Quantification of muco-obstructive lung disease variability in mice via laboratory X-ray velocimetry

Quantification of muco-obstructive lung disease variability in mice via laboratory X-ray velocimetry
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DOI:
10.1038/s41598-020-67633-y
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发表时间:
2020-07-02
期刊:
影响因子:
4.6
通讯作者:
Morgan, Kaye S.
Morgan, Kaye S.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Werdiger, Freda;Donnelley, Martin;Morgan, Kaye S.

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为了有效地诊断、监测和治疗呼吸系统疾病,临床医生应该能够准确地评估气流在肺部精细结构上的空间分布。这种能力将使任何健康状况的下降或改善都能够被定位和测量,从而能够设计出更好的治疗方案。目前的肺功能评估方法有许多局限性,包括无法准确定位肺内整体变化的起源。然而,X射线测速(XV)最近已被证明是一种复杂的和非侵入性的肺功能测量工具,能够显示整个肺在自然呼吸周期的气流的完整动态。在这项研究中,我们提出了XV分析的两个发展。首先,我们展示了基于实验室的XV检测β-ENaC小鼠中囊性纤维化(CF)样疾病的斑片状性质的能力。其次,我们提出了一种技术,在小鼠中的CF样疾病,可以划定两种主要模式的疾病症状的数值量化。我们提出这种分析模型作为一个简单的,易于解释的方法,并能够很容易地应用到大量的数据在XV成像。这些进展共同显示了XV评估局部气流变化的能力。我们建议XV应被视为一种新的肺功能测量工具,用于小动物模型中的肺治疗学开发,用于CF和其他粘膜阻塞性疾病。
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 beta -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.