Non-invasive airway health assessment: Synchrotron imaging reveals effects of rehydrating treatments on mucociliary transit in-vivo

被引:22
作者
Donnelley, Martin [1 ,2 ,3 ]
Morgan, Kaye S. [4 ]
Siu, Karen K. W. [4 ,5 ,6 ]
Farrow, Nigel R. [1 ,2 ,3 ]
Stahr, Charlene S. [7 ]
Boucher, Richard C. [8 ]
Fouras, Andreas [7 ]
Parsons, David W. [1 ,2 ,3 ]
机构
[1] Womens & Childrens Hosp, Adelaide, SA 5006, Australia
[2] Univ Adelaide, Ctr Stem Cell Res, Adelaide, SA 5001, Australia
[3] Univ Adelaide, Sch Paediat & Reprod Hlth, Adelaide, SA 5001, Australia
[4] Monash Univ, Sch Phys, Clayton, Vic 3800, Australia
[5] Monash Univ, Monash Biomed Imaging, Clayton, Vic 3800, Australia
[6] Australian Synchrotron, Clayton, Vic 3800, Australia
[7] Monash Univ, Clayton, Vic 3800, Australia
[8] Univ N Carolina, CF Pulm Res & Treatment Ctr, Chapel Hill, NC USA
来源
SCIENTIFIC REPORTS | 2014年 / 4卷
基金
澳大利亚国家健康与医学研究理事会;
关键词
CYSTIC-FIBROSIS; GENE-TRANSFER; CLEARANCE; TRANSPORT; DEPOSITION; POLLUTANT; PARTICLE; TRACHEA; MICE;
D O I
10.1038/srep03689
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
To determine the efficacy of potential cystic fibrosis (CF) therapies we have developed a novel mucociliary transit (MCT) measurement that uses synchrotron phase contrast X-ray imaging (PCXI) to non-invasively measure the transit rate of individual micron-sized particles deposited into the airways of live mice. The aim of this study was to image changes in MCT produced by a rehydrating treatment based on hypertonic saline (HS), a current CF clinical treatment. Live mice received HS containing a long acting epithelial sodium channel blocker (P308); isotonic saline; or no treatment, using a nebuliser integrated within a small-animal ventilator circuit. Marker particle motion was tracked for 20 minutes using PCXI. There were statistically significant increases in MCT in the isotonic and HS-P308 groups. The ability to quantify in vivo changes in MCT may have utility in pre-clinical research studies designed to bring new genetic and pharmaceutical treatments for respiratory diseases into clinical trials.
引用
收藏
页数:6
相关论文
共 28 条
[1]   Restoration of mucociliary transport in the fluid-depleted trachea by surface-active instillates [J].
Ballard, ST ;
Parker, JC ;
Hamm, CR .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2006, 34 (04) :500-504
[2]   New concepts of the pathogenesis of cystic fibrosis lung disease [J].
Boucher, RC .
EUROPEAN RESPIRATORY JOURNAL, 2004, 23 (01) :146-158
[3]   Mechanosensitive ATP Release Maintains Proper Mucus Hydration of Airways [J].
Button, Brian ;
Okada, Seiko F. ;
Frederick, Charles Brandon ;
Thelin, William R. ;
Boucher, Richard C. .
SCIENCE SIGNALING, 2013, 6 (279)
[4]   Phase objects in synchrotron radiation hard x-ray imaging [J].
Cloetens, P ;
Barrett, R ;
Baruchel, J ;
Guigay, JP ;
Schlenker, M .
JOURNAL OF PHYSICS D-APPLIED PHYSICS, 1996, 29 (01) :133-146
[5]   Mucociliary transport in porcine trachea: differential effects of inhibiting chloride and bicarbonate secretion [J].
Cooper, Jeffrey L. ;
Quinton, Paul M. ;
Ballard, Stephen T. .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2013, 304 (03) :L184-L190
[6]  
Donaldson Scott H, 2007, Proc Am Thorac Soc, V4, P399, DOI 10.1513/pats.200703-042BR
[7]   Mucus clearance and lung function in cystic fibrosis with hypertonic saline [J].
Donaldson, SH ;
Bennett, WD ;
Zeman, KL ;
Knowles, MR ;
Tarran, R ;
Boucher, RC .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 354 (03) :241-250
[8]   Synchrotron phase-contrast X-ray imaging reveals fluid dosing dynamics for gene transfer into mouse airways [J].
Donnelley, M. ;
Siu, K. K. W. ;
Jamison, R. A. ;
Parsons, D. W. .
GENE THERAPY, 2012, 19 (01) :8-14
[9]   Variability of In Vivo Fluid Dose Distribution in Mouse Airways Is Visualized by High-Speed Synchrotron X-Ray Imaging [J].
Donnelley, Martin ;
Morgan, Kaye S. ;
Siu, Karen K. W. ;
Parsons, David W. .
JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY, 2013, 26 (05) :307-316
[10]   Dry deposition of pollutant and marker particles onto live mouse airway surfaces enhances monitoring of individual particle mucociliary transit behaviour [J].
Donnelley, Martin ;
Morgan, Kaye S. ;
Siu, Karen K. W. ;
Parsons, David W. .
JOURNAL OF SYNCHROTRON RADIATION, 2012, 19 :551-558