Variability in Flow Distribution within the Lung and its Effects on Deposition and Clearance of Inhaled Particles in Normal and Reduced Gravity (First Award Fellowship)
Rui Carlos Sa, Ph.D.
University of California, San Diego
When astronauts return to the moon, one concern will be the inhalation of lunar dust, which has toxic properties. Dr. Rui Carlos Sa is conducting a study to better understand how the patterns of air movement inside the lungs affect the distribution of small, inhaled particles and the removal rates of such particles.
Sa’s project will incorporate and add to ongoing research at the University of California, San Diego. Sa will map the movement and distribution patterns in normal gravity and combine it with existing lunar dust research results. The comparison of the normal gravity results and lunar gravity data will increase the understanding of the role of gravity in the movement and removal of particles in the lungs.
NASA Taskbook Entry
The goal of this project is to provide a better understanding of how variability in convective flow patterns in the lung affects aerosol deposition, and thus subsequent clearance between individuals. Such an understanding will allow better characterization of the normal variability in deposition and clearance rates both in Earth’s gravity and in low gravity, such as on the lunar surface.
Three key factors define the toxicological risk to the lung of exposure to airborne lunar dust which is believed to be highly reactive:
1. The degree of deposition.
2. The toxicological properties of the material itself.
3. The residence time within the lung of the particles once they have been deposited.
The distribution of ventilation within the lung determines deposition and subsequent clearance. Previous studies using computational fluid dynamics (CFD) in realistic central airway trees show that ventilation varies widely at the lobar bronchiole level. However, typical boundary conditions for deposition simulations assume that lung expansion is uniform, which we know to be incorrect. This group has developed a magnetic resonance imaging (MRI) technique that allows the quantification of regional specific ventilation in the human lung providing realistic boundary conditions and an accurate prediction of particle deposition.
1) Map the spatial pattern of specific ventilation.
2) Map deposition in the supine position at Earth’s gravity and combine these with data on the spatial pattern of deposition of inhaled particles collected in low gravity as part of Dr. Prisk’s existing NSBRI studies.
3) The measured pattern of aerosol deposition will be compared with the CFD predictions, using uniform and more realistic boundary conditions.
By comparing across a number of subjects, the mechanisms underlying the observed variability in deposition and regional ventilation can be elucidated. By comparing the data collected in Earth’s gravity with data from low-gravity, the magnitude of the gravitational effect can be assessed.
The researchers have successfully applied the MRI technique for quantifying specific ventilation in the human lung-Specific Ventilation Imaging- completing aim a). We have used this technique to quantify the vertical, gravitational induced, gradient in specific ventilation that is present on the human lung on earth. The findings are in accordance with previous radiation based techniques for quantifying specific ventilation. An article describing the technique was published during the second year in the Journal of Applied Physiology. A patent, protecting the intellectual property of this and two other MRI methodologies developed at our lab is currently actively pursued.
During the second year we have mapped particle deposition for 4μm particles, when inhalation occurs in the supine position (10 subjects) and recently in low-gravity (six subjects), addressing aim b).
The successful completion of Aim 1 was essential to completion the project. The data for addressing Aim 2 was recently collected for 4μm particles. Data analysis is under way. These results allow us to start CFD modeling, addressing Aim 3.
The researchers have collected deposition data for 4μm particles (aim b). A second parabolic flight campaign (1μm particles) is expected in the spring 2012. MATLAB based software tools for the analysis of this data developed by the fellow are in use for the analysis of ground (1-G) data. Further development and optimization of these tools for application to low-gravity acquired data is underway. Computational Fluid Dynamic modeling will begin soon. The third year will be dedicated to the analysis of the outcomes of these models, and establishing a metric for comparison with the measured deposition patterns. The researchers expect that, by imposing realistic instead of idealized boundary conditions, we will significantly improve our ability to predict particle deposition. Time will be dedicated to compiling and writing these results into a
The overall goal of this project is to better understand how variability in convective flow patterns in the lung affect aerosol deposition and subsequent clearance between individuals. Such knowledge will help better characterize the normal variability, both on the ground and in low gravity (the lunar surface), and thus better characterize the risks of exposure to potentially toxic, aggressive dust. This improved risk assessment is important for future lunar exploration because lunar dust is aggressive, highly reactive. In low gravity, dust particles are likely to deposit further down in the lung with increased residence time. As well, this improved risk assessment is important on Earth where many people are exposed to airborne dust.
From a different and more long-term perspective, a better understanding of the individual variability in deposition might also help optimize aerosol drug delivery with aerosols that will more accurately target specific portions of the lung.
In the framework of this project, we have developed a novel magnetic resonance imaging (MRI) technique for the quantification of specific ventilation in the human lung. The technique requires a standard proton MRI machine with a 1.5 Tesla field. These machines are widely available in clinical setting. The technique does not require the use of radiation and is therefore suitable for repeated measures. At this stage, we are using the technique as a novel research tool, but its repercussions can be extended to the clinical setting. The fact that this technique does not involve radiation opens a novel diagnostic window, and as a result, measures can be applied repetitively. This can be of particular importance in patient populations suffering from chronic respiratory diseases, such as chronic obstructive pulmonary disease. Patients with chronic disease could benefit from a noninvasive, zero - radiation dose assessment of their lung function, allowing for a more regular follow-up than the existing techniques.