This is a proposal for a Bioengineering Partnership Grant to build a
CT-based Model of the normal human lung with associated parameters representing
the range of normal for the various measurable anatomic and physiologic
features with the notion that this will form a basis against which to compare
subjects with suspected pathology. Funds are included for the establishment
of a high speed, high resolution, multi-slice, spiral CT scanning facility
to be used for both human and animal research. The partnership includes
investigators from the University of Iowa, Mayo Clinic, Johns Hopkins
University, Marquette University, and Purdue University.
MIFAR is a set of software tools for storing medical image data along
with other associated post-image processing files, physiologic records,
lab notes, etc. In addition to storing the data, MIFAR provides a framework
for batch processing of image data. The heart of the system is a relational
database that coordinates the activities of multiple small server programs
spread across a network.
Lung Image Database with Pathologic Correlates
This is a multi-center NIH supported study involving 5
academic sites, the NCI and the FDA. The project's goal is to
create an internationally accessible database of CT scans with
and without lung nodules. This will be accompanied by pathology
ground truth. The database will be maintained by the NCI as a
resource for validating computer CAD methods for the detection
and characterization of early lung cancer. In a subset of subjects,
3D pathology will be obtained to compare against the CT findings.
Our group will provide:
a well characterized group of study subjects with lung cancer
expertise in the development of CT imaging protocols.
a functional electronic transfer system for CT data sets from multiple sites
methods for temporal matching of CT data points across time and to histopathological data.
expertise in computational morphology, (i.e. the mathematical description of complex structures, their visualization, and their derived CT images).
Image reconstruction algorithms.
data from two different CT manufacturers multi-slice helical CT scanners.
with mathematically derived virtual lung models.
MESA: Endothelial Dysfunction, Biomarkers And Lung Function
The Iowa Lung Reading Center will accept CTs images from the MESA CT
Reading Center (REI), upload images, analyze them for measures of lung density,
perform post-processing of results data, and transmit results to the MESA
Coordinating Center. The included CT images will be for all pairs of CT images
obtained from participants that are selected for inclusion in MESA-Lung, plus
a 10% QA sample.
Severe Asthma Research Program (SARP)
Severe asthma affects a ten percent of asthma patients but uses
a disproportionate amount of health care resources. It is also responsible
for a significant amount of the morbidity and mortality associated with
asthma. The purpose of this study to establish a collaborative program of eight
different sites
to investigate the mechanistic basis for severe asthma and how it differs
from mild-to-moderate asthma. Each site will work under a standardized definition
of severe asthma and follow uniform procedures. Our site will collect the CT
data from the eight sites and serve as a storeage site. Our site will
analyze the CT data and send the outcomes to the coordinating center for
the study.
ENDOCT -- High Resolution CT-based Evaluation Of Airway Responses To Endotoxin
Inhalation
Asthma, a disorder of airway inflammation, airflow obstruction, and
hyperresponsiveness, has been increasing in prevalence and severity over
the past several decades. An important subset of asthma is that seen in
the workplace, especially in agricultural settings. Following inhalation
of organic dusts, asthmatics (and many non-asthmatics) develop airflow obstruction.
Endotoxin is an important dust component that leads to airway inflammation
and airflow obstruction. Importantly, currently available asthma therapies
have little effect on endotoxin-induced lung disease 1, leading to few
options for asthmatics who wish to continue working on the farm. Inhaled
corticosteroids, the "gold standard" treatment, have been optimized for
delivery to relatively large airways; responses to endotoxin may occur
in smaller, more distal bronchi, thus reducing the benefit of these agents.
To better understand endotoxin-induced airways disease, we propose the
hypothesis that inhaled endotoxin induces a specific and characteristic
pattern of inflammation and bronchospasm among individuals with hyperreactive
airways, which we will study in the following Specific Aims:
Evaluate, using high-resolution computed tomography scanning,
the heterogeneity and spatial pattern of endotoxin-induced bronchospasm
in normal subjects.
Compare these effects of endotoxin inhalation between normal
and mild asthmatic subjects.
Compare the effects of inhaled endotoxin and inhaled methacholine
on patterns of bronchospasm in mild asthmatic subjects.
This study will improve our understanding of the natural history of asthma
as well as that of airway inflammation from inhaled organic dusts. In
addition, it may lead to novel therapeutic approaches to the treatment
of asthma and airway responses in farmers.
APLD -- Air Pollution And Lung Structure Study
Lung function growth is frequently quantified using spirometry in
environmental epidemiologic studies of air pollution. Many studies have
focused on the effects of acute exposures on short-term changes in airway
function; however, few have investigated the long-term effects of chronic
exposure on childhood lung function. Findings from the Children's Health
Study, a 10-year longitudinal study of the chronic effects of air pollution
among 6000 children residing in 12 Southern California communities, indicate
that current levels of particulate matter, nitrogen dioxide, and vapor acids
are associated with reduced lung function growth and lower maximum attained
measures of airway flows. The deficits (up to 8-10%) are largest and most
consistent for FEV1, MMEF and FEF75, suggesting that flows from small airways
are reduced. The magnitude of these deficits is of great concern, as irreversible
reduction in airway flows has been associated with increased risk for COPD,
cardiovascular disease and all cause mortality. A better understanding of
the mechanisms for the deficits is required to determine whether there are
long-term risks associated with the deficits in lung function. Although it
is essential to identity the mechanism for these deficits, the biologic
basis underlying these spirometric deficits has yet to be determined. It
is critically important to establish whether the deficits in flows occur
as a result of irreversible anatomic changes in the airway structure, size
or wall thickness that indicate elevated long-term risk for adverse health
outcomes, or whether the deficits arise from potentially reversible physiologic
changes that may not influence long-term risk. If the deficits reflect
structural changes, then individuals with deficits from air pollution are
likely to be at increased risk for developing COPD and perhaps cardiovascular
disease. Results from recent studies in primates by Plopper et al. show that
air pollution exposure produces marked structural changes in the airways and
parenchyma resulting in changes in branching structure as well as wall diameter.
These finding indicate that studies of the structural effects of air pollution
must consider both large and small-scale changes in airways structure.
Recent developments in lung imaging using High-Resolution Computerized
Tomography (HRCT) now make it feasible to non-invasively study the
structure of small airways as small as 2mm in diameter and the entire
airway using volumetric reconstructions. These developments make it
possible to investigate the anatomic relationship between air pollution
associated deficits in spirometric measures of airway flow and permanent
changes in the structure and function of small airways, overall airway
geometry and lung parenchymal changes.
In this study, we will:
Develop methods and test the feasibility for a study of the
effects of air pollution on lung structure using HRCT to assess small
airway diameter, wall thickness and luminal area, air trapping and
parenchymal changes among Children's Health Study participants with contrasting
exposure histories.
Determine the relationships between small airway diameter, wall
thickness and luminal area, air trapping and parenchymal changes and
childhood pollution exposures (Ozone, NO2, PM10, PM2.5).
Assess the relationships between anatomic CT measurements, lung function
deficits, and exhaled nitric oxide (NO) levels
Assessment of Variations in Human Airway Geometry and the Implications for Evaluation of Partical
Deposition and Dose to Different Populations
The project's goal is to develop methods for extraction of airway morphometry
data from individual CT scans in order to better understand the deposition of inhaled
particulate matter in the airways. One male and one female adult and pediatric subject
will be scanned. From each scan the airway tree will be recreated out to the first
3-4 generations. The airway cross sectional area will be measured along the airway
tree. Three-dimensional images will be made and then converted to a solid model by
stereolithograpy. The ultimate goal is to quantify the impact of the variability of
the human airway geometry on the deposition of inhaled particulate matter.
Use of Exogenous Surfactant to Mitigate Acute Lung Injury
The project's goal is to utilize state-of-the-art noninvasive
computed tomography (CT) imaging techniques to improve our understanding
of regional lung mechanics and ventilatory function in the pathogenesis
and treatment of acute lung injury, particularly with respect to early
intervention and treatment with exogenous surfactant. The observed regional
functional changes will be correlated with the measurements of local
surfactant function and gene expression for inflammation and surfactant
proteins, assessed from regional samples of lung tissue and secretions.
These new insights will lead to greatly improved diagnosis and therapy of
traumatic lung injuries. This project is in collaboration with Johns Hopkins
University.
The Transnational Alliance mission is to provide advantage to the broad
programs of the University of Iowa and the UIHC, and to participating
institutions in South Australia, by providing a mechanism for communication,
collaboration, and cooperation, in areas of basic and applied research,
in educational activities, and in clinical areas.
Environmental Health Science Research Center
The projects goal is to operate an interdisciplinary environmental
health sciences research center with a focus on agricultural and rural
environmental exposures and health effects. The center includes 51 faculty
from the Colleges of Public Health, Medicine, and Engineering in the
following research areas-the Environmental Epidemiology Research Core,
the Pulmonary Biology Research Core, and the Assessment and Control
Research Core. The Center will focus on health outcomes highly relevant
to agricultural and rural environmental health: cancer, adverse reproductive
outcomes, and respiratory disease.
Prognostication in Idiopathic Interstitial Pneumonia
The project's goal is to examine pronostic factors in patients with idiopathic
interstital pneumonia. The model will use a computerized analysis of the
computer tomography (CT) data using an Adaptive Multiple Feature Method
approach to determine baseline and serial optimal timing
for lung transplantation. This model will help patients and physicians decide
on the optimal timing for lung transplantation. This project is in
collaboration with the University of Michigan Medical Center.
Virtual True Color Bronchoscopy to Detect Lung Cancer
This is an NIH supported study. The project's goal is to
develop an integrated color-bronchoscopy and lung computerized
tomography (CT) based approach to diagnose lung cancer in large
airways. CT will provide will thickness morphology and airway
topology. The color-bronchoscopy will provide the airway topology
and color and texture information by showing the fluorescent markers
that could identify cancer. The project will develop an integrated
automated and analytic tool for assessing lung cancer.
Development of Airway Imaging Using HP 3He MRI
The project's goal is to show that the use of HP 3He and magnetic
resonance imaging (MRI) provides similar airway resolution as
computed tomography (CT) with out the risk of radiation exposure.
This project will develop both airway and ventilation quantification
methods in order to calculate airway diameters in both healthy and
asthmatic subjects. The airway hyper-reactivity of asthma can be
explored in this manner. These results will be compared to the standard
CT results as a method of validation of the HP 3He MRI protocol.
This project is in collaboration with Brigham and Women's
Hospital.
Development and Integrate Bioluminescence CT and Micro-CT for Molecular
and Dynamic Imaging
This is a joint project between Dr. Wang's Laboratory,
Dr. Hoffman's Division and Dr. McLennan's Laboratory. The project
is under NIH support to develop an integrated bioluminescence CT and
micro-CT system for imaging the mouse, especially the lungs.
The bioluminescent CT device will detect emitted photons and then
reconstruct the source distribution inside the mouse. The development
of the micro-CT with dual imaging chains permits about 20 micron
image resolution in a living mouse. Combining the bioluminescent
and CT images, sufficient details of gene expression, keyed to
micro-CT based structures, can be obtained, which may generate
critical physiological and pathological information on the anatomy
and function of the mouse lung.
3D Imaging and Computer Modeling of the Respiratory Tract
This project has several goals. The first goal is to develop
and apply magnetic resonance imaging and fluorescent microsphere
techniques to determine the dynamic, 3D structural and functional
properties of the respiratory tract. The second goal is to determine
the 3D cellular physiology. The third goal is to combine the 3D
modeling with the cellular module and to make a normative atlas of
the rat lung. The next goal is to conduct in vivo gas exchange and
particulate dosimetry studies for model validation. The last goal is
to provide a web-based database and web-based training on using the
normative rat lung atlas. This project is bioengineering research
partnership grant in collaboration with the Pacific Northwest
National Laboratory, the University of Washington, the University of
California at Davis, Oregon State University, the University of Utah,
CIIT Center for Health Research, The Mountain-Whisper-Light Statistical
Consulting, and the Computational Geometry Consulting.
National Lung Screening Trial
This is an NIH supported 25-center randomized study to
determine if screening for lung cancer with either chest x-ray, or
CT scan, makes any impact on lung cancer survival. The study has
just completed initial enrollment and will run for another 7 years
determining outcome.