarized xenon-129 MRI in an ex vivo rat model of asthma. Magnetic Resonance in Medicine . ISSN 1522-2594 pulmonary imaging; hyperpolarized noble gas MRI; hp 129Xe; ovalbumin (OVA) rat model of asthma; methacholine challenges; airway hyper-responsiveness http://onlinelibrary.wiley.com/doi/10.1002/mrm.26003/abstract doi:10.1002/mrm.26003 doi:10.1002/mrm.26003
spellingShingle pulmonary imaging; hyperpolarized noble gas MRI; hp 129Xe; ovalbumin (OVA) rat model of asthma; methacholine challenges; airway hyper-responsiveness
Lilburn, David M.L.
Tatler, Amanda L.
Six, Joseph S.
Lesbats, Clémentine
Habgood, Antony
Porte, Joanne
Hughes-Riley, Theodore
Shaw, Dominick E.
Jenkins, Gisli
Meersmann, Thomas
Investigating lung responses with functional hyperpolarized xenon-129 MRI in an ex vivo rat model of asthma
title Investigating lung responses with functional hyperpolarized xenon-129 MRI in an ex vivo rat model of asthma
title_full Investigating lung responses with functional hyperpolarized xenon-129 MRI in an ex vivo rat model of asthma
title_fullStr Investigating lung responses with functional hyperpolarized xenon-129 MRI in an ex vivo rat model of asthma
title_full_unstemmed Investigating lung responses with functional hyperpolarized xenon-129 MRI in an ex vivo rat model of asthma
title_short Investigating lung responses with functional hyperpolarized xenon-129 MRI in an ex vivo rat model of asthma
title_sort investigating lung responses with functional hyperpolarized xenon-129 mri in an ex vivo rat model of asthma
topic pulmonary imaging; hyperpolarized noble gas MRI; hp 129Xe; ovalbumin (OVA) rat model of asthma; methacholine challenges; airway hyper-responsiveness
url https://eprints.nottingham.ac.uk/31552/
https://eprints.nottingham.ac.uk/31552/
https://eprints.nottingham.ac.uk/31552/