Numerical and Experimental Analyses of Aerosol Deposition in a Novel and Standardized Human Nasal Cavity by Yuan Liu, M.A.Sc. Mechanical Engineering A Thesis submitted to the Faculty of Graduate Studies and Research in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Mechanical Engineering Ottawa-Carleton Institute for Mechanical and Aerospace Engineering Department of Mechanical and Aerospace Engineering Carleton University Ottawa, Ontario, Canada March 31, 2010 Copyright © 2010 -Yuan Liu Library and Archives Bibliothèque et ?F? Canada Archives Canada Published Heritage Direction du Branch Patrimoine de l'édition 395 Wellington Street 395, rue Wellington OttawaONK1A0N4 Ottawa ON K1 A 0N4 Canada Canada Your file Votre référence ISBN: 978-0-494-67866-4 Our nie Notre référence ISBN: 978-0-494-67866-4 NOTICE: AVIS: The author has granted a non- L'auteur a accordé une licence non exclusive exclusive license allowing Library and permettant à la Bibliothèque et Archives Archives Canada to reproduce, Canada de reproduire, publier, archiver, publish, archive, preserve, conserve, sauvegarder, conserver, transmettre au public communicate to the public by par télécommunication ou par l'Internet, prêter, telecommunication or on the Internet, distribuer et vendre des thèses partout dans le loan, distribute and sell theses monde, à des fins commerciales ou autres, sur worldwide, for commercial or non- support microforme, papier, électronique et/ou commercial purposes, in microform, autres formats. paper, electronic and/or any other formats. The author retains copyright L'auteur conserve la propriété du droit d'auteur ownership and moral rights in this et des droits moraux qui protège cette thèse. Ni thesis. Neither the thesis nor la thèse ni des extraits substantiels de celle-ci substantial extracts from it may be ne doivent être imprimés ou autrement printed or otherwise reproduced reproduits sans son autorisation. without the author's permission. In compliance with the Canadian Conformément à la loi canadienne sur la Privacy Act some supporting forms protection de la vie privée, quelques may have been removed from this formulaires secondaires ont été enlevés de thesis. cette thèse. While these forms may be included Bien que ces formulaires aient inclus dans in the document page count, their la pagination, il n'y aura aucun contenu removal does not represent any loss manquant. of content from the thesis. 1+1 Canada Abstract This thesis presents an investigation of flow and aerosol deposition patterns in a model human nasal cavity using both experimental measurements and numerical simulations. A novel, standardized human nasal cavity model was created as part of this work by processing 30 sets of computed tomography (CT) scans of nasal airways of healthy subjects. Aerosol deposition in the novel, "Carleton-Civic" standardized geometry of the human nasal cavity was studied both numerically and experimentally. Inhalation flow rates varied from 30 to 90 L/min in the experiments, and aerosol droplets had diameters ranging from 1.71 to 9.14 µ??, giving impaction parameters ranging from 123.3 to 2527.6 µ?? L/min. For the numerical simulations, both the RANS/EIM (Reynolds Averaged Navier-Stokes equations for the gas phase and Eddy-Interaction random walk Models for the particulate phase) and Large Eddy Simulations were used to better understand the limits of applicability and accuracy of standard numerical methods as available in many commercial packages. Both experimental and simulated results showed that the mechanisms of aerosol deposition in the standardized nasal cavity were dominated by inertial impaction. Measured deposition data from the standardized nasal cavity transected cited in vitro data based on individual subjects. The data correlated very well with cited in vivo measurements but generally showed less aerosol deposition for a given value of the impaction parameter. Regional particle deposition characteristics within the nasal passages were also investigated both experimentally and numerically, and new trends of i regional deposition versus impaction parameter are discussed. These provide new insight into the general deposition behaviour of various sized aerosols within the human nasal cavity. 11 Acknowledgements There were many people who were helpful and supportive while I was pursuing my PhD. I want to take this opportunity to express my gratitude to these people who offered me their help in the years that I was performing my research on aerosols. First, I want to extend many thanks to my thesis supervisors, Dr. Matthew Johnson and Dr. Edgar Matida, who offered me their guidance, patience, encouragement and support not only in my research, but also in my personal life, especially during the time when I was expecting my baby girl. Working with them has been an invaluable experience and will be priceless in my career and personal life. I am also grateful to my friends within our research group for their help while I was preparing my experimental setup. I want to acknowledge, in particular, the contributions of Brian and Scott. Thanks also go to Steve, Stefan, Gary, Alex, Kevin and Fred for their help in generating the nasal cavity model and setting up my experiments. I am also very grateful to Nancy, Christie and Marlene for their kind helps throughout my PhD degree program. I would like to thank my husband, Ying Chen, my parents, my parents-in-law, and my sister for their complete understanding and unconditional support. I send my love to my little girl, Sophia. I am so thankful for the confidence and courage she gives me every day. m Table of Contents ABSTRACT I ACKNOWLEDGEMENTS Ill TABLE OF CONTENTS IV LISTOFTABLES VIII LISTOFFIGURES IX NOMENCLATURE XIII CHAPTER 1 : INTRODUCTION 1 1.1 Nasal drug delivery 3 1.2 nasal anatomy and respiratory physiology 4 1 .3 Two-phase flow and mechanisms of particle deposition 8 1.3.1 Particle Deposition 10 1.4 focus of the current research 12 1.5 Thesis Organization 15 CHAPTER 2:LITERATURE REVIEW 16 2. 1 Previous Measurements of characteristic dimensions in human nasal cavities 16 2.1.1 Measurements Using Acoustic rhinometry 18 2.1.2 Nasal Cavity Measurements using Computed Tomography and Magnetic Resonance Imaging19 2.2 Published 3D human nasal cavity models 21 2.2.1 Methods ofManufacturing Nasal Cavity Replicas 25 2.3 Experimental studies of airflow patterns and particle deposition in human nasal cavities 28 2.3.1 Experimental studies ofnasal airflow 28 2.3.2 Experimental study ofparticle deposition in the airway passages 33 2.3.2.1 In-vivo experimental studies of nasal particle deposition fraction 33 2.3.2.2 In vitro experimental studies on nasal particle deposition fraction 37 2.4 Numerical simulation 41 2.4.1 Overview ofsimulation ofparticles in turbulentflow 41 2.4.2 Modeling methodology 44 IV 2.4.3 Previous Simulations ofparticles in human respiratory tract 47 2.5 Geometry Related Limitations of Previous Work 50 CHAPTER 3: CONSTRUCTION OF REALISTIC MODELS OF THE HUMAN NASALCAVITY 52 3 . 1 Baseline Data Used to Create a Standardized Human Nasal Cavity Model 53 3.2 Generation and alignment of individual 3D nasal cavity models 55 3.2.1 Construction ofcoarse 3D modelsfrom CT scans 55 3.2.2 Rotational alignment ofcoarse 3D models 57 3.2.2.1 Specifying the landmark and choana from the raw CT scans 58 3.2.2.2 Rotating coarse nasal models 59 3.3 Creation of the standardized human nasal cavity model 62 3.3.1 Measuring characteristic length and scaling individual coarse models 62 3.3.2 Slicing and smoothing individual coarse models 64 3. 3. 3 Measurement ofcharacteristic dimensions ofindividual coarse 3D nasal cavity models ....68 3.3.4 Image processing methodologyfor generating median coronalplane images 70 3.3.5 Determine the shape ofnostril and outlet ofthe standardized nasal cavity 74 3.3.6 Construction ofthefinal Carleton-Civic standardized nasal model 75 3 .4 Analysis of the Carleton-Civic standardized nasal model 76 CHAPTER 4:METHODOLOGY OF EXPERIMENTAL MEASUREMENT OF PARTICLE DEPOSITION IN HUMAN NASAL CAVITY 82 4.1 Construction of physical nasal model 82 4.1.1 Rapidprototype technique 82 4.1.2 Creation ofphysical nasal model using RP machine 83 A2 Experimental apparatus and procedures 86 4.2.1 Aerosol generation 88 4.2.1.1 The aerosol generator 88 4.2.1.2 Aerosol generation principle 89 4.2.1.3 Operation of aerosol generation 90 4.2.1.4 The charge neutralizer 91 4.2.2 The particle size distribution analyzer 91 4.2.3 Otherparts oftheflow system 94 4.2.3.1 The vacuum pump 94 4.2.3.2 The mass flow meter 94 4.2.4 Particle deposition measurement 95 V 4.2.4.1 Wash procedure 95 4.2.4.2 The spectrophotometer 96 4.3 Uncertainty analysis 98 4.3.1 Bias Error 99 4.3.1.1 Inertial parameter 100 4.3.1.2 Total particle deposition fraction 102 4.3.2 Precision 104 4.3.3 Total uncertainty 105 CHAPTER 5:EXPERIMENTAL DEPOSITION RESULTS 107 5.1 Measured and simulated total particle deposition fraction 107 5.1.1 Measured totalparticle depositionfraction 107 5.1.1.1 Comparison with in-vivodata..... 108 5.1.1.2 Comparison with published in vitro data 110 5.1.2 Measured regionalparticle depositionfraction 113 CHAPTER 6:NUMERICAL SIMULATION METHODOLOGY 115 6.1 Theory 115 6.2 The motion of particles 115 6.2.1 Particle equation ofmotion 118 6.3 Simulation approach 122 6.3.1 RANS/E1Mapproach 122 6.3.1.1 Averaged Navier-Stokes Equations (RANS) 122 6.3.1.2 Eddy Interaction Model (EIM) 123 6.3.2 Large eddy simulation 127 6.4 Simulation domain and method 129 6.4.1 Generation ofmesh 129