Possible role of differential growth in airway wall remodeling in asthma

Airway remodeling in patients with chronic asthma is characterized by a thickening of the airway walls. It has been demonstrated in previous theoretical models that this change in thickness can have an important mechanical effect on the properties of the wall, in particular on the phenomenon of mucosal folding induced by smooth muscle contraction. In this paper, we present a model for mucosal folding of the airway in the context of growth. The airway is modeled as a bi-layered cylindrical tube, with both geometric and material nonlinearities accounted for via the theory of finite elasticity. Growth is incorporated into the model through the theory of morphoelasticity. We explore a range of growth possibilities, allowing for anisotropic growth as well as different growth rates in each layer. Such nonuniform growth, referred to as differential growth, can change the properties of the material beyond geometrical changes through the generation of residual stresses. We demonstrate that differential growth can have a dramatic impact on mucosal folding, in particular on the critical pressure needed to induce folding, the buckling pattern, as well as airway narrowing. We conclude that growth may be an important component in airway remodeling

Geometric model generation for CFD simulation of blood and air flows

A new adaptive algorithm is developed for the reconstruction of geometric models of carotid arteries and human airways from CT images. Based on the patient-specific geometric models, Computational Fluid Dynamics (CFD) models of patient's blood and air flows are constructed to calculate hemodynamic parameters and particle deposition patterns for patient-specific clinical applications

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

Direct simulations and modelling of basic three-dimensional bifurcating tube flows

Three-dimensional bifurcating internal flow is studied for a single mother tube branching into two equal but diverging daughter tubes. The mother tube is straight and of circular cross-section, containing a fully developed incident motion, while the diverging daughters are straight and of semi-circular cross-section. This basic configuration is treated first by direct numerical simulation and secondly by slenderflow modelling, for a variety of Reynolds numbers and angles of divergence. The direct simulations and modelling highlight different forms of three-dimensional separation or flow reversal as well as enhanced upstream and downstream influence and pressure loss induced by the bifurcations especially at increased divergence angles. Comparisons between the results from the simulations and those from the slender-flow modelling show relatively close agreement at medium values of Reynolds number. In particular, as the angle of divergence increases for a given Reynolds number, there is generally first an increase in flow attachment on to the inner divider wall(s) and then, at higher angles, an increasing trend to flow reversal at the corners formed by the junctions of the outer wall with the divider; longitudinal vortex motion is also enhanced then. The agreement persists over a surprisingly wide range of divergence angles

Computational Simulation: Selected Applications In Medicine, Dentistry, And Surgery

This article presents the use of computational modelling software (e.g. ANSYS) for the purposes of simulating, evaluating and developing medical and surgical practice. We provide a summary of computational simulation mo delling that has recently been employed through effective collaborations between the medical, mathematical and engineering research communities. Here, particular attention is being paid to the modelling of medical devices as well as providing an overview o f modelling bone, artificial organs and microvascular blood flows in the machine space of a High Performance Computer (HPC)

Quantifying Airway Dilatation in the Lungs from Computed Tomography

Non CF bronchiectasis and idiopathic pulmonary fibrosis (IPF) are pulmonary diseases characterised by the abnormal and permanent dilatation of the airways. Computed tomography (CT) is used in clinical practice to diagnose and monitor patients with the disease. Currently, analysis of the scans is performed by manual inspection and there is no established computerised method to quantify the enlargement of airways. I developed a pipeline to quantify the cross-sectional area for a given airway track. Using an airway segmentation, my proposed algorithm measures the area at contiguous intervals along the airway arclength from the Carina to the most distal point visible on CT. I showed the use of the data generated from the pipeline in two applications. First, I proposed a novel tapering measure as the gradient of a linear regression between a logarithmic area against the arclength. The measurement was applied to airways affected by bronchiectasis. Second, I used Bayesian Changepoint Detection (BCD) with the area measurements to locate the progression of IPF along the airway track. The proposed pipeline was applied to a set of clinically acquired scans. I show a statistical difference (p = 3.4×10−4 ) in the tapering measurement between bronchiectatic (n = 53) and controlled (n = 39) airways. In addition, I report a statistical difference (p = 7.2×10−3 ) in the change in measurement between airways remaining healthy (n = 14) and airways that have become bronchiectatic (n = 5). I show the tapering measurement is reproducible independent to voxel size, CT reconstruction, and radiation dose. Using BCD, I show on simulated data (n = 14) my proposed method can detect the progression of IPF within 2.5mm. Finally, using results from BCD, I present a novel measure of IPF progression as the percentage volume change in the diseased region of the airways

Computed tomography image analysis for the detection of obstructive lung diseases

Damage to the small airways resulting from direct lung injury or associated with many systemic disorders is not easy to identify. Non-invasive techniques such as chest radiography or conventional tests of lung function often cannot reveal the pathology. On Computed Tomography (CT) images, the signs suggesting the presence of obstructive airways disease are subtle, and inter- and intra-observer variability can be considerable. The goal of this research was to implement a system for the automated analysis of CT data of the lungs. Its function is to help clinicians establish a confident assessment of specific obstructive airways diseases and increase the precision of investigation of structure/function relationships. To help resolve the ambiguities of the CT scans, the main objectives of our system were to provide a functional description of the raster images, extract semi-quantitative measurements of the extent of obstructive airways disease and propose a clinical diagnosis aid using a priori knowledge of CT image features of the diseased lungs. The diagnostic process presented in this thesis involves the extraction and analysis of multiple findings. Several novel low-level computer vision feature extractors and image processing algorithms were developed for extracting the extent of the hypo-attenuated areas, textural characterisation of the lung parenchyma, and morphological description of the bronchi. The fusion of the results of these extractors was achieved with a probabilistic network combining a priori knowledge of lung pathology. Creating a CT lung phantom allowed for the initial validation of the proposed methods. Performance of the techniques was then assessed with clinical trials involving other diagnostic tests and expert chest radiologists. The results of the proposed system for diagnostic decision-support demonstrated the feasibility and importance of information fusion in medical image interpretation.Open acces

Lung Circulation Modeling: Status and Prospect

Mathematical modeling has been used to interpret anatomical and physiological data obtained from metabolic and hemodynamic studies aimed at investigating structure-function relationships in the vasculature of the lung, and how these relationships are affected by lung injury and disease. The indicator dilution method was used to study the activity of redox processes within the lung. A steady-state model of the data was constructed and used to show that pulmonary endothelial cells may play an important role in reducing redox active compounds and that those reduction rates can be altered with oxidative stress induced by exposure to high oxygen environments. In addition, a morphometric model of the pulmonary vasculature was described and used to detect, describe,and predict changes in vascular morphology that occur in response to chronic exposure to low-oxygen environments, a common model of pulmonary hypertension. Finally, the model was used to construct simulated circulatory networks designed to aid in evaluation of competing hypotheses regarding the relative contribution of various morphological and biomechanical changes observed with hypoxia. These examples illustrate the role of mathematical modeling in the integration of the emerging metabolic, hemodynamic, and morphometric databases