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Department of Anesthesia and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-8711
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ABSTRACT |
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Xe-enhanced computed tomography (CT; Xe-CT) is a method for the noninvasive measurement of regional pulmonary ventilation in intact subjects, determined from the washin and washout rates of the radiodense, nonradioactive gas Xe, as measured in serial CT scans. We used the Xe-CT ventilation method, along with other quantitative CT measurements, to investigate the distribution of regional lung ventilation and air content in healthy, anesthetized, mechanically ventilated dogs in the prone and supine postures. Vertical gradients in regional ventilation and air content were measured in five mongrel dogs in both prone and supine postures at four axial lung locations. In the supine position, ventilation increased with dependent location, with a mean slope of 7.3%/cm lung height, whereas no ventilation gradients were found at any location in the prone position. These results agree quantitatively with other published studies. In addition, six different animals were studied (3 supine, 3 prone) to examine the longitudinal distribution of ventilation and air content. The prone lungs were more uniformly inflated compared with the supine, which were less well expanded at the base than apex. Ventilation index, a measure of regional ventilation relative to whole lung ventilation, increased steeply from apex to base in the supine animals, whereas it was again more uniform in the prone condition. We conclude that the Xe-CT method provides a reasonable, quantitative measurement of regional ventilation and promises to be a valuable tool for the noninvasive determination of regional lung function.
lung volume; lung mechanics; tidal volume; imaging
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INTRODUCTION |
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THE MEASUREMENT OF LUNG VENTILATION, lung volume, and tidal volume (VT) has traditionally been made for the entire lung, despite the fact that lung function in both health and disease is inhomogeneous. Attempts have been made to quantitate regional lung ventilation both directly and indirectly with a variety of invasive techniques or radioisotope imaging (1, 2, 7, 12, 24, 26, 27, 34, 41, 42), but these methods have been limited by their invasiveness, poor spatial and temporal resolution, qualitative nature, and/or complexity. Xe-enhanced computed tomography (CT; Xe-CT) is a method for the noninvasive measurement of regional pulmonary ventilation, determined from the washin and washout rates of the radiodense, nonradioactive gas Xe, as measured in serial CT scans. Although the prospect of measuring regional ventilation with stable Xe has been established for many years (17, 18), advances in CT technology have increased the speed and resolution of imaging studies and now make the application of this technique practical for physiological and clinical studies (39). Combined with the unique capability of CT to describe anatomic detail (49) and regional pulmonary perfusion (23), this single imaging modality can potentially provide a nearly complete, noninvasive structural and functional characterization of the lung.
The distributions of ventilation, perfusion, and lung expansion change dramatically between prone and supine body postures, events that have been explored by using a variety of methodologies over many years (1, 21, 26, 33, 40, 47). In fact, these changes are occasionally exploited to improve oxygenation in patients with acute lung injury by placing them into the prone position (15, 28). In this study, we applied the Xe-CT ventilation method and other CT measurements of regional lung function to examine changes in the distribution of ventilation and lung air content in anesthetized dogs in the prone and supine postures, primarily to present and validate the updated Xe-CT method and, in addition, to use these complementary imaging techniques to further explore the physiology of these phenomena.
Xe (atomic no. 54) is a nonradioactive, monatomic noble gas that is
denser than air. When imaged in a conventional CT scanner, the density
of Xe measured in Hounsfield units (HU) increases linearly with its
concentration (Fig. 1). In addition, the
degree of CT enhancement depends on the kilovolt setting used, with
lower kilovolt settings yielding greater enhancement due to the
physical properties of Xe gas. When Xe concentrations of 30-60%
in air are delivered to the lung, CT enhancements of parenchymal
density of 50-150 HU are obtained. If the Xe is introduced and
eliminated from the lung during a controlled washin-washout (wi/wo)
ventilation protocol, repeat CT scans taken at constant lung volume
(i.e., at the same point in the respiratory cycle) will yield a local exponential density curve for any specified region of interest (ROI)
within the lung field. The time constant (
) of this curve is equal
to the inverse of the local ventilation per unit volume (specific
ventilation, s
). By selection of different ROI, spatial patterns
of ventilation distribution and their changes in response to various
interventions can be analyzed. Thus this technique provides the direct,
noninvasive measurement of regional ventilation on a scale ranging from
<1 cm3 volume to the entire lung visible in the CT slice.
Furthermore, selecting the ROI over the trachea, through which all gas
entering and leaving the lung must pass, allows the calculation of
total lung specific ventilation (s
L).
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In addition to regional ventilation, CT techniques can be used to noninvasively measure many other aspects of lung mechanical function, including the distribution of lung air and tissue volumes (21, 22), the degree of air content of regional lung tissue and recruitment (13, 16, 43), the size of the conducting airways (3, 5), and changes in the configuration of the chest wall and diaphragm (30, 32). By following changes in lung volume and air content at specific anatomical locations as inflation pressure changes, regional mechanical properties may be measured and may provide information complementary to the functional ventilation data of Xe-CT.
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METHODS |
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Experimental preparation. This protocol was approved by the Animal Care and Use Committee of the Johns Hopkins University School of Medicine. Eleven chronic-conditioned male mongrel dogs (20-25 kg) were anesthetized with pentobarbital sodium (25 mg/kg) and fentanyl (15 µg/kg), and relaxed with pancuronium (3 mg) via a forelimb intravenous catheter. The trachea was intubated with a cuffed endotracheal tube (8.0 mm), and the animal was ventilated with a portable piston ventilator (PLV-102, Lifecare International, Westminster, CO) that was modified by the manufacturer to allow remote computer control of all ventilatory parameters. During the procedure, the animal's oxygen saturation (by Nellcor N-100) and end-tidal carbon dioxide pressure (PETCO2) were continuously monitored. Approximately 500-700 ml of Ringer lactate solution was slowly infused over the course of the experiment for maintenance of intravascular volume. At the end of the experimental protocol, residual neuromuscular blockade was reversed with atropine (2-3 mg iv) and neostigmine (2-3 mg iv). All dogs resumed spontaneous ventilation, were extubated, and recovered from anesthesia without incident.
After induction of anesthesia, the animal was carefully positioned on the CT table with gentle forelimb traction. The ventilator was set at 16 respirations/min and 15 ml/kg initial VT, with the VT adjusted to maintain a PETCO2 of 30-32 mmHg. Periodic sighs of three times the VT were given before each imaging run to minimize atelectasis. A four-channel strip chart recorder was used to record airway pressure, PETCO2, airway opening Xe concentration, and a synchronizing signal from the CT scanner. For ventilation studies, Xe was introduced into the breathing circuit by means of a specialized delivery device (Enhancer 3000, Diversified Diagnostic Products, Houston, TX) that meters Xe and O2 in a closed-circuit system with a CO2 absorber to provide tight control over the delivered Xe concentration and remote computer-controlled switching between air-O2 and Xe-O2 combinations. A Macintosh computer running Superscope II (GW Instruments, Somerville, MA) was used to automate the experiment by controlling the interface between the CT scanner, the Xe delivery device, and the ventilator, halting the ventilator after each breath to prevent motion artifact during imaging.Image specifications. All experiments were performed in a GE 9800 CT scanner with settings of 80 kV and 120 mA and were calibrated according to manufacturer's specifications immediately before each experiment. Imaging was performed at the maximum rate of this scanner, resulting in a 2-s scan interval with a 1.2-s prep delay and a 3.6-s interscan delay (net ~10 breaths/min during imaging). Image thickness was fixed at 10 mm for all CT scans, with a 512 × 512 field size and a 22-cm display field of view. Individual images were scaled in real dimensions based on the image field of view size and number of pixels, yielding 0.43 mm/pixel resolution.
Xe-CT ventilation measurement. For measurement of regional ventilation, a series of 40 consecutive end-expiratory CT scans was taken during Xe washin and washout without moving the table position. Two baseline images during 30% O2 breathing were first obtained, and the inspired gas was switched to 60% Xe-30% O2 for 18 breaths and then switched back to 30% O2 for the 20-breath washout period. After baseline conditions were reestablished, the table was moved to the next location and the process was repeated.
Protocols.
In protocol 1, regional ventilation was determined in five
animals, in both the prone and supine positions, at four discrete anatomic locations: midapex (apex), carina, mid-lower lung (midbase), and lung base (Fig. 2). The table
locations at these positions were selected from a functional residual
capacity (FRC) whole lung image series, with care taken not to move the
dog after this initial scanning. Discrete anatomic structures in the
lung fields (blood vessels, bronchi) were noted and matched when
turning the animal prone so that the same approximate longitudinal lung
location was imaged in both the prone and supine positions. These data were used to compare the vertical distribution of lung air content and
regional ventilation in the same animals when changing posture. A
second protocol (protocol 2) was performed to determine the longitudinal (apex to base) distribution of ventilation with greater spatial resolution. In six dogs (3 prone, 3 supine), Xe-CT ventilation was measured in every other 10-mm-thick slice from apex to base, resulting in 9-12 measurements per dog. Because of the time
required for these experiments, it was not possible to study the same
dogs prone and supine in one sitting. These data were analyzed in terms of average ventilation of the left and right lungs within each slice,
plotted as a function of their longitudinal position.
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Image analysis.
The images were archived and transferred over the hospital network to a
Macintosh computer, which was used for all subsequent analysis.
Quantitative image analysis was performed using NIH Image (a
public-domain software package available on the Internet from
http://rsb. info.nih.gov/nih-image/). This powerful program has a
variety of flexible analytical tools and programming capability that
allows the efficient automation of complex, multistep image analyses.
The 16-bit CT images were windowed and scaled to 8-bit, with a density
resolution of 5 HU. For convenience, the units of density used are HU
offset by 1,000 (HU + 1,000), so that air has a density of 0 and
water 1,000 (instead of
1,000 and 0, respectively, as with standard
HU). The lung tissue within a given slice is outlined with use of a
thresholding function, which separates lung tissue from the surrounding
structures by density range. Further subdivision of the lung into
smaller ROI for regional analysis may then be performed as required.
Was determined by fitting
this curve to a single-compartment exponential model using a nonlinear
least squares curve-fitting procedure (Igor Pro, WaveMetrics, Lake
Oswego, OR).
Is constrained to be the same for the washin and
washout portions of the curve (36). The starting points of
the washin and/or washout segments (t0 and
t1) are initially estimated by visual inspection
of the curves and then determined by the curve-fitting procedure.
Although imaging occurs once per breath, t0 and
t1 are permitted to take on fractional values,
reflecting that the arrival of Xe to the lung periphery may occur in
midcycle because of the variable amount of dead space relative to
VT in the system and down a given pathway. Goodness of fit
was assessed by examination of the normalized summed squared residuals
of the data, and 95% confidence intervals for
were estimated by
using a Monte Carlo method that has previously been described and
validated (36). Because images are obtained once per
breath,
is conveniently given in units of breaths, which may be
converted to time units by dividing by the respiratory frequency. To
normalize for differences in absolute ventilation between dogs, some
ventilation data are presented as ventilation index (VI), defined at
the regional s
/s
L, where
s
L is estimated from a ROI placed within the
trachea. A VI of 1 indicates that the region is being ventilated at a
rate equal to that of the whole lung.
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Statistical analysis. Data are presented as means ± SE unless otherwise noted. Differences between means were tested by paired t-tests (Statview 4.5, Abacus Concepts, Berkeley, CA) with a significance level of P < 0.05.
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RESULTS |
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Longitudinal volume profile.
A plot of the typical distribution of lung volume at FRC from apex to
base in supine and prone postures is presented in Fig. 4 (top). In the prone
position, the diaphragm assumes a flatter profile, resulting in a
smaller maximum cross-sectional area and a longer axial extent. Lung
volume at FRC, determined by summing the air volumes of all the
individual slices, was not significantly different in the supine vs.
prone position (supine-to-prone FRC volume ratio 95.4 ± 3.4%,
P = 0.21). The distribution of air content (%air) for
each slice is depicted in Fig. 4 (bottom). Note that, in the
supine position, the apex is well expanded, whereas there is
compression of the lung base under the diaphragm compared with the relatively uniform expansion seen in the prone position. The approximate position of the four imaging planes in protocol
1 are indicated in the figure.
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Gravitational ventilation gradients.
A graph of VI vs. vertical height shows a gravity-dependent gradient in
ventilation, with ventilation greatest in the most dependent regions,
at all four locations in the supine but not the prone dog (Fig.
5). Straight lines were fitted to these
individual left and right lung VI-vs.-height data for each animal to
determine average slopes or gradients (Table
1). There were no significant differences
in slope between any individual locations within the supine or prone
animals. However, the mean slope of all the supine lungs of
0.073 ± 0.007 (mean ± SE) was significantly steeper than
the slope of
0.008 ± 0.009 of the prone lungs
(P < 0.0001), indicating a mean ventilation gradient
of ~7% of the total s
per centimeter lung height in the
supine position, with s
greatest in the most dependent regions.
The slopes in the prone position were not significantly different from
zero (P = 0.37).
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Gravitational air content gradients.
Strong gravitational gradients in FRC lung air content were also seen
in the supine position at all imaging planes, with air content
increasing from dependent to nondependent ROI. In the prone position,
however, the gradient changed with location, being negative at the apex
(opposite that in the supine position), flat at the carina, and then
slightly positive at the midbase and base. Note that these gradients
are expressed in terms of the gravitational or vertical coordinate
rather than the animal's anatomic dorsal-ventral position. Thus
reversal of the gravitational air content gradient at the apex means
that the dorsal lung regions were least expanded in both supine and
prone positions. In the prone position, the air content gradient went
against gravity at the apex, was uniform at the carina, and went with
gravity at the midbase and base. Straight lines were fitted to the
data, and the resulting slopes are presented in Table 1. There were no
differences between left and right lungs at any location. In the supine
dogs, the slope at the apex was significantly steeper than at the other
three locations (P < 0.01), which were not different
from each other (P > 0.11). In the prone position, the
slopes at the apex and carina differed from each other
(P = 0.03) and from the midbase and base
(P < 0.03), which did not significantly differ from
each other (P > 0.28). The slopes of the VI and %air
gradients were weakly correlated in the supine position
(r =
0.32, P = 0.046) and not
correlated in the prone position (r =
0.11,
P = 0.51). Average air content for the entire lung was
66.8 ± 1.7% supine and 67.3 ± 2.1% prone.
Longitudinal ventilation distribution.
The distribution of ventilation from apex to base in three supine and
three prone dogs is presented (Fig. 6) as
both VI, which gives the slice s
normalized to the whole lung
s
, and as slice ventilation (%), which is the net slice
ventilation expressed as percentage of total measured lung ventilation
(sum of all slice ventilations). The VI gives the relative ventilation
of a region compared with that of the lung as a whole. The slice
ventilation (%) gives the fractional contribution of that region to
the total lung ventilation. Because the net slice ventilation is
obtained by multiplying the slice s
by the total volume of the
slice, its distribution is strongly influenced by the different FRC
volume distribution profiles (Fig. 4). In the supine position, s
steadily increases from apex to base (Fig. 6). Coupled with the volume profile of the supine lung (Fig. 4), this results in an even steeper distribution of slice ventilation moving toward the base (Fig. 6). On
the other hand, the distribution of s
in the prone animals is
flat or decreases toward the lung base (Fig. 6). Because the longitudinal distribution of prone lung volume is more uniform (Fig.
4), this causes a comparatively more even distribution of slice
ventilation that reaches a maximum between the carina and lung base
(Fig. 6).
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DISCUSSION |
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The use of imaging technology is supplanting, in many cases, more traditional physiological studies because of the need for noninvasive determination of regional structure and function in intact organisms. Although many technologies are available, X-ray CT is emerging as the preferred modality for imaging of the lung because of its widespread availability, resolution, high signal-to-noise ratio for lung tissue, and speed. Technology is advancing rapidly, and scanners are readily available that can perform high-resolution scans of an entire human lung in <30 s. In addition to its traditional role in identifying abnormal lung anatomy or pathological lesions, CT has been used to image changes in airway dimensions in studies of reactive airway diseases (4) and volume overload (6) and to describe changes that occur in chest wall and diaphragm configuration with position, anesthesia, pleural effusion, and lung resection (9, 30, 32). The bronchial and vascular trees have been extracted and reconstructed in three dimensions from high-resolution images (46), and CT techniques have been developed to measure regional pulmonary perfusion (23). CT measurements of the regional distribution of lung density/inflation in patients with acute respiratory distress syndrome, and how these parameters change with positive end-expiratory pressure and body position, have provided crucial insight into ventilator management of these critically ill patients (14, 33). The addition of the Xe-CT technique for measuring regional ventilation to these previously available methodologies makes possible the use of CT imaging to create a nearly complete anatomic and quantitative functional characterization of the lung.
Xe is a stable, nonradioactive, inert gas that is weakly radiodense (Fig. 1), making it useful as a radiographic contrast agent for highly sensitive imaging modalities such as CT but not plain radiographs or fluoroscopy (35, 45). It is relatively insoluble [blood-gas partition coefficient 0.14 (38)], but adequate radiodensity is transferred from the lung to the blood and tissues to make measurement of cerebral blood flow possible (11). This technique was extended to the measurement of local pulmonary ventilation in animals (17, 18) and in healthy and critically ill humans (20, 37) over 20 years ago. Although Xe is an inert gas, it is also an inhaled anesthetic (minimum alveolar concentration 71%), ~30% more potent than nitrous oxide (8) and in clinical use in many countries (10). A large number of human volunteers and patients have inhaled 30-50% Xe for cerebral blood flow studies with an excellent safety record, although sedating or other anesthetic side effects increase with concentrations above 35% (19, 48). Finally, Xe is a relatively expensive gas (10, 31), making a device such as the Enhancer 3000, which allows rebreathing of Xe in a closed circuit while absorbing CO2 and regulating the inspired Xe and O2 concentrations, essential for the economical application of this technique.
Methodological considerations.
The Xe-CT technique described here for measurement of pulmonary
ventilation is a variation of the familiar indicator-dilution method.
However, unlike radioactive tracer methods, in which essentially all
the radioactive counts measured are introduced by the tracer, changes
in density measured in the serial CT scans must be distinguished between those resulting from increasing concentration of the tracer gas
vs. changes in the underlying substrate (i.e., lung) density. Lung
density will change with small changes in lung volume, misregistration of the identical ROI from image to image, and changes in blood volume
within the ROI. The changes in lung density that occur with a single
inspiration are greater than the 50-80 HU enhancement typically
seen with 60% Xe equilibration, and thus it is critical that each
image be obtained at the same lung volume. In studies of mechanically
ventilated animals, this is most easily done at end-expiration;
end-inspiratory holds are potentially complicated by stress relaxation
or creep. Changes in background or lung density account for the
majority of the noise in estimating the regional time constants, and
this noise, rather than the spatial resolution of the CT scanner, is
what ultimately limits the spatial resolution of the measurement
(36). For example, because cardiac motion contributes to
this noise to a varying degree depending on the distance to the heart,
the actual spatial resolution realized may vary with location, as
indicated by the width of the confidence interval about a calculated
or s
value (36). Cardiac gating using an
ultrafast CT scanner has been shown to greatly reduce this particular
source of noise (39). Using relatively thick slices
(5-10 mm vs. 0.5-1.5 mm for high-resolution CT) can reduce noise by averaging density over a larger volume, reducing partial volume effects for small registration errors but at the expense of
increasing partial volume effects at the lung boundary and reducing
spatial resolution. In these animal studies, 60% Xe was used to
maximize the density-enhancement signal and thereby minimize these
noise effects. For human studies, a lower Xe concentration will be
required to limit anesthetic side effects, making the use of cardiac
gating and other methods to minimize error even more important.
estimates than either a washin or washout
protocol alone. This occurs because most of the information in
estimating an exponential is contained in the steep initial portion of
the curve, and the wi/wo model has two such segments compared with only
one for the washin and washout models. To maximize the data available
for parameter estimation, we imaged the lung every breath during the
protocol, because there was no concern about cumulative radiation
exposure for these studies. For application of this method to humans,
however, it is likely that an optimized imaging protocol that acquires
images more frequently during the early, rapidly changing portion of
the washin and washout phases would be more appropriate. Furthermore, a
single-compartment model was used. This appears to be adequate for the
healthy lung, but more complex, multicompartment models may be required
in injured lungs. However, if the ROI used is relatively small, it is
likely that single-compartment behavior may still be approximated, even in an abnormal lung.
Absolute values of s
will vary among animals, ventilator
settings, and different experimental conditions. To facilitate comparisons and to examine changes in the distribution of ventilation, the VI was used, in which regional s
was normalized by whole lung s
. Whole lung ventilation was estimated from the wi/wo curve of a ROI placed within the trachea. If the whole lung ventilation is over- or underestimated, as might occur if there is significant regional heterogeneity such that the whole lung washout departs from
the single exponential model, then all the VI for that study will
be biased. This may account for why some of the VI data in Fig. 6
do not appear to have a mean VI of 1. However, even if biased, the VI
parameter remains useful for looking at changes in the distribution of
ventilation within an animal.
The Xe-CT ventilation method requires a large number of serial scans to
be taken at each imaging location, typically 40-50 breaths or
4-6 min per study. Lung regions with very long time constants and
low ventilatory rates will require longer washin and washout times,
although total equilibration is not necessary to obtain accurate
regional time constants. On the other hand, these studies are performed
without interrupting ventilation and thus give an accurate reflection
of steady-state ventilatory conditions. The CT technology used in this
study required repeating the full imaging protocol at each location,
limiting the number of locations and/or conditions that could be
studied because of time constraints. More modern CT scanners are
already available that are capable of high-speed volumetric image
acquisition, allowing the simultaneous acquisition of multiple imaging planes.
Vertical gradients of ventilation and air content.
In agreement with the literature, important differences in the
distribution of regional ventilation between the prone and supine
postures were found (Table 1). In the supine posture, there was a steep
gradient in s
, with increased ventilation in the more dependent
regions. In contrast, no gradient in ventilation was found in the prone
position. Many other studies using a variety of techniques have shown
similar patterns of ventilation. The slope of VI vs. height for the
supine lungs (all locations combined) was
0.073 ± 0.007 cm
1 (mean ± SE) or 7.3%/cm, which is remarkably
close to the value of
0.069 ± 0.015 determined by Hubmayr
et al. (26) following the volumes of groups of implanted
marker with biplane X-ray cine during stepwise deflation from total
lung capacity in supine dogs. In another study using implanted markers
in mechanically ventilated dogs, these authors measured the vertical
gradient in regional VT/FRC (25), a parameter
comparable to our s
. They found mean gradients of 0.005 and
0.032 cm
1 in prone and supine postures, respectively,
compared with
0.002 and
0.014 cm
1 in our study. Using
aerosolized fluorescent microspheres, Robertson et al.
(34) found no significant vertical ventilation gradients in prone pigs. Treppo et al. (40) used radioactive
N-13N positron emission tomography imaging to
simultaneously measure ventilation, perfusion, alveolar volume, and
/
at the lung base in dogs and found a gradient in
s
of 5.52 ± 1.1%/cm (mean ± SD) in the supine
position vs. 0.34 ± 0.88%/cm when dogs were turned prone. Our
results agree quantitatively with these diverse studies, both
reiterating this important change in regional lung function with
posture and validating the Xe-CT technique.
0.36%air/cm prone. These values compare well to the 2.57 ± 0.16 and 0.27 ± 0.22%air/cm gradients found in our supine and
prone dogs, respectively (Table 1). Although these studies analyzed the
entire lung, they measured the gradient from the average air content of
coronal slices running from apex to base and thus did not examine
regional differences in vertical gradients. The average air content
described by these authors in the prone position, 66%, also agrees
well with the 67.3 ± 2.1% prone and 66.8 ± 1.7% supine
measured in our animals. Other studies looking at postural gradients of
pleural pressure (44), subpleural alveolar size (47), and positron emission tomography measurement of
alveolar volume (40) have similarly found steep gradients
in the supine position and minimal or no gradients when prone.
Longitudinal distributions of ventilation and volume. The apex-to-base distribution of lung volume consistently changes with posture (Fig. 4), as has been previously described by others (22, 23, 30), such that the profile of the prone lung is flatter. The region below the heart is more compressed and the diaphragm is steeper due to pressure from the abdominal contents in the supine position, resulting in compression of the dependent lung and distortion of the chest wall, which combine to create the strong gradients in regional pleural pressure and lung expansion noted above (29, 30).
VI, which describes the regional s
relative to that of the whole
lung, increases in the supine posture from apex to base (Fig. 5). This
increase must reflect the fact that the lung base and diaphragm, which
are compressed by the abdominal contents at FRC (Fig. 4), are initially
more compliant than the apex and midlung. In fact, relatively little
radial expansion of the apical chest wall occurs, even with inflation
to total lung capacity (21, 30). As the lung expands, it
moves caudally and displaces the diaphragm; in the supine dogs, the
abdominal contents are resting on the basal lung, and their
displacement apparently presents less impedance to lung expansion than
does the more rigid chest wall. The less expanded basal lung
tissue may also be more compliant, further contributing to the higher
s
of this region. Combining this pattern of s
with the
steeper profile of lung volume toward the base further accentuates the
apex-base increase in slice ventilation in the supine position (Fig.
5). In contrast, in the prone position, the heart and abdominal
contents fall away from the lung, the lung at FRC is very uniformly
inflated (Fig. 4), and the longitudinal distribution of s
is
likewise relatively uniform. Combined with the lung volume profile, the
net result for the prone condition is a more even distribution of slice
ventilation that reaches a maximum below the carina and falls off
toward the base.
The prone position has been shown to dramatically improve oxygenation
in a subset of patients with acute lung injury, a result of the
reduction in the vertical pleural pressure gradient and improved
recruitment of dependent lung regions (15, 28). Although the above findings in healthy animals need to be repeated in models of
lung injury, they highlight the importance of postural changes in the
distribution of lung expansion and ventilation, which are thought to be
critical factors contributing to this phenomenon. Indeed, although much
attention has been focused on the changing vertical gradient in
ventilation with the prone position, it is entirely possible that the
longitudinal differences in air content and ventilation are of equal or
greater importance.
Summary. CT imaging provides noninvasive information on lung structure and function that permits the extension of studies of lung mechanics and physiology from the whole organ to the regional level. The Xe-CT ventilation method adds to this armamentarium, providing a quantitative measure of regional pulmonary ventilation to complement the data on regional lung volumes and air content traditionally obtained from CT studies. Results of these Xe-CT studies of healthy animals in the prone and supine postures demonstrate significant regional nonuniformities and agree with findings from the literature and with commonly accepted concepts of regional lung mechanical function.
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ACKNOWLEDGEMENTS |
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We thank Dr. Wayne Mitzner for invaluable advice and encouragement, Dr. Elias Zerhouni for access to the CT imaging facilities, Vince Lerie for expert CT technological support, and especially Mansheung Fung for work developing the software for controlling the ventilator and Xe delivery system. We are indebted to Praxair Pharmaceuticals, Tarrytown, NY, for providing the Xe gas, Jerry Timpe of Diversified Diagnostic Products, Houston, TX, for providing the Enhancer 3000 Xe delivery system, and Lifecare International, Westminster, CO, for providing the computer-controlled PLV-102 ventilator.
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FOOTNOTES |
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This research was supported by National Heart, Lung, and Blood Institute Grant HL-58504 and American Heart Association Grant MDBG0495.
Address for reprint requests and other correspondence: B. A. Simon, Dept. of Anesthesia, Tower 711, Johns Hopkins Hospital, Baltimore, MD 21287-8711 (bsimon{at}jhmi.edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 7 January 2000; accepted in final form 3 August 2000.
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