Marine Pichelin

The use of combined single photon emission computed tomography and X-ray computed tomography to assess the fate of inhaled aerosol

BACKGROUND Gamma camera imaging is widely used to assess pulmonary aerosol deposition. Conventional planar imaging provides limited information on its regional distribution. In this study, single photon emission computed tomography (SPECT) was used to describe deposition in three dimensions (3D) and combined with X-ray computed tomography (CT) to relate this to lung anatomy. Its performance was compared to planar imaging. METHODS Ten SPECT/CT studies were performed on five healthy subjects following carefully controlled inhalation of radioaerosol from a nebulizer, using a variety of inhalation regimes. The 3D spatial distribution was assessed using a central-to-peripheral ratio (C/P) normalized to lung volume and for the right lung was compared to planar C/P analysis. The deposition by airway generation was calculated for each lung and the conducting airways deposition fraction compared to 24-h clearance. RESULTS The 3D normalized C/P ratio correlated more closely with 24-h clearance than the 2D ratio for the right lung [coefficient of variation (COV), 9% compared to 15% p < 0.05]. Analysis of regional distribution was possible for both lungs in 3D but not in 2D due to overlap of the stomach on the left lung. The mean conducting airways deposition fraction from SPECT for both lungs was not significantly different from 24-h clearance (COV 18%). Both spatial and generational measures of central deposition were significantly higher for the left than for the right lung. CONCLUSIONS Combined SPECT/CT enabled improved analysis of aerosol deposition from gamma camera imaging compared to planar imaging. 3D radionuclide imaging combined with anatomical information from CT and computer analysis is a useful approach for applications requiring regional information on deposition.

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

Glottal motion and its impact on the respiratory flow

The aim of this study was (i) to characterise the glottal dynamics during human breathing in vivo using laryngofiberscopy and synchronised airflow recordings and (ii) to quantify the effects of a mobile glottis and unsteady flow conditions on laryngeal jet-flow dynamics using CFD modelling. The in vivo study showed that the glottis can be extremely variable during breathing and hence influence airflow characteristics. A glottal area widening was quantified during inspiration, with a typical ratio of 3:1 as compared to expiration. Airflow rate variations differ from harmonic signal during eupnea as well as tachypnea. The correlation between flow-rate and glottal area will be discussed and compared to previous clinical investigations. Preliminary 2D CFD simulations of the glottal jet were carried out based on the measured flow-rate and glottal changes during eupnea. Impact of unsteady flow conditions on the jet development is demonstrated.

Categorization of Lung Morphology Based on FRC and Height: Computer Simulations of Aerosol Deposition

The aim of this study was to compare the human subject experimental measurements of particle deposition within the lungs using the aerosol bolus technique with the results of analytical modeling as a basis for assessing the influence of lung morphology on inhaled particle deposition patterns. A methodology for scaling the lung morphology, based on a classic symmetric dichotomous model, as a function of both functional residual capacity and height of the investigated population is presented. Because of the availability of deposition data for male and female lung morphologies, these were used as an example to address the importance of adjusting lung morphology in calculating the aerosol deposition rates. In order to represent the 2 groups based on gender enrolled in the experimental study, 2 lung morphologies have been built. An analytical and mechanistic model was used to mimic the bolus delivery technique and simulate the aerosol deposition in each of the 2 groups. Predicted results were compared with experimental data for both total deposition fraction and bolus recovery (fraction of exhaled particles compared with inhaled particles) for 3 flow rates and 3 particle sizes. Good agreement was found between theoretical and measured data, showing the primary importance of the differentiation of the lung morphology to predict the aerosol deposition within human lungs. This study presents a morphological lung model that is adaptable to specific populations (e.g., gender or race), groups (e.g., a clinical study population), or even individuals. Copyright 2012 American Association for Aerosol Research

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.

Comparison of pulsed versus continuous oxygen delivery using realistic adult nasal airway replicas

Background Portable oxygen concentrators (POCs) typically include pulse flow (PF) modes to conserve oxygen. The primary aims of this study were to develop a predictive in vitro model for inhaled oxygen delivery using a set of realistic airway replicas, and to compare PF for a commercial POC with steady flow (SF) from a compressed oxygen cylinder. Methods Experiments were carried out using a stationary compressed oxygen cylinder, a POC, and 15 adult nasal airway replicas based on airway geometries derived from medical images. Oxygen delivery via nasal cannula was tested at PF settings of 2.0 and 6.0, and SF rates of 2.0 and 6.0 L/min. A test lung simulated three breathing patterns representative of a chronic obstructive pulmonary disease patient at rest, during exercise, and while asleep. Volume-averaged fraction of inhaled oxygen (FiO2) was calculated by analyzing oxygen concentrations sampled at the exit of each replica and inhalation flow rates over time. POC pulse volumes were also measured using a commercial O2 conserver test system to attempt to predict FiO2 for PF. Results Relative volume-averaged FiO2 using PF ranged from 68% to 94% of SF values, increasing with breathing frequency and tidal volume. Three of 15 replicas failed to trigger the POC when used with the sleep breathing pattern at the 2.0 setting, and four of 15 replicas failed to trigger at the 6.0 setting. FiO2 values estimated from POC pulse characteristics followed similar trends but were lower than those derived from airway replica experiments. Conclusion For the POC tested, PF delivered similar, though consistently lower, volume-averaged FiO2 than SF rates equivalent to nominal PF settings. Assessment of PF oxygen delivery using POC pulse characteristics alone may be insufficient; testing using airway replicas is useful in identifying possible cases of failure and may provide a better assessment of FiO2.

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.