Cystic fibrosis (CF) is caused by a gene defect that compromises the ability of the mucociliary transit (MCT) system to clear the airways of debris and pathogens. To directly characterise airway health and the effects of treatments we have developed a synchrotron X-ray microscopy method that non-invasively measures the local rate and patterns of MCT behaviour. Although the nasal airways of CF mice exhibit the CF pathophysiology, there is evidence that nasal MCT is not altered in CF mice1. The aim of this experiment was to determine if our non-invasive local airway health assessment method could identify differences in nasal MCT rate between normal and CF mice, information that is potentially lost in bulk MCT measurements.

Experiments were performed on the BL20XU beamline at the SPring-8 Synchrotron in Japan. Mice were anaesthetized, a small quantity of micron-sized marker particles were delivered to the nose, and images of the nasal airways were acquired for 15 minutes. The nasal airways were treated with hypertonic saline or mannitol to increase surface hydration and MCT. Custom software was used to locate and track particles and calculate individual and bulk MCT rates.

No statistically significant differences in MCT rate were found between normal and CF mouse nasal airways or between treatments. However, we hope that the improved sensitivity provided by this technique will accelerate the ability to identify useful CF lung disease-modifying interventions in small animal models, and enhance the development and efficacy of proposed new therapies.

1.
B. R.
Grubb
,
J. H.
Jones
and
R. C.
Boucher
,
Am J Physiol Lung Cell Mol Physiol
286
(
3
),
L588
595
(
2004
).
2.
J. J.
Wine
,
J Clin Invest
103
(
3
),
309
312
(
1999
).
3.
E.
Daviskas
,
S. D.
Anderson
,
I.
Gonda
,
S.
Eberl
,
S.
Meikle
,
J. P.
Seale
and
G.
Bautovich
,
Eur Respir J
9
(
4
),
725
732
(
1996
).
4.
S. H.
Donaldson
,
W. D.
Bennett
,
K. L.
Zeman
,
M. R.
Knowles
,
R.
Tarran
and
R. C.
Boucher
,
N Engl J Med
354
(
3
),
241
250
(
2006
).
5.
M. R.
Elkins
,
M.
Robinson
,
B. R.
Rose
,
C.
Harbour
,
C. P.
Moriarty
,
G. B.
Marks
,
E. G.
Belousova
,
W.
Xuan
,
P. T.
Bye
and
G. National Hypertonic Saline in Cystic Fibrosis Study
,
N Engl J Med
354
(
3
),
229
240
(
2006
).
6.
M. L.
Aitken
,
G.
Bellon
,
K.
De Boeck
,
P. A.
Flume
,
H. G.
Fox
,
D. E.
Geller
,
E. G.
Haarman
,
H. U.
Hebestreit
,
A.
Lapey
,
I. M.
Schou
,
J. B.
Zuckerman
,
B.
Charlton
and
C. F.
Investigators
,
Am J Respir Crit Care Med
185
(
6
),
645
652
(
2012
).
7.
B. R.
Grubb
,
J. H.
Jones
and
R. C.
Boucher
,
American journal of physiology. Lung cellular and molecular physiology
286
(
3
),
L588
595
(
2004
).
8.
M. F.
Quinlan
,
S. D.
Salman
,
D. L.
Swift
,
H. N.
Wagner
, Jr.
and
D. F.
Proctor
,
Am Rev Respir Dis
99
(
1
),
13
23
(
1969
).
9.
M.
Donnelley
,
K. S.
Morgan
,
K. K.
Siu
,
A.
Fouras
,
N. R.
Farrow
,
R. P.
Carnibella
and
D. W.
Parsons
,
Journal of synchrotron radiation
21
(
Pt 4
),
768
773
(
2014
).
10.
M.
Donnelley
,
K. S.
Morgan
,
K. K.
Siu
and
D. W.
Parsons
,
Journal of synchrotron radiation
19
(
Pt 4
),
551
558
(
2012
).
11.
A. R.
Martin
,
R. B.
Thompson
and
W. H.
Finlay
,
J Aerosol Med Pulm Drug Deliv
21
(
4
),
335
342
(
2008
).
12.
U.
Griesenbach
,
F. M.
Munkonge
,
S.
Sumner-Jones
,
E.
Holder
,
S. N.
Smith
,
A. C.
Boyd
,
D. R.
Gill
,
S. C.
Hyde
,
D.
Porteous
,
E. W.
Alton
and
U. K. C. F. G. T.
Consortium
,
Methods in molecular biology
433
,
229
242
(
2008
).
13.
M.
Donnelley
,
K. S.
Morgan
,
K. K. W.
Siu
,
N. R.
Farrow
,
C. S.
Stahr
,
R. C.
Boucher
,
A.
Fouras
and
D. W.
Parsons
,
Sci Rep-Uk
4
(
2014
).
14.
M.
Donnelley
,
K. K.
Siu
,
K. S.
Morgan
,
W.
Skinner
,
Y.
Suzuki
,
A.
Takeuchi
,
K.
Uesugi
,
N.
Yagi
and
D. W.
Parsons
,
Journal of synchrotron radiation
17
(
6
),
719
729
(
2010
).