Research Papers

Role of Alveolar Topology on Acinar Flows and Convective Mixing

[+] Author and Article Information
Philipp Hofemeier

Department of Biomedical Engineering,
Technion—Israel Institute of Technology,
Haifa 32000, Israel
e-mail: philipph@bm.technion.ac.il

Josué Sznitman

Department of Biomedical Engineering,
Technion—Israel Institute of Technology,
Haifa 32000, Israel
e-mail: sznitman@bm.technion.ac.il

Contributed by the Bioengineering Division of ASME for publication in the Journal of Biomechanical Engineering. Manuscript received July 7, 2013; final manuscript received March 20, 2014; accepted manuscript posted April 2, 2014; published online May 6, 2014. Assoc. Editor: Francis Loth.

J Biomech Eng 136(6), 061007 (May 06, 2014) (10 pages) Paper No: BIO-13-1302; doi: 10.1115/1.4027328 History: Received July 07, 2013; Revised March 20, 2014; Accepted April 02, 2014

Due to experimental challenges, computational simulations are often sought to quantify inhaled aerosol transport in the pulmonary acinus. Commonly, these are performed using generic alveolar topologies, including spheres, toroids, and polyhedra, to mimic the complex acinar morphology. Yet, local acinar flows and ensuing particle transport are anticipated to be influenced by the specific morphological structures. We have assessed a range of acinar models under self-similar breathing conditions with respect to alveolar flow patterns, convective flow mixing, and deposition of fine particles (1.3 μm diameter). By tracking passive tracers over cumulative breathing cycles, we find that irreversible flow mixing correlates with the location and strength of the recirculating vortex inside the cavity. Such effects are strongest in proximal acinar generations where the ratio of alveolar to ductal flow rates is low and interalveolar disparities are most apparent. Our results for multi-alveolated acinar ducts highlight that fine 1 μm inhaled particles subject to alveolar flows are sensitive to the alveolar topology, underlining interalveolar disparities in particle deposition patterns. Despite the simplicity of the acinar models investigated, our findings suggest that alveolar topologies influence more significantly local flow patterns and deposition sites of fine particles for upper generations emphasizing the importance of the selected acinar model. In distal acinar generations, however, the alveolar geometry primarily needs to mimic the space-filling alveolar arrangement dictated by lung morphology.

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Darquenne, C., 2012, “Aerosol Deposition in Health and Diseases,” J. Aerosol Med. Pulm. Drug Delivery, 25, pp. 140–147. [CrossRef]
Nel, A., Xiao, T., Maedler, L., and Li, N., 2006, “Toxic Potential of Materials at the Nanolevel,” Science, 311, pp. 622–627. [CrossRef] [PubMed]
Schulz, H., Harder, V., Ibald-Mulli, A., Khandoga, A., Koenig, W., Krombach, F., Radykewicz, R., Stampfl, A., Thorand, B., and Peters, A., 2005, “Cardiovascular Effects of Fine and Ultrafine Particles,” J. Aerosol Med., 18(1), pp. 1–22. [CrossRef] [PubMed]
Choi, H. S., Ashitate, Y., Lee, J. H., Kim, S. H., Matsui, A., Insin, N., Bawendi, M. G., Semmler-Behnke, M., Frangioni, J. V., and Tsuda, A., 2010, “Rapid Translocation of Nanoparticles From the Lung Airspaces to the Body,” Nat. Biotechnol., 28, pp. 1300–1304. [CrossRef] [PubMed]
Geiser, M., Rothen-Rutishauser, B., Kapp, N., Schuerch, S., Kreylin, W., Schulz, H., Semmler, M., Im Hof, V., Heyder, J., and Gehr, P., 2005, “Ultrafine Particles Cross Cellular Membranes by Nonphagocytic Mechanisms in Lungs and in Cultured Cells,” Environ. Health Perspect., 113, pp. 1555–1560. [CrossRef] [PubMed]
Muehlfeld, C., Rothen-Rutishauser, B., Blank, F., Vanhecke, D., Ochs, M., and Gehr, P., 2008, “Interactions of Nanoparticles With Pulmonary Structures and Cellular Responses,” Am. J. Physiol.: Lung Cell Mol. Physiol., 294, pp. L817–L829. [CrossRef] [PubMed]
Adar, S., Sheppard, L., Vedal, S., Polak, J., Sampson, P., Roux, A. D., Budoff, M., Jacobs, D., Barr, R. G., Watson, K., and Kaufman, J., 2013, “Fine Particulate Air Pollution and the Progression of Carotid Intima-Medial Thickness: A Prospective Cohort Study From the Multi-Ethnic Study of Atherosclerosis and Air Pollution,” PLoS Med., 10, e1001430. [CrossRef] [PubMed]
Araujo, J., and Nel, A., 2009, “Particulate Matter and Atherosclerosis: Role of Particle Size, Composition and Oxidative Stress,” Part. Fibre Toxicol., 6, p. 24. [CrossRef] [PubMed]
Semmler-Behnke, M., Kreyling, W. G., Schulz, H., Takenaka, S., Butler, J. P., Henry, F. S., and Tsuda, A., 2012, “Nanoparticle Delivery in Infant Lungs,” Proc. Natl. Acad. Sci. U.S.A., 109(13), pp. 5092–5097. [CrossRef] [PubMed]
Sznitman, J., 2013, “Respiratory Microflows in the Pulmonary Acinus,” J. Biomech., 46, pp. 284–298. [CrossRef] [PubMed]
Tsuda, A., Henry, F., and Butler, J., 2008, “Gas and Aerosol Mixing in the Acinus,” Respir. Physiol. Neurobiol., 163, pp. 139–149. [CrossRef] [PubMed]
Darquenne, C., 2001, “A Realistic Two-Dimensional Model of Aerosol Transport and Deposition in the Alveolar Zone of the Human Lung,” J. Aerosol Sci., 32, pp. 1161–1174. [CrossRef]
Tsuda, A., Butler, J. P., and Fredberg, J. J., 1994, “Effects of Alveolated Duct Structure on Aerosol Kinetics. I. Diffusional Deposition in the Absence of Gravity,” J. Appl. Physiol., 76(6), pp. 2497–2509. [PubMed]
Tsuda, A., Butler, J., and Fredberg, J., 1994, “Effects of Alveolated Duct Structure on Aerosol Kinetics II. Gravitational Sedimentation and Inertial Impaction,” J. Appl. Physiol., 76, pp. 2510–1516. [PubMed]
Tsuda, A., Otani, Y., and Butler, J., 1999, “Acinar Flow Irreversibility Caused by Perturbations in Reversible Alveolar Wall Motion,” J. Appl. Physiol., 86, pp. 977–984. [CrossRef] [PubMed]
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. 403–414. [CrossRef] [PubMed]
Kumar, H., Vasilescu, D. M., Yin, Y., Hoffman, E. A., Tawhai, M. H., and Lin, C.-L., 2013, “Multi-Scale Imaging and Registration-Driven Model for Pulmonary Acinar Mechanics in the Mouse,” J. Appl. Physiol., 114, pp. 971–978. [CrossRef] [PubMed]
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. [CrossRef] [PubMed]
Schittny, J., Mund, S., and Stampanoni, M., 2008, “Evidence and Structural Mechanism for Late Lung Alveolarization,” Am. J. Physiol.: Lung Cell. Mol. Physiol., 294, pp. L246–L254. [CrossRef] [PubMed]
Hwang, J., Kim, M., Kim, S., and Lee, J., 2013, “Quantifying Morphological Parameters of the Terminal Branching Units in a Mouse Lung by Phase Contrast Synchrotron Radiation Computed Tomography,” PLoS One, 8, e63552. [CrossRef] [PubMed]
Tsuda, A., Filipovic, N., Haberthür, D., Dickie, R., Matsui, Y., Stampanoni, M., and Schittny, J., 2008, “Finite Element 3D Reconstruction of the Pulmonary Acinus Imaged by Synchrotron X-Ray Tomography,” J. Appl. Physiol., 105, pp. 964–976. [CrossRef] [PubMed]
Vasilescu, D. M., Gao, Z., Saha, P. K., Yin, L., Wang, G., Haefeli-Bleuer, B., Ochs, M., Weibel, E. R., and Hoffman, E. A., 2012, “Assessment of Morphometry of Pulmonary Acini in Mouse Lungs by Nondestructive Imaging Using Multiscale Microcomputed Tomography,” Proc. Natl. Acad. Sci. U.S.A., 109(42), pp. 17105–17110. [CrossRef] [PubMed]
Kumar, H., 2011, “Study of Airflow and Particle Transport in Acinar Airways of the Human Lung,” Ph.D. thesis, University of Iowa.
Sznitman, J., Sutter, R., Altorfer, D., Stampanoni, M., Rösgen, T., and Schittny, J. C., 2010, “Visualization of Respiratory Flows From 3D Reconstructed Alveolar Airspaces Using X-Ray Tomographic Microscopy,” J. Visualization, 13(4), pp. 337–345. [CrossRef]
Henry, F. S., Haber, S., Haberthür, D., Filipovic, N., Milasinovic, D., Schittny, J. C., and Tsuda, A., 2012, “The Simultaneous Role of an Alveolus as Flow Mixer and Flow Feeder for the Deposition of Inhaled Submicron Particles,” ASME J. Biomech. Eng., 134, p. 121001. [CrossRef]
Fung, Y. C., 1988, “A Model of the Lung Structure and Its Validation,” J. Appl. Physiol., 64, pp. 2132–2141. [PubMed]
Linhartová, A., Caldwell, W., and Anderson, A., 1986, “A Proposed Alveolar Model for Adult Human Lungs: The Regular Dodecahedron,” Anat. Rec., 214, pp. 266–272. [CrossRef] [PubMed]
Mead, J., Takishima, T., and Leith, D., 1970, “Stress Distribution in Lungs: A Model of Pulmonary Elasticity,” J. Appl. Physiol., 28, pp. 596–608. [PubMed]
Reifenrath, R., 1975, “The Significance of Alveolar Geometry and Surface Tension in the Respiratory Mechanics of the Lung,” Respir. Physiol., 24, pp. 115–137. [CrossRef] [PubMed]
Ryan, S., Dumais, C., and Ciannella, A., 1969, “The Structure of the Interalveolar Septum of the Mammalian Lung,” Anat. Rec., 165, pp. 467–483. [CrossRef] [PubMed]
Staub, N., and Storey, W., 1962, “Relation Between Morphological and Physiological Events in Lung Studied by Rapid Freezing,” J. Appl. Physiol., 17, pp. 381–390. [PubMed]
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, p. 031010. [CrossRef]
Kumar, H. T. 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, pp. 1635–1642. [CrossRef] [PubMed]
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. [CrossRef] [PubMed]
Haber, S., and Tsuda, A., 2006, “A Cyclic Model for Particle Motion in the Pulmonary Acinus,” J. Fluid Mech., 567, p. 157. [CrossRef]
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. [CrossRef] [PubMed]
Ma, B., and Darquenne, C., 2012, “Aerosol Bolus Dispersion in Acinar Airways—Influence of Gravity and Airway Asymmetry,” J. Appl. Physiol., 113, pp. 442–450. [CrossRef] [PubMed]
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. [CrossRef]
van Ertbruggen, C., Corieri, P., Theunissen, R., Riethmuller, M., and Darquenne, C., 2008, “Validation of CFD Predictions of Flow in a 3D Alveolated Bend With Experimental Data,” J. Biomech., 41, pp. 399–405. [CrossRef] [PubMed]
Tippe, A., and Tsuda, A., 1999, “Recirculating Flow in an Expanding Alveolar Model: Experimental Evidence of Flow-Induced Mixing of Aerosols in the Pulmonary Acinus,” J. Aerosol Sci., 31, pp. 979–986. [CrossRef]
Haefeli-Bleuer, B., and Weibel, E. R., 1988. “Morphometry of the Human Pulmonary Acinus,” Anat. Rec., 220(4), pp. 401–414. [CrossRef] [PubMed]
Fishler, R., Mulligan, M. K., and Sznitman, J., 2013, “Mapping Low-Reynolds-Number Microcavity Flows Using Microfluidic Screening Devices,” Microfluid. Nanofluid., 15, pp. 1–10. [CrossRef]
Shankar, P., and Deshpande, M., 2000, “Fluid Mechanics in the Driven Cavity,” Annu. Rev. Fluid Mech., 32, pp. 93–136. [CrossRef]
Shen, C., and Floryan, J., 1985, “Low Reynolds Number Flow Over Cavities,” Phys. Fluids, 28, pp. 3191–3202. [CrossRef]
Darquenne, C., and Paiva, M., 1996, “Two- and Three-Dimensional Simulations of Aerosol Transport and Deposition in Alveolar Zone of Human Lung,” J. Appl. Physiol., 80, pp. 1401–1414. [PubMed]
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. [PubMed]
Henry, F., Butler, J., and Tsuda, A., 2002, “Kinematically Irreversible Acinar Flow: A Departure From Classical Dispersive Aerosol Transport Theories,” J. Appl. Physiol., 92, pp. 835–845. [CrossRef] [PubMed]
Henry, F., and Tsuda, A., 2010, “Radial Transport Along the Human Acinar Tree,” ASME J. Biomech. Eng., 132, p. 101001. [CrossRef]
Tsuda, A., Laine-Pearson, F., and Hydon, P., 2011, “Why Chaotic Mixing of Particles Is Inevitable in the Deep Lung,” J. Theor. Biol., 286, pp. 57–66. [CrossRef] [PubMed]
Kumar, H., Tawhai, M. H., Hoffman, E. A., and Lin, C.-L., 2011, “Steady Streaming: A Key Mixing Mechanism in Low-Reynolds-Number Acinar Flows,” Phys. Fluids, 23(4), 041902. [CrossRef]
Womersley, J. R., 1955, “Method for the Calculation of Velocity, Rate of Flow and Viscous Drag in Arteries When the Pressure Gradient is Known,” J. Physiol., 127(3), pp. 553–563. [PubMed]
Haber, S., Butler, J. P., Brenner, H., Emanuel, I., and Tsuda, A., 2000, “Shear Flow Over a Self-Similar Expanding Pulmonary Alveolus During Rhythmical Breathing,” J. Fluid Mech., 405, pp. 243–268. [CrossRef]
Gil, J., Bachofen, H., Gehr, P., and Weibel, E. R., 1979, “Alveolar Volume-Surface Area Relation in Air-and Saline-Filled Lungs Fixed by Vascular Perfusion,” J. Appl. Physiol., 47(5), pp. 990–1001.
Ardila, R., Horie, T., and Hildebrandt, J., 1974, “Macroscopic Isotropy of Lung Expansion,” Respir. Physiol., 20(2), pp. 105–115. [CrossRef] [PubMed]
Amini, R., Creeden, K., and Narusawa, U., 2005, “A Mechanistic Model for Quasistatic Pulmonary Pressure-Volume Curves for Inflation,” ASME J. Biomech. Eng., 127(4), pp. 619–629. [CrossRef]
Jonson, B., and Svantesson, C., 1999, “Elastic Pressure–Volume Curves: What Information Do They Convey?,” Thorax, 54(1), pp. 82–87. [CrossRef] [PubMed]
Hickling, K. G., 1998, “The Pressure–Volume Curve Is Greatly Modified by Recruitment: A Mathematical Model of ARDS Lungs,” Am. J. Respir. Crit. Care Med., 158(1), pp. 194–202. [CrossRef] [PubMed]
Bastacky, J., Lee, C. Y., Goerke, J., Koushafar, H., Yager, D., Kenaga, L., Speed, T. P., Chen, Y., and Clements, J. A., 1995, “Alveolar Lining Layer Is Thin and Continuous: Low-Temperature Scanning Electron Microscopy of Rat Lung,” J. Appl. Physiol., 79(5), pp. 1615–1628. [PubMed]
Ferziger, J., and Peric, M., 2001, Computational Methods for Fluid Dynamics, 3rd ed., Springer Verlag, Berlin.
Hinds, W., 1999, Aerosol Technology: Properties, Behavior, and Measurement of Airborne Particles, Wiley-Interscience, New York.
Clift, R., Grace, J., and Weber, M., 1978, Drops and Particles, Academic Press, New York.
Tu, J., Inthavong, K., and Ahmadi, G., 2013, Computational Fluid and Particle Dynamics in the Human Respiratory System (Biological and Medical Physics, Biomedical Engineering), Springer Verlag, Heidelberg.
Berg, H., 1993, Random Walks in Biology, Princeton University Press, Princeton, NJ.
Kojic, M., and Tsuda, A., 2004, “A Simple Model for Gravitational Deposition of Non-Diffusing Particles in Oscillatory Laminar Pipe Flow and Its Application to Small Airways,” J. Aerosol Sci., 35(2), pp. 245–261. [CrossRef]
Tsuda, A., Henry, F. S., Otani, Y., Haber, S., and Butler, J. P., 1996, “Aerosol Transport and Deposition in the Rhythmically Expanding Pulmonary Acinus,” J. Aerosol Med., 9(3), pp. 389–408. [CrossRef] [PubMed]
Henry, F., Laine-Pearson, F., and Tsuda, A., 2009, “Hamiltonian Chaos in a Model Alveolus,” ASME J. Biomech. Eng., 131, p. 011006. [CrossRef]
Finlay, W. H., 2001, The Mechanics of Inhaled Pharmaceutical Aerosols: An Introduction, Academic Press, London.
Kleinstreuer, C., Zhang, Z., and Donohue, J., 2008, “Targeted Drug-Aerosol Delivery in the Human Respiratory System,” Annu. Rev. Biomed. Eng., 10, pp. 195–220. [CrossRef] [PubMed]
Kleinstreuer, C., and Zhang, Z., 2010, “Airflow and Particle Transport in the Human Respiratory System,” Annu. Rev. Fluid Mech., 42(1), pp. 301–334. [CrossRef]
Cassee, F. R., Muijser, H., Duistermaat, E., Freijer, J. J., Geerse, K. B., Marijnissen, J. C., and Arts, J. H., 2002, “Particle Size-Dependent Total Mass Deposition in Lungs Determines Inhalation Toxicity of Cadmium Chloride Aerosols in Rats. Application of a Multiple Path Dosimetry Model,” Arch. Toxicol., 76(5–6), pp. 277–286. [CrossRef] [PubMed]
Daigle, C. C., Chalupa, D. C., Gibb, F. R., Morrow, P. E., Oberdörster, G., Utell, M. J., and Frampton, M. W., 2003, “Ultrafine Particle Deposition in Humans During Rest and Exercise,” Inhalation Toxicol., 15(6), pp. 539–552. [CrossRef]
Shah, R., and London, A., 1978, Laminar Flow Forced Convection in Ducts, Academic, New York.


Grahic Jump Location
Fig. 1

Generic alveolar topology models. Top row: single alveolar models for local flow and convective mixing studies. Bottom row: corresponding multi-alveolar models for particle transport and deposition studies. ((a) and (e)) polyhedral-, ((b) and (f)) spherical-, ((c) and (g)) truncated spherical-, and ((d) and (h)) toroidal-alveolar model.

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Fig. 3

1D velocity profiles presented relative to the breathing motion along the alveolar midplane at peak inhalation (t = 0.25T) for medial acinar generation (QA/QD = 0.01): (a) profiles of spanwise velocity (uy) and (b) streamwise velocity (ux)

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Fig. 2

Relative streamlines along the 2D midplane of the polyhedral alveolus at peak inhalation (t = 0.25T): (a) proximal (QA/QD = 0.001), (b) medial (QA/QD = 0.01), and (c) distal acinar generation (QA/QD = 0.1)

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Fig. 4

Projection of passive tracer particle positions inside the polyhedral alveolus after t = 8T; (a) QA/QD = 0.001, (b) QA/QD = 0.01, and (c) QA/QD = 0.1. Particles are color-coded with respect to their final displacements (Δ/DD) at t = 8T, relative to their initial positions.

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Fig. 6

RMS displacement ΔRMS of ensembles of passive tracer particles for proximal (QA/QD = 0.001), medial (QA/QD = 0.01), and distal acinar generation (QA/QD = 0.1); data are sampled at the end of each exhalation phases (i.e., t=1T,2T,...,8T)

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Fig. 5

Root-mean-square displacement ΔRMS of ensembles of passive tracer particles. (a) ΔRMS for different QA/QD ratios inside the polyhedral alveolus model. (b) ΔRMS for different geometric models at QA/QD = 0.01. Note that the small indents seen in the curves for ΔRMS both in (a) and (b) correspond to tracer particles exiting the computational domain or depositing at a wall within the end of the first inhalation phase.

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Fig. 7

PDF for the relative particle displacements Δ/DD after t = 8T in the polyhedral model at QA/QD = 0.01. Inset: distribution for the upper quartile (i.e., 75% percentile).

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Fig. 9

Particle deposition in the polyhedral model at QA/QD = 0.01 for dp = 3 μm ((a) and (b)) and dp = 1 μm ((c) and (d)). ((a) and (c)) Deposition fraction over time and ((b) and (d)) breakdown of deposition patterns.

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Fig. 10

Root-mean-square displacement ΔRMS of massless tracer particle in a laminar oscillating pipe flow

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Fig. 8

Particle deposition sites in the polyhedral model for t = 4T, QA/QD = 0.01 and dp = 1 μm: (a) z-view and (b) x-view. Color-coding: red = deposition in duct, blue = deposition in alveoli. Note that particles are not moved further upon deposition such that deposited particles can be located outside of the domain in the above rendering.




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