Original Research
Chest Imaging
March 2008

Quantitative Assessment of Air Trapping in Chronic Obstructive Pulmonary Disease Using Inspiratory and Expiratory Volumetric MDCT

Abstract

OBJECTIVE. The purpose of our study was to determine the attenuation threshold value for the detection and quantification of air trapping using paired inspiratory and expiratory volumetric MDCT scans and to assess whether the densitometric parameter can be used for the quantification of airway dysfunction in chronic obstructive pulmonary disease (COPD) regardless of the degree of emphysema.
MATERIALS AND METHODS. This study included 36 patients with COPD who underwent 64-MDCT. The entire lung volume with attenuation between –500 and –1,024 H was segmented as whole lung. The lung volume with attenuation between –500 and –950 H was segmented as limited lung, while the lung volume of less than –950 H was segmented as emphysema and eliminated. The relative volumes for limited lung (relative volumen–950) with attenuation values below thresholds (n) ranging from –850 to –950 H, and relative volume for whole lung (relative volume<n) were obtained on inspiratory and expiratory CT. Then the differences of relative volumes after expiration in whole lung (relative volume change<n) and limited lung (relative volume changen–950) were calculated. Patients were classified into two groups according to mean relative volume less than –950 H. Correlations between densitometry parameters and pulmonary function tests (PFTs) reflecting airway dysfunction were evaluated.
RESULTS. The highest correlation with PFTs was observed at the upper threshold of –860 H. In the moderate to severe emphysema group (relative volume<–950 > 15%), relative volume change860–950 significantly correlated with the results of PFTs, whereas no significant correlations were seen between relative volume change<–860 and PFTs. In the minimal or mild emphysema group (inspiratory relative volume<–950 < 15%), all densitometric parameters correlated with PFTs.
CONCLUSION. The densitometric parameter of relative volume change calculated on paired inspiratory and expiratory MDCT using the threshold of –860 H in limited lung correlated closely with airway dysfunction in COPD regardless of the degree of emphysema.

Introduction

Chronic obstructive pulmonary disease (COPD) is characterized by the presence of airflow limitation [1] caused by small airways disease [2, 3], an increase in lung compliance due to emphysematous lung destruction [4], or both. Many studies have assessed the use of CT in the quantitative analysis of those structural abnormalities in COPD. Quantification of the extent and severity of pulmonary emphysema using CT has been reported in numerous studies [57].
Meanwhile, quantification of small airways disease using CT is less well developed than that of emphysema because recent CT techniques have not yet allowed direct morphologic assessment of small airways. However, some studies have shown that the densitometric parameters of lung calculated on paired inspiratory and expiratory CT scans allowed indirect evaluation of airway obstruction in several obstructive lung diseases [812]. These quantitative methods are based on the detection of air trapping. Air trapping reflects the retention of excess gas in all or part of the lung and is detected as decreased attenuation on expiratory CT as compared with the corresponding inspiratory images. However, in the case of COPD, the area of decreased attenuation includes not only air trapping but also emphysema. Thus, this method would be influenced by the extent of emphysema.
Recently, Matsuoka et al. [13] investigated the percentage change of relative area with attenuation values from –900 to –950 H between inspiratory and expiratory CT scans in patients with COPD. The lower threshold of –950 H was adopted to eliminate the influence of emphysema, and the upper threshold value of –900 H was adopted because the relative area in lung less than –900 H on expira-tory CT scans correlated to the degree of air trapping [8]. They found that the change in relative area with attenuation values from –900 to –950 H after expiration decreased with the deterioration of the pulmonary function tests (PFTs), reflecting airway obstruction, and that change correlated more closely with airway obstruction than change of relative area with attenuation values less than –900 H, including emphysema. Those authors concluded that their method using paired inspira-tory and expiratory CT could be useful for the quantitative evaluation of air trapping in COPD without the influence of emphysema.
Unfortunately, their study had several limitations: First, the validity of using a threshold of –900 H for the evaluation of air trapping was not confirmed. In fact, the appropriate attenuation threshold value for the quantification of air trapping on paired inspiratory and expiratory CT has not been clarified. Second, they obtained densitometric parameters from only six slices using a 2D analysis. Thus, the misregistration of CT slices between inspiration and expiration might have influenced their results. In addition, both emphysema and air trapping are heterogeneously distributed throughout the lung in COPD. Only six slices would not reflect morphologic and functional abnormalities in the whole lung. Those authors should have assessed whole-lung volumetric data. Third, most of their subjects had severe emphysema. The adaptability of this method to the patient without severe emphysema was not confirmed. Thus, the validity of this method is expected to improve by solving these limitations.
The first aim of our study was to determine the attenuation threshold value for the detection and quantification of air trapping using paired inspiratory and expiratory volumetric MDCT scans. The second aim of this study was to assess whether the densitometric parameter can be used for the quantification of airway dysfunction in COPD without being influenced by the degree of emphysema.

Materials and Methods

Subjects

This retrospective study was approved by our institutional review board, which waived the need for informed consent. One radiologist with 15 years of experience in chest CT reviewed medical records and MDCT images obtained between October 2005 and September 2006 in our institution, and 45 consecutive patients with COPD who underwent PFTs within 2 weeks of undergoing MDCT were selected. The clinical indications for these scans were variable, including detection or routine observation of emphysema. COPD subjects from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) [14] stages I–IV were included. Exclusion criteria were prior cardiopulmonary disease, obvious abnormal lung parenchymal lesions except for emphysema, pleural effusion, nondiagnostic CT image due to breathing motion artifact, and contrast-enhanced CT study. Nine patients were excluded from further analysis for the following reasons: prior cardiopulmonary disease (n = 2), obvious abnormal parenchymal lesions except for emphysema (n = 4), pleural effusion (n = 1), nondiagnostic CT image due to breathing motion artifacts (n = 1), and contrast-enhanced CT study (n = 1). Thus, 36 patients (31 men and five women; mean age, 71 years; range, 57–89 years) were included in this study. All patients had a history of smoking. Patient characteristics are summarized in Table 1.
TABLE 1: Patient Characteristics and Results of Pulmonary Function Texts in 36 Patients
CharacteristicMean ± SDMedianRange
Age (y)71.0 ± 7.371.057-89
Pack-years (no.)34.5 ± 21.233.05-120
Height (cm)161.9 ± 5.5162.5152-174
Weight (kg)54.4 ± 12.953.037-75
FVC (% predicted)94.6 ± 25.795.734.9-156.4
FEV1 (% predicted)67.8 ± 27.667.315.2-116.3
FEV1/FVC51.7 ± 13.448.927.6-69.9
FEF25-75% (% predicted)27.2 ± 18.621.04.1-67.8
FRC (% predicted)111.9 ± 19.8107.284.6-177.8
TLC (% predicted)109.6 ± 13.2107.184.7-134.6
RV (% predicted)120.4 ± 33.5116.260.1-240.0
RV/TLC47.0 ± 11.344.730.6-79.6
DLco (% predicted)
44.3 ± 28.2
36.9
7.6-126.9
Note—FVC = forced vital capacity, FEV1 = forced expiratory volume in 1 second, FEF25-75% = mid expiratory phase of forced expiratory flow, FRC = functional residual capacity, RV = residual volume, TLC = total lung capacity, RV/TLC = ratio of residual volume to total lung capacity, DLco = diffusing capacity of lung for carbon monoxide.

MDCT

All patients were scanned with a 64-MDCT scanner (Aquilion-64, Toshiba Medical Systems). The scanner was calibrated regularly with air and a water phantom to allow reliable measurements. CT was performed during deep inspiratory and expiratory breath-holding with the patient in the supine position. Every patient was carefully instructed how to breathe before the study and again right before the scanning. MDCT parameters for both scans were as follows: collimation, 0.5 mm; 120 kV; 200 mA; gantry rotation time, 0.5 second; beam pitch, 53/64. All images were reconstructed using a standard reconstruction algorithm with a slice thickness of 1 mm and a reconstruction interval of 0.5 mm.

Quantitative Assessment of Lung Attenuation

The reconstruction images were transferred to a workstation (Ziostation, Ziosoft). This workstation uses a semiautomatic threshold technique to isolate lung volume from other tissues and structures using CT attenuation values of –500 to –1,024 H; the volume of the entire lung was calculated by summing the voxels in those attenuation values and was defined as the whole lung. Minimal user intervention by one radiologist was required to exclude nonlung structures that satisfied the threshold criteria, such as the trachea and large bronchi near the hilum. Then the lung volumes with attenuation values lower than thresholds ranging from –850 to –950 H (–850, –860, –870, –880, –890, –900, –910, –920, –930, and –950 H) were obtained on both inspiratory and expiratory scans. The percentage of the lung volume with attenuation values lower than each threshold value for the whole lung were calculated as relative volume of the whole lung on both inspiratory and expiratory scans (relative volume<n [%] = volume with attenuation values less than each threshold/volume with attenuation value of –500 to –1,024 H; for inspir atory relative volume<n and expiratory relative volume<n, n = each selected attenuation threshold value between –850 and –950 H) (Fig. 1A, 1B, 1C, 1D, 1E, 1F).
Next, the lung volume with attenuation values between –500 and –950 H was segmented as the limited lung (Fig. 1A, 1B, 1C, 1D, 1E, 1F), which was considered eliminating emphysematous lesions from the whole lung. The lowest threshold of –950 H was chosen because this threshold has been validated macroscopically and microscopically for thin-section CT studies of the extent of emphysema [5, 6]. Then the percentage of lung volume with attenuation values between –950 H and each threshold value ranging from –850 to –930 H for the limited lung were calculated as relative volume of the limited lung on both inspiratory and expiratory scans (relative volumen–950 (%) = lung volume with attenuation values between –950 H and each threshold value/volume with attenuation value of –500 to –950 H; for inspiratory relative volumen–950 and expiratory relative volumen–950, n = each selected attenuation threshold value between –850 and –930 H) (Fig. 1A, 1B, 1C, 1D, 1E, 1F).
Fig. 1A 74-year-old man with chronic obstructive pulmonary disease. Three-dimensional images, anterior view, reconstructed from inspiratory and expiratory MDCT. Segmented whole-lung volume with voxels of attenuation values between –500 and –1,024 H on inspiratory CT (blue).
Fig. 1B 74-year-old man with chronic obstructive pulmonary disease. Three-dimensional images, anterior view, reconstructed from inspiratory and expiratory MDCT. Segmented lung volume with attenuation values less than –860 H in inspiratory CT (red).
Fig. 1C 74-year-old man with chronic obstructive pulmonary disease. Three-dimensional images, anterior view, reconstructed from inspiratory and expiratory MDCT. Segmented lung volume with attenuation values less than –860 H in expiratory CT (red). Relative volumes for whole lung with attenuation value less than –860 H are calculated as follows: relative volume on inspiratory CT (inspiratory relative volume<–860) = (red in B)/(blue in A), and relative volume on expiratory CT (expiratory relative volume<–860) = (red in C)/segmented whole-lung volume on expiratory CT. Relative volume change<–860 (%) = expiratory relative volume<–860 – inspiratory relative volume<–860.
Fig. 1D 74-year-old man with chronic obstructive pulmonary disease. Three-dimensional images, anterior view, reconstructed from inspiratory and expiratory MDCT. Segmented limited-lung volume with voxels having attenuation values between –500 and –950 H on inspiratory CT (yellow).
Fig. 1E 74-year-old man with chronic obstructive pulmonary disease. Three-dimensional images, anterior view, reconstructed from inspiratory and expiratory MDCT. Segmented lung volume with attenuation values between –860 and –950 H at upper threshold of –860 H on inspiratory CT (green).
Fig. 1F 74-year-old man with chronic obstructive pulmonary disease. Three-dimensional images, anterior view, reconstructed from inspiratory and expiratory MDCT. Segmented lung volume with attenuation values between –860 and –950 H at upper threshold of –860 H on expiratory CT (green). Relative volume for limited lung is obtained as follows: relative volume on inspiratory CT (inspiratory relative volume860–950) = (green in E)/(yellow in D), and relative volume on expiratory CT (expiratory relative volume860–950) = (green in F)/segmented limited-lung volume on expiratory CT. Relative volume change860–950 (%) = expiratory relative volume860–950 – inspiratory relative volume860–950.
To evaluate the change of relative volume after expiration, the difference between the relative volumes on expiratory CT and inspiratory CT in the whole lung (relative volume change<n) and the limited lung (relative volume changen–950) were calculated using the following formulas: relative volume change<n (%) = expiratory relative volume<n – inspiratory relative volume<n; relative volume changen–950 (%) = expiratory relative volumen–950 – inspiratory relative volumen–950; n = each selected attenuation threshold value between –850 and –930 H.

Pulmonary Function Tests

PFTs were performed within 2 weeks of obtaining thin-section CT scans. PFTs, including spirometry and measurement of diffusing capacity for carbon monoxide (DLco), were performed. Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were measured according to standard techniques, and the ratio of FEV1 to the forced vital capacity (FEV1/FVC) and mid expiratory phase of the forced expiratory flow (FEF25–75%) were obtained. The lung volume subdivisions of functional residual capacity (FRC), residual volume (RV), and total lung capacity (TLC) were measured with the helium dilution method. Values for each PFT, except for RV/TLC and FEV1/FVC, were expressed as percentages of predicted values according to the prediction equations described previously [15]. DLco was measured by the single-breath method, and the predicted values for DLco were determined as described previously [15].

Statistical Analysis

To obtain the attenuation threshold value for the detection and quantification of air trapping, we calculated Spearman's correlation coefficients between each relative volume changen–950 and the results of PFTs (FEV1, FEV1/FVC, FEF25–75%, and RV/TLC). Next, all patients were classified into two groups according to the extent of emphysema obtained on the basis of the mean value of inspiratory relative volume<–950. Using that threshold value (n*) obtained from this study, Spearman's correlation coefficients between the expiratory relative volume<n*, expiratory relative volumen*–950, relative volume change<n*, or relative volume changen*–950 and the results of PFTs (FEV1, FEV1/FVC, FEF25–75%, FVC, RV/TLC, and DLco) in both groups were obtained. Comparisons of expiratory relative volume<n*, expiratory relative volumen*–950, relative volume change<n*, or relative volume changen*–950 between the moderate to severe emphysema group and the minimal or mild emphysema group were done using the Wilcoxon's signed rank test. All statistical analyses were performed using JMP 5.0.1 software (SAS Institute). Data are expressed as mean ± SD. For all statistical analyses, a p value of less than 0.05 was considered significant.

Results

Threshold Value of Relative Volume Changen–950

The correlations between the measured relative volume changen–950 values and the results of PFTs are shown in Table 2. Relative volume changen–950 with threshold values from –850 to –880 H had significant correlations with the results of FEV1, FEV1/FVC, FEF25–75%, and RV/TLC. Depending on the results of correlations with FEF25–75% and RV/TLC, the highest correlation was observed at the upper threshold value of –860 H (r = –0.75, p < 0.001 for FEF25–75%; and r = 0.70, p < 0.001 for RV/TLC, respectively). Thus, we chose the upper threshold value of –860 H for the subsequent evaluation. The relationships between relative volume change860–950 and FEF25–75% or RV/TLC are illustrated in Figure 2A, 2B.
TABLE 2: Correlation Between Measured Relative Volume Change in Limited Lung and Results of Pulmonary Function Tests
Relative Volume Change (%)FEV1 (%P)FEV1/FVCFEF25-75% (%P)RV/TLCFVC (%P)DLco (%P)
Upper Threshold (H)Mean ± SDMedianrprprprprprp
-930-5.6 ± 4.7-4.8-0.070.703-0.070.683-0.050.7920.010.962-0.120.4750.170.310
-920-9.2 ± 7.0-7.4-0.220.188-0.210.224-0.180.3070.140.424-0.290.0910.020.902
-910-4.6 ± 7.8-3.5-0.510.001-0.510.001-0.460.0050.340.045-0.480.003-0.320.053
-900-16.7 ± 11.3-15.3-0.540.001-0.510.001-0.470.0040.400.016-0.550.001-0.360.029
-890-19.4 ± 13.2-18.9-0.63< 0.001-0.64< 0.001-0.58< 0.0010.510.001-0.62< 0.001-0.55< 0.001
-880-22.0 ± 14.4-18.4-0.72< 0.001-0.73< 0.001-0.67< 0.0010.55< 0.001-0.64< 0.001-0.63< 0.001
-870-22.9 ± 16.0-19.6-0.76< 0.001-0.75< 0.001-0.70< 0.0010.63< 0.001-0.65< 0.001-0.64< 0.001
-860-22.7 ± 15.5-20.7-0.80< 0.001-0.78< 0.001-0.75< 0.0010.70< 0.001-0.70< 0.001-0.61< 0.001
-850
-21.8 ± 17.4
-18.6
-0.73
< 0.001
-0.71
< 0.001
-0.68
< 0.001
0.70
< 0.001
-0.59
< 0.001
-0.56
< 0.001
Note—Relative volume change is difference in relative volume of limited lung between inspiratory and expiratory CT. %P = % predicted. FVC = forced vital capacity, FEV1 = forced expiratory volume in 1 second, FEF25-75% = mid expiratory phase of forced expiratory flow, FRC = functional residual capacity, RV = residual volume, TLC = total lung capacity, RV/TLC = ratio of residual volume to total lung capacity, DLco = diffusing capacity of the lung for carbon monoxide.

Densitometric Parameters in Whole and Limited Lung

Mean value of the inspiratory relative volume<–950 was 15.1% ± 14.3%. According to the mean value of the inspiratory relative volume<–950, all patients were divided into two groups as follows: moderate to severe emphysema group (inspiratory relative volume<–950 > 15%): 14 patients (13 men and one woman; mean age, 72.1 years; mean inspiratory relative volume<–950, 23.7% ± 12.3%), minimal or mild emphysema group (inspiratory relative volume<–950 < 15%): 22 patients (18 men and four women; mean age, 70.4 years; mean inspiratory relative volume<–950, 5.0% ± 4.6%). The results of densitometric parameters are shown in Table 3. Significant differences were seen in expiratory relative volume<–860, expiratory relative volume860–950, relative volume change<–860, or relative volume change860–950 between the moderate to severe emphysema group and the minimal or mild emphysema group (p < 0.001, respectively).
TABLE 3: Results of Densitometry Parameters
Relative Volume Change860-950a (%)Relative Volume Change<-860b (%)Expiratory Relative Volume860-950c (%)Expiratory Relative Volume<-860d (%)
Patient GroupMean ± SDMedianMean ± SDMedianMean ± SDMedianMean ± SDMedian
All patients (n = 36)-22.7 ± 15.5-20.5-22.7 ± 15.7-21.243.1 ± 19.442.948.6 ± 22.546.0
Moderate to severe emphysema group (n = 14)-10.2 ± 6.3-11.3-9.9 ± 6.8-9.756.2 ± 11.255.768.1 ± 8.467.4
Minimal or mild emphysema group (n = 22)
-30.6 ± 14.4
-30.6
-30.9 ± 14.2
-30.7
34.8 ± 19.1
34.7
36.2 ± 19.6
35.6
a
Difference in relative volume of limited lung between inspiratory and expiratory CT.
b
Difference in relative volume of whole lung between inspiratory and expiratory CT.
c
Percentage of lung volume with attenuation values between -860 and -950 H for limited lung.
d
Percentage of lung volume with attenuation values <-860 H for whole lung.
In the moderate to severe emphysema group, relative volume change860–950 significantly correlated with results of PFTs that associate with airway dysfunction (r = –0.76, p = 0.002 for FEV1; r = –0.64, p = 0.013 for FEV1/FVC; r = –0.61, p = 0.02 for FEF25–75%; and r = 0.79, p < 0.001 for RV/TLC). No significant correlations were seen between relative volume change<–860, expiratory relative volume860–950, or expiratory relative volume<–860 and results of PFTs.
In the minimal or mild emphysema group, relative volume change860–950 significantly correlated with results of PFTs that associate with airway dysfunction (r = –0.56, p = 0.007 for FEV1; r = –0.56, p = 0.006 for FEV1/FVC; r = –0.55, p = 0.008 for FEF25–75%; and r = 0.50, p = 0.001 for RV/TLC). The correlation coefficients between relative volume change<–860 and the results of PFTs were the same as the correlation between relative volume change860–950 and the results of PFTs that associate with airway dysfunction. No significant correlations were seen between relative volume change860–950, relative volume change<–860, expiratory relative volume860–950, or the expiratory relative volume<–860 and the DLco in the minimal or mild emphysema group. The correlation between the densito-metric parameters and the results of PFTs are shown in Table 4.
TABLE 4: Correlation Between Densitometry Parameters and Results of Pulmonary Function Tests
Relative Volume Change860-950a (%)Relative Volume Change<-860b (%)Expiratory Relative Volume860-950c (%)Expiratory Relative Volume<-860d (%)
Pulmonary Function Testrprprprp
All patients (n=36)        
    FEV1 (%P)-0.80<0.001e-0.77<0.001e-0.75<0.001e-0.78<0.001e
    FEV1/FVC-0.78<0.001e-0.75<0.001e-0.76<0.001e-0.77<0.001e
    FEF25-75% (%P)-0.75<0.001e-0.71<0.001e-0.73<0.001e-0.74<0.001e
    RV/TLC0.70<0.001e0.63<0.001e0.62<0.001e0.60<0.001e
    FVC (%P)-0.60<0.001e-0.63<0.001e-0.53<0.001e-0.59<0.001e
    DLco (%P)-0.56<0.001e-0.61<0.001e-0.58<0.001e-0.64<0.001e
Moderate to severe emphysema group (n=14)        
    FEV1 (%P)-0.760.002e-0.400.149-0.100.725-0.140.626
    FEV1/FVC-0.640.013e-0.310.281-0.100.725-0.050.852
    FEF25-75% (%P)-0.610.020e-0.210.474-0.090.7710.030.922
    RV/TLC0.79<0.001e0.440.1180.260.3660.260.375
    FVC (%P)-0.570.034e-0.300.2990.100.725-0.070.811
    DLco (%P)0.230.4310.200.4970.400.1530.220.454
Minimal or mild emphysema group (n=22)        
    FEV1 (%P)-0.560.007e-0.570.006e-0.600.003e-0.590.003e
    FEV1/FVC-0.560.006e-0.570.005e-0.67<0.001e-0.68<0.001e
    FEF25-75% (%P)-0.550.008e-0.570.005e-0.640.001e-0.66<0.001e
    RV/TLC0.500.017e0.500.017e0.490.020e0.430.047e
    FVC (%P)-0.540.010e-0.520.012e-0.360.096-0.340.120
    DLco (%P)
-0.54
0.010e
-0.54
0.010e
-0.56
0.006e
-0.61
0.001e
Note—%P = % predicted.
a
Difference in relative volume of limited lung between inspiratory and expiratory CT.
b
Difference in relative volume of whole lung between inspiratory and expiratory CT.
c
Percentage of lung volume with attenuation values between -860 and -950 H for limited lung.
d
Percentage of lung volume with attenuation values < -860 H for whole lung.
e
p < 0.05, Spearman's correlation analysis.
Fig. 2A Relationships with relative volume change. Excellent correlation is observed at upper threshold value of –860 H with pulmonary function tests that reflect peripheral airway obstruction and air trapping. Graphs show relationships between relative volume change860–950 and forced expiratory flow (FEF)25–75% (r = –0.75, p < 0.001) (A) and between relative volume change860–950 and ratio of residual volume to total lung capacity (RV/TLC) (r = 0.70, p < 0.001) (B).
Fig. 2B Relationships with relative volume change. Excellent correlation is observed at upper threshold value of –860 H with pulmonary function tests that reflect peripheral airway obstruction and air trapping. Graphs show relationships between relative volume change860–950 and forced expiratory flow (FEF)25–75% (r = –0.75, p < 0.001) (A) and between relative volume change860–950 and ratio of residual volume to total lung capacity (RV/TLC) (r = 0.70, p < 0.001) (B).

Discussion

In our study, we found that the change of relative volume of limited lung with attenuation values between –860 and –950 H after expiration had the best correlation with results of PFTs that associate with airway dysfunction. In the moderate to severe emphysema group, relative volume change860–950 was the only parameter that could reflect airway dys-function. Moreover, even in the minimal or mild emphysema group, relative volume change860–950 correlated with the results of PFTs reflecting airway dysfunction. Consequently, the parameter of relative volume change860–950 can be used for the quantification of airway dysfunction in patients with COPD regardless of the degree of emphysema.
Although emphysema is now detectable with the use of CT, it is difficult to quantify airway obstruction and air trapping in patients with COPD. However, several researchers have tried to quantify the degree of air trapping using densitometric techniques on expiratory or paired inspiratory and expiratory CT in various obstructive lung diseases [812]. It has been reported that the area of air trapping does not show an increase in CT attenuation and remains more radiolucent than the surrounding normal pulmonary tissue [1618]. Consequently, the degree of the change of the lung attenuation value after expiration has been quantified using some densitometric parameters such as the relative area below a certain threshold value or the ratio of mean lung attenuation value of inspiration and expiration. However, these densitometric parameters were calculated from lung attenuation including values less than –950 H that reflect the extent of emphysema. Moreover, the relative area with attenuation values less than –950 H is not appreciably changed after expiration as compared with the relative area of decreased attenuation with values more than –950 H [12, 13, 19].
Therefore, the exclusion of the pixels less than –950 H on both inspiratory and expira-tory CT is desirable for the quantification of air trapping without influence of the extent of emphysema. Actually, in the moderate to severe emphysema group, relative volume change860–950 was the only parameter that related to the result of PFTs associated with airway obstruction and air trapping. Meanwhile, no significant correlations were seen between the results of PFTs reflecting airway dysfunction and relative volume change<–860, which is the parameter including voxels with attenuation values less than –950 H regarding the extent of emphysema. In addition, no significant correlations were found between airway dysfunction and the densitometric parameters obtained on only expiratory CT such as expiratory relative volume<–860 or expiratory relative volume860–950 in the emphysema-dominant group. These results could support the necessity of using paired inspira-tory and expiratory CT for the quantification of airway dysfunction in COPD with emphysema.
Although the value of –950 H is recognized as an acceptable cutoff for segmentation of emphysema, emphysema also exists in areas having lung attenuation greater than –950 H [20]. Furthermore, Gevenois et al. [21] showed that the threshold of –910 H on expiratory CT scans correlated better with the macroscopic assessment of emphysema. Therefore, the emphysematous lesions cannot be completely excluded using the cutoff value of –950 H, and they contribute to airway dysfunction to some degree. However, in our study and in a previous study [13], densitometric parameters with attenuation less than –950 H are not strongly related to airway dysfunction. Therefore, although airflow limitation in COPD is a dynamic phenomenon related to both small airways disease [13] and an increase in lung compliance due to emphysematous lung destruction [4], our results suggest that the extent of emphysema is not the major cause of airflow limitation in COPD.
The threshold value that regulates the extent and degree of air trapping also has not sufficiently been clarified. In our study, the upper attenuation threshold value of –860 H had the highest correlation with results of FEF25–75% and RV/TLC, which indicate airway obstruction and air trapping. However, we cannot explain why the attenuation value of –860 H is the best threshold to quantify the extent of air trapping. Using lung volume data from all subjects in our study, the frequency distribution of pixels in the lung on both inspiration and expiration shows that the percentages of pixels at the attenuation value of –860 H on both inspiration and expiration are equivalent, and at more than –860 H, the percentage of pixels on expira-tory CT is greater than that on inspiratory CT (Fig. 3). Thus, differences in relative volume between inspiration and expiration could be detected effectively at the attenuation value of less than –860 H. Future evaluation of the relationship between the change in relative volume after expiration and the physiologic bases is required.
Fig. 3 Frequency distribution of pixels in lung on inspiratory (•) and expiratory (○) CT in this study. Percentages of pixels at attenuation of –860 H on both inspiratory and expiratory CT are equivalent; at more than –860 H, percentage of pixels on expiratory CT is greater than on inspiratory CT.
Meanwhile, in our study, although the upper attenuation threshold value of –860 H had the highest correlation with results of PFTs, most correlations with the results of PFTs are similar to each other, especially between –850 and –880 H. Actually, in both the moderate to severe emphysema group and the minimal or mild emphysema group, the correlation between the densitometry parameters with attenuation values of –850, –870, and –880 H were not quite different from the result of using a threshold value of –860 H (data not shown). Therefore, the optimal threshold could vary between –850 and –880 H because of variable conditions such as calibration of the CT scanner.
In this study, no significant correlation was seen between all densitometric parameters and DLco in the moderate to severe emphysema group. In contrast, the reduction of DLco correlated with the increased values of all densitometric parameters in the minimal or mild emphysema group. The decrease of DLco is probably the result of loss of alveolar surface area, such as occurs in emphysema [22, 23]. However, DLco alone is not specific for the diagnosis of emphysema [24]. Many studies have also found that measurement of DLco has a weak correlation with the pathologic assessment of emphysema [25]. At the same time, airflow obstruction, especially that induced by airway dysfunction, may enhance functional inhomogeneities and impairs DLco [26]. In the minimal or mild emphysema group, reduction of DLco might correlate with functional inhomogeneities due to airway obstruction. Hence, it could be reasonable to find correlations between relative volume change, which reflects air dysfunction, and the reduction of DLco in the minimal or mild emphysema group.
Several studies have addressed the ability of 3D volumetric data to accurately quantify the extent and severity of emphysema [2729]. In previous studies, comparing only a few single inspiratory and expiratory image pairs, the misregistrations of CT slices between inspiration and expiration might be due to disturbances of accurate evaluation of airway dysfunction. Because MDCT has the major advantage that the entire thorax is imaged during a single breath-hold, the disadvantage of using single-detector CT has been overcome. Meanwhile, expiratory CT does expose patients to additional radiation, and multidetector technology can further increase the delivered dose. Therefore, further research is needed to optimize radiation dose for the quantification of airway dysfunction.
In the past few years, much attention has been paid to therapeutic agents that specifically address airflow obstruction in patients with COPD [3032]. Although emphysematous lesions are irreversible, there is a good chance for treatment and prevention of airway obstruction in patients with COPD. Quantitative CT analysis has been used to assess the relative efficacy of drugs on small airway hyperreactivity and regional air trapping [30]. The evaluation of drug efficacy in the peripheral airways is important, and progress toward specific treatment for COPD might be accelerated by moving beyond the measurement of airflow limitation to the precise diagnosis of the specific targets responsible for the airflow limitation. The efficacy of various drugs might be best assessed using the paired inspiratory and expiratory CT analysis in the limited lung, especially in COPD patients, because this method allows a more accurate assessment of peripheral airway obstruction without the influence of the extent of emphysema.
Our study has several limitations. First, the number of patients was relatively small. To prove the validity of our method for the quantification of air trapping, this method should be applied to a prospective larger set of patients with various degrees of emphysema. Second, the concept and definition of air trapping are still confusing and not agreed upon. On CT images, it is generally accepted that the area of air trapping does not show a significant increase in CT attenuation. According to this concept, to quantify air trapping, we must match each lung area on inspiratory and expiratory CT and compare the CT density between inspiratory and expira-tory scans. However, we did not perform pixel-by-pixel comparison. Thus, some areas having a value less than –950 H on inspiration CT may have the value of –860 to –950 H on expiration CT, which may affect the results to some degree. Moreover, we decided on the optimal upper threshold value of –860 H depending on correlations with the results of FEF25–75% and RV/TLC. However, in the strict sense, FEF25–75% and RV/TLC are not entirely representative of small airway obstruction and air trapping. Therefore, relative volume change860–950 might reflect not only a limitation in airflow caused by small airways disease but also other pathophysiologic conditions. Third, CT densitometry is influenced by the level of inspiration during CT [33]. A spirometrically controlled CT technique has been developed, offering the opportunity to obtain CT scans at defined levels of inspiration [34, 35].
In conclusion, using paired inspiratory and expiratory MDCT, the change in relative lung volume with attenuation values from –860 to –950 H after expiration correlated closely with results of PFTs, reflecting the severity of airway dysfunction. Furthermore, the result of the correlations of densitometry parameters and PFTs indicated that the relative volume change860–950 was the only parameter that could reflect airway dysfunction in both the moderate to severe emphysema group and the minimal or mild emphysema group. Thus, the densitometry parameter of relative volume change860–950 can be used for the quantification of air trapping in patients with COPD regardless of the degree of emphysema.

Footnote

Address correspondence to S. Matsuoka ([email protected]).

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Information & Authors

Information

Published In

American Journal of Roentgenology
Pages: 762 - 769
PubMed: 18287450

History

Submitted: July 4, 2007
Accepted: October 3, 2007

Keywords

  1. air trapping
  2. chronic obstructive pulmonary disease
  3. CT
  4. emphysema
  5. lung

Authors

Affiliations

Shin Matsuoka
Department of Radiology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-Ku, Kawasaki City, Kanagawa 216-8511, Japan.
Present address: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115.
Yasuyuki Kurihara
Department of Radiology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-Ku, Kawasaki City, Kanagawa 216-8511, Japan.
Kunihiro Yagihashi
Department of Radiology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-Ku, Kawasaki City, Kanagawa 216-8511, Japan.
Makoto Hoshino
Division of Respiratory and Infectious Diseases, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan.
Naoto Watanabe
Division of Respiratory and Infectious Diseases, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan.
Yasuo Nakajima
Department of Radiology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-Ku, Kawasaki City, Kanagawa 216-8511, Japan.

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