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

Abstract

PurposeAsthma 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.MethodsHyperpolarized (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.ResultsSignificant 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 three‐fold increase in heterogeneity for the asthma model organs.ConclusionThe 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.

Effect of T1 relaxation on ventilation mapping using hyperpolarized 129Xe multiple breath wash‐out imaging

“…Skewness, a measure of histogram asymmetry, may be a useful marker for measuring the progression of lung regions that experience acute losses of function, leading to greatly reduced r values. Future studies of animal models of lung disease, such as an ovalbumin‐induced model of asthma, will be important in future to investigate how ventilation heterogeneity changes with disease …”

Magnetic resonance imaging with hyperpolarized agents: methods and applications

“…Allergic inflammation models demonstrated ventilation defects and localized inflammation in response to segmental challenge with allergen insufflation [222] and aerosolized methacholine challenge using 3 He MRI [223]. Similar studies have been duplicated with 129 Xe MRI and have gone a step further by demonstrating resolution of ventilation defects in response to bronchodilator [224]. However, such models remain limited in their ability to mimic the full complexity of asthma.…”

Electron and nuclear spin polarization in Rb-Xe spin-exchange optical hyperpolarization

“…The use of hyperpolarized noble gases, such as 129 Xe, 83 Kr, and 3 He, significantly helps to overcome the central problem of weak signal in noble-gas nuclear magnetic resonance (NMR) spectroscopy [1,2] and magnetic resonance imaging [3,4] experiments. Hyperpolarization also plays a vital role in atomic magnetometry [5], 129 Xe NMR biosensors [6], and many other specialized applications, such as in vivo 129 Xe NMR detection of cells [7], as well as the optical detection of 129 Xe NMR in a microfluidic chip [8].…”