Abstract

To effectively diagnose, monitor and treat respiratory disease clinicians should be able to accurately assess the spatial distribution of airflow across the fine structure of lung. This capability would enable any decline or improvement in health to be located and measured, allowing improved treatment options to be designed. Current lung function assessment methods have many limitations, including the inability to accurately localise the origin of global changes within the lung. However, X-ray velocimetry (XV) has recently been demonstrated to be a sophisticated and non-invasive lung function measurement tool that is able to display the full dynamics of airflow throughout the lung over the natural breathing cycle. In this study we present two developments in XV analysis. Firstly, we show the ability of laboratory-based XV to detect the patchy nature of cystic fibrosis (CF)-like disease in β-ENaC mice. Secondly, we present a technique for numerical quantification of CF-like disease in mice that can delineate between two major modes of disease symptoms. We propose this analytical model as a simple, easy-to-interpret approach, and one capable of being readily applied to large quantities of data generated in XV imaging. Together these advances show the power of XV for assessing local airflow changes. We propose that XV should be considered as a novel lung function measurement tool for lung therapeutics development in small animal models, for CF and for other muco-obstructive diseases.

Highlights

  • To effectively diagnose, monitor and treat respiratory disease clinicians should be able to accurately assess the spatial distribution of airflow across the fine structure of lung

  • Cystic fibrosis (CF) is a progressive, chronic and debilitating genetic disease caused by mutations in the cystic fibrosis (CF) Transmembrane-conductance Regulator (CFTR) gene

  • Effective lung health assessment tools must capture the patchy nature of muco-obstructive lung diseases such as cystic fibrosis, and this is important during the early stages of the disease when local treatments could be applied to prevent disease progression

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Summary

Introduction

Monitor and treat respiratory disease clinicians should be able to accurately assess the spatial distribution of airflow across the fine structure of lung. The forced oscillation technique (FOT) measures the resistive properties of the respiratory system and has been used in obstructive lung disease assessment, the results can be difficult to interpret It suffers from the same problems as F­ EV1 with respect to lumping regional information into single whole-lung p­ arameters[3]. Progress in MRI research has lagged behind x-ray-based methods, most likely because spatial resolution is poor and the properties of the lung— the low proton density, present since the lung is comprised primarily of air—make it less appropriate for ­MRI5 Recent innovations such as hyperpolarised gas and ultrashort echo time imaging continue to advance human chest MRI ­research[6, 7]

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