Lung Airway Model Research Articles

157 Patient-derived 3-D lung airway model to study mucociliary clearance

157 Patient-derived 3-D lung airway model to study mucociliary clearance

Predicting particle deposition using a simplified 8-path in silico human lung prototype

Understanding particle deposition in the human lung is crucial for the assessment of environmental pollutants and the design of new drug delivery systems. Traditionally, research has been carried out by experimental analysis, but this generally requires expensive equipment and exposure of volunteers to radiation, resulting in limited data. To overcome these drawbacks, there is an emphasis on the development of numerical models capable of accurate predictive analysis. The most advanced of these computer simulations are based on three-dimensional computational fluid dynamics. Solving the flow equations in a complete, fully resolved lung airway model is currently not feasible due to the computational resources required. In the present work, a simplified lung model is presented and validated for accurate prediction of particle deposition. Simulations are performed for an 8-path approximation to a full lung airway model. A novel boundary condition method is used to ensure accurate results in truncated flow branches. Simulations are performed at a steady inhalation flow rate of 18 l min−1, corresponding to a low activity breathing rate, while the effects of particle size and density are investigated. Comparison of the simulation results with available experimental data shows that reasonably accurate results can be obtained at a small fraction of the cost of a full airway model. The simulations clearly evaluate the effect of both particle size and particle density. Most importantly, the results show an improvement over a previously documented single-path model, both in terms of accuracy and the ability to obtain regional deposition rates. The present model represents an improvement over previously used simplified models, including single-path models. The multi-path reduced airway approach described can be used by researchers for general and patient-specific analyses of particle deposition and for the design of effective drug delivery systems.

A computational study of droplet-spray formation from pressurized metered dose inhalers with applications to drug deposition in a human lung-airway model

Orally administered drugs using portable devices, such as pressurized metered dose inhalers (pMDIs), can alleviate the symptoms of various respiratory diseases. The basic non-isothermal fluid-particle dynamics of pMDIs have been simulated, including computer model validations and different inhalation techniques, using the Ventolin HFA from GlaxoSmithKline (UK) as a representative application. Specifically, the evolution of thermal droplet sprays has been realistically simulated and experimentally validated, employing the open-source computational fluid dynamics (CFD) toolbox OpenFOAM. The segmental droplet temperature results show elevated temperatures for higher inhalation flow rates because of stronger convective flow around the evaporating droplets. The general problems of high, wasteful oropharyngeal deposition and cold impacting droplets were tackled by devising a new ‘pulsed injection’ strategy in which the spray was broken into pulses with a time delay between them. This new methodology indicated up to a 20% increase in useful lung deposition beyond the oropharynx over conventional drug administration methods. In addition, compared to the conventional single injection approach, the segmental variations in temperature of the deposited aerosols show an increase in temperature of around 10% and 7% for the 30 LPM and 60 LPM cases up to segment 4 for pulsed injection. An increase of 23% and 13% for the 30 LPM and 60 LPM cases were observed for segments 5–7 for pulsed injection. Also, a reduction in inertia of the droplets at 30 LPM, where the spray was broken into eight pulses with 100 ms delay between them, resulted in higher residence times and an increase in temperature of over 35°C.Copyright © 2023 American Association for Aerosol Research

Particle Deposition in Large-Scale Human Tracheobronchial Airways Predicted by Single-Path Modelling.

The health effects of particles are directly related to their deposition patterns (deposition site and amount) in human airways. However, estimating the particle trajectory in a large-scale human lung airway model is still a challenge. In this work, a truncated single-path, large-scale human airway model (G3-G10) with a stochastically coupled boundary method were employed to investigate the particle trajectory and the roles of their deposition mechanisms. The deposition patterns of particles with diameters (dp) of 1-10 μm are investigated under various inlet Reynolds numbers (Re = 100-2000). Inertial impaction, gravitational sedimentation, and combined mechanism were considered. With the increasing airway generations, the deposition of smaller particles (dp < 4 μm) increased due to gravitational sedimentation, while that of larger particles decreased due to inertial impaction. The obtained formulas of Stokes number and Re can predict the deposition efficiency due to the combined mechanism in the present model, and the prediction can be used to assess the dose-effect of atmospheric aerosols on the human body. Diseases in deeper generations are mainly attributed to the deposition of smaller particles under lower inhalation rates, while diseases at the proximal generations mainly result from the deposition of larger particles under higher inhalation rates.

Feasibility of a lung airway navigation system using fiber-Bragg shape sensing and artificial intelligence for early diagnosis of lung cancer.

Currently early diagnosis of malignant lesions at the periphery of lung parenchyma requires guidance of the biopsy needle catheter from the bronchoscope into the smaller peripheral airways via harmful X-ray radiation. Previously, we developed an image-guided system, iMTECH which uses electromagnetic tracking and although it increases the precision of biopsy collection and minimizes the use of harmful X-ray radiation during the interventional procedures, it only traces the tip of the biopsy catheter leaving the remaining catheter untraceable in real time and therefore increasing image registration error. To address this issue, we developed a shape sensing guidance system containing a fiber-Bragg grating (FBG) catheter and an artificial intelligence (AI) software, AIrShape to track and guide the entire biopsy instrument inside the lung airways, without radiation or electromagnetic navigation. We used a FBG fiber with one central and three peripheral cores positioned at 120° from each other, an array of 25 draw tower gratings with 1cm/3nm spacing, 2 mm grating length, Ormocer-T coating, and a total outer diameter of 0.2 mm. The FBG fiber was placed in the working channel of a custom made three-lumen catheter with a tip bending mechanism (FBG catheter). The AIrShape software determines the position of the FBG catheter by superimposing its position to the lung airway center lines using an AI algorithm. The feasibility of the FBG system was tested in an anatomically accurate lung airway model and validated visually and with the iMTECH platform. The results prove a viable shape-sensing hardware and software navigation solution for flexible medical instruments to reach the peripheral airways. During future studies, the feasibility of FBG catheter will be tested in pre-clinical animal models.

A Quantitative Study of Transport of Surfactant Boli in a Three-Dimensional Lung Model of Neonates.

Neonatal respiratory distress syndrome is mainly treated with the intratracheal delivery of pulmonary surfactants. The success of the therapy depends on the uniformity of distribution and efficiency of delivery of the instilled surfactant solution to the respiratory zone of the lungs. Direct imaging of the surfactant distribution and quantifying the efficiency of delivery is not feasible in neonates. To address this major limitation, we designed an eight-generation computational model of neonate lung airway tree using morphometric and geometric data of human lungs and fabricated it using additive manufacturing. Using this model, we performed systematic studies of delivery of a clinical surfactant either at a single aliquot or at two aliquots under different orientations of the airway tree in the gravitational space to mimic rolling a neonate on its side during the procedure. Our study offers both a novel lung airway model and new insights into effects of the orientation of the lung airways and presence of a pre-existing surfactant film on how the instilled surfactant solution distributes in airways.

413 Patient-derived lung airway model to study cystic fibrosis transmembrane conductance regulator function

413 Patient-derived lung airway model to study cystic fibrosis transmembrane conductance regulator function

Nanoparticle transport and deposition in a heterogeneous human lung airway tree: An efficient one path model for CFD simulations

Understanding nano-particle inhalation in human lung airways helps targeted drug delivery for treating lung diseases. A wide range of numerical models have been developed to analyse nano-particle transport and deposition (TD) in different parts of airways. However, a precise understanding of nano-particle TD in large-scale airways is still unavailable in the literature. This study developed an efficient one-path numerical model for simulating nano-particle TD in large-scale lung airway models. This first-ever one-path numerical approach simulates airflow and nano-particle TD in generations 0–11 of the human lung, accounting for 93% of the whole airway length. The one-path model enables the simulation of particle TD in many generations of airways with an affordable time. The particle TD of 5 nm, 10 nm and 20 nm particles is simulated at inhalation flow rates for two different physical activities: resting and moderate activity. It is found that particle deposition efficiency of 5 nm particles is 28.94% higher than 20 nm particles because of the higher dispersion capacity. It is further proved that the diffusion mechanism dominates the particle TD in generations 0–11. The deposition efficiency decreases with the increase of generation number irrespective of the flow rate and particle size. The effects of the particle size and flow rate on the escaping rate of each generation are opposite to the corresponding effects on the deposition rate. The quantified deposition and escaping rates at generations 0–11 provide valuable guidelines for drug delivery in human lungs.

A model-based approach to generating annotated pressure support waveforms

Large numbers of asynchronies during pressure support ventilation cause discomfort and higher work of breathing in the patient, and are associated with an increased mortality. There is a need for real-time decision support to detect asynchronies and assist the clinician towards lung-protective ventilation. Machine learning techniques have been proposed to detect asynchronies, but they require large datasets with sufficient data diversity, sample size, and quality for training purposes. In this work, we propose a method for generating a large, realistic and labeled, synthetic dataset for training and validating machine learning algorithms to detect a wide variety of asynchrony types. We take a model-based approach in which we adapt a non-linear lung-airway model for use in a diverse patient group and add a first-order ventilator model to generate labeled pressure, flow, and volume waveforms of pressure support ventilation. The model was able to reproduce basic measured lung mechanics parameters. Experienced clinicians were not able to differentiate between the simulated waveforms and clinical data (P = 0.44 by Fisher’s exact test). The detection performance of the machine learning trained on clinical data gave an overall comparable true positive rate on clinical data and on simulated data (an overall true positive rate of 94.3% and positive predictive value of 93.5% on simulated data and a true positive rate of 98% and positive predictive value of 98% on clinical data). Our findings demonstrate that it is possible to generate labeled pressure and flow waveforms with different types of asynchronies.

A Patent Review of Lung-airway Modeling with Tangential Digital Twin Technology

Background: The digital twin as an integrated technology has been widely used in the medical field. Currently, the application of digital twin technology in the field of respiratory science is mostly theoretical exploration, with less applied technical research. Therefore, this has greatly limited the development of lung-airway models and devices that cope with digital twin technology in clinical settings and has also hindered the development of digital twin technology. Objective: The aim of this study is to propose an effective physical model to simulate the human environment as an efficient means to develop and improve the digital twin technology. Method: A representative set of patents related to physical models of the respiratory tract and lungs is presented, including methods for model building and ways to assess and predict the diagnosis of respiratory diseases. Results: Current patents are analyzed and compared in three aspects: physical models, model building methods, and respiratory disease assessment and prediction. A digital twin modeling approach, including mechanical effects, biological evolution, physiological tissue changes, and physical entity coupling is proposed based on the hardware support involved in rapid prototyping techniques and method patents. The advantages and disadvantages of the existing models are analyzed, and the systematicity, applicability, modeling techniques, and fidelity of the digital twin physical model are discussed. Conclusion: Lung airway models are already based on complete morphological data, but purely physical models cannot reproduce the real environment of the human body. Therefore, in order to reach the heights of digital twins, the intervention of numerical theory and related auxiliary hardware is often required.

Numerical simulation of the unsteady flow field in the human pulmonary acinus

Understanding of airflow dynamics in the human pulmonary acinus is important for increasing targeted drug effectiveness and determining the health impact of toxic aerosols. However, there is a lack of quantitative data about the pulmonary airflow in realistic and flexible idealized geometries. This paper aims to numerically analyse the flow field of the pulmonary acinus using the computational fluid dynamics (CFD) model during transient breathing. Three-dimensional models with rhythmically expanding-contracting alveolar walls were developed for representing the pulmonary region of the human lung. Three different breathing scenarios were applied in the CFD simulations. The results showed that the transient flow conditions determined the transitions between flow types. The recirculating flow in the alveoli was observed for all cases and it was determined that its intensity depended on the breathing scenario. The flow velocity in the alveoli was slower than that of the channel flow. As we moved deeper into the lung, the flow pattern inside the alveoli exhibited a radial velocity profile. It was found that the alveolar flow exhibited a typical stenotic channel flow characteristics. As a result, the acinus models used in this study takes into account the alveolar wall motion based on physiological breathing conditions. To simulate or estimate the airflow dynamics, thus, the results obtained in this study can be easily utilized in the human lung airway models.

A hybrid in vitro in silico framework for albuterol delivery through an adult ventilator circuit to a patient-specific lung airway model

An integrated in vitro in silico approach was employed to investigate albuterol administration to an adult lung airway. Particle size characterization of aerosolized albuterol generated by a jet- and vibrating mesh nebulizer was evaluated in vitro using an adult ventilator circuit that consisted of an endotracheal tube (ETT) connected to a cooled Next Generation Impactor. The aerosol particle size distribution sampled by spectrophotometry was used to predict particle deposition in an in silico patient-specific seven-generation airway model using computational fluid dynamics (CFD). A Lagrangian particle tracking algorithm was used to investigate the effect of nebulizer type and position on drug delivery and compare the efficacy of drug administration through endotracheal intubation and oral route. A vibrating mesh nebulizer produced a larger lung dose than the jet nebulizer, with the aerosol characteristics being dependent on the location of the nebulizer in the ventilator circuit. The CFD analysis showed that the vibrating mesh nebulizer placed at the ventilator had a lower global and local deposition fraction down to the 7th airway generation with higher penetration beyond. Besides, delivery through the ETT was more efficient than oral delivery for the studied conditions. Particle deposition patterns in the various lung lobes were evaluated. Placement of the nebulizer in an adult ventilator circuit could target different areas of the lung.

Effect of Non-Newtonian Dynamics on the Clearance of Mucus From Bifurcating Lung Airway Models.

Mucus hypersecretion is a common pathophysiological manifestation of several obstructive airway diseases in which the mucociliary clearance is impaired, and the airflow generated by a cough or a forced expiratory maneuver called the huff is primarily responsible for clearing mucus. This airflow driven clearance of mucus is a complex process that is affected by the mucus rheology, airflow rate, airway geometry, and gravity. This study examines the role of mucus rheology in the transport and distribution of mucus in idealized 3D airway geometries. The complex air-mucus interface was tracked by the volume-of-fluid (VOF) model, and the turbulence in the core airflow was modeled using the k-ω shear stress transport (SST) model. Mucus was modeled as a shear-thinning liquid by using a power-law model. The computational model was validated using in vitro experimental data available in the literature. Gravity-dominated eccentric core-annular flow was observed with the core biased toward the outer wall in the inclined daughter branches of the bifurcation models, which transitions into concentric core-annular flow in the trachea. The increase in tangential shear at the interface due to the secondary flow structures developed in the flow divider location resulted in a region of enhanced mucus clearance with reduced mucus layer thickness. Secondary flow developed due to the curvature in the airway geometry resulted in a local redistribution of mucus that reduced the eccentricity. The accumulation of mucus around the carinal ridges and the regions with reduced clearance are sites with the potential for microbial growth.

High-temperature effects on the mucus layers in a realistic human upper airway model

Firefighters and workers in some industries often inhale (polluted) air at high temperatures, eg, 50–200°C, and very low relative humidity, say, 5–10%. Such severe environmental conditions may cause health problems or further aggravate existing ones. As in vivo tests are very complex, potentially harmful and costly, and in vitro experiments often lack high resolution and predictive capability, in silico studies become a priority. They may include computer simulations of the air-particle dynamics in human lung-airway models to understand the convection heat transfer as well as pollutant transport, deposition and uptake at high inlet temperatures and low relative humidity. In this study, detailed modeling, simulation and analysis focuses on two-phase flow in a human upper lung-airway model with a realistic 3D mucus lining. Especially modeling of the upper airway mucus layers was of interest in order to simulate the vapor mass transfer to the airflow because of its primary function for airway humidification. Naturally, the humidification causes water loss in the mucus layer, which leads to its reduction or even depletion when exposed to relatively high temperatures. Accounting for the changes in thickness and the rise in temperature in the mucus layer allows for the determination of locations of thermal injury in the human airways due to continuous exposure of such abnormal inhalation conditions. Different temperature profiles and local changes in mucus layer thickness were studied for ranges of severe inlet temperature conditions at a representative flow rate of 20 LPM (liters per minute). For inlet temperature reaching 100°C, mucus-layer thinning was observed in the upper airways. Interestingly, as a confirmation of the Reynolds analogy, the areas of significant wall heat flux and associated wall shear stress coincided with the regions of highest mucus evaporation, resulting in the humidification of the air with low relative humidity. Model development and mucus layer generation were done using C++ programming. All computer simulations were carried out using the open-source computational fluid dynamics toolbox OpenFOAM.

Helical fluid-particle flow dynamics for controlling micron-particle deposition in a representative human upper lung-airway model

The transport and deposition of inhaled micron particles is largely determined by their inlet conditions, breathing rate, and the individual airway geometry. In this study, helical air-particle flow is introduced, which significantly affects the particle dynamics with applications to targeted drug delivery. Specifically, helical flow, which reduces axial momentum, can be controlled by varying the swirl number and hence the characteristics of the fluid-particle stream. In case of drug-aerosol delivery, the waste of inhaled drugs in the human upper respiratory tract due to inertial impaction can be mitigated by implementing a controlled helical flow with a modified inhaler. For example, 2 μm-particle deposition was reduced in the oral cavity for a helical fluid-particle stream with 10 l/min inhalation by 39.7% when the swirl number was increased from 0 to 0.6. Considering a 30 l/min inhalation flow rate, the deposition fraction of 2 μm-particles in the oral cavity was reduced by 73.5% as the swirl number increased from 0 to 2. A new non-dimensional parameter called the swirl number threshold (Sth), is also discussed, which is useful in assessing the impact of helical streams in drug-aerosol delivery. All computer experiments were performed with an enhanced version of the open-source computational fluid dynamics toolbox OpenFOAM.

Robotic System for Catheter Navigation during Medical Procedures

Lung cancer is the most common cancer globally with over 2 million new cases diagnosed every year. Fortunately, if caught early, the likelihood of survival is greatly improved. If diagnosed in Stage I, survival rates are &gt;75% over 5 years, vs. just 1% if diagnosed in Stage IV. Early diagnosis requires finding and sampling (biopsy) small, peripheral nodules that are located in the parenchima of the lung and predominately outside small airways. Currently, for early diagnosis a bronchoscope is inserted into the lung airway but due to large size it cannot reach the small airways. Therefore, the doctor has to advance a sharp biopsy needle blindly from the tip of the bronchoscope and into the lung tissue in the approximate direction of the nodule. This blind procedure has low accuracy and carries a high risk of misdiagnosis. Currently, to improve the accuracy, real time x-ray (fluoroscopy) is use which causes exposure of the patient and physician to harmful radiation. Computer and image assisted surgery and medical robotics present viable solutions but are not optimal at present. The scope of our research was to develop a robotic solution for increased precision and accuracy of early diagnosis and treatment of lung cancer, to increase procedure success rate, decrease patient radiation and stress exposure, and reduce the procedure cost. For this purpose, we developed an advanced prototype of a robotic system which is small in size, easy to use and effective. To demonstrate its effectiveness in navigating to peripheral small size lung cancer lesions, we performed laboratory tests or a realistic lung airway model. The preliminary tests of a novel medical robot using a complex lung airway model proved that our catheter driving robotic system is working as designed and allows navigation, through a complex 3D channels structure like the bronchial tree, in both manipulator and robotic modes without fluoroscopy scanning. The robotic system is more precise and stable, and can avoid patient injury and instrument damage due to accidental impact with the airway wall. Because it could be controlled from a different room via the software platform, using this robotic system can drastically reduce radiation exposure of the patient and totally avoid the exposure of the doctor. Another benefit of the proposed robotic system is that it uses currently available catheters in which a reusable electromagnetic guide wire is temporarily inserted to guide the tip of the catheter towards hard to reach targets. After the target is confirmed, the sensor can be retracted and the catheter can be used for its routine function such as biopsy collection. Future development will include placement of a force sensor at the tip of the catheter to “feel” the wall and adapt the speed of insertion in order to avoid wall damage and an improved algorithm to increase the speed in the automatic mode.

Modeling of Human Airways CAD model Using CT Scan Data

Abstract Present study describes a systematic process involved in the preparation of a suitable lung airway model using MIMICS 20.0 software. The CAD model can be prepared using manual, automatic and semi-automatic process. The current model in this study is extracted from the CT scan data of the Thoracic region through semi-automatic process available in materialize imaging software MIMICS. The study will be beneficial to pulmonologist to obtain maximum deposition efficiency of the aerosol drug into the lungs

Bioinspired in Vitro Lung Airway Model for Inflammatory Analysis via Hydrophobic Nanochannel Membrane with Joint Three-Phase Interface.

Because of the extremely low solubility of gas pollution, elucidating the pathogenetic mechanism between air pollution and the lung inflammatory response has remained a significant challenge. Here, we develop a bioinspired nanoporous membrane (BNM) with a three-phase interface as a gas exposure model that mimicks the airway mechanism, gas molecules contacting with alveolar cells directly, enabling high cell viability and sensitive inflammatory response analysis. Specifically, the top side of the porous anodic alumina (PAA) membrane was in contact with the medium for cell culture, and the bottom side contacted the gas phase directly for gas exposure. Compared with the two-phase interface, the viability of cells on the BNM was enhanced up to 3-fold. Additionally, results demonstrated that the inflammatory responses of cells stimulated by gas pollution (formaldehyde and benzene as models) from the gas phase were more obvious than those induced by gas pollution from solution, especially the increment of interleukin-2 (IL-2), IL-6, and tumor necrosis factor α (TNF-α), which was almost 2 times greater than that induced by gas pollution from solution. Furthermore, an enzyme inhibitor was introduced to evaluate potential applications of the BNM.

Implementation of a specific boundary condition for a simplified symmetric single-path CFD lung model with OpenFOAM

CFD modeling research about the lung airflow with a complete resolution and an adequate accuracy at all scales requires a great amount of computational resources due to the vast number of necessary grid elements. As a result, a common practice is to conduct simplifications that allows to manage it with ordinary computational power. In this study, the implementation of a special boundary condition in order to develop a simplified single conductive lung airway model, which exactly represents the effect of the removed airways, is presented. The boundary condition is programmed in the open-source software OpenFOAM®, and the developed source code is presented in the proper syntax. After this description, modeling accuracy is evaluated under different flow rate conditions typical of human breathing processes, including both inspiration and expiration movements. Afterward, a validation process is conducted using results of a Weibel's model (0-4 generations) simulation for a medium flow rate of 50 L/min. Finally, a comparison against the proposed boundary condition implemented in the commercial code ANSYS Fluent is made, which highlights the benefits of using the free code toolbox. The specific contribution of this paper will be to show that OpenFOAM® developed model can perform even better than other commercial codes due to a precise implementation and coupling of the default solver with the in-house functions by virtue of the open-source nature of the code.

Numerical assessment of respiratory airway exposure risks to diesel exhaust particles

Exposure to ambient air pollution presents great adverse health risks to respiratory health, and assessing the respiratory exposure doses, especially in the human deep lung regions, remains difficult due to the sheer complexity of the process. To bridge this gap, an extended large-to-small conducting lung airway model was adopted in this study, which includes a broad scope containing bronchial airways up to the 15th generation. Accumulation mode particles in the size range of 100 nm to 3.0 μm representing major size spectrum of coarse diesel exhaust were released at the inlet of respiratory airway model, and both airflow and particle deposition characteristics were numerically investigated. The simulation results showed that the particle deposition in the respiratory airway is sensitive to the variation of inhalation flow rates. For inhalation exposure at lower breathing rate of 18 L/min, both deposited diffusive and inertia particles were very unevenly distributed in the lower respiratory airway. For inhalation exposure at higher breathing rate of 50 L/min, deposited diffusive and inertia particles were both scattered over the lower respiratory airway. In addition, high inhalation flow rate enabled inertia particles to be deposited further d ownstream of the airway with deposition hot spots observed in distal airways.