Abstract
Ex vivo rodent lung models are explored for physiological measurements of respiratory function with hyperpolarized (hp) 129Xe MRI. It is shown that excised lung models allow for simplification of the technical challenges involved and provide valuable physiological insights that are not feasible using in vivo MRI protocols. A custom designed breathing apparatus enables MR images of gas distribution on increasing ventilation volumes of actively inhaled hp 129Xe. Straightforward hp 129Xe MRI protocols provide residual lung volume (RV) data and permit for spatially resolved tracking of small hp 129Xe probe volumes during the inhalation cycle. Hp 129Xe MRI of lung function in the excised organ demonstrates the persistence of post mortem airway responsiveness to intravenous methacholine challenges. The presented methodology enables physiology of lung function in health and disease without additional regulatory approval requirements and reduces the technical and logistical challenges with hp gas MRI experiments. The post mortem lung functional data can augment histological measurements and should be of interest for drug development studies.
Highlights
The use of animal models of pulmonary diseases is well established in many areas of biomedical research, in vivo functional respiratory measurements of ventilated and anesthetized small animals are technically challenging to achieve [1,2,3]
The most basic hp 129Xe protocol that can be used for residual lung volume (RV) determination, using non slice selective and non-spatially resolved 1D NMR spectroscopic measurements is described by Eq 1: Inhalation0?5mL{30pulseNMRacquisition{ ð1Þ
The hp gas will be diluted by the gas in the residual volume RV (i.e. N2 or thermally polarized, Magnetic Resonance Imaging (MRI) nondetectable xenon with N2) to an unknown hp gas concentration with total volume Vi+RV
Summary
The use of animal models of pulmonary diseases is well established in many areas of biomedical research, in vivo functional respiratory measurements of ventilated and anesthetized small animals are technically challenging to achieve [1,2,3]. In addition isolated and perfused murine lungs have been used to investigate pharmacokinetics of inhaled aerosols [14,15]. Uhlig et al have performed technically challenging experiments on the intact ex vivo murine lungs examining both the airway and the vascular responses to intravenous delivery of a variety of pharmacologically active substances including methacholine, serotonin, endothelin-1 and leukotriene C4. The reported changes in airway resistance and vasoconstriction correlated well with the results obtained from precision cut lung slice models
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
