2002 Progress Report: X-ray CT-based Assessment of Variations in Human Airway Geometry: Implications for Evaluation of Particle Deposition and Dose to Different Populations

EPA Grant Number: R827351C002
Subproject: this is subproject number 002 , established and managed by the Center Director under grant R827351
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: EPA NYU PM Center: Health Risks of PM Components
Center Director: N/A
Title: X-ray CT-based Assessment of Variations in Human Airway Geometry: Implications for Evaluation of Particle Deposition and Dose to Different Populations
Investigators: Cohen, Beverly S. , Hoffman, Eric
Institution: New York University School of Medicine , University of Iowa
EPA Project Officer: Chung, Serena
Project Period: June 1, 1999 through May 31, 2005 (Extended to May 31, 2006)
Project Period Covered by this Report: June 1, 2002 through May 31, 2003
RFA: Airborne Particulate Matter (PM) Centers (1999) RFA Text |  Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air

Objective:

The objective of this research project is to address the paucity of data regarding particulate matter (PM) deposition in the lungs of people with preexisting pulmonary disease and the normal elderly; subpopulations which may be at special risk. This project is investigating the potential for retrieval of morphometric data from three-dimensional images of tracheobronchial airways obtained in vivo by x-ray computerized tomography (CT). The study also is exploring the potential for the use of stereolithography (STL) to produce hollow airway casts of normal and abnormal lung airways for the experimental determination of site-specific deposition and for experimental verification of particle deposition models. We are using these tools to compare inhaled particle deposition pattern and efficiency in sheep in vivo with the deposition measured in a hollow airway cast prepared from the same animal’s three-dimensional image for a variety of breathing patterns, and when particles are inhaled at different points in the respiratory cycle. We also plan to: (1) select representative lungs of patients with clinically diagnosed lung diseases using the extensive database being established at the University of Iowa; (2) prepare hollow airway casts; and (3) test deposition in these casts. These data will test and validate theoretical and empirical models used to predict detailed particle deposition in living individuals, including those representative of various potentially susceptible subgroups. The ultimate goal of the project is to quantify the impact of the airway variability on PM deposition and dose. This project is a collaboration between the extensive imaging expertise at the University of Iowa and New York University (NYU) PM Center particle deposition expertise.

Progress Summary:

Progress in Years 1-2 of the Project. A volumetric rendering of the interior surface of a hollow airway cast (used in previous studies at NYU) was generated, producing a surface representation of the airway tree. These three-dimensional images then were converted to a STL file format required for the rapid prototyping of airway casts. This was accomplished by shape-based interpolation to create isotropic voxels and to smooth the surface, after which a volumetric rendering of the resultant segmented luminal space of the airway tree phantom was generated. The stereolithography unit uses a computer-controlled arm connected to a plastic extrusion device to build volumetric structures layer by layer. Two heads are present on the machine, one to lay down the plastic compound for the structure of interest, and a second head to lay down needed support material for the structure as it is being built and which can later be separated from the structure. Close concordance was seen between the original hollow airway cast and the STL-produced replicate. The casting process was subsequently converted to utilize a water soluble material to cast supporting structures.

Thin multislice helical CT scanning allows the acquisition of high-resolution volumetric image data sets of the lung in a breath-hold or at multiple phases within a respiratory cycle. From these scans, hollow airway casts that include five or six bronchial generations can be created. The process was utilized to obtain an image and then produce a cast from a living person. The casts can be accurately replicated for use in studies of inhaled particle deposition in replicate casts of both healthy and diseased airways using realistic air flow rates.

Progress in Years 3 and 4 (Follow-up Study). We have performed preparatory work for our in vivo studies to compare inhaled particle deposition pattern and efficiency in sheep, with the deposition measured in a hollow airway cast prepared from the same animal’s three-dimensional image. Our Iowa collaborators have continued to work on the development of sheep models for the testing of various measures of pulmonary perfusion, regional ventilation, airway structure and distensibility, diaphragm and rib cage mechanics, etc. We have fine-tuned our methods of respiratory gating and have succeeded in developing methodology that allows us to gate image acquisition very accurately to an inductance plethysmographic (Respitrace) signal, and acquire volumetric images of the lung at multiple points within the respiratory cycle over a period of 30 cycles. Although it is common to monitor airflow at the mouth and lung volumes, the accuracy required by the above-described respiratory gated image acquisition requires much tighter tolerances than most pulmonary function testing equipment. Significant advancements in computerized analysis have been made in the areas of lung, lobe and airway segmentation, airway tree matching, and lung feature matching. A set of reproducible feature points are first identified, including airway branching points, for each CT image to establish correspondences across subjects.

The binary airway tree is skeletonized to identify the three-dimensional centerlines of individual branches and to determine the branchpoint locations. Graph algorithms then can be applied to match corresponding branchpoints. A program was developed that visualizes two airway trees side by side and allows a human observer to navigate through the trees in the three-dimensional space and to define matching branchpoints by hand. This is an invaluable tool that provides independent standards. An evaluation using phantom data as well as in vivo scans showed excellent agreement (between 85 percent and 97 percent) between the automatically obtained matches and matches provided by human experts. These methods will assist development of concordant measures across bronchial branches in different individuals. We also have begun to establish methodology to perform computational fluid dynamics measures on specific airway geometries imaged by CT so as to predict deposition patterns and then to compare them with direct CT-based measures of deposition.

The Iowa team also is examining how spatial resolution varies as a function of position in the field of view. A phantom was made containing 37 copper spheres 1/32" (0.8 mm) in diameter that were placed in three concentric rings at 50 mm, 100 mm, and 150 mm. The phantom was scanned and reconstructed and a computer simulation was performed to construct a volume similar to that generated by the scanners. Issues of falloff of resolution away from the isocenter remain to be resolved. Work at NYU is in progress to develop a suitable monodisperse radio-opaque test aerosol. We have x-ray tested common contrast media to determine the smallest layer that can be distinguished from a unit density background, but results to date are not satisfactory. We currently are preparing casts of the sheep thorax to be used for the cast deposition experiments.

Future Activities:

We will continue efforts to establish methodology to perform computational fluid dynamics measures on specific airway geometries imaged by CT so as to predict deposition patterns and then to compare them with direct CT-based measures of deposition. We will continue to develop a suitable monodisperse radio-opaque test aerosol, and to determine the smallest layer that can be distinguished from a unit density background. We will initiate the sheep thorax cast deposition experiments. The artificial thorax will enable us to use both excised sheep lungs and airway casts with realistic simulated breathing. The lungs will be obtained from sheep that are sacrificed in other studies at the University of Iowa. Inhalation and exhalation patterns can be controlled with a synthetic flexible diaphragm. This artificial thorax can be used to further establish experimental parameters prior to carrying out studies in a live animal.

Journal Articles:

No journal articles submitted with this report: View all 1 publications for this subproject

Supplemental Keywords:

air pollution, air pollutants, particulate matter, PM, fine particles, fine particulates, PM2.5, pulmonary disease, respiratory disease, lung disease, health effects, PM deposition, elderly, susceptible populations, tracheobronchial airways, stereolithography, x-ray computerized tomography, airway variability, PM deposition and dose., RFA, Health, Scientific Discipline, PHYSICAL ASPECTS, Air, ENVIRONMENTAL MANAGEMENT, particulate matter, Environmental Chemistry, Health Risk Assessment, Risk Assessments, Environmental Monitoring, Physical Processes, Atmospheric Sciences, Risk Assessment, ambient air quality, atmospheric particulate matter, particulates, air toxics, atmospheric particles, chemical characteristics, toxicology, ambient air monitoring, acute lung injury, airborne particulate matter, environmental risks, exposure, epidemelogy, air pollution, aerosol composition, atmospheric aerosol particles, human exposure, PM, X-ray tomagraphy, airway contractile properties, exposure assessment

Relevant Websites:

http://charlotte.med.nyu.edu/epa-pm-center/ Exit

Progress and Final Reports:

Original Abstract
  • 1999 Progress Report
  • 2000 Progress Report
  • 2001 Progress Report
  • 2003 Progress Report
  • 2004
  • Final Report

  • Main Center Abstract and Reports:

    R827351    EPA NYU PM Center: Health Risks of PM Components

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R827351C001 Exposure Characterization Error
    R827351C002 X-ray CT-based Assessment of Variations in Human Airway Geometry: Implications for Evaluation of Particle Deposition and Dose to Different Populations
    R827351C003 Asthma Susceptibility to PM2.5
    R827351C004 Health Effects of Ambient Air PM in Controlled Human Exposures
    R827351C005 Physicochemical Parameters of Combustion Generated Atmospheres as Determinants of PM Toxicity
    R827351C006 Effects of Particle-Associated Irritants on the Cardiovascular System
    R827351C007 Role of PM-Associated Transition Metals in Exacerbating Infectious Pneumoniae in Exposed Rats
    R827351C008 Immunomodulation by PM: Role of Metal Composition and Pulmonary Phagocyte Iron Status
    R827351C009 Health Risks of Particulate Matter Components: Center Service Core
    R827351C010 Lung Hypoxia as Potential Mechanisms for PM-Induced Health Effects
    R827351C011 Urban PM2.5 Surface Chemistry and Interactions with Bronchoalveolar Lavage Fluid (BALF)
    R827351C012 Subchronic PM2.5 Exposure Study at the NYU PM Center
    R827351C013 Long Term Health Effects of Concentrated Ambient PM2.5
    R827351C014 PM Components and NYC Respiratory and Cardiovascular Morbidity
    R827351C015 Development of a Real-Time Monitoring System for Acidity and Soluble Components in Airborne Particulate Matter
    R827351C016 Automated Real-Time Ambient Fine PM Monitoring System