Structural and functional alterations of the tracheobronchial tree after left upper pulmonary lobectomy for lung cancer

© 2019 The Author(s). Background: Pulmonary lobectomy has been a well-established curative treatment method for localized lung cancer. After left upper pulmonary lobectomy, the upward displacement of remaining lower lobe causes the distortion or kink of bronchus, which is associated with intractable cough and breathless. However, the quantitative study on structural and functional alterations of the tracheobronchial tree after lobectomy has not been reported. We sought to investigate these alterations using CT imaging analysis and computational fluid dynamics (CFD) method. Methods: Both preoperative and postoperative CT images of 18 patients who underwent left upper pulmonary lobectomy are collected. After the tracheobronchial tree models are extracted, the angles between trachea and bronchi, the surface area and volume of the tree, and the cross-sectional area of left lower lobar bronchus are investigated. CFD method is further used to describe the airflow characteristics by the wall pressure, airflow velocity, lobar flow rate, etc. Results: It is found that the angle between the trachea and the right main bronchus increases after operation, but the angle with the left main bronchus decreases. No significant alteration is observed for the surface area or volume of the tree between pre-operation and post-operation. After left upper pulmonary lobectomy, the cross-sectional area of left lower lobar bronchus is reduced for most of the patients (15/18) by 15-75%, especially for 4 patients by more than 50%. The wall pressure, airflow velocity and pressure drop significantly increase after the operation. The flow rate to the right lung increases significantly by 2-30% (but there is no significant difference between each lobe), and the flow rate to the left lung drops accordingly. Many vortices are found in various places with severe distortions. Conclusions: The favorable and unfavorable adaptive alterations of tracheobronchial tree will occur after left upper pulmonary lobectomy, and these alterations can be clarified through CT imaging and CFD analysis. The severe distortions at left lower lobar bronchus might exacerbate postoperative shortness of breath

Effect of upper airway on tracheobronchial fluid dynamics

The upper airways play a significant role in the tracheal flow dynamics. Despite many previous studies, however, the effect of the upper airways on the ventilation distribution in distal airways has remained a challenge. The aim of this study is to experimentally and computationally investigate the dynamic behaviour in the intratracheal flow induced by the upper respiratory tract and to assess its influence on the subsequent tributaries. Patient-specific images from 2 different modalities (magnetic resonance imaging of the upper airways and computed tomography of the lower airways) were segmented and combined. An experimental phantom of patient-specific airways (including the oral cavity, larynx, trachea, down to generations 6-8) was generated using 3D printing. The flow velocities in this phantom model were measured by the flow-sensitised phase contrast magnetic resonance imaging technique and compared with the computational fluid dynamics simulations. Both experimental and computational results show a good agreement in the time-averaged velocity fields as well as fluctuating velocity. The flows in the proximal trachea were complex and unsteady under both lower- and higher-flow rate conditions. Computational fluid dynamics simulations were also performed with an airways model without the upper airways. Although the flow near the carina remained unstable only when the inflow rate was high, the influence of the upper airways caused notable changes in distal flow distributions when the 2 airways models were compared with and without the upper airways. The results suggest that the influence of the upper airways should be included in the respiratory flow assessment as the upper airways extensively affect the flows in distal airways and consequent ventilation distribution in the lungs

Simulation of fluid dynamics and particle transport in realistic human airways

The aim of this research is to numerically study the flow characteristics and particle transport within human airways, specifically, the upper airways starting from the trachea to major bronchi. Different entering flow rates and frequencies are the major parameters varied in order to analyze the effect on particle deposition. There have been numerous flow-particle studies in human airways at the current level of knowledge, but one major contribution from this research is that realistic geometries of human airways are used to study flow-particle interaction, in which the airway models are reconstructed from computerized tomography (CT) data of real human tracheobronchial airways. CFD techniques for this particular study are developed based on the literature review of other similar studies. The k-omega turbulence model was found to be suitable for this type of study. Evaluation and validation of the numerical approach and results were carried out by comparing with other experimental studies in terms of geometrical details, lobar flow distribution in percentage of the tracheal flow, velocity profile, and deposition efficiency. This approach was found to be appropriate. Based on the developed techniques, two aerosol delivery methods used clinically were studied. Similarly, results were compared with experimental and theoretical results for validation. It was found that slower breathing gives better transportation into the lung periphery and faster breathing gives higher deposition rate in the first few generations of the tracheobronchial airways. Visualization techniques were also developed where deposition pattern provided easy-to-understand illustration to personnel with no engineerin g background. It showed that particles often concentrate along the carinal ridges at the bifurcations and inner walls leading down from carinal ridges. The study of the interaction between flow and particle described how skewed velocity profile and vortices in secondary velocity profile affected regional deposition efficiency as well as deposition pattern. The study also confirmed that right main bronchi usually capture more particles than left side as other researchers observed. Several important findings are summarized based on this research: • Stokes number although is a good indicator in providing regional deposition efficiency information, the local "hot-spots" still heavily rely on visualization of deposition pattern. • Generally speaking, high flow rate and/or large particle size lead to high deposition efficiency in the first bifurcation and cartilaginous rings along the trachea. • Bronchi in the right hand side usually capture more particles than bronchi in the left hand side. • Particles often concentrate along the carinal ridges at the bifurcations and inner walls leading down from carinal ridges. • In the aerosol delivery study, short inhalation and exhalation with small air volume gives lower deposition in the first six generations than long inhalation with large air volume. Therefore, if deposition into deeper locations of the lung is preferred, then slower breathing is required. On the contrary, if the treatment location is in the first few generations, then faster or moderate breathing is more ideal. • Deposition efficiency and deposition pattern can be estimated roughly from the velocity profile along the airway

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

Acute asthma and recovered airway tree geometry modeling and CFD simulation

This study focuses primarily on the development of modeling approaches for the reconstruction of lung airway tree and arterial vessel geometry models which will assist practical clinical studies. Anatomically-precise geometric models of human airways and arterial vessels play a critical role in the analysis of air and blood flows in human bodies. The generic geometric modeling methods become invalid when the model consists of both trachea and bronchioles or very small vessels. This thesis presents a new region-based method to reconstruct the entire airway tree and carotid vessels from point clouds obtained from CT or MR images. A novel layer-by-layer searching algorithm has been developed to recognize the branches of the airway tree and arterial vessels from the entire point clouds. Instead of applying a uniform accuracy on all branches regardless of the number of available points, the surface patches on each branch are constructed adaptively based on the number of available elemental points, which leads to the elimination of distortions occurring at small bronchi and vessels. Acute asthma is a serious disease of the respiratory system. To understand the difference in geometry and airflow patterns between acute asthma affected and recovered airway trees, a comparison study has been conducted in this research. Two computational models of the airway tree up to six generations deep were reconstructed from computed tomography (CT) scans from a single patient. The first scan was taken one day after an acute asthma episode and the second scan was taken thirty days later when the patient had recovered. The reconstructed models were used to investigate the effects of acute asthma on realistic airway geometry, airflow patterns, pressure drops, and the implications for targeted drug delivery. Comparisons in the geometry found that in general the right side of the airway is larger in diameter than the left side. The recovery of the airway was most significant in the severely asthma affected regions. Additionally the right airway branches exhibited greater dilation after recovery in comparison with the left airway especially from the fifth generation onwards. It was also found that bifurcation angles do not vary significantly between the two models, however small changes were observed which may be caused by the physical scans of the patient being taken at different times. The inhalation effort to overcome airway resistance in the asthma affected model was twice as high as that for the recovered model. Local flow patterns showed that the changes in the airway had significant influence on flow patterns. This was especially true in the region where the airway narrowing was most severe

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

Regional aerosol deposition in the human airways: the SimInhale benchmark case and a critical assessment of in silico methods

Regional deposition effects are important in the pulmonary delivery of drugs intended for the topical treatment of respiratory ailments. They also play a critical role in the systemic delivery of drugs with limited lung bioavailability. In recent years, significant improvements in the quality of pulmonary imaging have taken place, however the resolution of current imaging modalities remains inadequate for quantifying regional deposition. Computational Fluid-Particle Dynamics (CFPD) can fill this gap by providing detailed information about regional deposition in the extrathoracic and conducting airways. It is therefore not surprising that the last 15 years have seen an exponential growth in the application of CFPD methods in this area. Survey of the recent literature however, reveals a wide variability in the range of modelling approaches used and in the assumptions made about important physical processes taking place during aerosol inhalation. The purpose of this work is to provide a concise critical review of the computational approaches used to date, and to present a benchmark case for validation of future studies in the upper airways. In the spirit of providing the wider community with a reference for quality assurance of CFPD studies, in vitro deposition measurements have been conducted in a human-based model of the upper airways, and several groups within MP1404 SimInhale have computed the same case using a variety of simulation and discretization approaches. Here, we report the results of this collaborative effort and provide a critical discussion of the performance of the various simulation methods. The benchmark case, in vitro deposition data and in silico results will be published online and made available to the wider community. Particle image velocimetry measurements of the flow, as well as additional numerical results from the community, will be appended to the online database as they become available in the future

Numerical studies of fluid-particle dynamics in human respiratory system

 This thesis investigates particle inhalation and its deposition in the human respiratory system for therapeutic and toxicology studies. Computational Fluid Dynamics (CFD) techniques including the Lagrangian approach to simulate gas-particle flows based on the domain airflow are used. The Lagrangian approach is used as it tracks each individual particle and determines its fate (e.g deposition location, or escape from computational domain). This has advantages over a Eulerian approach for respiratory inhalation flows as the volume fraction of the second phase can be neglected and a disperse phase for one-way coupling can be used. However, the very first step is to simulate and detail airflow structures. For the external airflow structures, the heat released from the human body has a significant effect on the airflow micro-environment around it in an indoor environment, which suggests that the transport and inhalation characteristics of aerosol particulates may also be affected since they are entrained by the air and their movement is dependent on the airflow field. Emphasis was put on the effect of human body heat on particle tracks. It was found that body heat causes a significant rising airflow on the downstream side of the body, which transports particles from a lower level into the breathing zone. The importance of body heat decreases with increasing indoor wind speed. Since the rising airflow exists only on the downstream side of an occupant, the occupant-wind orientation plays an important role in particle inhalation. The effect of body heat has to be taken into account when an occupant had his or her back to the wind, and the effect of body heat could be neglected when the occupant is facing the wind. A CFD model that integrates the three aspects of contaminant exposure by including the external room, human occupant with realistic facial features, and the internal nasal-trachea airway is presented. The results from the simulations visualize the flow patterns at different contaminant concentrations. As the particles are inhaled, they are transported through the respiratory airways, where some are deposited onto surrounding mucus walls while others may navigate through the complex geometry and even reach the lung airways, causing deleterious health effects. The studies in this thesis demonstrated that the transport and deposition of micron sized particles are dominated by its inertial property while submicron and nano sized particles are influenced by diffusion mechanisms. Studies based on an isolated model of the human nasal cavity or tracheobronchial airway tree rely on idealised inlet boundary condition imposed at the nostril or where, were a blunt, parabolic or uniform profile is applied. It is apparent that an integrated model made up of: i) room and ventilation, ii) aspiration efficiency, iii) and particle deposition efficiencies in the respiratory airway is needed. This leads to a more complete and holistic set of results, which can greatly contribute towards new knowledge in identifying preventative measures for health risk exposure assessment. With regards to the internal airflow structures and particle inhalation, ultrafine particle deposition sites in the human nasal cavity regions often omit the paranasal sinus regions. Because of the highly diffusive nature of nanoparticles, it is conjectured that deposition by diffusion may occur in the paranasal sinuses, which may affect the residual deposition fraction that leaves the nasal cavity. Thus a nasal-sinus model was created for analysis. In general there was little flow passing through the paranasal sinuses. However, flow patterns revealed that some streamlines reached the upper nasal cavity near the olfactory regions. These flow paths promote particle deposition in the sphenoid and ethmoid sinuses. Some differences were discovered in the deposition fractions and patterns for 5 and 10nm particles between the nasal-sinus and the nasal cavity models. This difference is amplified when the flow rate is decreased and at a flow rate of 4L/min the maximum difference was 17%. It is suggested that future evaluations of nanoparticle deposition should consider some deposition occurring in the paranasal sinuses especially if flow rates are of concern. Inhaled particles with pharmacological agents (e.g. histamine, methacholine) are introduced into the nasal cavity for targeted delivery. Effective nasal drug delivery is highly dependent on the delivery of the drug from the nasal spray device. Atomization of liquid spray occurs through the internal atomizer that can produce many forms of spray patterns and two of these, hollow-cone and full-cone sprays, are evaluated in this study to determine which spray pattern produced greater deposition in the middle regions of the nasal cavity. Past studies of spray particle deposition have ignored the device within the nasal cavity. Experimental measurements from a Particle Droplet Image Analyzer (PDIA) were taken in order to gain confidence to validate the initial particle conditions for the computational models.. Subsequent airflow patterns and its effects on particle deposition, with and without a spray device, are compared. Contours and streamlines of the flow field revealed that the presence of a spray device in the nasal vestibule produced higher levels of disturbed flow, which helped the dispersion of the sprayed particles. Particle deposition was found to be high in the anterior regions of the nasal cavity due to its inertia. Evaluation of the two spray types found that hollow spray cones produced more deposition in the middle regions of the nasal cavity

Deposition of Smoke Particles in Human Airways with Realistic Waveform

Exposure to toxic particles from smoke generated either from bush fire, stable burning, or direct smoking is very harmful to our health. The tiny particles easily penetrate deep into the lungs after exposure and damage the airways. Tobacco smoking causes the direct emission of 2.6 million tons of CO2 and 5.2 million tons of methane annually into the atmosphere. Nevertheless, it is one of the significant contributors to various respiratory diseases leading to lung cancer. These particles’ deposition in the human airway is computed in the present article for refining our understanding of the adverse health effects due to smoke particle inhalation, especially cigarette smoke. Until recently, little work has been reported to account for the transient flow pattern of cigarette smoking. Consideration of transient flow may change the deposition pattern of the particle. A high-resolution CT scan image of the respiratory tract model consisting of the oral cavity, throat, trachea, and first to sixth generations of the lungs helps predict cigarette smoke particle (CSP) deposition. With the same scan, a realistic geometric model of the human airways of an adult subject is used to simulate the transport of air and particle. The CSP deposition is determined at different locations from the oral cavity to the sixth generation of the bronchi. In addition, an unsteady breathing curve indicative of realistic smoking behavior is utilized to represent the breathing conditions accurately. The discrete phase model (DPM) technique is used to determine smoke particle deposition in the human airways. It is found that the deposition increases with the size of the smoke particle. Particles tend to deposit in the oral cavity around the bifurcation junction of the airways. The deposition fraction of CSP with the realistic waveform of smoking is found to be smaller compared to that during the stable flow condition. It is also observed that the fine particles (0.1–1.0 micron) escape to lower generations, leading to higher deposition of fine particles in the deeper airways. The outcome of the study is helpful for understanding smoke-related pulmonary complications