Investigating lung responses with functional hyperpolarized xenon-129 MRI in an ex vivo rat model of asthma.
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 using an ex vivo small animal ovalbumin (OVA) model of human asthma.



Hyperpolarized (hp) (129) Xe was actively inhaled by the excised lungs exposed to a constant pressure differential that mimicked negative pleural cavity pressure. The method enabled hp (129) Xe MRI of airway responsiveness to intravenous methacholine (MCh) and airway challenge reversal through salbutamol.



Significant differences were demonstrated between control and OVA challenged animals on global lung hp (129) Xe gas inhalation with P < 0.05 at MCh dosages above 460 μg. Spatial mapping of the regional hp gas distribution revealed an approximately three-fold increase in heterogeneity for the asthma model organs.



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. Magn Reson Med 76:1224-1235, 2016. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham, Nottingham, United Kingdom.
David M L
DM
Lilburn
Division of Respiratory Medicine, Nottingham University Hospitals, City Campus, University of Nottingham, Nottingham, United Kingdom.
Amanda L
AL
Tatler
Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham, Nottingham, United Kingdom.
Joseph S
JS
Six
Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham, Nottingham, United Kingdom.
Clémentine
C
Lesbats
Division of Respiratory Medicine, Nottingham University Hospitals, City Campus, University of Nottingham, Nottingham, United Kingdom.
Anthony
A
Habgood
Division of Respiratory Medicine, Nottingham University Hospitals, City Campus, University of Nottingham, Nottingham, United Kingdom.
Joanne
J
Porte
Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham, Nottingham, United Kingdom.
Theodore
T
Hughes-Riley
Division of Respiratory Medicine, Nottingham University Hospitals, City Campus, University of Nottingham, Nottingham, United Kingdom.
Dominick E
DE
Shaw
Division of Respiratory Medicine, Nottingham University Hospitals, City Campus, University of Nottingham, Nottingham, United Kingdom.
Gisli
G
Jenkins
Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham, Nottingham, United Kingdom. thomas.meersmann@Nottingham.ac.uk.
Thomas
T
Meersmann
D000280:Administration, Inhalation; D000818:Animals; D001249:Asthma / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D003198:Computer Simulation; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008168:Lung / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008954:Models, Biological; D057054:Molecular Imaging / Q000379:methods; D011659:Pulmonary Gas Exchange; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D014979:Xenon Isotopes / Q000008:administration & dosage / Q000493:pharmacokinetics*
D019275:Radiopharmaceuticals; D014979:Xenon Isotopes
airway hyper-responsiveness; hp 129Xe; hyperpolarized noble gas MRI; methacholine challenges; ovalbumin (OVA) rat model of asthma; pulmonary imaging