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Departments of 1 Medicine and 2 Physiology and Biophysics, University of Washington, Seattle 98195-6522; and 3 Mountain-Whisper-Light Statistical Consulting, Seattle, Washington 98112
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
THEORY
METHODS
RESULTS
DISCUSSION
REFERENCES
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We propose a model to
measure both regional ventilation (
) and perfusion (
) in
which the regional radiodensity (RD) in the lung during xenon (Xe)
washin is a function of regional (increasing RD) and
(decreasing RD). We studied five anesthetized, paralyzed,
mechanically ventilated, supine sheep. Four 2.5-mm-thick computed
tomography (CT) images were simultaneously acquired immediately cephalad to the diaphragm at end inspiration for each breath during 3 min of Xe breathing. Observed changes in RD during Xe washin were used to determine regional and . For 16 mm3, displayed more variance than : the
coefficient of variance of (CV) = 1.58 ± 0.23, the CV of (CV) = 0.46 ± 0.07, and the ratio of CV to
CV = 3.5 ± 1.1. CV
(1.21 ± 0.37) and the ratio of CV to
CV (2.4 ± 1.2) were smaller at
1,000-mm3 scale, but CV (0.53 ± 0.09) was not. / distributions also displayed scale
dependence: log SD of and log SD of were 0.79 ± 0.05 and 0.85 ± 0.10 for 16-mm3 and 0.69 ± 0.20 and 0.67 ± 0.10 for 1,000-mm3 regions of lung,
respectively. and measurements made with CT and Xe also
demonstrate vertically oriented and isogravitational heterogeneity,
which are described using other methodologies. Sequential images
acquired by CT during Xe breathing can be used to determine both
regional and noninvasively with high spatial resolution.
functional imaging; in vivo imaging; gas exchange; blood solubility; recirculation
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
THEORY
METHODS
RESULTS
DISCUSSION
REFERENCES
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EFFICIENT GAS EXCHANGE
IN the lung requires close matching of regional ventilation
() and perfusion (). It has been demonstrated that
and and -to- ratio (/) vary
spatially throughout the lung (1, 2, 11, 12, 15, 36, 41)
and that this spatial variation affects overall gas exchange in the
lung (3, 23, 45). Therefore, measurement of regional
movement of gas and blood in the lung is required to fully understand
the factors governing gas exchange. Much has been learned about
regional lung function in healthy and diseased lungs using a variety of
techniques, such as aerosolized and injected microspheres, positron
emission tomography, computed tomography (CT), and magnetic resonance
imaging. Because and both demonstrate scale-dependent
spatial heterogeneity (2, 12, 17, 19, 41), obtaining
measurements at higher resolution than previously reported will provide
further insight into the mechanism of gas exchange in the lung.
Because of its ability to obtain high-resolution images of the lung in
vivo, CT has been used to obtain measurements using nonradioactive xenon (Xe; mol wt = 131), a gas with significant X-ray absorption (42). Early studies obtained rough
estimates of by digitally subtracting images of the lung
obtained before and after inhalation of Xe (24).
Subsequent measurement of changing regional Xe concentration ([Xe]),
over multiple breaths, allowed estimation of regional with high
spatial resolution (20, 21, 31, 35, 37, 38). Although this
was a promising advance in measurement, regional
remained unmeasured, limiting the technique's ability to study gas exchange.
These previous studies used the simplifying assumption that Xe is
insoluble in blood, and, therefore, the change of regional density
during Xe washin or washout is dependent only on regional .
Although the solubility of Xe in blood is low, it is not insignificant; therefore, [Xe] in the lung is actually dependent on both regional and . Two examples of loss of Xe into pulmonary blood
flow are the application of Xe in cerebral blood flow studies and the anesthetic properties of Xe at high [Xe] in inhaled gas (8, 22,
44). In humans, the blood-to-air Ostwald partition coefficient (
blood/air) is ~0.13 at 37°C and is a function of Xe
solubility in red blood cells (RBC) (RBC/air = 0.21) and plasma (plasma/air = 0.10) (28, 32,
40).
We propose an improved model of inert tracer-gas movement in the lung
that takes into account the solubility of the gas in tissue and blood.
Using CT, we demonstrate that sequential images acquired at end
inspiration during Xe washin can be used to simultaneously measure
regional and in the lung with a high degree of spatial resolution.
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THEORY |
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TOP
ABSTRACT
INTRODUCTION
THEORY
METHODS
RESULTS
DISCUSSION
REFERENCES
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An idealized volume element of the lung (voxel) is illustrated in
Fig. 1. This representative voxel is
displayed at end inspiration and contains air space [alveolar volume
(VA)] and tissue and capillary blood [tissue volume
(Vtissue)] compartments. Tracer gas is delivered or
removed from the alveolar space via four routes: 1) delivery of gas through inhalation, 2) loss of gas through
exhalation, 3) loss of gas into capillary blood, and
4) delivery of gas through mixed venous blood. Mass
conservation of the tracer gas into the alveolar and tissue
compartments within the voxel boundary is
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(1) |
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This model includes the following simplifications: 1) tidal
can be adequately represented by unidirectional flow with a constant VA; 2) for each voxel, dead space
[dead space volume (VD)] is a fixed fraction of
VA and contains only exhaled gas from the voxel in question
("personal" dead space); 3) CI, regional , and regional do not change during the period of tracer gas washin; 4) tracer gas fully equilibrates among all
alveolar gas, lung parenchyma (Ctissue = tissue/air CA, where tissue/air is the tissue-to-air Ostwald partition
coefficient), and end-capillary blood (Ccapillary = blood/air CA) within the voxel.
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(2) |
1,000 HU; RD of
water, approximately zero HU; and RD of bone, approximately +1,000 HU).
Assuming a linear relationship between CT and tracer concentration
within a voxel (30, 31, 35, 38), the evolution of RD for a
voxel containing air and tissue follows the same form as the evolution of CA during Xe breathing (2)
![&Dgr;HU<SUP><IT>i</IT></SUP><SUB>voxel</SUB><IT>=</IT><FR><NU><AR><R><C>(V<SC>a</SC><IT>+&lgr;</IT><SUB>tissue/air</SUB>V<SUB>tissue</SUB>)[(V<SC>a</SC><IT>+&lgr;</IT><SUB>tissue/air</SUB>V<SUB>tissue</SUB></C></R><R><C><IT>+</IT>V<SC>d</SC>)<IT>&Dgr;</IT>HU<SUP><IT>i−</IT>1</SUP><SUB>A</SUB><IT>+</IT>(<A><AC>V</AC><AC>˙</AC></A><IT>−</IT>V<SC>d</SC>)<IT>&Dgr;</IT>HU<SUB>I</SUB><IT>+</IT><A><AC>Q</AC><AC>˙</AC></A><IT>&Dgr;</IT>HU<SUP><IT>i−</IT>1</SUP><SUB><A><AC>v</AC><AC>&cjs1171;</AC></A></SUB>]</C></R></AR></NU><DE>V<SUB>voxel</SUB>(V<SC>a</SC><IT>+&lgr;</IT><SUB>tissue/air</SUB>V<SUB>tissue</SUB><IT>+</IT><A><AC>V</AC><AC>˙</AC></A><IT>+&lgr;</IT><SUB>blood/air</SUB><A><AC>Q</AC><AC>˙</AC></A>)</DE></FR>](/content/vol91/issue4/fulltext/1741/img005.gif)
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(3) |
HUvoxel is change in RD of a voxel of lung
referenced to baseline RD (in HU), HUA is
change in RD of alveolar fraction of a voxel of lung referenced to
baseline RD (in HU), HUI is the difference in RD between
the room-air gas (HUair) and the gas mixture containing
~65% Xe, and HU| |
METHODS |
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TOP
ABSTRACT
INTRODUCTION
THEORY
METHODS
RESULTS
DISCUSSION
REFERENCES
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Animal Model
This study was approved by the University of Washington Institutional Animal Care and Use Committee, and the National Institutes of Health guidelines for animal use and care were followed throughout. Five adult sheep (27.5-36 kg) of either sex were studied and remained in the supine posture throughout the study. The sheep were anesthetized with an intravenous bolus of thiopental sodium (20 mg/kg) followed by a constant infusion titrated to suppress hemodynamic and motor responses to noxious stimuli. Tracheotomy was performed, and the animal was mechanically ventilated through a short no. 9 endotracheal tube. Additional instrumentation included catheterization of 1) the femoral artery for blood pressure and blood-gas monitoring, 2) the femoral vein for administration of fluid and anesthesia, and 3) the right external jugular vein for cardiac output and pulmonary arterial and pulmonary capillary wedge pressure measurement via a Swan Ganz catheter. Hemodynamic and blood-gas measurements were made immediately before Xe breathing and immediately after washout of Xe. Before scanning, the sheep were paralyzed with a 2.5-mg iv injection of pancuronium bromide. The sheep were killed after completion of the study using a concentrated pentobarbital injection. was maintained throughout the study with a custom
circuit consisting of two Servo 900C ventilators (Siemens-Elema): one
delivering an N2-O2 mixture and the other a
Xe-O2 mixture, both with an inspired O2
fraction of ~0.35. Both devices were connected to the endotracheal
tube via a three-port valve with switching between ventilators
performed manually. Before the switch from
N2-O2 to Xe-O2, the bellows of the
Xe ventilator were purged to ensure consistent [Xe] during washin.
parameters for both devices were identical: pressure cycled
respiratory rate (RR) = 10 breaths/min, maximum airway
pressure set to maintain PCO2 between 30 and 35 Torr, inspiratory time = 67% (combination of inspiratory and
breath-hold time), and positive end-expiratory pressure = 0. A
personal computer was used to synchronize the respiratory pattern of
both ventilators, overriding the RR setting of each ventilator.
Scanning Protocol
Scans were performed using a LightSpeed CT scanner (GE Medical Systems, Milwaukee, WI). Scan settings included standard reconstruction, kVp = 80, mA = 400, scan time = 1 s, interscan delay = 5 s, slice thickness = 2.5 mm, peristalsis filter, field of view = 25 cm, axial mode, and four images per rotation. The washin protocol lasted 4.5 min and consisted of 15 breaths of 35% O2-balance N2 breathing (baseline) and 30 breaths of 35% O2-balance Xe breathing (Xe washin). Images were obtained during end-inspiratory breath holds for each breath of the washin protocol. The initial image was triggered manually with the remaining images occurring at 6-s intervals, matching exactly the respiratory period of the ventilators. The scanning area remained the same for each breath and was located immediately cephalad to the dome of the diaphragm, chosen to obtain the maximum amount of lung possible for analysis.Data Analysis
Identification of lung parenchyma.
Before , , and VA were obtained from
parameter matching, all structures that were not pulmonary parenchyma
(chest wall, airways, blood vessels, and mediastinal structures) were
eliminated from analysis by discarding all pixels with >95% or <10%
air space. The RD of each pixel for each of the 15 baseline breaths was
used to estimate VA and Vtissue
(26)
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(4) |
VA. HUwater was defined as the mean RD of a
region of the heart for all 15 baseline images (before Xe inhalation).
Similarly, HUair was defined as the mean RD of an airway
for all 15 baseline images.
Next, with the use of a grid overlay, each 2.5-mm-thick axial slice was
divided into voxels of 6 × 6 pixels (2.52 × 2.52 mm) for a
resultant voxel volume of 16 mm3. For the
1,000-mm3 voxel size, the four 2.5-mm-thick axial images
were combined to form one 10-mm-thick image, with this resulting image
divided into 25 × 25 pixel voxels.
The RD of each voxel was defined as the mean RD of all of its
constituent pixels. Voxels were eliminated from analysis if the slope
of RD of all 15 baseline scans was less than 2 or greater than 2 HU
per breath, eliminating regions demonstrating significant registration
artifact (changes in regional tissue density) during baseline scanning.
Voxels were also eliminated if 
80% of the possible pixels were discarded.
Parameter matching.
With the use of the relationship described in Eq. 3, values
for , , and VA were determined that best fit
the observed RD readings over a 30-breath Xe washin for each voxel in
each series of lung images. The values of HUI,
HUblood/air, and
tissue/air are determined as described below. The value
of VD is assumed to be similar throughout the lung image and is assigned a value of 0.25 VA for each voxel.
HUI AND HU
HUI is the difference in RD between the room-air gas
(HUair) and the gas mixture containing ~65% Xe.
HUI was determined by subtracting the RD of the lumen of
a large airway during room-air breathing from the RD of the same airway
lumen during Xe breathing. To minimize the effect of noise on this
measurement, the mean RD of 15 baseline breaths was subtracted from the
mean RD of 30 Xe breaths.
HUHUblood/air · CI). Baseline RD for IVC was obtained by averaging the RD of the first 15 breaths (baseline ), and the amplitude of the exponential was given by
blood/air · HUI, the maximum
possible RD change in the IVC for a given [Xe] in the inhaled gas.
TRACER GAS SOLUBILITY.
Xe solubility is similar in human, dog, and cow blood and depends on
hematocrit (Hct). For a Hct of 27% (the mean Hct of our sheep),
blood/air = 0.13 for human (28, 32,
40), dog (6, 9, 32), and cow (32)
based on published values of plasma/air and
RBC/air. Therefore, for our study, we assumed
blood/air = 0.13. For Xe solubility in tissue, we
use the value reported for Xe solubility in plasma, which is also
conserved across these species (tissue/air = 0.10).
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RESULTS |
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ABSTRACT
INTRODUCTION
THEORY
METHODS
RESULTS
DISCUSSION
REFERENCES
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Xe inhalation did not alter hemodynamic or gas-exchange parameters
(Table 1). RD measurements, during
inspiratory hold, for a representative voxel of lung and the IVC are
shown in Fig. 2; 15 room-air (baseline)
breaths precede 30 breaths of Xe (65% inhaled gas). The baseline RD of
the IVC curve is higher than that of the lung voxel because of aeration
of the lung. The magnitude of the IVC curve is smaller than the voxel
curve because of the limited solubility of Xe in blood; the maximum
[Xe] in the IVC is 13% of that of the [Xe] in the inhaled gas. The
onset of RD change in the IVC lags behind that of the voxel because of
the time required for blood to traverse the systemic circulatory system and the large volume of distribution of Xe in the systemic circulation because of its significant lipid solubility.
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Figure 3 shows how changes in
, , and VD affect the time evolution of RD
for an idealized voxel during Xe washin, assuming no recirculation of
tracer gas. Increasing regional increases the rate and
magnitude of RD change; conversely, increasing either VD or
results in a decrease in the rate and magnitude of RD change.
Because both and VD have similar effects, these
variables cannot be distinguished from each other.
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In this study, we have assumed VD to be a fixed fraction of
VA (25%). For a representative voxel of lung from
sheep 5, if VD is assumed to be 25% of VA
(VD/VA), then = 1.55 mm3/s, = 1.55 mm3/s, and
/ = 1.0. If this voxel were reanalyzed with an
assumed VD/VA of 30%, then = 1.69 mm3/s (a 9% increase), = 1.61 mm3/s (a 4% increase), and / = 1.05. If
we assume a lower dead space fraction, VD/VA = 20%, then = 1.41 mm3/s (a 9% decrease),
= 1.49 mm3/s (a 4% decrease), and
/ = 0.95.
Figure 4 demonstrates regional
, , and / at a 16-mm3 scale for
a 2.5-mm-thick transverse region of lung. These in vivo measurements
can be correlated with lung anatomy by comparing , , and
/ maps to CT images of the same portion of the lung.
Because the CT-Xe method requires air space for sufficient detection of
tracer gas, measurements of or in atelectatic regions
of lung are not possible, and these regions are not represented in the
lung function maps.
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Examination of Fig. 4 reveals vertically oriented and
isogravitational heterogeneity for both and . Figure
5 shows that, in 16-mm3
voxels, both vertically oriented and isogravitational
heterogeneity are greater for than .
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Table 2 lists the coefficients of
variance (CV) for (CV) and
(CV) at 16-mm3 and 1,000-mm3
scales of resolution. For 16 mm3, displayed more
variance than : CV = 1.58, CV = 0.46, and
CV/CV = 3.5. CV (1.21) and
CV/CV (2.4) were smaller at the
1,000-mm3 scale of resolution, but CV
was not (0.53).
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- and -weighted / distributions for a
single transverse portion of lung, as measured by CT-Xe, demonstrate an
approximate unimodal log normalized shape (Fig.
6) similar to findings from multiple
inert-gas elimination technique (MIGET) and microsphere studies of
normal whole lungs. The width of the -weighted / distributions decreases with increasing voxel size. For sheep 5, log SD of was 0.62 at a 16-mm3 scale and
0.79 at a 1,000-mm3 scale. Log SD of was 0.63 at a
16-mm3 scale and 0.82 at a 1,000-mm3 scale.
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
THEORY
METHODS
RESULTS
DISCUSSION
REFERENCES
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Advantages of CT-Xe
We describe an improved model of inhaled radiodense tracer gas kinetics, the soluble gas model, that allows for the simultaneous quantification of absolute regional and in vivo using
Xe and CT (Fig. 4). Although multiple methods have been employed to
measure regional and , CT-Xe is nondestructive and
permits simultaneous measurement with very high spatial resolution.
High-resolution measurements are key to understanding gas exchange
because the spatial variability of both and
increases as piece size decreases (2, 5, 17, 19, 41).
Unlike previous studies using CT and Xe that only measured regional
, we have maximized the changes in regional RD and incorporated
blood solubility of Xe, dead space ventilation, and recirculation of
tracer gas into a model that allows for measurement of regional
and .
Maximizing Xe signal.
Because Xe is only 13% as soluble in blood as in air, the magnitude of
effect of on regional tracer gas concentration is expected to
be smaller than that of . To reliably assess regional ,
we maximized the Xe RD signal by 1) inhaling ~65% Xe,
2) scanning at a low-beam energy (80 kVp) to increase X-ray
absorption of Xe (31, 42), and 3) scanning at
large lung volumes (end inhalation). As a result, we obtained a maximum
change in RD in airways (HUI) of 165 HU, which exceeds the
mean change in RD of 30-80 HU reported by others (31, 35,
37, 38).
Dead space ventilation.
The effect of reinspired dead space has not been accounted for in
previous models using CT, magnetic resonance imaging, microspheres, or
single-photon-emission computed tomography (SPECT) to image regional
(1, 29, 31, 36-38). This simplification can introduce error if the difference in gas concentration between breaths
is significant. The effect of dead space ventilation is to slow the
rate of rise of [Xe] in the air spaces (Fig. 3C). The
content of the gas entering a region of lung with each breath is not
exactly the same as the gas inspired at the mouth but is a mixture of
fresh gas and a small portion of gas remaining in the airways after the
previous exhalation. The magnitude of this error is correlated
with both the blood solubility of the tracer gas and regional ;
loss of tracer into blood increases the discrepancy between tracer gas
concentration at the mouth and in the previously exhaled alveolar gas.
also serves to slow the rate of Xe accumulation in the lung (Fig.
3B), it is not possible to differentiate the
effects of and VD in the present model. Therefore,
for the purposes of this study, VD is assumed to be a fixed
percentage of the VA for all voxels studied, namely, 25%
of VA.
Recirculation of tracer gas.
Our model predicts that Xe solubility in blood may affect
regional alveolar [Xe] in two ways: loss of Xe into arterial blood and delivery of Xe via venous blood (Fig. 1). Using CT, we are able to
measure the concentration of tracer gas in a region of lung as well as
estimate the concentration of tracer gas returning to the lung via
recirculation by measuring RD changes in the vena cava. For washin
periods of 0.5-1 min, the effect of recirculated tracer gas on
and measurements is minimal. However, accurate analysis
of low- regions requires an extended washin period, necessitating the inclusion of this recirculation effect.
Comparison to Other Methods
Direct comparison of regional and measurements
obtained by CT-Xe and ex vivo methods on a region-by-region basis may be difficult because of registration differences introduced by removing
lungs from the chest wall. Comparison of gas-exchange data between
CT-Xe and whole lung methods, such as MIGET, is difficult because CT-Xe
is presently only able to measure and in portions of
the lung and MIGET does not allow for regional analysis. Because significant regional differences in and exist,
measurements from one region of the lung may not adequately represent
global gas exchange. However, comparisons of spatial patterns, such as the vertical distributions of and , - and
-weighted / distributions, and the
scale-dependence of and heterogeneity, between data
obtained by CT-Xe and that reported by other methods is possible.
Comparison to other measures of regional and .
Because there are no published measurements of regional and
at the scale of resolution reported here, direct comparison of
spatial variance in and measured by CT-Xe and other
methods is not possible. However, because the scale-dependent
properties of regional have been well established for larger
scales of resolution (2, 17, 19, 41), and this fractal
nature has been confirmed to continue well below the scale of the
acinus in rats (12), we can compare the variance
for the 16-mm3 scale predicted by other methods to that
measured by CT-Xe. The mean CV at a
16-mm3 scale of resolution for all five sheep in this study
was 1.58. This is similar to the CV of 1.53 predicted for a regional volume of 16 mm3 using the fractal
dimension (i.e., 1.14) for measured in sheep by Caruthers and
Harris (5).
two to five times
that of CV at a 16-mm3 scale of
resolution. Studies using other techniques do not demonstrate a
significant difference between CV and
CV or significant differences in fractal dimensions
between and at larger scales of resolution. Similarly,
we observed less disparity between CV and
CV at a resolution of 1,000 mm3. A
possible explanation for the dramatic difference between
CV and CV at 16 mm3
may be that this lung volume is below the functional unit of ,
the volume of lung at which is homogeneous. Whereas it has been
shown using microspheres that variance does increase below the
level of the acinus, there have been no comparable studies of .
An alternative explanation for why CV appears more
sensitive to voxel size than CV may be that the
measurement of is more sensitive to noise in this model. This
may be the case because Xe is only 13% as soluble in blood as it is in
air. If the Xe washin signal becomes significantly more noisy with
smaller voxel volumes, this could result in increased variance of both
and , but measurements may be affected to a
greater degree. Because there is no increase in CV between the two voxel volumes measured, this explanation would have to
assume that all variance due to noise is represented in the
measurement. Further analysis of the sensitivity of and
to noise will be needed to evaluate the limitations of the CT-Xe method.
The caudal region of the lung was imaged to afford a wide range of
, , and / for study. This section of lung
has the largest possible vertical gradient as well as areas of
atelectasis and low aeration, enabling us to examine regions with
extremes of , , and /. The finding of
vertical and isogravitational heterogeneity in both and
in this study (Fig. 5) is consistent with the findings of
heterogeneity using microspheres (13, 14, 16). These prior
studies have concluded that gravity is not the predominant factor
determining regional , and our results appear to support this hypothesis.
Comparison to other measures of whole lung gas exchange.
- and -weighted / distributions can be
calculated using data obtained by CT-Xe (Fig. 6). For a transverse
region of lung, the - and -weighted /
distributions obtained by CT-Xe approximate a unimodal log-normalized
shape in normal sheep. Unlike the MIGET method, CT-Xe assumed no
particular shape for the - and -weighted /
distributions and does not apply smoothing to /
distributions. It is interesting to note that the shape of the
/ distributions is similar to that found for the entire
lung using different methodologies, although data from each transverse
region of lung need not mimic the findings for the entire lung.
being delivered to
regions of lung with / < 1, whereas the lung as a
whole is hyperventilated. Alveolar / for the whole lung
is estimated at 1.25 for the sheep in Fig. 6 and 1.34 ± 0.32 for
all sheep studied; alveolar / was calculated from values
for tidal volume, RR, and cardiac output immediately before and after
Xe inhalation, assuming VD/tidal volume = 0.25. In addition, arterial PCO2 = 30.4 ± 2.7 Torr, which was likely due to a combination of both hyperventilation and decreased CO2 production secondary to
general anesthesia and paralysis. The observation of low
/ areas in the dorsal lung of these anesthetized,
paralyzed supine sheep is consistent with previous studies (4,
14, 33, 39).
The - and -weighted / distributions,
measured by CT-Xe, show scale dependence. Figure 6 demonstrates that
the - and -weighted / distributions are
wider at 16 mm3 than at 1,000 mm3. This
scale-dependent variance may eventually be used to identify the size of
the functional unit of gas exchange. The scale of resolution at which
/ distributions obtained by CT-Xe best match those
obtained using MIGET may represent the scale at which gas exchange occurs.
Potential Limitations
Fixed personal dead space.
Whereas this study assumes a fixed VD/VA, this
is not likely the case in vivo. Just as regional and
vary regionally, so too may VD/VA. In addition,
VD/VA may be scale dependent. If the assumed
VD/VA in this model does not represent the true
VD/VA in a region of lung, the calculated
values of and will be affected. For a representative
voxel of lung with a / = 1, a 20% increase (or
decrease) in the dead space fraction above the 25% value assumed in
the model results in a 9% change, increase (or decrease) in , a
4% increase (or decrease) in , and a 5% increase (or decrease)
in /.
and
heterogeneity. If region A (high /)
shared common dead space with region B (low
/), the mixed dead space gas would have a lower [Xe]
than the exhalate of region A and a higher [Xe] than the
exhalate of region B. Region A would have less Xe delivered per breath, which would be interpreted by the model as a
decreased /; conversely, region B would have
more Xe delivered per breath, resulting in a higher measured
/. This effect is likely small because and
are spatially clustered, limiting dramatic differences between
adjacent lung regions. Additionally, it has been demonstrated that the
effects of common dead space can be adequately approximated by assuming
that dead space is personal in a multicompartment model of gas exchange
(10).
Image noise.
Image-related noise affects the calculation of and . The
most significant sources of image noise in our study are registration artifact and reconstruction artifact. Registration artifact occurs when
movement of the lung between images causes changes in regional tissue
density, resulting in changes in regional RD. These changes in tissue
RD may overwhelm the changes in RD due to Xe inhalation because the
difference between end-inspiratory and end-expiratory RD can be on the
order of 300 HU, and the maximum Xe signal possible during our study is
<175 HU. Scanning at identical lung volumes at each breath minimizes
this effect.
Gas density. When bulk quantities of imaging agent are used, the properties of the tracer agent itself may affect the measurements being made. For example, the density of our Xe-O2 mixture is nearly four times that of room air, and the viscosity is 20% greater than air. The effect of increased gas density on pulmonary gas exchange is complex. Low-density gases (He) decrease the efficiency of O2 exchange but increase the efficiency of CO2 exchange. Conversely, more dense gases such as Ar and SF6 have been shown to produce the opposite effects on gas exchange (7, 43). Neither high- nor low-density gases affect the transport of carbon monoxide in the lung. Extrapolation of these findings to our study are difficult because the changes noted are significantly more pronounced during hypoxia and have not been studied during conditions similar to those in our study.
In conclusion, we report the first noninvasive method that simultaneously measures regional and in vivo. These
measurements are possible using an improved model of tracer-gas
movement in the lungs that includes the effects of gas solubility in
blood, tracer gas recirculation, and dead space . Using Xe and
CT, we can measure and in regions of lung 20- to
100-fold smaller than reported using positron emission tomography or
microspheres and correlate gas-exchange data with anatomic structure.
Further evaluation of this method is required to determine spatial
resolution limits, the range for which and can be
accurately assessed, and the effect of image noise on and
determination. Ultimately, CT-Xe may be used to study gas
exchange in the human lung.
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ACKNOWLEDGEMENTS |
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The authors thank Ian Starr, Jan Walker, James Anderson, Trisha Jonas, and Drs. Steve McKinney, Derek Stanford, and Martin Kushmeric for technical assistance and consultation.
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FOOTNOTES |
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This study was supported by National Heart, Lung, and Blood Institute Grants HL-09811 and HL-12174.
Address for reprint requests and other correspondence: M. P. Hlastala, Box 356522, Division of Pulmonary and Critical Care Medicine, Univ. of Washington, Seattle, WA 98195-6522 (E-mail: hlastala{at}u.washington.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 19 September 2000; accepted in final form 25 April 2001.
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REFERENCES |
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TOP
ABSTRACT
INTRODUCTION
THEORY
METHODS
RESULTS
DISCUSSION
REFERENCES
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