PNNL-13501 - Pacific Northwest National Laboratory

other particulate defense systems to describe the overall
fate of matter and further refine the definition of dose to
the target cells.
Current, state-of-the-art dosimetry models, such as the
ICRP lung model (ICRP 1994) and the multiple path
particle deposition model (Anjilvel and Asgharian 1995;
Asgharian and Anjilvel 1998), are either empirical, do not
incorporate various clearance mechanisms, or are not
amenable to inclusion of altered lung function in
potentially sensitive human populations. These models
are, therefore, limited in their ability to extrapolate
beyond the experimental conditions from which the
models were based. The only modeling approaches that
can function reliably under a variety of exposure
scenarios are those that are developed with a strong
biological basis for the model structure. The goal for this
project is to develop and experimentally validate a threedimensional,
biologically based model of the respiratory
tract (virtual respiratory tract) capable of quantitating
dosimetry, clearance, and biological response in both
normal and compromised mammalian systems following
exposure to complex particulate matter. To accomplish
this goal, advancements were necessary in constructing
three-dimensional grid structures of the respiratory tract
and the development of new tools for imaging the
structure of the lung and to quantitate particles in specific
regions of the respiratory tract.
Approach
The project involved three, integrated thrust areas:
1) virtual lung model development and simulation,
2) NMR imaging of particulate matter and lung
morphometrics, and 3) in vivo/in vitro model
parameterization and validation studies.
Results and Accomplishments
Virtual Lung Model Development
An initial mathematical model was developed to establish
the computational requirements for the three-dimensional
models and to provide a backbone for overlaying a threedimensional
grid structure. Due to the high
computational requirements, the NW Phys/NW Grid
software was modified to operate on the massively
parrallel computer in EMSL. A three-dimensional grid
structure of the human lung (Figure 1), detailed to the
level of the terminal bronchiolar region (about 2 16
generations of airways), was developed using available
data. The alveolar region was structured using a simple
286 FY 2000 Laboratory Directed Research and Development Annual Report
Figure 1. A three-dimensional grid structure for the human
trachea and lung using NWGrid generation code
grid geometry to approximate the shapes of pulmonary
acini. This model was subsequently modified to include
visco-elasticity for expansion and contraction of airways
and linked with a computational fluid model for airflows
associated with inhalation and exhalation (Figure 2) and
particle movement within the airways. The lung model
was encased in a three-dimensional chest cavity with a
diaphragm and chest expansion to drive inhalation and
exhalation in the lungs (Figure 3). A particle deposition
model (Anjilvel and Asgharian 1995) was obtained to
compare simulations of the regional dosimetry (upper
respiratory tract, bronchiolar and alveolar regions) in rats
and humans with those predicted by the virtual lung
model. Grid structures and original morphometric data
for the upper respiratory tract were also obtained from
Dr. Julie Kimbell (Chemical Industry Institute of
Toxicology), a collaborator on the project to complete
the description of the entire respiratory tract.
Figure 2. Contour plot of airflows determined by a
computational fluid dynamics model through the terminal
bronchiole region of the human lung using NWPhys code