PNNL-13501 - Pacific Northwest National Laboratory

Figure 3. Use of the chest cavity and diaphragm to drive the
expansion/contraction of the grid structure for the human
lungs to simulate respiration
NMR Imaging Particle Deposition/Clearance and Lung
Morphometry
To image particulate matter in the lungs by NMR,
particles must have paramagnetic properties that alter the
relaxation properties of surrounding water (T1 relaxation
time) in biological tissues. Therefore, initial efforts
focused on assessing the properties of various particles
and developing the imaging methods required for
performing measurements of particle concentration. The
paramagnetic properties of fusinite (carbon black)
coupled with the extensive toxicity and dosimetry
database and similarity to diesel exhaust made this
particle an ideal candidate for further evaluation. Initial
dose-response measurements for the uptake of carbon
black by pulmonary macrophages indicated that this
technique is useful for determining rate constants
associated with this particle clearance mechanism.
A 2-tesla magnet, console, and high-resolution imaging
software were configured to image mouse lungs. To
quantify the concentration of particles in the lung,
methods were developed for mapping the T1 relaxation
time for water throughout lung tissue (Figure 4). The
results suggest that maps of particle concentration (T1)
with submillimeter resolution could be derived from
magnetic resonance image data.
In Vivo/In Vitro Model Parameterization and Validation
Studies
Preexisting disease conditions can dramatically alter the
function of the lung and thus the dosimetry of inhaled
particulate matter. Pulmonary macrophages may be
activated by certain particulates and release reactive
RT = 0.3 sec RT = 0.7 sec RT = 1.4 sec
RT = 3.0 sec RT = 6.0 sec
A B
Figure 4. A spatial map of the T 1 relaxation time for water
in lung tissue is created by first collecting a series of T 1weighted
magnetic resonance images. In the example shown
above, five T 1-weighted magnetic resonance images of a
mouse are shown. Each was acquired using a saturationrecovery
sequence run with a different recovery time. All
images show the same 2.0-millimeter-thick slice in which the
heart (A), spinal column (B), and lung parenchyma (outlined
in red) are clearly visible. By post-processing the raw image
data, a synthetic T 1-map of the lung parenchyma is created
where contrast only depends on the measured T 1 in each
pixel of the image data. In the example shown, planar
resolution is 0.5 x 0.5 squared millimeters and raw image
data required 40 minutes to collect.
oxygen species, cytokines, or growth factors which may
lead to further tissue damage and affect lung function.
Various inhibitors of these pathways were used in
preliminary studies to determine which cell signaling or
inflammatory pathways were activated by particulates to
evaluate their roles in tissue response.
Summary and Conclusions
T1 Map
0.5 1.4
An initial, three-dimensional lung model was developed
that will serve as the basis for simulating the deposition of
particles in the lung in the second year of the project. The
three-dimensional grid structure and computational fluid
dynamics model for the respiratory tract represents a
significant improvement over existing models for defining
detailed, regional-specific dosimetry of inhaled particles
over a broad range of potential exposure scenarios. The
model will ultimately have the flexibility to simulate the
effects of preexisting disease conditions on particulate
dosimetry. Preliminary studies with NMR imaging also
demonstrated that this technique may be useful in
developing the necessary data for further refinement of
three-dimensional grid structures of the respiratory tract
as well as particle quantitation. As further refinements
are made to the imaging techniques, NMR may
revolutionize experimental techniques for determining the
deposition and clearance of inhaled particulate matter.
Human Health and Safety 287