PNNL-13501 - Pacific Northwest National Laboratory

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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
References Anjilvel S, and B Asgharian. 1995. “A multi-path model of particle deposition in the rat lung.” Fund. Appl. Toxicol, 28:41-50. Asgharian B, and S Anjilvel. 1998. “A multi-path model of fiber deposition in the rat lung.” Tox. Sci. 44:80–86. ICRP. 1994. Human respiratory tract model for radiological protection. A report of a Task Group of the International Commission on Radiation Protection. ICRP Publication 66. Ann. Of the ICRP 24, Nos. 1-3. 288 FY 2000 Laboratory Directed Research and Development Annual Report National Research Council. 1998. Research priorities for airborne particulate matter. I. Immediate priorities and a long range research portfolio. National Academy Press, Washington, D.C. Presentation Timchalk C, RA Corley, HE Trease, K Minard, SH Elder, JS Oliveira, and DA Dixon. June 2000. “Development of a three-dimensional virtual respiratory tract model for studying the health implications of airborne particulate matter.” Human Biology Models for Environmental Health. A Virtual Body Workshop sponsored by NIEHS/PNNL. RTP, North Carolina.
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Laboratory Directed Research and De
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Laboratory Directed Research and De
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Computational Science and Engineeri
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Policy and Management Sciences Asse
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Introduction Department of Energy O
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5. After reviews by the Technical a
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• The Technical Council peer revi
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methods applicable to combustion, s
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Summary Each national laboratory mu
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Study Control Number: PN0004/1411 A
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Table 1. Positive and negative ions
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m/z Arbitrary Units Figure 1. Mass
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introduce low-volatility compounds
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arrangement, but the charge is reta
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two liquid chromatographic gradient
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Integrated Microfabricated Devices
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Matrix Assisted Laser Desorption/Io
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Molecular Beam Synthesis and Charac
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temperature distribution of the des
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expected to result in significant a
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Study Control Number: PN99069/1397
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Seuss DT and KA Prather. 1999. “M
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Analysis of Receptor-Modulated Ion
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laboratory (Lu and Xie 1997; Lu et
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Automated DNA Fingerprinting Microa
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Comparison of 4 Xanthomonas Isolate
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Approach Hematopoietic (bone marrow
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Anti-Human lgG Human lgG Protein G
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Characterization of Global Gene Reg
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PCR products for immobilization on
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identify novel proteins of importan
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Immunoprecipitaton of tyrosinephosp
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Coupled NMR and Confocal Microscopy
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In the optical microscopy image, th
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Development and Applications of a M
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Figure 3. Hepa-1 cells undergoing a
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cellular processing (such as post-t
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8. Initial demonstration of an off-
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expression systems for several year
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accumulation of protein products, i
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Fungal Conversion of Agricultural W
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Fungal Conversion of Waste Glucose/
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Summary and Conclusions We demonstr
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are shown in Figure 1(a) and 1(b),
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Anchorage-Independent Growth (% con
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selection of seedlings demonstratin
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NMR-Based Structural Genomics Micha
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Solution-State Structure and Fold-C
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Plant Root Exudates and Microbial G
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Summary and Conclusions • The gre
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Jones-Oliveira JB, JS Oliveira, HE
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• securely moves files to a targe
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Plenary invited lecture, “The Ele
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Figure 1. X3DGEN tetrahedral mesh o
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Figure 5a. OSO volume rendering of
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Development of Models of Cell-Signa
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SOS p 23 EGFR Professor Rodland at
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Oliveira JS, JB Jones-Oliveira, and
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Figure 2. Associating a dataset mar
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to 1) incorporate three-dimensional
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shown in Figure 1. Simulated result
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HostBuilder: A Tool for the Combina
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Invariant Discretization Methods fo
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Graphics, Inc., workstation. The co
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Mixed Hamiltonian Methods for Geoch
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guyanaite, and grimaldiite (see Fig
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in the Environmental Molecular Scie
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Simulation and Modeling of Electroc
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Summary and Conclusions We implemen
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Since the implementation of the gen
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asis of previous performance, perce
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Bioinformatics for High-Throughput
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Summary and Conclusions In previous
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User Cat - Supervisor (client) Anal
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The second goal was to research way
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Figure 1. A visualization technique
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and interactions. The flexibility o
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Figure 4. A filtered version of Fig
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Development of Modeling Tools for J
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Figure 2. Schematic of experimental
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Integrated Modeling and Simulation
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(a) (b) (c) (d) Figure 1. Results o
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Thurman DA. August 2000. Collaborat
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MARC Input initial m esh and result
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(Johnson 1999; Colligan 1999; Gould
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Modeling of High-Velocity Forming f
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Global divergence error 1 10 -14 0
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that users were unlikely to appreci
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Earth System Science
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the lateral extent of the plume so
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Biogeochemical Processes and Microb
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Analyses of populations of viable a
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The first task was to establish fiv
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purged for 2 minutes. The gas sampl
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developing code architecture to min
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Berkowitz, CM. June 2000. “Atmosp
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environmental monitoring, 2) portab
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corresponded to a current density o
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Enhancing Emissions Pre-Processing
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Environmental Fate and Effects of D
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nitrogen and unpredictable eutrophi
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Figure 1. Ordinary kriging of 2 m d
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precipitation of calcite occurred i
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Interrelationships Between Processe
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phenanthrene resistant fraction con
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Page 250 and 251: Application of a Crop Model The res
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Development of Novel Photo-Catalyst
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-2 -1 Energy (eV) 0 1 2 Cu2O SrTiO3
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Here, we perform adsorption and des
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exceed those in the all-metal devic
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Intensity (a.u.) 0 100 200 300 400
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integrated voltage (V) 0.10 0.08 0.
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The first step was to implement thi
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Spontaneous Formation of Cu2O Nano-
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Actinide Chemistry at the Aqueous-M
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Figure 5. Close-up atomic force mic
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to 300°C and 400°C. Unfortunately
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Summary and Conclusions Transmutati
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Advanced Calibration/Registration T
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Figure 1a. Violet filter Figure 1b.
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Autonomous Ultrasonic Probe for Pro
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containing nitrous oxide, an optica
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Chemical Detection Using Cavity Enh
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Figure 3 is a color rendered simula
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appropriate study has been performe
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Exploitation of Conventional Chemic
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Figures 3 and 4 illustrate the impa
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enefits of using a modified spread-
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Single Channel Signal 0.0025 0.0020
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Therefore, in order to extract the
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A next-generation technology is nee
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Wind Dir. Figure 2. Negative ion co
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Volumetric Imaging of Materials by
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amplitude and peak frequency change
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Figure 3. 13 C NMR spectrum of corn
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Approach Two flow loops, one that o
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Modification of Ion Exchange Resins
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Permanganate Treatment for the Deco
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minimized by medium exchange. After
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Figure 1. Thermogravimetric analysi
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Validation and Scale-Up of Monosacc
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Concentration (g/100g solution) Con
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Analysis of High-Volume, Hyper-Dime
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ecent figure of merit values. Shoul
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Probabilistic Methods Development f
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a) Traditional PCA-based process co
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Acronyms and Abbreviations 2-D two-
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PNNL-13501 - Pacific Northwest National Laboratory

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