Abstract

We visualized the flow patterns in an alveolated duct model with breathing-like expanding and contracting wall motions using particle image velocimetry, and then, we investigated the effect of acinar deformation on the flow patterns. We reconstructed a compliant, scaled-up model of an alveolated duct from synchrotron microcomputed tomography images of a mammalian lung. The alveolated duct did not include any bifurcation, and its entire surface was covered with alveoli. We embedded the alveolated duct in a sealed container that was filled with fluid. We oscillated the fluid in the duct and container simultaneously and independently to control the flow and duct volume. We examined the flow patterns in alveoli, with the Reynolds number (Re) at 0.03 or 0.22 and the acinar volume change at 0%, 20%, or 80%. At the same Re, the heterogeneous deformation induced different inspiration and expiration flow patterns, and the recirculating regions in alveoli changed during respiratory cycle. During a larger acinar deformation at Re = 0.03, the flow patterns tended to change from recirculating flow to radial flow during inspiration and vice versa during expiration. Additionally, the alveolar geometric characteristics, particularly the angle between the alveolar duct and mouth, affected these differences in flow patterns. At Re=0.22, recirculating flow patterns tended to form during inspiration and expiration, regardless of the magnitude of the acinar deformation. Our in vitro experiments suggest that the alveolated flows with nonself-similar and heterogeneous wall motions may promote particle mixing and deposition.

References

1.
Darquenne
,
C.
,
2012
, “
Aerosol Deposition in Health and Disease
,”
J. Aerosol. Med. Pulm. Drug Deliv.
,
25
(
3
), pp.
140
147
.10.1089/jamp.2011.0916
2.
Tsuda
,
A.
,
Rogers
,
R. A.
,
Hydon
,
P. E.
, and
Butler
,
J. P.
,
2002
, “
Chaotic Mixing Deep in the Lung
,”
Proc. Natl. Acad. Sci. U. S. A.
,
99
(
15
), pp.
10173
10178
.10.1073/pnas.102318299
3.
Tsuda
,
A.
,
Henry
,
F. S.
, and
Butler
,
J. P.
,
1995
, “
Chaotic Mixing of Alveolated Duct Flow in Rhythmically Expanding Pulmonary Acinus
,”
J. Appl. Physiol.
,
79
(
3
), pp.
1055
1063
.10.1152/jappl.1995.79.3.1055
4.
Haber
,
S.
,
Yitzhak
,
D.
, and
Tsuda
,
A.
,
2003
, “
Gravitational Deposition in a Rhythmically Expanding and Contracting Alveolus
,”
J. Appl. Physiol.
,
95
(
2
), pp.
657
671
.10.1152/japplphysiol.00770.2002
5.
Sznitman
,
J.
,
Heimsch
,
F.
,
Heimsch
,
T.
,
Rusch
,
D.
, and
Rösgen
,
T.
,
2007
, “
Three-Dimensional Convective Alveolar Flow Induced by Rhythmic Breathing Motion of the Pulmonary Acinus
,”
ASME J. Biomech. Eng.
,
129
(
5
), pp.
658
665
.10.1115/1.2768109
6.
Darquenne
,
C.
,
Harrington
,
L.
, and
Prisk
,
G. K.
,
2009
, “
Alveolar Duct Expansion Greatly Enhances Aerosol Deposition: A Three-Dimensional Computational Fluid Dynamics Study
,”
Philos. Trans. A Math. Phys. Eng. Sci.
,
367
(
1896
), pp.
2333
2346
.10.1098/rsta.2008.0295
7.
Harding
,
E. M.
, and
Robinson
,
R. J.
,
2010
, “
Flow in a Terminal Alveolar Sac Model With Expanding Walls Using Computational Fluid Dynamics
,”
Inhalation Toxicol.
,
22
(
8
), pp.
669
678
.10.3109/08958371003749939
8.
Sznitman
,
J.
,
Heimsch
,
T.
,
Wildhaber
,
J. H.
,
Tsuda
,
A.
, and
Rösgen
,
T.
,
2009
, “
Respiratory Flow Phenomena and Gravitational Deposition in a Three-Dimensional Space-Filling Model of the Pulmonary Acinar Tree
,”
ASME J. Biomech. Eng.
,
131
(
3
), p.
031010
.10.1115/1.3049481
9.
Ma
,
B.
, and
Darquenne
,
C.
,
2011
, “
Aerosol Deposition Characteristics in Distal Acinar Airways Under Cyclic Breathing Conditions
,”
J. Appl. Physiol.
,
110
(
5
), pp.
1271
1282
.10.1152/japplphysiol.00735.2010
10.
Harding
,
E. M.
,
Berg
,
E. J.
, and
Robinson
,
R. J.
,
2013
, “
Diffusion in Replica Healthy and Emphysematous Alveolar Models Using Computational Fluid Dynamics
,”
ISRN Biomed. Eng.
,
2013
, p.
e919802
.10.1155/2013/919802
11.
Shachar-Berman
,
L.
,
Ostrovski
,
Y.
,
Koshiyama
,
K.
,
Wada
,
S.
,
Kassinos
,
S. C.
, and
Sznitman
,
J.
,
2019
, “
Targeting Inhaled Fibers to the Pulmonary Acinus: Opportunities for Augmented Delivery From in Silico Simulations
,”
Eur. J. Pharm. Sci.
,
137
, p.
105003
.10.1016/j.ejps.2019.105003
12.
Koshiyama
,
K.
, and
Wada
,
S.
,
2015
, “
Mathematical Model of a Heterogeneous Pulmonary Acinus Structure
,”
Comput. Biol. Med.
,
62
, pp.
25
32
.10.1016/j.compbiomed.2015.03.032
13.
Sera
,
T.
,
Uesugi
,
K.
,
Yagi
,
N.
, and
Yokota
,
H.
,
2015
, “
Numerical Simulation of Airflow and Microparticle Deposition in a Synchrotron Micro-CT-Based Pulmonary Acinus Model
,”
Comput. Methods Biomech. Biomed. Eng.
,
18
(
13
), pp.
1427
1435
.10.1080/10255842.2014.915030
14.
Sera
,
T.
,
Higashi
,
R.
,
Naito
,
H.
,
Matsumoto
,
T.
, and
Tanaka
,
M.
,
2017
, “
Distribution of Nanoparticle Depositions After a Single Breathing in a Murine Pulmonary Acinus Model
,”
Int. J. Heat Mass Transfer
,
108
(
Part A
), pp.
730
739
.10.1016/j.ijheatmasstransfer.2016.12.057
15.
Tippe
,
A.
, and
Tsuda
,
A.
,
2000
, “
Recirculating Flow in an Expanding Alveolar Model: Experimental Evidence of Flow-Induced Mixing of Aerosols in the Pulmonary Acinus
,”
J. Aerosol Sci.
,
31
(
8
), pp.
979
986
.10.1016/S0021-8502(99)00572-8
16.
Karl
,
A.
,
Henry
,
F. S.
, and
Tsuda
,
A.
,
2004
, “
Low Reynolds Number Viscous Flow in an Alveolated Duct
,”
ASME J. Biomech. Eng.
,
126
(
4
), pp.
420
429
.10.1115/1.1784476
17.
van Ertbruggen
,
C.
,
Corieri
,
P.
,
Theunissen
,
R.
,
Riethmuller
,
M. L.
, and
Darquenne
,
C.
,
2008
, “
Validation of CFD Predictions of Flow in a 3D Alveolated Bend With Experimental Data
,”
J. Biomech.
,
41
(
2
), pp.
399
405
.10.1016/j.jbiomech.2007.08.013
18.
Ma
,
B.
,
Ruwet
,
V.
,
Corieri
,
P.
,
Theunissen
,
R.
,
Riethmuller
,
M.
, and
Darquenne
,
C.
,
2009
, “
CFD Simulation and Experimental Validation of Fluid Flow and Particle Transport in a Model of Alveolated Airways
,”
J. Aerosol Sci.
,
40
(
5
), pp.
403
141
.10.1016/j.jaerosci.2009.01.002
19.
Davidson
,
M. R.
, and
Fitz-Gerald
,
J. M.
,
1972
, “
Flow Patterns in Models of Small Airway Units of the Lung
,”
J. Fluid Mech.
,
52
(
1
), pp.
161
177
.10.1017/S0022112072003015
20.
Fishler
,
R.
,
Mulligan
,
M. K.
, and
Sznitman
,
J.
,
2013
, “
Acinus-on-a-Chip: A Microfluidic Platform for Pulmonary Acinar Flows
,”
J Biomech
,
46
(
16
), pp.
2817
2823
.10.1016/j.jbiomech.2013.08.020
21.
Lv
,
H.
,
Dong
,
J.
,
Qiu
,
Y.
,
Yang
,
Y.
, and
Zhu
,
Y.
,
2020
, “
Microflow in a Rhythmically Expanding Alveolar Chip With Dynamic Similarity
,”
Lab Chip
,
20
(
13
), pp.
2394
2402
.10.1039/C9LC01273G
22.
Fishler
,
R.
,
Hofemeier
,
P.
,
Etzion
,
Y.
,
Dubowski
,
Y.
, and
Sznitman
,
J.
,
2015
, “
Particle Dynamics and Deposition in True-Scale Pulmonary Acinar Models
,”
Sci. Rep.
,
5
(
1
), p.
14071
.10.1038/srep14071
23.
Berg
,
E. J.
,
Weisman
,
J. L.
,
Oldham
,
M. J.
, and
Robinson
,
R. J.
,
2010
, “
Flow Field Analysis in a Compliant Acinus Replica Model Using Particle Image Velocimetry (PIV)
,”
J. Biomech.
,
43
(
6
), pp.
1039
1047
.10.1016/j.jbiomech.2009.12.019
24.
Berg
,
E. J.
, and
Robinson
,
R. J.
,
2011
, “
Stereoscopic Particle Image Velocimetry Analysis of Healthy and Emphysemic Alveolar Sac Models
,”
ASME J. Biomech. Eng.
,
133
(
6
), p.
061004
.10.1115/1.4004251
25.
Hofemeier
,
P.
, and
Sznitman
,
J.
,
2016
, “
The Role of Anisotropic Expansion for Pulmonary Acinar Aerosol Deposition
,”
J. Biomech.
,
49
(
14
), pp.
3543
3548
.10.1016/j.jbiomech.2016.08.025
26.
Kumar
,
H.
,
Tawhai
,
M. H.
,
Hoffman
,
E. A.
, and
Lin
,
C.-L.
,
2009
, “
The Effects of Geometry on Airflow in the Acinar Region of the Human Lung
,”
J. Biomech.
,
42
(
11
), pp.
1635
1642
.10.1016/j.jbiomech.2009.04.046
27.
Sera
,
T.
,
Yokota
,
H.
,
Tanaka
,
G.
,
Uesugi
,
K.
,
Yagi
,
N.
, and
Schroter
,
R. C.
,
2013
, “
Murine Pulmonary Acinar Mechanics During Quasi-Static Inflation Using Synchrotron Refraction-Enhanced Computed Tomography
,”
J. Appl. Physiol.
,
115
(
2
), pp.
219
228
.10.1152/japplphysiol.01105.2012
28.
Weibel
,
E. R.
,
1963
,
Morphometry of the Human Lung
,
Academic Press
, New York.
29.
Sznitman
,
J.
,
2013
, “
Respiratory Microflows in the Pulmonary Acinus
,”
J. Biomech.
,
46
(
2
), pp.
284
298
.10.1016/j.jbiomech.2012.10.028
30.
Pedley
,
T. J.
,
1977
, “
Pulmonary Fluid Dynamics
,”
Annu. Rev. Fluid Mech.
,
9
(
1
), pp.
229
274
.10.1146/annurev.fl.09.010177.001305
You do not currently have access to this content.