(Chest. 2001;119:1878-1885.)
© 2001
American College of Chest Physicians
Methacholine-Induced Temporal Changes in Airway Geometry and Lung Density by CT*
Israel Amirav, MD
;
Sandra S. Kramer, MD and
Michael M. Grunstein, MD, PhD
*
From the Division of Pulmonary Medicine (Drs. Amirav and Grunstein) and Department of Radiology (Dr. Kramer), The Children’s Hospital of Philadelphia, Philadelphia, PA.
Currently at the Division of Pediatrics Pulmonology, Sieff Government
Hospital, Safed, Israel.
Correspondence to: Israel Amirav, MD, Hanarkis 41 Rosh Pina, 12000 Israel; e-mail: amirav{at}012.net.il
 |
Abstract
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Purpose: Electron-beam CT (EBCT) was utilized to assess
the time course of changes in airways cross-sectional area (CSA) and
lung density during methacholine-induced bronchoconstriction.
Materials and methods: EBCT scans (200 ms, 3-mm thickness,
2 mm increments) were obtained before (baseline) and 30 s, 2 min,
and 4 min after bolus IV injection of methacholine to pigs receiving
mechanical ventilation. A total of seven experiments were analyzed
using custom-made image analysis software. With each challenge, five
different airways and 50 lung regions of interest were studied.
Results: The time course of lung density changes paralleled
the time course for CSA changes. The maximal response to methacholine,
measured in terms of both CSA and lung density changes, occurred
30 s after injection. Lung density changes were unaffected by
reconstruction algorithm, normal (standard) or sharp (high resolution).
Overall, there was increased air content in the lung during
bronchoconstriction. This effect was significantly greater at the
dependent lung regions.
Conclusions: EBCT is an
effective tool to assess temporal and regional changes in the lung
during bronchoconstriction. Measurements of lung density during
bronchoconstriction allow for assessment of peripheral changes that are
beyond the CT spatial resolution of airways anatomy.
Key Words: bronchoconstriction • CT • electron beam CT • image processing • lung density • methacholine
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Introduction
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Recent
advances in the use of high-resolution CT (HRCT) techniques have led to
improved tools for the assessment of lung structure and function
related to a number of clinically relevant questions, including airway
reactivity. We have previously demonstrated1
the
feasibility of electron-beam CT (EBCT) to objectively measure
dose-related changes in airway geometry during IV methacholine-induced
bronchoconstriction. These changes may influence more peripheral
regional lung response to methacholine, namely lung density,
which in turn may allow us to analyze peripheral events beyond the CT
spatial resolution of bronchial anatomy. In addition, the temporal
aspects of methacholine-induced changes in both airway geometry and
lung density have not been well defined. The purpose of the present
study was twofold: (1) to use EBCT with HRCT as a noninvasive method to
evaluate the time course of changes in airway geometry following a
single IV bolus injection of methacholine to pigs, and (2) to assess
associated changes in lung density. In order to determine the validity
of lung density measurements made from HRCT scans, we also compared CT
data reconstructed with "normal" and "sharp" algorithms.
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Materials and Methods
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Experimental Protocol
Experiments were performed on pigs aged 5 to 7 weeks, with a
mean (± SD) weight of 15.1 ± 1.2 kg. They were handled in
accordance with national standards, and the protocol was
approved by the Children’s Hospital of Philadelphia’s Animal Care and
Use Committee.
Three pigs were anesthetized with sodium pentobarbital (30 mg/kg given
intraperitoneally) and droperidol (2 mg IV every half hour).
Additional anesthesia was administered as necessary judged by altered
heart rate from baseline, arterial BP, and compliance with
positive-pressure ventilation. After induction of anesthesia, a
tracheostomy was performed using a shortened No. 6 endotracheal tube
tightly bound in place. Fluid and drugs were administered via a jugular
venous line. Animals were placed in a supine position and received
ventilation with a programmable ventilator (model CTP-9000; CWE;
Ardmore, PA) set for constant flow of room air. All animals were
paralyzed IV with pancuronium bromide (100 µg/kg initially and 75 to
100 µg/kg supplementary), ensuring complete control over lung volume
and apnea during scanning. Heart rate and arterial BP were monitored
continuously. Respiratory measurements consisted of pressure at the
airway opening (airway pressure [Pao]) and airflow. All signals were
amplified using Gould amplifiers, passed through a 12-bit analog to
digital converter on an NB-M10–16 h interface board (National
Instruments; Austin, TX), sampled at a rate of 150 Hz, and stored on a
personal computer running a programmable monitoring software package
(Labview; National Instruments). The Pao pressure signals were also
displayed and recorded on a Gould X-Y plotter (Gould Electronics;
Eastlake, OH).
CT scans were obtained before (baseline) and after bolus IV injection
of methacholine to pigs. In previous experiments in which we measured
dose-response curves to methacholine in pigs,1
we
determined that a single methacholine dose of
10-7 mmol/kg resulted in approximately
200% increase in peak Pao. We found also that this dose was tolerated
by all animals without significant side effects and was thus used
throughout the present study. Methacholine, freshly prepared before
each experiment, was administered IV in 3 mL of saline solution
followed by a 3-mL saline solution flush. We initiated the first
postmethacholine scan immediately following peak Pao response at
approximately 30 s after the IV bolus. The EBCT scan protocol
lasted approximately 25 s and was repeated at 2 min and 4 min
after methacholine injection. This scan sequence was carried out seven
times using three pigs. Each pig was studied on a separate day. Two
scans were performed on the first animal, two on the second, and three
on the third. There was at least a 1-h interval between the end of a
study to the beginning of the next study in individual pigs, allowing
all physiologic indexes to return to baseline values.
Tracings of Pao from a representative study shown in Figure 1 serve to demonstrate the protocol. To ensure a standard volume history,
the ventilator was programmed to stop ventilation temporarily at
end-expiration functional residual capacity (FRC), then inflate the
lungs to a Pao of 25 cm H2O for 5 s, and
then deflate the lungs to FRC for 5 s for two consecutive breaths
after which ventilation was resumed. One minute later, ventilation was
suspended at FRC for a baseline scan. Following the scan, ventilation
was resumed; 1 min later, methacholine was administered. Ventilation
continued uninterrupted for 30 s after injection. At that point,
ventilation was stopped at FRC and a first postmethacholine scan was
obtained. Ventilation was resumed at the end of scanning, and
subsequent scans (without a standard volume history maneuver) were
obtained at 2 min and 4 min after methacholine administration.
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Figure 1. Tracings of Pao from a representative study. After
a standard volume history, HRCT scans were obtained before, and 30
s, 2 min, and 4 min after IV injection of methacholine (MCh).
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EBCT
This study utilized the FASTRAC C-100 CT scanner (Imatron; South
San Francisco, CA), an electron-beam scanner, employing the
"high-resolution" mode. The following parameters were used:
512 x 512 matrix, 12.7-cm reconstruction circle (in plane pixel
dimension = 0.248 mm), 3 mm-slice thickness, 2-mm-slice increments,
125 kilovoltage peak and 310 mA, and 200-ms scan times. Multiple
slices are acquired with table motion between slice scans. Each scan
protocol took 25 s to complete. There was no synchronization of
scanning to the cardiac cycle.
For each study, the pig was placed in a supine position and vertically
centered within the imaging field. With respiration suspended at FRC, a
scout scan was obtained. A preliminary 40-level data set was acquired
from just above the carina to the approximate dome of the diaphragm.
From these 40 levels, 10 levels of interest were selected in the lower
lobes to use in the remainder of the study.
Data Analysis
Image Selection:
The EBCT hard copy images, filmed at lung
window level of - 450 Hounsfield units (HU) and a window width of
1,350 HU, were used to select the slices for analysis. By using
prominent and defined parenchymal landmarks, such as vascular or
bronchial branching points, the same anatomic levels before and after
methacholine administration could be matched, ensuring that the same
airways at the same levels and the same regions of the lungs were
analyzed throughout each experiment.
Luminal Area Measurement:
To quantitate the luminal
cross-sectional area (CSA) of the airway on a CT image, analysis of the
matched airways in the selected images was performed using an
objective, semiautomatic edge-detection algorithm in a custom-made
software package called Volumetric Image Display and
Analysis,2
running on a Sun Sparc II workstation (Sun
Microsystems; Palo Alto, CA). The use of this algorithm has been
fully described and validated previously.1
3
In brief, it
applies the "half-maximum" principle to the regional CT density
values around the perimeter of a user-drawn estimate of the airway edge
to adjust the contour to the correct position.
To compensate for potential through plane motion of the airway
location from scan to scan, we evaluated the stack of CT slices
gathered at each premethacholine and postmethacholine time point to
locate the same anatomic landmarks as previously
described.1
To further compensate for any potential error
in misselection of slice, we also used one slice above and one slice
below the "matched" level (in addition to the matched level) for
airway luminal measurements. Airway area was measured five times at
each level for the three levels; thus, each airway CSA value reflects
an average of 15 measurements. In each pig, five different-sized
airways were chosen at baseline scan. These airways were grouped by
size (baseline diameter): (1) 8 to 10 mm, (2) 6 to 8 mm, (3) 4 to 6 mm,
(4) 2 to 4 mm, and (5) 1 to 2 mm.
Lung Density Measurements:
To assess the effects of
methacholine-induced bronchoconstriction on lung density, we measured
the density (in HU) of selected regions in the lung. Using a region of
interest (ROI) module within the Volumetric Image Display and Analysis
software,2
we carefully selected 50 ROIs in one of the
baseline slices obtained for each of the seven studies from three pigs.
The scan level for analysis was chosen at baseline to have maximal lung
CSA and a good selection of airways appropriate for cross-sectional
analysis. Each ROI consisted of a 4-mm by 2-mm rectangle that
was carefully drawn on the CT image to avoid inclusion of visible large
blood vessels and airways and to achieve broad-based sampling
distributed throughout the ventral-dorsal and medial-to-lateral aspect
of the right lung section (Fig 2
). As with airway CSA measurements, in order to compensate for possible
positional shifts, one slice above and one slice below the matched
slice also were analyzed. Thus, a total of 150 (50 x 3) ROIs were
analyzed for each time point (30 s, 2 min, and 4 min) in each
experiment. The ROIs were copied from the baseline slices and pasted to
postmethacholine scans, so that for each experiment the same ROIs were
analyzed at each of the different time points (baseline, 30 s, 2
min, and 4 min). Position of copied regions were adjusted slightly in
cases where a major blood vessel or airway migrated into the boundaries
of the region so that the final position of the ROI again avoided these
structures. The density measurements, which were corrected to measured
100% air content and 100% blood content levels (see below), were then
compared before and after methacholine injection.
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Figure 2. Fifty ROIs were selected in each baseline scan for
the density measurements. Regions were carefully placed to avoid
inclusion of visible blood vessels and airways. To compensate for
possible positional shifts, one slice above and one slice below also
were analyzed.
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To look for potential radial regional differences in the lung, a
similar analysis was performed separating the selected ROIs into
peripheral and central locations. Peripheral ROIs were located within 5
to 7 mm of the lung border, while the rest of the lung field was
defined as central.
Because of concern that using the sharp (high resolution)
reconstruction algorithm might influence our density measurements, we
reconstructed the images from a slice of one of the pigs a second time
using a normal (standard) reconstruction algorithm. Densities of 100
identical regions for both the normal and sharp reconstructions were
compared.
Air Content Correction:
To convert HU in the lung field into
a percentage of air content value, we used a formula previously
described by Hoffman.4
The lung is considered to be
composed only of structures equal in CT density to air or water (lung
tissue and blood density of 1.055 g/mL is very close to the density of
water). Assuming a linear scale between air and water, it is possible
to use a linear transformation to calculate the relative air content of
any selected region of the lung. To transform a specific ROI density to
percentage of air content, the following equation was used:
where CTx is the density value (HU) of the lung voxel (x) under
study; CTair is the density value of voxels within a region of known
100% air content (lumen of trachea or mainstem bronchus); and CTwater
is the density value of voxels in a region of 100% "water"
(chamber of heart, lumen of descending aorta, pulmonary trunk, etc).
For each time point (baseline, 30 s, 2 min, and 4 min) in every
experiment, the mean (n = 150) and coefficient of variance (CV) of
the percentage of air content were computed
(CV = SDs/mean x 100).
Gravitational Gradient of Lung Density:
Since there is a
gravitational gradient of lung CT density under normal physiologic,
supine-position conditions in numerous species, including dogs,
rabbits, sloths, horses, and humans,4
5
6
7
8
and because
density gradient changes have been shown to relate to regional indexes
of lung function,4
5
we investigated whether this gradient
is affected by bronchoconstriction. In each of the experimental
conditions, the air content values of the 150 regions that were
analyzed were plotted against their corresponding lung height. The
latter was defined as the anteroposterior distance from the
dependent (posterior in the supine animal) aspect of the lung. In these
pigs, the relationship (air content vs lung height) was found to be
best described by a logarithmic function of the type:
Air content = a log (lung height) + b
Use of a logarithmic scale for the lung height axis converted
this relationship into a linear function (Y = aX+b) from which the
following indexes were determined for each experimental condition:
slope of the relationship (a), its intercept (b), and correlation
coefficient (r). The slope (a) represents the magnitude of
the gravitational gradient (ie, the greater the slope, the
greater is the gradient), the intercept (b) represents the air content
at the most dependent region of the lung, and the correlation
coefficient (r) represents the degree by which the actual
air content measurements agree with the fitted curve.
Statistical Analysis:
Statistical evaluation included the
mean values for percentage of air content, CV, slope, intercept, and
r of the percentage of air content to lung height
relationship, SEMs, and comparison of means using Student’s two-tailed
paired t test, with a significance level of p < 0.05.
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Results
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As shown in Figure 3
, both normal (standard) and sharp reconstruction algorithms yielded
nearly identical measurements of lung density for the same image
(slope = 1.006, r = 0.99). Thus we used the sharp (high
resolution) reconstruction algorithm for both airway CSA and lung
density measurements.
An example of the CT images obtained from the same scan level at
the four time points (before methacholine injection, and 30 s, 2
min, and 4 min after methacholine injection) is depicted in Figure 4
. The insert to the upper right of each image demonstrates the
constriction of a single airway. Maximal bronchoconstriction was always
found at the first time point evaluated, at approximately 30 s
after methacholine bolus, with the airway CSA decreasing by 31 ± 3%
(mean ± SEM) from baseline (p < 0.001; Fig 5
). The CSAs at 2 min and 4 min were not significantly different from
baseline values, although they tended to remain lower. No significant
statistical difference was observed between the different groups of
airways in any of the time points.
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Figure 4. Images obtained at the four time points (before
methacholine [baseline], and 30 s, 2 min, and 4 min after
methacholine injection) in one of the experiments. The insert to the
upper right of each image demonstrates the changes in CSA of a single
airway.
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Figure 5. Mean ( ± SEM) temporal changes in airway CSA in
all experiments (n = 7). No significant statistical difference was
observed between the different groups of airways in any of the time
points. Changes were significant (p < 0.001) at 30 s vs all
other time points. See Figure 1
for expansion of abbreviation.
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The density measurements (percentage of air content) showed no
difference between the peripheral and central lung regions. Thus, all
regions, both central and peripheral, were used for further analysis. A
logarithmic relationship between the lung percentage of air content and
the lung height was demonstrated in all pigs, at each time point.
Figure 6
illustrates this relationship in one of the pigs at baseline. Air
content in this pig increases with the transition from dependent to
nondependent regions (Fig 6
, top, A). Using a
logarithmic scale for the lung height (Fig 6
, bottom,
B), the slope of this relationship was 38.35% air per
centimeter of lung height, and the Y-intercept (percentage of air) was
5.32. Figure 7
shows this relationship in the same pig during all experimental
time points. At 30 s, the relationship substantially changed from
baseline, particularly in the dependent lung regions (Fig 7
,
top, A). On a logarithmic scale (Fig 7
,
bottom, B), the slope was now 28.52% air per
centimeter of lung height and the intercept was 24.46% air. Of
interest is the fact that the variability of the data also
significantly increased at 30 s. At 2 min and 4 min, the air
content measurements returned to baseline levels. Figure 8
plots these data by relating the percentage of air content of the same
regions (ROIs) of this pig at various time points after methacholine
bolus to their baseline percentage of air content values. This plot
clearly demonstrates that in most of the regions, air content increased
at 30 s (ie, during maximal bronchoconstriction), thus
deviating from the line of identity. Again note that the variability of
percentage of air content measurements at 30 s was significantly
greater than that observed at other time points (p < 0.001). The
figure also illustrates that while in general there was increase in air
content in 30 s compared to baseline, a few regions showed
decreased air content. The same pattern was observed in all other
experiments. Figure 9
summarizes the positional gradients of lung density for all
experiments, showing the relationship between lung density as expressed
by percentage of air content vs (log) lung height at various time
points. At 30 s, during maximal bronchoconstriction, there is, in
general, an increase in air content that is greater at the dependent
lung regions. At 2 min and 4 min, the air content returned to baseline
levels, paralleling the time changes that we observed with the airways
CSA. The various parameters that summarize the density measurements and
indexes of the relationship between lung density and lung height for
all the experiments are presented in Table 1
.
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Figure 6. Relationship between percentage of air content and
the lung height in one of the experiments at baseline
(top, A). The best fitted curve for this
relationship is also plotted. The same relationship can be depicted as
a linear function when using a logarithmic scale for the lung height
axis (bottom, B).
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Figure 7. Relationships between percentage of air
content and the lung height in one of the experiments at baseline,
30 s (dashed line), 2 min, and 4 min after methacholine injection
(top, A: linear scale for the lung height
axis; bottom, B: logarithmic scale).
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Table 1. Lung Density (Percentage of Air Content) Indexes and
the Parameters of the Relationship Between Lung Density and Lung
Height*
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Discussion
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The results of the present study demonstrated that within the time
frame used in this investigation, the maximal response to a bolus of
methacholine to pigs as detected by CT occurred 30 s following the
challenge. This maximal response could be measured in terms of changes
in airway CSA (mean decrease of 31 ± 3%) and lung density. At 2
min, the response was always smaller than at 30 s and had
essentially returned to baseline. The time course of lung density
changes paralleled the airway CSA response.
Previous studies4
5
6
7
have demonstrated that
reconstructed radiograph CT attenuation coefficients can be used as an
accurate index of regional lung density. The current comparison of lung
density assessed with both sharp and normal reconstruction algorithms
shows that the sharp algorithm used in HRCT does not alter the basic
lung density information content. Thus, the same reconstructed CT
section can be used for simultaneous assessment of central airways CSA
and peripheral lung density. Our current study supports the concept
that HRCT-based lung density measurements may be used as an index of
peripheral changes occurring in response to bronchoconstrictive agents
correlating to measurable structural responses. These measurements
allow for assessment of lung structure and function beyond the spatial
resolution of CT scanning techniques.
Several investigators9
10
have shown HRCT to be a useful
tool in assessing airway reactivity. Those studies, along with other
imaging methods,11
12
have utilized single time points to
assess airway response, and no previous study has directly assessed
density changes associated with induced bronchoconstriction. The speed
of the EBCT scanner in the present study has allowed us to verify the
time course of the bronchoconstrictive response to bolus methacholine
and to relate this response to peripheral lung density temporal
variations. Airway CSA for all size ranges was found to be least (31%
decrease from baseline) at the 30 s time point and to return to
baseline within 2 to 4 min. Overall, the density of the lung decreased
during bronchoconstriction.
Decreased lung density in response to methacholine injection was found
to be greater in the dependent lung regions. Given that the density
changes were maximal at 30 s and resolved within 2 to 4 min, it is
unlikely for changes in extravascular lung water or lung tissue to
account for these findings. More likely explanations for the observed
changes in lung density in the present study are an increase in
regional lung air content and/or a decrease in regional intravascular
blood volume.
An increase in regional lung air content in the lung during
methacholine-induced bronchoconstriction would suggest air trapping.
Air trapping as measured by nonimaging methods has been shown to occur
in response to methacholine,13
presumably due to closure
of peripheral airways.14
15
However, it is also possible
that constriction of peripheral airways may serve to expand alveoli
through interdependence phenomena or to strengthen the peripheral
interstitial "skeleton" of the lung, preventing dependent alveolar
compression. Gradients in regional lung expansion have previously been
observed by numerous techniques.4
5
6
7
16
17
18
19
20
Regional CT
density changes in both dogs4
5
and humans20
show that in the dependent lung regions where lung density is greatest,
there is greater decrease in density with lung inflation. These data
imply that in the nondependent lung region where the lung is least
dense, the parenchyma is more inflated at baseline and therefore less
able to expand further. It could be that in our current study the
effect of air trapping is greatest in the dependent lung regions where
the lung is more compliant.4
5
21
The possibility exists that "increased air content" reflected
reduced blood volume in the lung. This could be caused either by direct
effects of methacholine, such as altered pulmonary artery BP or by
secondary effects, such as air trapping with associated vascular
compression and/or hypoxic vasoconstriction or reflex vascular
constriction to allow for good ventilation-perfusion balance. The
assumption that a vascular component attributed to the density changes
is supported by Figure 4
. In the cross-sectional image at 30 s
following methacholine injection, one can observe constriction of
pulmonary arteries. Unfortunately, measurements of pulmonary arterial
pressure or pulmonary vascular resistance were not obtained in the
present experiments. These data could have considerably elucidated the
possible mechanisms of lung density changes.
During methacholine-induced bronchoconstriction, there was also a
marked increase in the degree of regional variability as reflected in
the CV and the r values of the air content and lung height
relationships. Moreover, although, on average, the air content of the
lung increased, changes at similar lung height points were quite
variable, with some regions demonstrating a large increase in air
content, others demonstrating a much smaller increase, and a few
demonstrating reduced air content, as shown by the example in Figure 7
.
CT studies of airway reactivity have led to a better appreciation of
heterogeneity of the airway response to bronchoconstrictive
challenges.1
9
22
23
The variability of lung density
changes during methacholine challenge parallels the directly measured
airway CSA response.
In conclusion, HRCT imaging can be used to assess alterations in
regional airway geometry and lung density. EBCT techniques defined the
time frame of the response to IV bolus injection of methacholine in
pigs. The maximal response observed at the 30-s time point was detected
both in terms of decreased CSA of airways > 1 mm and in terms of the
lung density. Overall, there was increased air content during
bronchoconstriction, and this effect was significantly greater in the
dependent lung regions.
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Acknowledgements
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Major parts of this work were conducted in
collaboration with Dr. Eric Hoffman at the Cardiothoracic Imaging
Research Center of the Pennsylvania University Hospital. The authors
thank Dr. Hoffman for his guidance and invaluable support.
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Footnotes
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Abbreviations: CSA = cross-sectional area;
CV = coefficient of variance; EBCT = electron-beam CT;
FRC = functional residual capacity; HRCT = high-resolution CT;
HU = Hounsfield units; Pao = airway pressure; ROI = region of
interest
Received for publication January 19, 2000.
Accepted for publication December 27, 2000.
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References
|
|---|
-
Amirav, I, Kramer, SS, Grunstein, MM, et al (1993) Assessment of methacholine-induced airway constriction by ultrafast high-resolution computed tomography (UHRCT). J Appl Physiol 75,2239-2250[Abstract/Free Full Text]
-
Hoffman, EA, Gnanaprakasam, D, Gupta, KB, et al (1992) VIDA: an environment for multidimensional image display and analysis. Proc SPIE 1660,694-711[CrossRef]
-
Schwab, RJ, Gefter, WB, Pack, AI, et al (1993) Dynamic imaging of the upper airway during respiration in normal subjects. J Appl Physiol 74,1504-1514[Abstract/Free Full Text]
-
Hoffman, EA (1985) Effect of body orientation on regional lung expansion: a CT approach. J Appl Physiol 59,468-480[Abstract/Free Full Text]
-
Hoffman, EA, Ritman, EL (1985) Effect of body orientation on regional lung expansion in dog and sloth. J Appl Physiol 59,481-491[Abstract/Free Full Text]
-
Hedlund, LW, Vock, P, Efmann, EL (1983) Computed tomography of the lung: densitometric studies. Radiol Clin North Am 4,775-788
-
Millar, AB, Denison, DM (1989) Vertical gradients of lung density in healthy supine men. Thorax 44,485-490[Abstract]
-
Rosenblum, LJ, Mauceri, RA, Wellenstein, DE, et al (1980) Density patterns in the normal lung as determined by computed tomography. Radiology 137,409-416[Abstract/Free Full Text]
-
Herold, CJ, Brown, RH, Mitzner, W, et al (1991) Assessment of pulmonary airway reactivity with high-resolution CT. Radiology 181,369-374[Abstract/Free Full Text]
-
McNamara, AE, Muller, NL, Okazawa, M, et al (1992) Airway narrowing in excised canine lungs measured by high-resolution computed tomography. J Appl Physiol 73,307-316[Abstract/Free Full Text]
-
Shioya, D, Solway, J, Munoz, NM, et al (1987) Distribution of airway contractile responses within the major diameter bronchi during exogenous bronchoconstriction. Am Rev Respir Dis 135,1105-1111[ISI][Medline]
-
Murphy, TM, Roy, L, Phillips, IJ, et al (1991) Effect of maturation on topographic distribution of bronchoconstrictor responses in large diameter airways of young swine. Am Rev Respir Dis 143,126-131[ISI][Medline]
-
Breen, PH, Becker, LJ, Ruygrok, P, et al (1987) Canine bronchoconstriction, gas trapping, and hypoxia with methacholine. J Appl Physiol 63,262-269[Abstract/Free Full Text]
-
Murtagh, PS, Proctor, DF, Permutt, S, et al (1971) Bronchial closure with Mecholyl in excised dog lobes. J Appl Physiol 31,409-415[Free Full Text]
-
Smith, LJ, Inners, CR, Terry, PB, et al (1979) Effects of methacholine and hypocapnia on airways and collateral ventilation in dogs. J Appl Physiol 46,966-972[Abstract/Free Full Text]
-
Kaneko, K, Milic-Emili, J, Dolovich, MB, et al (1966) Regional distribution of ventilation and perfusion as a function of body position. J Appl Physiol 21,767-777[Free Full Text]
-
Glazier, JB, Hughes, JMB, Malone, JE, et al (1967) Vertical gradient of alveolar size in lung of dogs frozen intact. J Appl Physiol 23,694-705[Free Full Text]
-
West, JB (1977) Regional differences in the lung. ,302-319 Academic Press New York, NY.
-
Vock, P, Salzmznn, CH (1986) Comparison of CT lung density with hemodynamic data of the pulmonary circulation. Clin Radiol 37,459-464[CrossRef][ISI][Medline]
-
Verschakelen, JA, Van Fraeyenhoven, L, Laureys, G, et al (1993) Differences in CT density between dependent and nondependent portions of the lung: influence of lung volume AJR Am J Roentgenol 161,713-717[Abstract/Free Full Text]
-
Milic-Emili, J (1977) Ventilation. West, JB eds. Regional differences in the lung ,167-199 Academic Press New York, NY.
-
Hoffman, EA, Tajik, JK, Kugelmass, SD (1995) Matching pulmonary structure and function via combined dynamic multislice CT and thin-slice high-resolution CT. Comput Med Imaging Graph 19,101-112[CrossRef][ISI][Medline]
-
Brown, RH, Herold, CJ, Hirshman, CA, et al (1993) Individual airway constrictor response heterogeneity to histamine assessed by high-resolution computed tomography. J Appl Physiol 74,2615-2520[Abstract/Free Full Text]
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Abstract
Introduction
