Controlled, parametric, individualized, 2D and 3D imaging measurements of aerosol deposition in the respiratory tract of healthy human volunteers: in vivo data analysis

Background: To provide a validation dataset for aerosol deposition modeling, a clinical trial was performed in which the inhalation parameters and the inhaled aerosol were controlled or characterized.Methods: Eleven, healthy, never-smokers, male participants completed the study. Each participant performed two inhalations of 99mTc-labeled aerosol from a vibrating mesh nebulizer, which differed by a single controlled parameter (aerosol particle size: “small” or “large”; inhalation: “deep” or “shallow”; carrier gas: air or a helium–oxygen mix). The deposition measurements were made by planar imaging, and single photon emission computed tomography–computed tomography (SPECT-CT).Results: The difference between the mean activity measured by two-dimensional imaging and that delivered from the nebulizer was 2.7%, which was not statistically significant. The total activity deposited was significantly lower in the left lung than in the right lung (p&lt;0.0001) with a mean ratio (left/right) of 0.87±0.1 standard deviation (SD). However, when normalized to lung air volume, the left lung deposition was significantly higher (p=0.0085) with a mean ratio of 1.08±0.12 SD. A comparison of the three-dimensional central-to-peripheral (nC/P3D) ratio showed that it was significantly higher for the left lung (p&lt;0.0001) with a mean ratio (left/right) of 1.36±0.20 SD. The effect of particle size was statistically significant on the nC/P3D ratio (p=0.0014), extrathoracic deposition (p=0.0037), and 24-hr clearance (p&lt;0.0001), contrary to the inhalation parameters, which showed no effect.Conclusions: This article presents the results of an analysis of the in vivo deposition data, obtained in a clinical study designed to provide data for model validation. This study has demonstrated the value of SPECT imaging over planar, the influence of particle size on regional distribution within the lung, and differences in deposition between the left and right lungs.<br/

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

International audienceIn 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

Determination of regional lung air volume distribution at mid-tidal breathing from computed tomography: A retrospective study of normal variability and reproducibility

© 2014 Fleming et al.; licensee BioMed Central Ltd. Background: Determination of regional lung air volume has several clinical applications. This study investigates the use of mid-tidal breathing CT scans to provide regional lung volume data.Methods: Low resolution CT scans of the thorax were obtained during tidal breathing in 11 healthy control male subjects, each on two separate occasions. A 3D map of air volume was derived, and total lung volume calculated. The regional distribution of air volume from centre to periphery of the lung was analysed using a radial transform and also using one dimensional profiles in three orthogonal directions.Results: The total air volumes for the right and left lungs were 1035 +/- 280 ml and 864 +/- 315 ml, respectively (mean and SD). The corresponding fractional air volume concentrations (FAVC) were 0.680 +/- 0.044 and 0.658 +/- 0.062. All differences between the right and left lung were highly significant (p < 0.0001). The coefficients of variation of repeated measurement of right and left lung air volumes and FAVC were 6.5% and 6.9% and 2.5% and 3.6%, respectively. FAVC correlated significantly with lung space volume (r = 0.78) (p < 0.005). FAVC increased from the centre towards the periphery of the lung. Central to peripheral ratios were significantly higher for the right (0.100 +/- 0.007 SD) than the left (0.089 +/- 0.013 SD) (p < 0.0001).Conclusion: A technique for measuring the distribution of air volume in the lung at mid-tidal breathing is described. Mean values and reproducibility are described for healthy male control subjects. Fractional air volume concentration is shown to increase with lung size.Air Liquid

Development of improved analysis of radionuclide images of aerosol deposition

Over the last few years, there has been an increase in the clinical methods targeting the human tracheobronchial tree, both for therapeutic and diagnostic purposes. For these methods to be effective, a good understanding of the lung structure is necessary. This knowledge can be attained through the use of medical imaging protocols such as CT and MRI, and can in turn be used to predict aerosol deposition for particles employed for inhalation therapy via the simultaneous use of radionuclide imaging. However, due to limitations imposed by the technologies currently available, not enough information can be gathered in-vivo about the respiratory tract. Consequently, widespread use of anatomical models of the lung is being made by clinicians in order to enable them to fill this gap in information. The thesis is concerned with the improvement of such models and the introduction of new, more advanced ones in an effort to accurately describe the human lung using mathematical and physical principles.A method is developed for improving the Conceptual Model constructed in the Nuclear Medicine Department of Southampton General Hospital by incorporating to it real, patient-specific data obtained through CT imaging. A model of the bronchopulmonary segments of the lung is also created and an atlas that can be used for the identification of these sub-structures in any lung space is formed. An algorithm for the generation of a fully-descriptive 3D model of the airway tree is then designed and implemented, the morphometry of which is assessed to confirm that it is a realistic representation of the target organ. The deterministic algorithm reveals the 3D geometry and orientation of the lung airways, thus enabling aerosol deposition and flow-pattern studies to be performed in a comprehensive way in previously inaccessible regions of the lung

The effect of disease and respiration on airway shape in patients with moderate persistent asthma

Computational models of gas transport and aerosol deposition frequently utilize idealized models of bronchial tree structure, where airways are considered a network of bifurcating cylinders. However, changes in the shape of the lung during respiration affect the geometry of the airways, especially in disease conditions. In this study, the internal airway geometry was examined, concentrating on comparisons between mean lung volume (MLV) and total lung capacity (TLC). A set of High Resolution CT images were acquired during breath hold on a group of moderate persistent asthmatics at MLV and TLC after challenge with a broncho-constrictor (methacholine) and the airway trees were segmented and measured. The airway hydraulic diameter (Dh) was calculated through the use of average lumen area (Ai) and average internal perimeter (Pi) at both lung volumes and was found to be systematically higher at TLC by 13.5±9% on average, with the lower lobes displaying higher percent change in comparison to the lower lobes. The average internal diameter (Din) was evaluated to be 12.4±6.8% (MLV) and 10.8±6.3% (TLC) lower than the Dh, for all the examined bronchi, a result displaying statistical significance. Finally, the airway distensibility per bronchial segment and per generation was calculated to have an average value of 0.45±0.28, exhibiting high variability both between and within lung regions and generations. Mixed constriction/dilation patterns were recorded between the lung volumes, where a number of airways either failed to dilate or even constricted when observed at TLC. We conclude that the Dh is higher than Din, a fact that may have considerable effects on bronchial resistance or airway loss at proximal regions. Differences in caliber changes between lung regions are indicative of asthma-expression variability in the lung. However, airway distensibility at generation 3 seems to predict distensibility more distally

Number of acini and generations between trachea and terminal bronchioles.

<p>Number of acini and generations between trachea and terminal bronchioles.</p

The Creation and Statistical Evaluation of a Deterministic Model of the Human Bronchial Tree from HRCT Images - Fig 7

<p>a) The average, major and minor child branching angle for our model (blue) and the model of Tawhai et al. <b>[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0168026#pone.0168026.ref031" target="_blank">31</a>]</b> (red) and Bordas et al. <b>[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0168026#pone.0168026.ref032" target="_blank">32</a>]</b> (green). The error bars are standard deviations. b) The statistical distribution of the branching angle in our model.</p

The branching, diameter and length ratios for Horsfield order (RB_H, RD_H, RL_H) and Strahler order (RB_S, RD_S, RL_S) respectively.

<p>The branching, diameter and length ratios for Horsfield order (RB_H, RD_H, RL_H) and Strahler order (RB_S, RD_S, RL_S) respectively.</p

The frequency distribution of the planar rotation angle in our model.

<p>The frequency distribution of the planar rotation angle in our model.</p