title: Quantification of heterogeneity in lung disease with image-based pulmonary function testing.
abstract: 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.
authors.affiliation: Department of Mechanical &Aerospace Engineering, Monash University, Melbourne, VIC, Australia.
authors.forename: Charlene S
authors.initials: CS
authors.lastname: Stahr
authors.affiliation: 4Dx Limited, Melbourne, VIC, Australia.
authors.forename: Chaminda R
authors.initials: CR
authors.lastname: Samarage
authors.affiliation: Robinson Research Institute, University of Adelaide, SA, Australia.|Women's and Children's Hospital, North Adelaide, SA, Australia.
authors.forename: Martin
authors.initials: M
authors.lastname: Donnelley
authors.affiliation: Robinson Research Institute, University of Adelaide, SA, Australia.|Women's and Children's Hospital, North Adelaide, SA, Australia.
authors.forename: Nigel
authors.initials: N
authors.lastname: Farrow
authors.affiliation: School of Physics and Astronomy, Monash University, Melbourne, VIC, Australia.
authors.forename: Kaye S
authors.initials: KS
authors.lastname: Morgan
authors.affiliation: School of Medicine, University of Tasmania, Hobart, TAS, Australia.
authors.forename: Graeme
authors.initials: G
authors.lastname: Zosky
authors.affiliation: Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Boucher
authors.affiliation: School of Physics and Astronomy, Monash University, Melbourne, VIC, Australia.
authors.forename: Karen K W
authors.initials: KK
authors.lastname: Siu
authors.affiliation: Department of Translational Pulmonology Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), University of Heidelberg, Heidelberg, Germany.
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Mall
authors.affiliation: Robinson Research Institute, University of Adelaide, SA, Australia.|Women's and Children's Hospital, North Adelaide, SA, Australia.
authors.forename: David W
authors.initials: DW
authors.lastname: Parsons
authors.affiliation: Department of Mechanical &Aerospace Engineering, Monash University, Melbourne, VIC, Australia.|4Dx Limited, Melbourne, VIC, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Dubsky
authors.affiliation: Department of Mechanical &Aerospace Engineering, Monash University, Melbourne, VIC, Australia.|4Dx Limited, Melbourne, VIC, Australia.
authors.forename: Andreas
authors.initials: A
authors.lastname: Fouras
mesh_terms: D000465:Algorithms; D000818:Animals; D003198:Computer Simulation; D005260:Female; D008168:Lung / Q000000981:diagnostic imaging / Q000502:physiology / Q000503:physiopathology; D008171:Lung Diseases / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009038:Motion; D009504:Neutrophils / Q000378:metabolism; D011859:Radiography; D012129:Respiratory Function Tests / Q000379:methods*; D013147:Spirometry; D014057:Tomography, X-Ray Computed; D014965:X-Rays