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Sci Rep. 2016 Jul 27;6:29438. doi: 10.1038/srep29438.

Quantification of heterogeneity in lung disease with image-based pulmonary function testing.

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Department of Mechanical &Aerospace Engineering, Monash University, Melbourne, VIC, Australia.
4Dx Limited, Melbourne, VIC, Australia.
Robinson Research Institute, University of Adelaide, SA, Australia.
Women's and Children's Hospital, North Adelaide, SA, Australia.
School of Physics and Astronomy, Monash University, Melbourne, VIC, Australia.
School of Medicine, University of Tasmania, Hobart, TAS, Australia.
Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Translational Pulmonology Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), University of Heidelberg, Heidelberg, Germany.


Computed tomography (CT) and spirometry are the mainstays of clinical pulmonary assessment. Spirometry is effort dependent and only provides a single global measure that is insensitive for regional disease, and as such, poor for capturing the early onset of lung disease, especially patchy disease such as cystic fibrosis lung disease. CT sensitively measures change in structure associated with advanced lung disease. However, obstructions in the peripheral airways and early onset of lung stiffening are often difficult to detect. Furthermore, CT imaging poses a radiation risk, particularly for young children, and dose reduction tends to result in reduced resolution. Here, we apply a series of lung tissue motion analyses, to achieve regional pulmonary function assessment in β-ENaC-overexpressing mice, a well-established model of lung disease. The expiratory time constants of regional airflows in the segmented airway tree were quantified as a measure of regional lung function. Our results showed marked heterogeneous lung function in β-ENaC-Tg mice compared to wild-type littermate controls; identified locations of airway obstruction, and quantified regions of bimodal airway resistance demonstrating lung compensation. These results demonstrate the applicability of regional lung function derived from lung motion as an effective alternative respiratory diagnostic tool.

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