X-Ray based Lung Function measurement-a sensitive technique to quantify lung function in allergic airway inflammation mouse models.

C Dullin,M A Markus,F Alves,E Larsson,S Hülsmann,G Tromba

doi:10.1038/srep36297

Abstract

In mice, along with the assessment of eosinophils, lung function measurements, most commonly carried out by plethysmography, are essential to monitor the course of allergic airway inflammation, to examine therapy efficacy and to correlate animal with patient data. To date, plethysmography techniques either use intubation and/or restraining of the mice and are thus invasive, or are limited in their sensitivity. We present a novel unrestrained lung function method based on low-dose planar cinematic x-ray imaging (X-Ray Lung Function, XLF) and demonstrate its performance in monitoring OVA induced experimental allergic airway inflammation in mice and an improved assessment of the efficacy of the common treatment dexamethasone. We further show that XLF is more sensitive than unrestrained whole body plethysmography (UWBP) and that conventional broncho-alveolar lavage and histology provide only limited information of the efficacy of a treatment when compared to XLF. Our results highlight the fact that a multi-parametric imaging approach as delivered by XLF is needed to address the combined cellular, anatomical and functional effects that occur during the course of asthma and in response to therapy.

Highlights

Accurate lung function data in mice, in particular in response to novel therapeutic strategies, may allow a better preclinical evaluation of drug efficacy as well as a better comparison with patient data
By correlating the results with histology, broncho-alveolar lavage (BAL), synchrotron phase contrast CT and unrestrained whole body plethysmography (UWBP) we demonstrate that XLF is easy to use in vivo and shows a significantly higher sensitivity than UWBP for the reliable assessment of experimental allergic airway inflammation and the efficacy of dexamethasone treatment
The x-ray transmission function (XTF) over time describes the difference of these values normalized by the average background signal (ROIBkg), in order to account for variations in intensity fluctuations of the x-ray tube (Supplementary Figure S1): XTF(t) = regions of interest (ROI)(t) − ROIBgk (t) /average_ROIBgk

Summary

Introduction

Accurate lung function data in mice, in particular in response to novel therapeutic strategies, may allow a better preclinical evaluation of drug efficacy as well as a better comparison with patient data. We present a novel lung function measurement approach utilizing low dose planar cinematic x-ray imaging, which we designate “X-Ray Lung Function” [XLF]. By correlating the results with histology, BAL, synchrotron phase contrast CT and UWBP we demonstrate that XLF is easy to use in vivo and shows a significantly higher sensitivity than UWBP for the reliable assessment of experimental allergic airway inflammation and the efficacy of dexamethasone treatment

Methods

Results

Conclusion