Abstract

Lung imaging in mouse disease models is crucial for the assessment of the severity of airway disease but remains challenging due to the small size and the high porosity of the organ. Synchrotron inline free-propagation phase-contrast computed tomography (CT) with its intrinsic high soft-tissue contrast provides the necessary sensitivity and spatial resolution to analyse the mouse lung structure in great detail. Here, this technique has been applied in combination with single-distance phase retrieval to quantify alterations of the lung structure in experimental asthma mouse models of different severity. In order to mimic an in vivo situation as close as possible, the lungs were inflated with air at a constant physiological pressure. Entire mice were embedded in agarose gel and imaged using inline free-propagation phase-contrast CT at the SYRMEP beamline (Synchrotron Light Source, `Elettra', Trieste, Italy). The quantification of the obtained phase-contrast CT data sets revealed an increasing lung soft-tissue content in mice correlating with the degree of the severity of experimental allergic airways disease. In this way, it was possible to successfully discriminate between healthy controls and mice with either mild or severe allergic airway disease. It is believed that this approach may have the potential to evaluate the efficacy of novel therapeutic strategies that target airway remodelling processes in asthma.

Highlights

  • Mouse lung disease models are widely used in preclinical asthma research (Bates et al, 2009)

  • We show that XPCT can discriminate between the two airway disease models and that this technique provides the necessary sensitivity for quantitative analysis of structural differences in the lungs by comparing parameters like softtissue content and changes in the lung tissue composition, parameters that correlate with typical hallmarks of asthma and thereby with the severity of the disease

  • By applying inline phase-contrast computed tomography (CT) in combination with single-distance phase retrieval we found that the differences in severity of the disease in these two experimental allergic airway models in comparison with healthy controls are reflected in an increase in the soft-tissue content of the lung

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Summary

Introduction

Mouse lung disease models are widely used in preclinical asthma research (Bates et al, 2009). We show that XPCT can discriminate between the two airway disease models and that this technique provides the necessary sensitivity for quantitative analysis of structural differences in the lungs by comparing parameters like softtissue content and changes in the lung tissue composition, parameters that correlate with typical hallmarks of asthma and thereby with the severity of the disease.

Results
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