Stable Small Animal Ventilation for Dynamic Lung Imaging to Support Computational Fluid Dynamics Models

Pulmonary computational fluid dynamics models require that three-dimensional images be acquired over multiple points in the dynamic breathing cycle without breath holds or changes in ventilatory mechanics. With small animals, these requirements can result in long imaging times (∼90 minutes), over which lung mechanics, such as compliance, may gradually change if not carefully monitored and controlled. These changes, caused by derecruitment of parenchymal tissue, are manifested as an upward drift in peak inspiratory pressure (PIP) or by changes in the pressure waveform and/or lung volume over the course of the experiment. We demonstrate highly repeatable mechanical ventilation in anesthetized rats over a long duration for dynamic lung x-ray computed tomography (CT) imaging. We describe significant updates to a basic commercial ventilator that was acquired for these experiments. Key to achieving consistent results was the implementation of periodic deep breaths, or sighs, of extended duration to maintain lung recruitment. In addition, continuous monitoring of breath-to-breath pressure and volume waveforms and long-term trends in PIP and flow provide diagnostics of changes in breathing mechanics

Comparison of particle deposition for realistic adult and adolescent upper airway geometries using unsteady computational fluid dynamics

Particle deposition in the respiratory tract is studied in order to better understand the negative health effects due to cigarette smoke inhalation. Until recently, idealized models of the respiratory airways based on the original Weibel model have been used to calculate deposition. These models consist of symmetric bifurcating airways and do not take into account variations of airway diameter, and asymmetry in the human respiratory tract. Until recently, little work has been done to accurately recreate the entire upper respiratory tract including the oral cavity, pharynx, and larynx. Technological improvement has changed the way in which researchers approach this problem. With the advent of high resolution scans of the respiratory tract, accurate replica models can be created to better predict cigarette smoke particle (CSP) deposition. These models recreate actual lung geometries found in patients. For this thesis, two realistic geometric models are created. One is based on an adult male and the other on an adolescent male. CSP deposition is determined for both models in order to compare the difference cased by age in smoking. In addition, an unsteady breathing curve, indicative of realistic smoking behavior is utilized to more accurately represent the breathing conditions. Both models consist of the oral cavity, throat, larynx, trachea, and first five to seven generations of the lungs. The adult model is based on a dental cast of the mouth, a CT scan of the throat and larynx, and images based on the National Institute of Health\u27s Visible Human Project for the tracheobronchial tree. The adolescent model is based upon a scaled oral cavity and CT scans of the rest of the reparatory tract. The program 3D Doctor is used to reconstruct the two dimensional CT scan images into a three dimensional model. VPSculpt and SolidWorks are used to combine the different parts of the models and clean up the geometry. The geometry is meshed in Gambit and exported to the Computational Fluid Dynamics (CFD) software package Fluent to perform the fluid flow and particle deposition analysis. The Fluent Discrete Phase Model (DPM) is used to determine particle trajectories and deposition. It is found that deposition increases with the size of the inhaled particles. Particles tend to deposit towards the back of the throat, the area of the trachea just below the glottis, and at bifurcations in the airways. However, when compared to other studies in literature, deposition tended to be higher with smaller particle sizes, but more comparable with larger particle sizes. Adolescent deposition was found to be lower than adult deposition for all particle sizes

Investigation of charged aerosol transport and deposition in human airway models

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Several theoretical and experimental studies of charged aerosol deposition in human airways have been reported. These studies suggest that higher charge values on particles lead to improve deposition efficiency in the human lung, especially in the alveolar region. Most of the previous numerical studies in realistic 3D geometrical models have been investigated only for uncharged particles. Hence, this research was aimed at numerically investigating aerosol transport and deposition by including the effect of electrostatic forces (both space and image charge forces). The numerical models that have been developed and presented in this thesis, treat the aerodynamics and electrodynamics as a coupled problem and successfully integrate both mechanisms. The physical model of the human lung used for this research consists of three sub-models: a 3D bifurcation airway model, a 3D reconstructed airway model representing the tracheobronchial region, and a 2D alveolar airway model representing the alveolar region. The airflow dynamics in these geometrical models were carried out using a Computational Fluid Dynamic software (CFD) with given boundary conditions related to corresponding breathing conditions. The space charge force was calculated using the Particle Mesh (PM) method, and the image charge force was computed using the mesh configuration. Both airflow dynamics and electrodynamics are integrated in the newly developed software, and the particle trajectories are then calculated. The numerical study of electrostatic forces is primarily focused on the submicron particle. The numerical study in the 3D tubular airway model gives a better understanding of parameters affecting the predicted deposition efficiency. The numerical study in the 3D tubular airway model focuses on the transport and deposition of particles near the branching regions between the parent and daughter tubes, where airflow profile is significantly altered, and secondary airflow also arises. Many charged particles are deposited near the carinae by the strong skewed axial velocity and image charge force. The space charge will influence the deposition efficiency if the number concentration of particles is high. Similarly, the charged particles in the 3D reconstructed airway model tends to have the deposition pattern near the branching regions, depending on the local airflow and charge value. In the 2D alveolar model, the image charge force can improve deposition efficiency. The outcome of this research clearly shows how the electrostatic forces play an important role in aerosol transport and deposition in human airways. The integrated numerical model provides a valuable tool for respiratory clinicians and the pharmaceutical industry to study the complex mechanism of drug aerosol deposition in human airways. Although this model is adequate for the intended purpose, it can be further improved by extending this work to develop a complete 3D model of entire human airways incorporating the full breathing cycle. Such a model would require extensive computing facilities, nevertheless it would be an enormous benefit to develop a better treatment for respiratory diseases.Financial support obtained from the Overseas Research Students Awards Scheme (ORS)and System Engineering department

MODELING OF FLOW AND PARTICLE DYNAMICS HUMAN RESPIRATORY SYSTEM USING FLUID DYNAMICS

The aim of this research is to study numerically the flow characteristics and particle transport within a human respiratory system, including the human nasal cavity and the bifurcation. Various flow rates and particle sizes are main parameters varied in order to analyze the effects on particle movements and deposition on the human respiratory system. There are three main systems considered in this research: flow around a blockage in a channel, flow in the Final particle deposition with Stokes number, St = 0.12 for inlet flow rates of: (a) 30 L/min; (b) 60 L/min in human nasal cavity, and flow in the double bifurcation. Computational Fluid Dynamics (CFD) is used to solve gas-particle flow equations using a commercial software, FLUENT. Flow around a blockage in a channel was performed to gain confidence in the CFD model that has recirculation zone behind the block. The unsteady vortices flow around this blockage is investigated for Reynolds numbers, Re = 150, 300, 600, 900, and 1200 and Stokes numbers, St = 0.01, 0.1, 0.5, 1.0 and 2.0 by solving momentum and particle model equations. A detailed airflow structures such as vortices, flow distribution are obtained. It was found that the particle distribution depends on vortical structures and Stokes number. A model of real human nasal cavity is reconstructed from computerized tomography (CT) scans. The flow structure is validated with experimental data for flowrates of 7.5 L/min (Re = 1500) and 15 L/min (Re = 3000). The total particle deposition in nasal cavity is also validated with experimental data using inertial parameter. Then the model is further investigated the effect of turbulence on particle deposition with flowrates of 20, 30 and 40 L/min. Deposition was found to increase with Stoke number for the same Reynolds number. vii Three-dimensional double bifurcations with coplanar configurations are employed to investigate the flow. Results of laminar flow (Re = 500, Re = 1036, and Re = 2000) are used to compare with experimental and numerical solution for validation. The model is further used to investigate the turbulent flow and particle deposition for heavy breathing with flowrates of 30 L/min (Re = 7300) and 60 L/min (Re = 14600). It was found that the deposition efficiency is dependent on Reynolds number and Stokes numbers. This research outcome will guide to improve the injection particle drugs to human lungs and to develop nasal mask to protect the lungs from hazardous particles

Simulation of fluid dynamics and particle transport in a realistic human nasal cavity

Airflow and particle transport through the nasal cavity was studied using Computational Fluid Dynamics (CFD). A computational model of the human nasal cavity was reconstructed through CT scans. The process involved defining the airway outline through points in space that had to be fitted with a closed surface. The airflow was first simulated and detailed airflow structures such as local vortices, wall shear stresses, pressure drop and flow distribution were obtained. In terms of heat transfer the differences in the width of the airway especially in the frontal regions was found to be critical as the temperature difference was greatest and therefore heating of the air is expedited when the air is surrounded by the hotter walls. Understanding the effects of the airway geometry on the airflow patterns allows better predictions of particle transport through the airway. Inhalation of foreign particles is filtered by the nasal cilia to some degree as a defence mechanism of the airway. Particles such as asbestos fibres, pollen and diesel fumes can be considered as toxic and lead to health problems. These particles were introduced and the effects of particle morphology were considered by customising the particle trajectory equation. This mainly included the effects of the drag correlation and its shape factor. Local particle deposition sites, detailed deposition efficiencies and particle trajectories were obtained. High inertial particles tended to be filtered within the anterior regions of the cavity due to a change in direction of the airway as the air flow changes from vertical at the inlet to horizontal within the main nasal passage. Inhaled particles with pharmacological agents are often deliberately introduced into the nasal airway with a target delivery. The mucous lined airway that is highly vascular provides an avenue for drug delivery into the blood stream. An initial nasal spray experiment was performed to determine the parameters that were important for nasal spray drug delivery. The important parameters were determined to be the spray angle, initial particle velocity and particle swirl. It was found that particles were formed at a break-up length at a cone diameter greater than the spray nozzle diameter. The swirl fraction determined how much of the velocity magnitude went into a tangential component. By combining a swirling component along with a narrow spray into the main streamlines, greater penetration of larger particles into the nasal cavity may be possible. These parameters were then used as the boundary conditions for a parametric study into sprayed particle drug delivery within the CFD domain. The results were aimed to assist in the design of more efficient nasal sprays

Numerical Modelling of Transport in Complex Porous Media: Metal Foams to the Human Lung

Transport in porous media has many practical applications in science and engineering. This work focuses on the development of numerical methods for analyzing porous media flows and uses two major applications, metal foams and the human lung, to demonstrate the capabilities of the methods. Both of these systems involve complex pore geometries and typically involve porous domains of complex shape. Such geometric complexities make the characterization of the relevant effective properties of the porous medium as well as the solution of the governing equations in conjugate fluid-porous domains challenging. In porous domains, there are typically too many individual pores to consider transport processes directly; instead the governing equations are volume-averaged to obtain a new sets of governing equations describing the conservation laws in a bulk sense. There are, however, unknown pore-level terms remaining in the volume-averaged equations that must be characterized using effective properties that account for the effects of processes at the pore level. Once closed, the volume-averaged equations can be solved numerically, however currently available numerical methods for conjugate domains do not perform well at fluid-porous interfaces when using unstructured grids. In light of the preceding discussion, the goals of this work are: (i) to develop a finite-volume-based numerical method for solving fluid flow and non-equilibrium heat transfer problems in conjugate fluid-porous domains that is compatible with general unstructured grids, (ii) to characterize the relevant flow and thermal properties of an idealized graphite foam, (iii) to determine the permeability of an alveolated duct, which is considered as a representative element of the respiratory region of the human lung, and (iv) to conduct simulations of airflow in the human lung using a novel fluid-porous description of the domain. Results show that the numerical method that has been developed for conjugate fluid-porous systems is able to maintain accuracy on all grid types, flow directions, and flow speeds considered. This work also introduces a comprehensive set of correlations for the effective properties of graphite foam, which will be useful for studying the performance of devices incorporating this new material. In order to model air flow in the lung as a porous medium, the permeability of an alveolated duct is obtained using direct pore-level simulations. Finally, simulations of air flow in the lung are presented which use a novel fluid-porous approach wherein the upper airways are considered as a pure fluid region and the smaller airways and alveoli are considered as a porous domain

Investigation of charged aerosol transport and deposition in human airway models

Several theoretical and experimental studies of charged aerosol deposition in human airways have been reported. These studies suggest that higher charge values on particles lead to improve deposition efficiency in the human lung, especially in the alveolar region. Most of the previous numerical studies in realistic 3D geometrical models have been investigated only for uncharged particles. Hence, this research was aimed at numerically investigating aerosol transport and deposition by including the effect of electrostatic forces (both space and image charge forces). The numerical models that have been developed and presented in this thesis, treat the aerodynamics and electrodynamics as a coupled problem and successfully integrate both mechanisms. The physical model of the human lung used for this research consists of three sub-models: a 3D bifurcation airway model, a 3D reconstructed airway model representing the tracheobronchial region, and a 2D alveolar airway model representing the alveolar region. The airflow dynamics in these geometrical models were carried out using a Computational Fluid Dynamic software (CFD) with given boundary conditions related to corresponding breathing conditions. The space charge force was calculated using the Particle Mesh (PM) method, and the image charge force was computed using the mesh configuration. Both airflow dynamics and electrodynamics are integrated in the newly developed software, and the particle trajectories are then calculated. The numerical study of electrostatic forces is primarily focused on the submicron particle. The numerical study in the 3D tubular airway model gives a better understanding of parameters affecting the predicted deposition efficiency. The numerical study in the 3D tubular airway model focuses on the transport and deposition of particles near the branching regions between the parent and daughter tubes, where airflow profile is significantly altered, and secondary airflow also arises. Many charged particles are deposited near the carinae by the strong skewed axial velocity and image charge force. The space charge will influence the deposition efficiency if the number concentration of particles is high. Similarly, the charged particles in the 3D reconstructed airway model tends to have the deposition pattern near the branching regions, depending on the local airflow and charge value. In the 2D alveolar model, the image charge force can improve deposition efficiency. The outcome of this research clearly shows how the electrostatic forces play an important role in aerosol transport and deposition in human airways. The integrated numerical model provides a valuable tool for respiratory clinicians and the pharmaceutical industry to study the complex mechanism of drug aerosol deposition in human airways. Although this model is adequate for the intended purpose, it can be further improved by extending this work to develop a complete 3D model of entire human airways incorporating the full breathing cycle. Such a model would require extensive computing facilities, nevertheless it would be an enormous benefit to develop a better treatment for respiratory diseases.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

MODELING OF FLOW AND PARTICLE DYNAMICS HUMAN RESPIRATORY SYSTEM USING FLUID DYNAMICS

The aim of this research is to study numerically the flow characteristics and particle transport within a human respiratory system, including the human nasal cavity and the bifurcation. Various flow rates and particle sizes are main parameters varied in order to analyze the effects on particle movements and deposition on the human respiratory system. There are three main systems considered in this research: flow around a blockage in a channel, flow in the Final particle deposition with Stokes number, St = 0.12 for inlet flow rates of: (a) 30 L/min; (b) 60 L/min in human nasal cavity, and flow in the double bifurcation. Computational Fluid Dynamics (CFD) is used to solve gas-particle flow equations using a commercial software, FLUENT. Flow around a blockage in a channel was performed to gain confidence in the CFD model that has recirculation zone behind the block. The unsteady vortices flow around this blockage is investigated for Reynolds numbers, Re = 150, 300, 600, 900, and 1200 and Stokes numbers, St = 0.01, 0.1, 0.5, 1.0 and 2.0 by solving momentum and particle model equations. A detailed airflow structures such as vortices, flow distribution are obtained. It was found that the particle distribution depends on vortical structures and Stokes number. A model of real human nasal cavity is reconstructed from computerized tomography (CT) scans. The flow structure is validated with experimental data for flowrates of 7.5 L/min (Re = 1500) and 15 L/min (Re = 3000). The total particle deposition in nasal cavity is also validated with experimental data using inertial parameter. Then the model is further investigated the effect of turbulence on particle deposition with flowrates of 20, 30 and 40 L/min. Deposition was found to increase with Stoke number for the same Reynolds number. vii Three-dimensional double bifurcations with coplanar configurations are employed to investigate the flow. Results of laminar flow (Re = 500, Re = 1036, and Re = 2000) are used to compare with experimental and numerical solution for validation. The model is further used to investigate the turbulent flow and particle deposition for heavy breathing with flowrates of 30 L/min (Re = 7300) and 60 L/min (Re = 14600). It was found that the deposition efficiency is dependent on Reynolds number and Stokes numbers. This research outcome will guide to improve the injection particle drugs to human lungs and to develop nasal mask to protect the lungs from hazardous particles

CFD Study of the Flow Field and Particle Dispersion and Deposition in the Upper Human Respiratory System

Das Einatmen von Partikeln in den menschlichen Körper hat zwei verschiedene Aspekte im Hinblick auf die Gesundheit des Menschen. Einerseits existieren schädliche Partikel wie beispielsweise Feinstaub in der Umwelt, der nach Eintreten in den menschlichen Körper Krankheiten wie Herzerkrankungen und Erkrankungen der Atemwege auslösen kann, und der sogar zum Tod führen kann. Hier sind insbesondere Partikel, die kleiner als 2,5 µm sind, relevant. Andererseits ist es in der medizinischen Therapie einiger Atemwegerkrankungen wünschenswert, gezielt Partikel den Atemwegen zuzuführen. Die medikamentöse Aerosol-Therapie, bei der das Medikament durch den nasalen oder oralen Atemweg in die Lunge oder einen anderen Ort des Atemtrakts gebracht wird, wird gern verwendet, um Krankheiten wie z.B. Asthma oder chronisch obstruktive Lungenerkrankungen zu behandeln. Diese Therapie hat den Vorteil der kleinen Dosierung, der minimalen systemischen Nebenwirkungen und der schnellen Wirkung. Das Medikament soll hier tief in die Lunge, in der die Krankheit auftritt, eindringen. Die typische Größe dieser Partikel liegt im Bereich von 1 bis 5 µm. Fokus ist die gezielte Steuerung des Medikaments in spezielle Regionen wie beispielsweise zu einer Tumorposition, sodass Nebenwirkungen durch Ablagerung in anderen Regionen vermieden werden. Ein verbessertes Verständnis des Gesamtprozesses beinhaltet die Kenntnis der charakteristischen Luftströmung und des Partikeltransports sowie deren gegenseitige Beeinflussung. In der vorliegenden Arbeit, in der die Luftströmung sowie die Partikelverteilung und -ablagerung in den menschlichen oberen Atemwegen untersucht werden, werden vier verschiedene Geometrien verwendet: die verengte Luftröhre, das auf einem Gussstück basierende Mund-Rachen-Modell, das auf Computertomographie (CT) basierende Mund-Rachen-Modell und das auf CT-Skans basierende Nasenhöhlen-Modell. Die Software NeuRa2 wird zur Generierung des numerischen Oberflächengitters verwendet und ANSYS ICEM CFD-11.0, um Volumengitter zu erzeugen. Ein-Weg- und Zwei-Wege-Kopplung zwischen der Gasphase und den Partikeln werden in der Arbeit in Abhängigkeit verschiedener Partikelvolumenanteile angewendet. Dreidimensionale inkompressible Navier-Stokes (N-S) Gleichungen werden zur Beschreibung der Luftströmung verwendet. Large Eddy Simulation (LES) wird zur Modellierung der turbulenten Strömung herangezogen, und das Smagorinsky Feinskalen-Modell sowie das dynamische Smagorinsky Modell dienen der Beschreibung der kleinen turbulenten Skalen. Unter der Annahme eines großen Partikel-Luft Dichteverhältnisses, der Vernachlässigbarkeit der Partikelrotation und der Kollision zwischen den Partikeln sowie der Annahme, dass die Trägheitskraft die Partikelbewegung dominiert, werde Lagrange-Gleichungen herangezogen, um die Bewegung der Partikel zu modellieren. Im Falle von Partikeln, die kleiner als ein Mikrometer sind, wird die Brownsche Kraft zusätzlich berücksichtigt. Zur Lösung der Gleichungen wird die Software-Plattform OpenFOAM 1.5 benutzt, für die neue Solver entwickelt werden, die die Luftströmung mit LES und die Teilchenbewegung mit Hilfe einer Lagrange-Formulierung lösen können. Abhängig von der Partikelbeladung wird Ein-Weg- oder Zwei-Wege-Kopplung mit oder ohne Berücksichtigung des Einflusses des Partikelimpulses auf die Gasphase verwendet. Zunächst wird die Luftgeschwindigkeit an der Mittellinie und in unterschiedlichen Querschnitten stromabwärts der Glottis in der verengten Luftröhre mit numerischen Ergebnissen und experimentellen Daten aus der Literatur verglichen, hier wird ein Modell der Reynolds-gemittelten Navier-Stokes-Gleichungen (RANS) bei niedriger Reynolds-Zahl, das k-omega; Modell, verwendet. Die hier verwendete Methode verbessert die vorliegenden Literaturergebnisse, sodass sie die Basis für weitere Berechnungen in den verbleibenden Geometrien bildet. Die Luftströmung wird im Gussstück-basierten Mund-Rachen-Modell für drei verschiedene Inhalationsgeschwindigkeiten simuliert. Die numerischen Ergebnisse zeigen, dass das Geschwindigkeitsfeld der instationären Luftströmung sehr stark vom mittleren Geschwindigkeitsfeld abweicht, dies gilt insbesondere für das Auftreten von Wirbeln. Die numerische Simulation zeigt, dass die Partikelablagerung von der Partikelgröße, ihrer Ausgangsposition, der Inhalationsgeschwindigkeit sowie von der Geometrie abhängt. Turbulenz und Existenz von Rezirkulationszonen haben ebenfalls großen Einfluss auf den Partikeltransport. Eine polydisperse Partikelverteilung, die aus Messungen an einem Trockenpulver-Inhalator zur Verfügung steht, wird ebenfalls zur Simulation herangezogen. In diesem Fall wird Zwei-Wege-Kopplung verwendet. Polydisperse Partikelablagerung zeigt im Vergleich zur monodispersen Partikelablagerung stark unterschiedliche Charakteristika. Deshalb ist es notwendig, polydisperse Partikelverteilung und Zwei-Wege-Kopplung zu verwenden, wenn die reale medikamentöse Dosis eines Hubs berücksichtigt wird, die bei der klinischen Behandlung Anwendung findet. Um das Strömungsfeld bei einer realistischeren zeitabhängigen Inhalation zu untersuchen, wird eine numerische Simulation für das Gussstück-basierte Mund-Rachen-Modell unter den gleichen Bedingungen durchgeführt. Die Untersuchung zeigt, dass das Strömungsfeld signifikant verschieden ist in der beschleunigenden und der verlangsamenden Phase der Inhalation: In der Beschleunigungsphase ist die Luftströmung laminar während sie in der verlangsamenden Phase eher turbulent ist. Zur Untersuchung des Einflusses geometrischer Eigenschaften auf die Partikelablagerung werden numerische Simulationen für das CT-basierte Mund-Rachen-Modell durchgeführt. Im Ergebnis ist das Strömungsfeld im CT-basierten Mund-Rachen-Modell sehr verschieden von dem im Gussstück-basierten Mund-Rachen-Modell. Obwohl das Geschwindigkeitsfeld sowohl im mittleren als auch im zeitabhängigen Fall ähnlich ist, hat das Strömungsfeld ein sehr kompliziertes Wirbelfeld mit hoher räumlicher und zeitlicher Dynamik. Partikel der Größe 2 µm können den Pharynx passieren, sich in der Luftröhre ablagern oder weiter in die Lungenregion vordringen. Um die Eigenschaften des Geschwindigkeitsfelds in der Nasenhöhle zu untersuchen, wurde ein geometrisches Modell der Nasenhöhle aus CT-Skans konstruiert. Die numerischen Ergebnisse zeigen, dass die Luft durch die Hauptluft-Passage der Nasenhöhle fließt und nur wenig Luft die Spitzen der Nasengänge und der olfaktorischen Region erreicht