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

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1 Chest Imaging Original Research Matsuoka et al. MDCT of Air Trapping in COPD Chest Imaging Original Research Shin Matsuoka 12 Yasuyuki Kurihara 1 Kunihiro Yagihashi 1 Makoto Hoshino 3 Naoto Watanabe 3 Yasuo Nakajima 1 Matsuoka S Kurihara Y Yagihashi K Hoshino M Watanabe N Nakajima Y Keywords: air trapping chronic obstructive pulmonary disease CT emphysema lung DOI: /AJR Received July ; accepted after revision October Department of Radiology St. Marianna University School of Medicine Sugao Miyamae-Ku Kawasaki City Kanagawa Japan. 2 Present address: Department of Radiology Brigham and Women s Hospital Harvard Medical School 75 Francis St. Boston MA Address correspondence to S. Matsuoka (shin4114@mac.com). 3 Division of Respiratory and Infectious Diseases Department of Internal Medicine St. Marianna University School of Medicine Kanagawa Japan. AJR 2008; 190: X/08/ American Roentgen Ray Society Quantitative Assessment of Air Trapping in Chronic Obstructive Pulmonary Disease Using Inspiratory and Expiratory Volumetric MDCT 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 1024 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 volume n 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 change n 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 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. C hronic 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 [5 7]. 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 densitomet- ric parameters of lung calculated on paired inspiratory and expiratory CT scans allowed indirect evaluation of airway obstruction in several obstructive lung diseases [8 12]. 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 762 AJR:190 March 2008

2 MDCT of Air Trapping in COPD 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 expiratory 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 inspiratory 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 contrastenhanced 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 contrastenhanced CT study (n = 1). Thus 36 patients (31 men and five women; mean age 71 years; range years) were included in this study. All patients had a history of smoking. Patient characteristics are summarized in Table 1. 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 1024 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 ( 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 1024 H; for inspir atory TABLE 1: Patient Characteristics and Results of Pulmonary Function Texts in 36 Patients Characteristic Mean ± SD Median Range Age (y) 71.0 ± Pack-years (no.) 34.5 ± Height (cm) ± Weight (kg) 54.4 ± FVC (% predicted) 94.6 ± (% predicted) 67.8 ± /FVC 51.7 ± (% predicted) 27.2 ± FRC (% predicted) ± TLC (% predicted) ± RV (% predicted) ± RV/TLC 47.0 ± (% predicted) 44.3 ± Note FVC = forced vital capacity = forced expiratory volume in 1 second = 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. AJR:190 March

3 Matsuoka et al. relative volume <n and expiratory relative volume <n n = each selected attenuation threshold value between 850 and 950 H) (Fig. 1). Next the lung volume with attenuation values between 500 and 950 H was segmented as the limited lung (Fig. 1) 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 thinsection 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 A the limited lung were calculated as relative volume of the limited lung on both inspiratory and expiratory scans (relative volume n 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 volume n 950 and expiratory relative volume n 950 n = each selected attenuation threshold value between 850 and 930 H) (Fig. 1). 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 change n 950 ) were calculated using the following formulas: relative volume change <n = expiratory relative volume <n inspiratory relative volume <n ; relative volume change n 950 = expiratory relative volume n 950 inspiratory relative volume n 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 ( ) were performed. Forced expiratory volume in 1 second ( ) and forced vital capacity (FVC) were measured according to standard D E F Fig year-old man with chronic obstructive pulmonary disease. Three-dimensional images anterior view reconstructed from inspiratory and expiratory MDCT. A Segmented whole-lung volume with voxels of attenuation values between 500 and 1024 H on inspiratory CT (blue). B Segmented lung volume with attenuation values less than 860 H in inspiratory CT (red). C 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. D Segmented limited-lung volume with voxels having attenuation values between 500 and 950 H on inspiratory CT (yellow). E Segmented lung volume with attenuation values between 860 and 950 H at upper threshold of 860 H on inspiratory CT (green). F 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 volume ) = (green in E) / (yellow in D) and relative volume on expiratory CT (expiratory relative volume ) = (green in F) / segmented limited-lung volume on expiratory CT. Relative volume = expiratory relative volume inspiratory relative volume B C 764 AJR:190 March 2008

4 MDCT of Air Trapping in COPD TABLE 2: Correlation Between Measured Relative Volume Change in Limited Lung and Results of Pulmonary Function Tests Upper Threshold (H) Relative Volume Change (%P) /FVC (%P) RV/TLC FVC (%P) DLco (%P) Mean ± SD Median r p r p r p r p r p r p ± ± ± ± ± < < < < < ± < < < < < < ± < < < < < < ± < < < < < < ± < < < < < < Note Relative volume change is difference in relative volume of limited lung between inspiratory and expiratory CT. %P = % predicted. FVC = forced vital capacity = forced expiratory volume in 1 second = 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. techniques and the ratio of to the forced vital capacity ( /FVC) and mid expiratory phase of the forced expiratory flow ( ) 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 /FVC were expressed as percentages of predicted values according to the prediction equations described previously [15]. was measured by the singlebreath method and the predicted values for 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 change n 950 and the results of PFTs ( /FVC 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 volume n* 950 relative volume change <n* or relative volume change n* 950 and the results of PFTs ( /FVC FVC RV/TLC and ) in both groups were obtained. Comparisons of expiratory relative volume <n* expiratory relative volume n* 950 relative volume change <n* or relative volume change n* 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 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 Change n 950 The correlations between the measured relative volume change n 950 values and the results of PFTs are shown in Table 2. Relative volume change n 950 with threshold values from 850 to 880 H had significant correlations with the results of /FVC and RV/TLC. Depending on the results of correlations with and RV/TLC the highest correlation was observed at the upper threshold value of 860 H (r = 0.75 p < for ; and r = 0.70 p < for RV/ TLC respectively). Thus we chose the upper threshold value of 860 H for the subsequent evaluation. The relationships between relative volume and or RV/ TLC are illustrated in Figure 2. 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 < % ± 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 < % ± 4.6%). The results of densitometric parameters are shown in Table 3. Significant differences were seen in expiratory relative volume < 860 expiratory relative volume relative volume change < 860 or relative volume between the moderate to severe emphysema group and the minimal or mild emphysema group (p < respectively). In the moderate to severe emphysema group relative volume significantly correlated with results of PFTs that associate with airway dysfunction (r = 0.76 p = for ; r = 0.64 p = for /FVC; r = 0.61 p = 0.02 for ; and r = 0.79 p < for RV/TLC). No significant correlations were seen between relative volume change < 860 expiratory relative volume or expiratory relative volume < 860 and results of PFTs. In the minimal or mild emphysema group relative volume significantly correlated with results of PFTs that associate with airway dysfunction (r = 0.56 p = for ; r = 0.56 p = for / FVC; r = 0.55 p = for ; and r = 0.50 p = 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 and the results of PFTs that associate with airway dysfunction. No significant correlations were seen between relative volume relative volume change < 860 expiratory relative volume or the expiratory relative volume < 860 and the in the minimal or mild emphysema AJR:190 March

5 Matsuoka et al FEF 25 75% (% predicted) Relative Volume Change group. The correlation between the densitometric parameters and the results of PFTs are shown in Table 4. 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 was the only parameter that could reflect airway dysfunction. Moreover even in the minimal or mild emphysema group relative volume correlated with the results of PFTs reflecting airway dysfunction. Consequently the parameter of relative volume A B Fig. 2 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. A and B Graphs show relationships between relative volume and forced expiratory flow (FEF) 25 75% (r = 0.75 p < 0.001) (A) and between relative volume and ratio of residual volume to total lung capacity (RV/TLC) (r = 0.70 p < 0.001) (B). TABLE 3: Results of Densitometry Parameters Patient Group Relative Volume Change a RV/TLC 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 [8 12]. 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 [16 18]. Consequently the degree of the change of the lung attenuation value after expiration has been quantified using some densitometric parameters such as Relative Volume Change < 860 b Relative Volume Change Expiratory Relative Volume c 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 [ ]. Therefore the exclusion of the pixels less than 950 H on both inspiratory and expiratory 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 was the only parameter that 0 Expiratory Relative Volume < 860 d Mean ± SD Median Mean ± SD Median Mean ± SD Median Mean ± SD Median All patients (n = 36) 22.7 ± ± ± ± Moderate to severe emphysema group (n = 14) Minimal or mild emphysema group (n = 22) 10.2 ± ± ± ± ± ± ± ± 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 AJR:190 March 2008

6 MDCT of Air Trapping in COPD TABLE 4: Correlation Between Densitometry Parameters and Results of Pulmonary Function Tests Pulmonary Function Test All patients (n = 36) Relative Volume Change a 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 volume in the emphysema-dominant group. These results could support the necessity of using paired inspiratory 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 Relative Volume Change < 860 b 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 [1 3] 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. Expiratory Relative Volume c Expiratory Relative Volume < 860 d r p r p r p r p (%P) 0.80 < e 0.77 < e 0.75 < e 0.78 < e /FVC 0.78 < e 0.75 < e 0.76 < e 0.77 < e (%P) 0.75 < e 0.71 < e 0.73 < e 0.74 < e RV/TLC 0.70 < e 0.63 < e 0.62 < e 0.60 < e FVC (%P) 0.60 < e 0.63 < e 0.53 < e 0.59 < e (%P) 0.56 < e 0.61 < e 0.58 < e 0.64 < e Moderate to severe emphysema group (n = 14) (%P) e /FVC e (%P) e RV/TLC 0.79 < e FVC (%P) e (%P) Minimal or mild emphysema group (n = 22) (%P) e e e e /FVC e e 0.67 < e 0.68 < e (%P) e e e 0.66 < e RV/TLC e e e e FVC (%P) e e (%P) e e e e 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. 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 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 expiratory CT is greater than that on inspiratory CT (Fig. 3). Thus differences in relative volume between inspiration and expiration AJR:190 March

7 Matsuoka et al. Pixels Lung Attenuation Value (H) 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. 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 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 in the moderate to severe emphysema group. In contrast the reduction of correlated with the increased values of all densitometric parameters in the minimal or mild emphysema group. The decrease of is probably the result of loss of alveolar surface area such as occurs in emphysema [22 23]. However alone is not specific for the diagnosis of emphysema [24]. Many studies have also found that measurement of 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 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. functional inhomogeneities and impairs [26]. In the minimal or mild emphysema group reduction of 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 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 [27 29]. 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 [30 32]. 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 expiratory 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 and RV/TLC. However in the strict sense and RV/TLC are not entirely representative of small airway obstruction and air trapping. Therefore relative volume 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 768 AJR:190 March 2008

8 MDCT of Air Trapping in COPD 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 can be used for the quantification of air trapping in patients with COPD regardless of the degree of emphysema. References 1. Pauwels RA Buist AS Calverley PM Jenkins CR Hurd SS; GOLD Scientific Committee. Global strategy for the diagnosis management and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary. Am J Respir Crit Care Med 2001; 163: Hogg JC Macklem PT Thurlbeck WM. Site and nature of airways obstruction in chronic obstructive lung disease. N Engl J Med 1968; 278: Yanai M Sekizawa K Ohrui T Sasaki H Takishima T. Site of airway obstruction in pulmonary disease: direct measurement of intrabronchial pressure. 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