Helium-Oxygen Mixture Model for Particle Transport in CT-Based Upper Airways.

The knowledge of respiratory particle transport in the extra-thoracic pathways is essential for the estimation of lung health-risk and optimization of targeted drug delivery. The published literature reports that a significant fraction of the inhaled aerosol particles are deposited in the upper airways, and available inhalers can deliver only a small amount of drug particles to the deeper airways. To improve the targeted drug delivery efficiency to the lungs, it is important to reduce the drug particle deposition in the upper airways. This study aims to minimize the unwanted aerosol particle deposition in the upper airways by employing a gas mixture model for the aerosol particle transport within the upper airways. A helium-oxygen (heliox) mixture (80% helium and 20% oxygen) model is developed for the airflow and particle transport as the heliox mixture is less dense than air. The mouth-throat and upper airway geometry are extracted from CT-scan images. Finite volume based ANSYS Fluent (19.2) solver is used to simulate the airflow and particle transport in the upper airways. Tecplot software and MATLAB code are employed for the airflow and particle post-processing. The simulation results show that turbulence intensity for heliox breathing is lower than in the case of air-breathing. The less turbulent heliox breathing eventually reduces the deposition efficiency (DE) at the upper airways than the air-breathing. The present study, along with additional patient-specific investigation, could improve the understanding of particle transport in upper airways, which may also increase the efficiency of aerosol drug delivery

Fluid-structure interaction in lower airways of CT-based lung geometries

In this study, the deformability of airway walls is taken into account to study airflow patterns and airway wall stresses in the first generations of lower airways in a real lung geometry. The lung geometry is based on CT-scans that are obtained from in-vivo experiments on humans. A partitioned fluid-structure interaction (FSI) approach, realized within a parallel in-house finite element code, is employed. It is designed for the robust and eficient simulation of the interaction of transient incompressible Newtonian flows and (geometrically) nonlinear airway wall behavior. Arbitrary Lagrangian Eulerian (ALE)-based stabilized tetrahedral finite elements are used for the fluid and Lagrangian-based 7-parametric mixed/hybrid shell elements are used for the airway walls using unstructured meshes due to the complexity of the geometry. Air flow patterns as well as airway wall stresses in the bronchial tree are studied for a number of different scenarios. Thereby, both models for healthy and diseased lungs are taken into account and both normal breathing and mechanical ventilation scenarios are studied

Numerical modelling of airflow dynamics and particle deposition in human lungs

Research into airflow dynamics and particle transport in human lungs is receiving considerable attention from many researchers because of its significance for human health. Drug delivery through inhalation of air into the human lung is important to prevent/cure respiratory diseases. Many researchers have investigated the process of particle transport and deposition (TD) in the respiratory airway through analytical as well as numerical methods, during the last century. Nowadays, numerical methods are used to model various biomechanical engineering problems, including particle flow in the respiratory system. The greatest challenge in numerical modelling of particle TD is the complexity of human lungs. This thesis mainly focuses on developing numerical models and investigating the effectiveness of aerosol particle inhalation as drug delivery. Particle inhalation and deposition in human lungs is affected by the lung anatomy, breathing pattern and particle properties (Rissler et al. 2017). Therefore, airflow dynamics and inhaled aerosol particle transport in the lung airways are significant for human health; thus it is important to measure both the efficiency of inhaled drug therapy and the health implications of air pollution (Deng et al. 2018). Further, the lung airways become larger as people grow into adults, and the shape of the airway structure and breathing habits change. Therefore, aging is an important factor in respiratory health. Hence, a comprehensive age-specified particle TD study is necessary to better predict drug delivery to the targeted position in a human lung. This study aims to develop an advanced and efficient three-dimensional (3D) numerical model to analyse airflow characteristics and aerosol particle TD in human lungs. The model is used to analyse the contribution of fundamental impaction and diffusion mechanisms for nanoand microscale particle TD in age-specific terminal bronchiole airways. The outcomes of this study will help improve the effectiveness of delivery of drug aerosols into human lungs to treat obstructive lung diseases including asthma, lung cancer and COPD. In addition, the inhalation of different types of pollutant particles into human lungs is investigated further to understand the consequence of the pollution particle on lung health

Pulmonary fluid dynamics and aerosol drug delivery in the upper tracheobronchial airways under mechanical ventilation conditions

The effects of mechanical ventilation conditions on fluid flow and particle deposition were studied in a computer model of the human airways. The frequency with which aerosolized drugs are delivered to mechanically ventilated patients demonstrates the importance of understanding the effects that ventilation parameters have on particle deposition in the human airways. Past studies that modeled particle deposition in silico frequently used an idealized geometry with steady inlet conditions. With recent advancements in computational power and medical imaging capabilities, studies have begun to use more realistic geometries or unsteady inlet conditions that model normal breathing. This study focuses specifically on the effects of mechanical ventilation waveforms using a computer model of the airways from the endotracheal tube to generation 07, in the lungs of a patient undergoing mechanical ventilation treatment. Computational fluid dynamics (CFD), using the commercial software package ANSYS® CFX®, combined with realistic respiratory waveforms commonly used by commercial mechanical ventilators, large eddy simulation (LES) to model turbulence, and user defined particle force models were applied to solve for fluid flow and particle deposition parameters. The endotracheal tube (ETT) was found to be an important geometric feature, causing a fluid jet towards the right main bronchus, increased turbulence, and a recirculation zone in the right main bronchus. In addition to the enhanced deposition seen at the carinas of the airway bifurcations, enhanced deposition was also seen in the right main bronchus due to impaction and turbulent dispersion resulting from the fluid structures created by the ETT. The dependence of local particle deposition on respiratory waveforms implies that great care should be taken when selecting ventilation parameters --Abstract, page iii

CFD simulation of the airflow through the human respiratory tract

This study compares the effect of extra-thoracic airways (ETA) on the flow field through the lower airways by carrying out simulations of the airflow through the human respiratory tract. Three geometries, consisting of the ETA, CT-derived lower airway, and a combination of the two were utilized in simulations that were performed for transient breathing in addition to constant inspiration/expiration. Physiologically-appropriate regional ventilation for two different flow rates was induced at the distal boundaries by imposing appropriate lobar specific flow rates. Two breathing rates were considered, i.e., 7.5 and 15 breaths per minute with a tidal volume of 0.5 liter. For comparison, the flow rates for constant inspiration/expiration were selected to be identical to the peak flow rates during the transient breathing. Significant differences indicate that simulations that utilize constant inspiration or expiration may not be appropriate for gaining insight into the flow patterns through the human airways

In silico assessment of mouth-throat effects on regional deposition in the upper tracheobronchial airways

Regional deposition of inhaled medicines is a valuable metric of effectiveness in drug delivery applications to the lung. In silico methods are now emerging as a valuable tool for the detailed description of localized deposition in the respiratory airways. In this context, there is a need to minimize the computational cost of high-fidelity numerical approaches. Motivated by this need, the present study is designed to assess the role of the extrathoracic airways in determining regional deposition in the upper bronchial airways. Three mouth-throat geometries, with significantly different geometric and filtering characteristics, are merged onto the same tracheobronchial tree that extends to generation 8, and Large Eddy Simulations are carried out at steady inhalation flowrates of 30 and View the MathML source. At both flowrates, large flow field differences in the extrathoracic airways across the three geometries largely die out below the main bifurcation. Importantly, localized deposition fractions are found to remain practically identical for particles with aerodynamic diameters of up to View the MathML source and View the MathML source at 30 and View the MathML source, respectively. For larger particles, differences in the localized deposition fractions are shown to be mainly due to variations in the mouth-throat filtering rather than upstream flow effects or differences in the local flow field. Deposition efficiencies in the individual airway segments exhibit strong correlations across the three geometries, for all particle sizes. The results suggest that accurate predictions of regional deposition in the tracheobronchial airways can therefore be obtained if the particle size distribution that escapes filtering in the mouth-throat (ex-cast dose) of a particular patient is known or can be estimated. These findings open the prospect for significant reductions in the computational expense, especially in the context of in silico population studies, where the aerosol size distribution and precomputed flow field from standardized mouth-throat models could be used with large numbers of tracheobronchial trees available in chest-CT databases

Pulmonary Gas Transport and Drug Delivery in a Patient Specific Lung Model During Invasive High Frequency Oscillatory Ventilation

The objective of this dissertation research was to investigate gas transport, mixing and aerosol-drug delivery during high frequency oscillatory ventilation (HFOV) for various ventilator specific conditions that are vital to critical care clinicians. A large eddy simulation based computational fluid dynamics approach was used in a patient specific human lung model to analyze the effect of invasive HFOV on patient management. Different HFOV waveform shapes and frequencies was investigated and the square waveform was found to be most efficient for gas mixing; resulting in the least wall shear stress on the lung epithelium layer thereby reducing the risk of barotrauma to both airways and the alveoli for patients undergoing therapy. Traditional (outlet) boundary conditions based on mass fraction or outlet pressures were found to be inadequate in describing the complex flow physics that occurs during HFOV. Physiological boundary conditions that used the time-dependent pressure coupled with the airways resistance and compliance (R&C) were derived and used for the first time to investigate the lung lobar ventilation and gas exchange for accurate HFOV modeling. A Lagrangian approach was then used to model gas-solid two-phase flow that allowed investigation of the potential of aerosol-drug delivery under HFOV treatment. We report, for the first time, computational fluid dynamics studies to investigate the possibilities of aerosol drug delivery under HFOV. Understanding the role of different carrier gases on the gas exchange and particle deposition, which may allow for optimum drug delivery and ventilation strategy during HFOV. Increasing the operating frequency resulted in a significant change in the global and local deposition indicating strong dependency on the frequency, which could be beneficial for the targeted drug delivery. The global deposition as a fraction of the total injected particles at the endotracheal tube inlet was equivalent to the cases of normal breathing and conventional mechanical ventilation signifying a potential for efficient drug delivery during HFOV. In addition, HFOV had a unique characterization of the local particle deposition due to the rapid ventilation process and a strong influence of the endotracheal tube jet. Very often during ventilation therapy, a clinician uses a cocktail of various gases to enhance targeted therapy. To quantify this process for a futuristic HFOV based patient management, we undertook detailed studies to understand the role of carrier gas properties in gas exchange and particle transport during HFOV. A substantial amplification of the pendelluft flow was achieved by utilizing a low-density carrier gas instead of air, which resulted in gas exchange improvement. Reducing the carrier gas density was found to significantly alter the aerosol-drug delivery under HFOV management. As the density decreased, the deposition fraction in the upper tracheobronchial tree decreased, indicating enhancement of the lung periphery delivery. Furthermore, the filtered aerosol-drug in the ventilator circuit could be significantly reduced by using Heliox, and further reduction could be achieved by reducing the operating frequency. In general, high-frequency oscillatory ventilation therapy could be improved under Heliox with greater content of Helium, thereby reducing the lung hyperinflation risk

Flow characterization inside airways with unsteady breathing patterns

Flow through human airways is characterized by unsteady flows, with flow separations at airway bifurcations. The oscillatory nature of airflow, unequal durations of inhalation time (IT), and exhalation time (ET) can facilitate gas exchange in higher generations of the human airway. Normal respiratory rate (RR) in adults ranges between 10-15 breaths per minute (bpm). RR varies in exercise conditions, mechanical ventilation strategies such as high-frequency oscillatory ventilation (HFOV), metabolic activities and pathological state to facilitate alveolar gas exchange. Previous studies characterized flows at steady inhalation and exhalation through airways. The individual effects of varying inhalation duration and breathing flow rate on flow through airways remains unknown. Our study focuses on various unsteady breathing patterns inside idealized airway models. The goal of this study is to characterize the effects of unsteady internal airflow through idealized airway geometries. Various scenarios of unsteady breathing patterns were simulated in ANSYS software (ANSYS, Inc., Canonsburg, PA, USA) to characterize the fluid dynamics involved in such an unsteady airflow mechanism. The first study includes unsteady breathing patterns such as normal, moderate, and high-frequency ventilation were investigated with variation in inhalation time (IT) to breathing time (BT) ratio. The second study includes abnormal breathing patterns such as tachypnea (~ 1.5x increase in RR), bradypnea (~ 1.5x decrease in RR), hyperpnea (deep breathing with abnormally large peak flow rate), and hypopnea (shallow breathing with abnormally low peak flow rate); and final study includes single nostril inhalation as in yoga pranayama breathing techniques. Simulations were performed for each breathing pattern as in internal airflow studies. Our results showed that secondary flow was an effective transport mechanism for flow inside idealized human airways. Airway local geometry plays a key role in flow distribution in higher generations. Discrepancy in the oscillatory flow relation Re/Wo^2 = 2L/D (L = stroke length; D = trachea diameter) was observed for IT/BT does not equal 50%, as L changed with IT/BT. We developed a modified dimensionless stroke length term including IT/BT. While viscous forces and convective acceleration were dominant for lower Wo, unsteady acceleration was dominant for higher Wo. Time to peak jet length during inhalation increased with an increase in breathing time. Single nostril and double nostril inhalation showed equal ventilation at higher generations in an idealized airway geometry