Spyridon Montesantos

A spatial model of the human airway tree: the hybrid conceptual model.

BACKGROUND The conceptual model of the lung describes the spatial distribution of the air volume of each airway generation within the lung. It is a generic model that can be used as a powerful tool in interpreting images of aerosol deposition. The model divides the lung volume into 10 concentric shells, and specifies the volume of each airway generation in each shell based on a statistical analysis of morphometric data available in the literature. In this study, an updated version of the conceptual model, called the Hybrid Conceptual Model (HCM), is introduced. This model incorporates individual morphometric data from upper bronchial airways (generations 0-5) available from High Resolution Computed Tomography (HRCT). METHODS The HCM has been tested on one 27-year-old healthy male volunteer, on which magnetic resonance imaging (MRI) and HRCT scans of the thorax have been performed. Four major changes have been introduced in the HCM; (1) the incorporation of in vivo data, (2) a better distribution of airway volume within each shell, (3) the adoption of more accurate morphometric assumptions, and (4) the incorporation of the spatial definition of the segmental divisions of the lung. RESULTS AND CONCLUSIONS The resulting model was shown to compare very well to past literature models with respect to airway volume per generation and mean airway position within the lung. It can be concluded that the HCM can be used to describe the spatial location of different airway generations of the lung with good spatial and quantitative accuracy. This represents a further step toward the personalization of the conceptual model to an individual subject.

Using Helium-Oxygen to Improve Regional Deposition of Inhaled Particles: Mechanical Principles

BACKGROUND Helium-oxygen has been used for decades as a respiratory therapy conjointly with aerosols. It has also been shown under some conditions to be a means to provide more peripheral, deeper, particle deposition for inhalation therapies. Furthermore, we can also consider deposition along parallel paths that are quite different, especially in a heterogeneous pathological lung. It is in this context that it is hypothesized that helium-oxygen can improve regional deposition, leading to more homogeneous deposition by increasing deposition in ventilation-deficient lung regions. METHODS Analytical models of inertial impaction, sedimentation, and diffusion are examined to illustrate the importance of gas property values on deposition distribution through both fluid mechanics- and particle mechanics-based mechanisms. Also considered are in vitro results from a bench model for a heterogeneously obstructed lung. In vivo results from three-dimensional (3D) imaging techniques provide visual examples of changes in particle deposition patterns in asthmatics that are further analyzed using computational fluid dynamics (CFD). RESULTS AND CONCLUSIONS Based on analytical modeling, it is shown that deeper particle deposition is expected when breathing helium-oxygen, as compared with breathing air. A bench model has shown that more homogeneous ventilation distribution is possible breathing helium-oxygen in the presence of heterogeneous obstructions representative of central airway obstructions. 3D imaging of asthmatics has confirmed that aerosol delivery with a helium-oxygen carrier gas results in deeper and more homogeneous deposition distributions. CFD results are consistent with the in vivo imaging and suggest that the mechanics of gas particle interaction are the source of the differences seen in deposition patterns. However, intersubject variability in response to breathing helium-oxygen is expected, and an example of a nonresponder is shown where regional deposition is not significantly changed.

Airway Morphology From High Resolution Computed Tomography in Healthy Subjects and Patients With Moderate Persistent Asthma

Models of the human respiratory tract developed in the past were based on measurements made on human tracheobronchial airways of healthy subjects. With the exception of a few morphometric characteristics such as the bronchial wall thickness (WT), very little has been published concerning the effects of disease on the tree structure and geometrical features. In this study, a commercial software package was used to segment the airway tree of seven healthy and six moderately persistent asthmatic patients from high resolution computed tomography images. The process was assessed with regards to the treatment of the images of the asthmatic group. The in vivo results for the bronchial length, diameter, WT, branching, and rotation angles are reported and compared per generation for different lobes. Furthermore, some popular mathematical relationships between these morphometric characteristics were examined in order to verify their validity for both groups. Our results suggest that, even though some relationships agree very well with previously published data, the compartmentalization of airways into lobes and the presence of disease may significantly affect the tree geometry, while the tree structure and airway connectivity is only slightly affected by the disease. Anat Rec, 296:852–866, 2013.

Controlled, Parametric, Individualized, 2D, and 3D Imaging Measurements of Aerosol Deposition in the Respiratory Tract of Healthy Human Subjects: Preliminary Comparisons with Simulations

Preliminary comparisons of simulation results from existing extrathoracic (ET) models and a lung deposition model with individualized, two-dimensional and three-dimensional (3D) imaging measurements of aerosol deposition in the respiratory tract of healthy human subjects have been presented. In general, the ET models did not correspond well with each individuals experimental data. However, there is rather good agreement between simulated and experimental results for regional lung deposition comparable to those previously found in the literature. Comparisons of generational distributions are relatively poor. These preliminary results suggest not only the need for further developments in deposition modeling, but also the need for better methods for analyzing experimentally determined 3D deposition distributions for comparison to simulated results. Copyright 2013 American Association for Aerosol Research

A technique for determination of lung outline and regional lung air volume distribution from computed tomography.

BACKGROUND Determination of the lung outline and regional lung air volume is of value in analysis of three-dimensional (3D) distribution of aerosol deposition from radionuclide imaging. This study describes a technique for using computed tomography (CT) scans for this purpose. METHODS Low-resolution CT scans of the thorax were obtained during tidal breathing in 11 healthy control male subjects on two occasions. The 3D outline of the lung was determined by image processing using minimal user interaction. A 3D map of air volume was derived and total lung air volume calculated. The regional distribution of air volume from center to periphery of the lung was analyzed using a radial transform and the outer-to-inner ratio of air volume determined. RESULTS The average total air volume in the lung was 1,900±126 mL (1 SEM), which is in general agreement with the expected value for adult male subjects in the supine position. The fractional air volume concentration increased from the center toward the periphery of the lung. Outer-to-inner (O/I) ratios were higher for the left lung [11.5±1.8 (1 SD)] than for the right [10.1±0.8 (1 SD)] (p<0.001). When normalized for the region sizes, these ratios were 1.37±0.16 and 1.20±0.04, respectively. The coefficient of variation of repeated measurement of the normalized O/I ratio was 5.9%. CONCLUSIONS A technique for outlining the lungs from CT images and obtaining an image of the distribution of air volume is described. The normal range of various parameters describing the regional distribution of air volume is presented, together with a measure of intrasubject repeatability. This technique and data will be of value in analyzing 3D radionuclide images of aerosol deposition.

The Creation and Statistical Evaluation of a Deterministic Model of the Human Bronchial Tree from HRCT Images.

A quantitative description of the morphology of lung structure is essential prior to any form of predictive modeling of ventilation or aerosol deposition implemented within the lung. The human lung is a very complex organ, with airway structures that span two orders of magnitude and having a multitude of interfaces between air, tissue and blood. As such, current medical imaging protocols cannot provide medical practitioners and researchers with in-vivo knowledge of deeper lung structures. In this work a detailed algorithm for the generation of an individualized 3D deterministic model of the conducting part of the human tracheo-bronchial tree is described. Distinct initial conditions were obtained from the high-resolution computed tomography (HRCT) images of seven healthy volunteers. The algorithm developed is fractal in nature and is implemented as a self-similar space sub-division procedure. The expansion process utilizes physiologically realistic relationships and thresholds to produce an anatomically consistent human airway tree. The model was validated through extensive statistical analysis of the results and comparison of the most common morphological features with previously published morphometric studies and other equivalent models. The resulting trees were shown to be in good agreement with published human lung geometric characteristics and can be used to study, among other things, structure-function relationships in simulation studies.

A tree-parenchyma coupled model for lung ventilation simulation

In this article, we develop a lung ventilation model. The parenchyma is described as an elastic homogenized media. It is irrigated by a space-filling dyadic resistive pipe network, which represents the tracheobronchial tree. In this model, the tree and the parenchyma are strongly coupled. The tree induces an extra viscous term in the system constitutive relation, which leads, in the finite element framework, to a full matrix. We consider an efficient algorithm that takes advantage of the tree structure to enable a fast matrix-vector product computation. This framework can be used to model both free and mechanically induced respiration, in health and disease. Patient-specific lung geometries acquired from computed tomography scans are considered. Realistic Dirichlet boundary conditions can be deduced from surface registration on computed tomography images. The model is compared to a more classical exit compartment approach. Results illustrate the coupling between the tree and the parenchyma, at global and regional levels, and how conditions for the purely 0D model can be inferred. Different types of boundary conditions are tested, including a nonlinear Robin model of the surrounding lung structures.

Calculated Ventilation and Effort Distribution as a Measure Of Respiratory Disease and Heliox Effectiveness

In spite of numerous clinical studies, there is no consensus on the benefit Heliox mixtures can bring to asthmatic patients in terms of work of breathing and ventilation distribution. In this article we use a 3D finite element mathematical model of the lung to study the impact of asthma on effort and ventilation distribution along with the effect of Heliox compared to air. Lung surface displacement fields extracted from computed tomography medical images are used to prescribe realistic boundary conditions to the model. Asthma is simulated by imposing bronchoconstrictions to some airways of the tracheo-bronchial tree based on statistical laws deduced from the literature. This study illuminates potential mechanisms for patient responsiveness to Heliox when affected by obstructive pulmonary diseases. Responsiveness appears to be function of the pathology severity, as well as its distal position in the tracheo-bronchial tree and geometrical position within the lung.

The influence of lung volume during imaging on CFD within realistic airway models

ABSTRACT In this article, we address a fundamental question regarding computational fluid dynamics (CFD) modeling within lung airways: does the inhaled volume during imaging have a significant effect on CFD computations of aerosol deposition? High resolution computed tomography (HRCT) images taken at mean lung volume (MLV) and at total lung capacity (TLC) obtained as part of a previous study of ventilation and aerosol deposition using positron emission tomography (PET) in challenged asthmatics were utilized to construct two airway models for each subject, and the differences in CFD calculated deposition metrics were subsequently quantified. These models included all the airway generations that could be rendered from the HRCT images. CFD calculations for three inhalation flow rates and four monodisperse aerosol sizes used images at MLV and at TLC from 24 volunteer subjects. Both large scale and detailed measures of particle deposition distribution were used in the analysis. The influence of lung volume during imaging is to increase airway dimensions in realistic models and thus reduce flow velocity and deposition due to impaction in the upper airways as calculated by CFD. However, large-scale deposition measures are confounded when the TLC models include deeper generations in the lung that increase the total airway deposition. These trends are modulated by the flow and particle characteristics of the aerosol, making consistent quantifiable differences between MLV and TLC difficult to predict unless both models consider the same anatomical airways.

An in silico analysis of oxygen uptake of a mild COPD patient during rest and exercise using a portable oxygen concentrator

Oxygen treatment based on intermittent-flow devices with pulse delivery modes available from portable oxygen concentrators (POCs) depends on the characteristics of the delivered pulse such as volume, pulse width (the time of the pulse to be delivered), and pulse delay (the time for the pulse to be initiated from the start of inhalation) as well as a patient’s breathing characteristics, disease state, and respiratory morphology. This article presents a physiological-based analysis of the performance, in terms of blood oxygenation, of a commercial POC at different settings using an in silico model of a COPD patient at rest and during exercise. The analysis encompasses experimental measurements of pulse volume, width, and time delay of the POC at three different settings and two breathing rates related to rest and exercise. These experimental data of device performance are inputs to a physiological-based model of oxygen uptake that takes into account the real dynamic nature of gas exchange to illustrate how device- and patient-specific factors can affect patient oxygenation. This type of physiological analysis that considers the true effectiveness of oxygen transfer to the blood, as opposed to delivery to the nose (or mouth), can be instructive in applying therapies and designing new devices.