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Keywords: CFD, drug delivery, airflow, particle deposition, nasal airway.
The human nasal cavities, each with an effective length of only 10cm, feature a wide array of basic flow phenomena due to their complex geometries. Dependent on such airflow fields are the transport and deposition of micro- and nano- particles in the human nasal cavities, of interest to engineers, scientists, air-pollution regulators, and healthcare officials. By utilizing advanced CAD and reverse engineering skills, a realistic model of the human nasal cavity was constructed from MRI image data for 3-D computer simulations. Assuming laminar quasi-steady airflow, dilute micro- and nano-particle suspension flows and local deposition efficiencies were analyzed for 7.5
Traditional research methodologies in the human respiratory system have always been challenging due to their invasive nature. Recent advances in medical imaging and computational fluid dynamics (CFD) have accelerated this research. This book compiles and details recent advances in the modelling of the respiratory system for researchers, engineers, scientists, and health practitioners. It breaks down the complexities of this field and provides both students and scientists with an introduction and starting point to the physiology of the respiratory system, fluid dynamics and advanced CFD modeling tools. In addition to a brief introduction to the physics of the respiratory system and an overview of computational methods, the book contains best-practice guidelines for establishing high-quality computational models and simulations. Inspiration for new simulations can be gained through innovative case studies as well as hands-on practice using pre-made computational code. Last but not least, students and researchers are presented the latest biomedical research activities, and the computational visualizations will enhance their understanding of physiological functions of the respiratory system.
Nanoparticle holds significant promise as the next generation of drug carrier that can realize targeted therapy with minimal toxicity. To improve the delivery efficiency of nanoparticles, it is important to study their transport and deposition in blood flow. Many factors, like particle size, vessel geometry and blood flow rate, have significant influence on the particle transport, thus on the deposition fraction and distribution. In this thesis, computational fluid dynamics (CFD) simulations of blood flow and drug particle deposition were conducted in four models representing the human lung vasculature: artificial artery geometry, artificial vein geometry, original geometry and over-smoothed original geometry. Flow conditions used included both steady-state inlet flow and pulsatile inlet flow. Parabolic flow pattern and lumped mathematic model were used for inlet and outlet boundary conditions respectively. Blood flow was treated as laminar and Newtonian. Particle trajectories were calculated in each of these models by solving the integrated force balance on the particle, and adding a stochastic Brownian term at each step. A receptor-ligand model was integrated to simulate the particle binding probability. The results indicate the following: (i) Pulsatile flow can accelerate the particle binding activity and improve the particle deposition fraction on bifurcation areas; (ii) Unlike drug delivery in lung respiratory system, particle diffusion is very weak in blood flow, no clear relationship between the particle size and deposition area was found in our four-generation lung vascular model; and (iii) Surface imperfections have the dominant effect on particle deposition fraction over a wide range of particle sizes. Ideal artificial geometry is not sufficient to predict drug deposition, and an accurate image based geometry is required.
Prolonged exposure to inhaled micron-sized airborne particles is a known public health concern. These particles impact the health of staggering numbers of residents of polluted urban areas, as well as significant portions of the third world where it is still common to burn wood or charcoal indoors for cooking or heating. An understanding of the fate of inhaled particles in the lungs is useful for assessing their associated health risks, as well as improving the effectiveness of respiratory drug delivery techniques. The transport of microparticles is inseparable from behavior of the suspending airflow and this is studied using computational fluid dynamics techniques. The anatomy of the airways seems to have evolved to encourage turbulent airflow for functions such as mixing of flow to promote the warming and humidification of inhaled air, as well as for filtration. Large eddy simulation models are employed to capture turbulent flow in extremely complex patient-specific airway geometries. These collectively comprise the oral and nasal cavities, larynx, trachea, and the bronchial tree. The flow in anatomically-accurate rhesus macaque airways is also studied. Simulations are carried out for inspiratory flow rates corresponding to nominal Reynolds numbers in the hundreds to low-thousands yet somewhat surprisingly yield unsteady flows due to local geometric factors. A computed mean flow field is compared extensively with magnetic resonance velocimetry measurements carried out in the same computed-tomography--based lung geometry, showing good agreement. Microparticle deposition predictions are also verified. Focus is placed on the dynamics of the flow in the nasal airway, trachea, and bronchial tree. After becoming unsteady at constrictions in the upper airways, the flow is found to be chaotic, exhibiting fluctuations with broad-band spectra even at the most distal simulated airways in which the Reynolds numbers are as low as 300. The unsteadiness is attributed to the convection of turbulent structures produced in the upper airways as well as to local kinetic energy production throughout the bronchial tree.
People may inhale 100 millions of particles each day, including toxic particulate matter as well as drug aerosols. Some of those deposited in the respiratory system can be either harmful or therapeutic to humans depending upon the particle material, deposition site, and local concentration. These transport and deposition phenomena as well as the resulting biomedical processes are greatly determined by the airflow field, particle properties, breathing pattern, and geometric airway characteristics. Realistic models of tracheobronchial and nasal⁄oral- tracheobronchial airways were built. Airflow and particle transport and deposition in these airway models were investigated in detail by mainly using the validated, in-house FORTRAN code CFPD (computational fluid-particle dynamics), which is a cell-centered, finite volume multi-block code. Both laminar and transitional-turbulent-laminar flows were considered for different transient and steady inhalation flow rates and inlet velocity profiles. The resulting effects of transients, upstream conditions and geometric characteristics, i.e., spatial angle and/or cartilaginous rings, are fully discussed. A new code based on the lattice-Boltzmann method (LBM) has been developed and validated to investigate airflow patterns and pressure changes in representative alveolar structures of the human respiratory zone. The new idea of targeted drug aerosol delivery technology was numerically tested for a more realistic human airway configuration and thereby addressing the problem of inter-subject variability. Specifically, controlled air-particle streams were studied using the oral and asymmetric tracheobronchial airway models. The results were compared with data obtained for a symmetric Weibel Type A tracheobronchial airway model.
Aerosol therapy has significantly improved the treatment of a variety of respiratory diseases. Besides the treatment of respiratory diseases there is currently also a great interest to use the lungs as a portal to introduce drugs for systemic therapy. The success of therapy with the application of aerosolized medicaments depends on the possibility to deliver the proper amount of drug to the appropriate sites in the respiratory system, thus limiting the side effects to a minimum. Aerosolized delivery of drugs to the lung is optimized if, for a given chemical composition of a medicine, the target of deposition and the required mass of drug to be deposited are precisely defined. The next step is the specification of the number of respirable particles or droplets, to be generated by appropriate devices. Another very important factor for successful aerosol therapy is the condition of the patient coupled with his or her inhalation technique.
Even though the direct nose-to-brain drug delivery has many clinical benefits, there are limited successes in delivering medication aerosols to the olfactory mucosa with standard inhalation devices. In this study, different delivery techniques were assessed in terms of their capacities to deliver drug aerosols to the olfactory epithelium. Specifically, the feasibility of electric field guidance of charged aerosols to the olfactory mucosa was evaluated in an image-based nose model both numerically and experimentally. Multi-sectional nasal cast replicas were fabricated using a 3-D printer to measure the olfactory deposition rates and visualize the deposition distributions. An intranasal deposition test platform was developed that comprised an electric field guidance system, a dry powder charging device, and a point-release nozzle. Numerical simulations were conducted using both ANSYS Fluent and COMSOL. We demonstrated that it is feasible to control charged particles inside the human nose use an external electric field. Both the point-release technique and electric field guidance of drug particles are essential in attaining optimal olfactory doses. Consistent deposition patterns were achieved between in vitro experiments and computational simulations. Future investigations are warrnated for further improvements of olfactory delivery through refining the particle generation, charging, and releasing, and navigation systems.
Extrapolation Modeling, Advancements and Research Issues in Lung Dosimetry; Lung Structure, Function Relationships; Species Differences in Airway Cell Distribution and Morphology; Alternative Methods to Evaluate Species Differences in Upper Airway Structure, Function; Preparation of Rat Nasal Airway Casts and Their Application to Studies of Nasal Airflow; Age Related Morphometric Analysis of Human Lung Casts; Anatomical Modeling of Microdosimetry of Inhaled Particles and Gases in the Lung; Experimental Dosimetry; Particle Deposition at the Alveolar Duct Bifurcations; Effects of Airway Branch Angle, Branch Point Number, and Gravity on Particle Deposition and Retention; Regional Deposition of Inhaled Particulates in Conducting Airways and Lung Segments; The Physical Properties of Mainstream Cigarette Smoke and Their Relationship to Deposition in the Respiratory Tract; Localization of 14C Dotriacontane Labeled Cigarette Smoke Particulate in the Dog Lung; Human Lung Clearance Following Bolus Inhalation of Radioaerosols; Effects of Ventilatory Patterns and Pre-existing Disease on Deposition of Inhaled Particles in Animals; Nasopharyngeal Uptake of Ozone in Humans and Animals; New Methods; Regional Dosimetry of Inhaled Particles Using SPECT; Dual Laser Doppler System for Real Time, Simultaneous Characterization of Aerosols by Size and Concentration; Dosimetry of Inhaled Particles by Means of Light Scattering; Modeling Approaches; Issues That Must Be Addressed When Constructing Anatomical Models of the Developing Lung; Significances of the Variability of Tracheobronchial Airway Paths and Their Air Flow Rates to Dosimetry Model Predictions of the Absorption of Gases; Predicting Respiratory Tract Clearance in Man; The Role of Particle Hygroscopicity in Aerosol Therapy and Inhalation Toxicology; Age-Dependent Lung Dosimetry of Radon Progeny; Deposition and Retention Modeling of Inhaled Cadmium in Rat and Human Lung, An Example for Extrapolation of Effects and Risk Estimation.