Quantitative CT in Chronic Obstructive Pulmonary Disease: Inspiratory and Expiratory Assessment

Transcription

1 Cardiopulmonary Imaging Original Research kira et al. CT of Chronic Obstructive Pulmonary Disease Cardiopulmonary Imaging Original Research Masanori kira 1 Kazushige Toyokawa 1 Yoshikazu Inoue 2 Toru rai 2 kira M, Toyokawa K, Inoue Y, rai T Keywords: chronic obstructive pulmonary disease (COPD), emphysema, MDCT DOI: /JR Received March 6, 2008; accepted after revision ugust 5, Partially supported by a grant to the Respiratory Failure Research Group from the Ministry of Health Labour and Welfare, Japan, and National Hospital Organization Research Grant, Japan. 1 Department of Radiology, National Hospital Organization, Kinki-Chuo Chest Medical Center, 1180 Nagasonecho, Kita-ku, Sakai City, Osaka , Japan. ddress correspondence to M. kira (kira@kch.hosp.go.jp). 2 Department of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan. JR 2009; 192: X/09/ merican Roentgen Ray Society Quantitative CT in Chronic Obstructive Pulmonary Disease: Inspiratory and Expiratory ssessment OJECTIVE. The purpose of this study was to determine whether measurements of lung attenuation at inspiration and expiration obtained from 3D lung reconstructions reflect the severity of chronic obstructive pulmonary disease. SUbjects and METHODS. Seventy-six patients with chronic obstructive pulmonary disease underwent MDCT with 3D postprocessing at full inspiration and full expiration. Inspiratory and expiratory mean lung density, percentage of lung volume with attenuation values less than 910 HU and 950 HU at inspiration and expiration, expiratory to inspiratory mean lung density ratio, and fifth and 15th percentiles of the lung attenuation distribution curve at inspiration and expiration were measured. RESULTS. When forced expiratory volume in the first second of expiration ( ) was 50% or greater than predicted value, mean lung density and lower attenuation volume measured from inspiratory MDCT scans correlated better with and ratio of to forced vital capacity (FVC) than did those from expiratory scans. When was less than 50% of predicted value, mean lung density and lower attenuation volume measured from expiratory MDCT scans correlated better with and ratio of residual volume to total lung capacity than did those values from inspiratory scans. Fifth percentile and 15th percentile of the lung attenuation distribution curve at both full inspiration and full expiration correlated well with /FVC and diffusing capacity of the lung for carbon monoxide as a percentage of predicted value but not well with as a percentage of predicted value regardless of. CONCLUSION. Measurements of lung attenuation obtained at inspiration and visual score better reflect abnormal results of pulmonary function tests in patients with less severe chronic obstructive pulmonary disease than do measurements obtained at expiration. Measurements of lung attenuation obtained at expiration better reflect pulmonary function abnormalities in patients with severe chronic obstructive pulmonary disease. T he potential usefulness of CT for identification of regions of pulmonary emphysema and air trapping has been addressed in many investigations [1]. Low-attenuation areas on CT scans in vivo have been found to represent macroscopic and microscopic emphysematous changes in the lungs of patients [2 4]. To objectively quantify pulmonary emphysema with CT, several lung attenuation parameters based on results of histogram analysis of the frequency distribution of the attenuation values of the lung have been developed. The most commonly used methods are based on measurement of mean lung attenuation, the areas of lung occupied by attenuation values lower than predetermined thresholds, and a predetermined percentile of the lung attenuation distribution curve. Many reports have confirmed good correlations of histogram-derived quantitative CT techniques with the results of lung function tests and pathologic evidence of emphysema [1]. The purpose of our study was to determine whether measurements of lung attenuation obtained from 3D lung reconstructions at inspiration and expiration reflect the severity of chronic obstructive pulmonary disease (COPD). We correlated lung function measurements at inspiration and expiration with measurements of lung attenuation on 3D lung reconstructions. We also evaluated the relation between the severity of COPD, reflected by Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage [5], and measurements of lung attenuation on 3D lung reconstructions. JR:192, January

2 kira et al. Subjects and Methods total of 76 smokers were recruited at our institution. The 67 men and nine women (mean age, 67.3 years; range, years) were included because they had a diagnosis of COPD according to the criteria of the merican Thoracic Society [6]. ll subjects were long-term cigarette smokers with an average smoking history of 1,142 ± 592 on the rinkman index (cigarettes/day years). ccording to the GOLD classification [5], six patients had stage 0; two, stage 1; 20, stage 2; 30, stage 3; and 18, stage 4 COPD (Table 1). The study was approved by the ethics committee of our hospital, and informed consent was obtained from each participant. Lung Function Studies ll pulmonary function studies were performed in the same laboratory with methods consistent with merican Thoracic Society recommendations [7] when the patients were in clinically stable condition. The results were compared with predicted values [8]. The pulmonary function tests were performed at the time of 3D lung CT. Lung CT Studies ll CT examinations were performed with a 16- MDCT scanner (HiSpeed Ultra 16, GE Healthcare). The scanner was subject to a weekly quality assessment with a phantom check including uniformity, linearity, and noise. ir and water phantoms were used to calibrate the CT scanner. In addition, an engineering check of spatial and contrast resolution was performed every 3 months and a medical physics check once a year. Scanning voltage was 120 kv and current was 160 m. In each case, CT of the thorax was performed from the lung apices through the level of the adrenal glands at full inspiration and was repeated at full expiration. ll imaging was performed with a collimation of mm, table feed of 30 mm/ rotation, and rotation time of 0.6 second/360 tube rotation with a standard reconstruction algorithm. The mean breath-hold was 7 seconds for one scan. Three-dimensional models of the lungs were reconstructed with analysis software (dvantage Windows 3D, GE Healthcare). Threshold limits of 500 to 1,024 HU were applied to exclude soft tissue surrounding the lung and large vessels within the lung. The 3D model was viewed as a shaded surface display at multiple angles to ensure that the model was valid. The trachea, mainstem bronchi, and gastrointestinal structures were selectively removed manually from the model (Fig. 1). histogram of the model showed the volume, attenuation distribution, mean attenuation, and SD of attenuation of the whole lung. The histogram provided a frequency distribution of voxels TLE 1: Clinical Characteristics ccording to Global Initiative for Chronic Obstructive Lung Disease of Chronic Obstructive Pulmonary Disease Characteristic with special attenuation values in the lung. The percent age of voxels with attenuation values below a specified level was defined as the lower attenuation volume at that threshold. Values for the lower attenuation volume at thresholds of 910 and 950 HU and the fifth and 15th percentiles were measured by moving the boundary line on the histogram. The ratio of expiration to inspiration (E/I) was obtained by dividing the mean lung density at full expiration by that at full inspiration [9]. On hard-copy inspiratory CT images photographed at a window width of 1,200 HU and centered at a level of 700 HU, visual emphysema scores for all axial sections were determined for each patient. Emphysema was identified as areas of hypovascular low attenuation and was graded on a 5-point scale based on the percentage of lung involved: 0, no emphysema; 1, up to 25% of lung parenchyma involved; 2, between 26% and 50% of lung parenchyma involved; 3, between 51% and 75% of lung parenchyma involved; and 4, 0 or 1, t Risk or Mild 2, Moderate 3, Severe 4, Very Severe No. of patients ge (y) 62.7 ± ± ± ± 9.3 (% of predicted) 90.2 ± ± ± ± 3.9 /FVC 72.5 ± ± ± ± 5.2 Dl c o (% of predicted) 82.5 ± ± ± ± 21.1 RV/TLC 33.4 ± ± ± ± 11.8 Note FEV = forced expiratory volume in first second of expiration, /FVC = ratio of to forced vital capacity; Dl c o = diffusing capacity of the lung for carbon monoxide, RV/TLC = ratio of residual volume to total lung capacity. Fig year-old man with chronic obstructive pulmonary disease. and, nterior view 3D images reconstructed from inspiratory () and expiratory () MDCT scans. between 76% and 100% of lung parenchyma involved. Grades for the axial images of each lung were added and divided by the number of images evaluated to yield emphysema scores that ranged from 0 to 4 [10]. Statistical nalysis Statistical analysis was performed with SPSS software (version 12.0, SPSS) by comparison of entity to pulmonary function test values with Spearman s correlation coefficients. For evaluation between different COPD levels, the Mann- Whitney U test was used. value of p < 0.05 was considered statistically significant. stepwise procedure was used to identify the subset of independent variables that were good predictors of the pulmonary function measurements. Results Table 2 shows the Spearman s correlation between CT parameters and results of pulmonary 268 JR:192, January 2009

3 CT of Chronic Obstructive Pulmonary Disease TLE 2: Spearman s Correlation Coefficients for Comparison etween CT and Pulmonary Function Data in the Evaluation of Chronic Obstructive Pulmonary Disease (n = 76) CT Parameter function tests. Histogram-derived quantitative CT techniques and visual score had significant good correlation with pulmonary function test results. However, when was 50% of the predicted value or greater (Table 3), mean lung density and lower attenuation volume measured from inspiratory MDCT scans correlated better with and /FVC than did those values on expiratory scans. Fifth percentile at full inspiration and at full expiration and 15th percentile at full inspiration and at full expiration had a strong correlation with /FVC and diffusing capacity of the lung for carbon monoxide (Dl c o) as percentage of predicted value but a much weaker correlation with. E/I correlated well with residual volume (RV)/TLC alone. Visual score correlated well with, /FVC, and Dl c o. In patients with less than 50% of predicted value (Table 4), mean lung density and lower attenuation volume measured from expiratory MDCT scans correlated better with and RV/TLC than did those values from inspiratory scans. Fifth and 15th percentiles at both full inspiration and full expiration correlated well with /FVC, RV/TLC, and Dl c o, but the correlation with was much weaker. E/I correlated well with and (% of Predicted) /FVC RV/TLC RV/TLC. Visual score correlated well with Dlco alone. Figures 2 6 show a variety of CT parameters in relation to GOLD stage of COPD. There were trends for lower attenuation volume, visual score, and E/I to increase with advancing disease stage. Trends were also observed for mean lung density and percentile of the frequency distribution curve to decrease with advancing disease stage. Statistically significant differences in none of CT parameters were found between patients with GOLD stage 0 and those with GOLD stage 1 disease. Statistically significant differences TLE 3: Spearman s Correlation Coefficients for Comparison etween CT and Pulmonary Function Data in the Evaluation of Chronic Obstructive Pulmonary Disease ( 50%, n = 28) CT Parameter (% of Predicted) /FVC RV/TLC Dl c o (% of Predicted) Inspiratory mean lung density a a a Expiratory mean lung density a a Proportion of lung volume with attenuation value less than 910 HU at inspiration a a Proportion of lung volume with attenuation value less than 910 HU at expiration a a Proportion of lung volume with attenuation value less than 950 HU at inspiration a a a Proportion of lung volume with attenuation value less than 950 HU at expiration a a a Fifth percentile of the lung attenuation distribution curve at inspiration a a Fifth percentile of the lung attenuation distribution curve at expiration a a 15th percentile of the lung attenuation distribution curve at inspiration a a 15th percentile of the lung attenuation distribution curve at expiration a a Ratio of expiratory mean lung density to inspiratory mean lung density a Dl c o (% of Predicted) Inspiratory mean lung density Expiratory mean lung density Proportion of lung volume with attenuation value less than 910 HU at inspiration Proportion of lung volume with attenuation value less than 910 HU at expiration Proportion of lung volume with attenuation value less than 950 HU at inspiration Proportion of lung volume with attenuation value less than 950 HU at expiration Fifth percentile of the lung attenuation distribution curve at inspiration Fifth percentile of the lung attenuation distribution curve at expiration th percentile of the lung attenuation distribution curve at inspiration th percentile of the lung attenuation distribution curve at expiration Ratio of expiratory mean lung density to inspiratory mean lung density Visual score Note ll differences are statistically significant. FEV = forced expiratory volume in first second of expiration, /FVC = ratio of to forced vital capacity; RV/TLC = ratio of residual volume to total lung capacity, Dl c o = diffusing capacity of the lung for carbon monoxide. Visual score a a a Note FEV = forced expiratory volume in first second of expiration, /FVC = ratio of to forced vital capacity; RV/TLC = ratio of residual volume to total lung capacity, Dlco = diffusing capacity of the lung for carbon monoxide. a Statistically significant difference. JR:192, January

4 kira et al. TLE 4: Spearman s Correlation Coefficients for Comparison etween CT and Pulmonary Function Data in the Evaluation of Chronic Obstructive Pulmonary Disease ( < 50%, n = 48) Mean Lung Density p = p = p = in inspiratory mean lung density were found from GOLD stage 1 (combined stages 0 and 1) to GOLD stage 4 (Fig. 2). No significant differences in lower attenuation volume measured from inspiratory scans (Fig. 3) or visual score (Fig. 4) were found between patients with GOLD stage 3 and those with GOLD stage 4 disease. Significant differences in expiratory mean lung density (Fig. 2) and lower attenuation volume measured from expiratory scans (Fig. 3) were found between patients with GOLD stage 3 and those with GOLD stage 4 disease, but no significant differences in these values were found between patients with GOLD stages 0 and 1 and those with GOLD stage 2 disease. Significant differences in fifth percentile at full inspiration (Fig. 5), fifth percentile at full expiration (Fig. 5), 15th percentile at full CT Parameter (% of Predicted) /FVC RV/TLC Dl c o (% of Predicted) Inspiratory mean lung density a a Expiratory mean lung density a a a Proportion of lung volume with attenuation value less than 910 HU at inspiration a a Proportion of lung volume with attenuation value less than 910 HU at expiration a a a Proportion of lung volume with attenuation value less than 950 HU at inspiration a a Proportion of lung volume with attenuation value less than 950 HU at expiration a a a Fifth percentile of the lung attenuation distribution curve at inspiration a a a Fifth percentile of the lung attenuation distribution curve at expiration a a a 15th percentile of the lung attenuation distribution curve at inspiration a a a 15th percentile of the lung attenuation distribution curve at expiration a a a Ratio of expiratory mean lung density to inspiratory mean lung density a a Visual score a a Note FEV = forced expiratory volume in first second of expiration, /FVC = ratio of to forced vital capacity; RV/TLC = ratio of residual volume to total lung capacity, Dlco = diffusing capacity of the lung for carbon monoxide. a Statistically significant difference. Mean Lung Density p = p = p = inspiration, 15th percentile at full expiration, and E/I (Fig. 6) were found only between patients with GOLD stage 2 and those with GOLD stage 3 disease. Stepwise multiple regression analysis revealed that the combination of visual score and mean lung density at full expiration was associated with as percentage of predicted value (r = 0.752, p < 0.001). The following equation was derived: as percentage of predicted value = (0.980 visual score) + (0.291 mean lung density at full expiration). Discussion The chronic airflow limitation characteristic of COPD is caused by a mixture of small airways disease (obstructive bronchiolitis) and parenchymal destruction (emphysema), the Fig. 2 Mean lung density according to Global Initiative for Chronic Obstructive Lung Disease stage in patients with chronic obstructive pulmonary disease., Graph shows results at full inspiration., Graph shows results at full expiration. relative contributions of which vary from person to person [5]. Gelb et al. [11] found a strong negative correlation between diffusing capacity as percentage of predicted value and diffusing capacity per alveolar volume and CT emphysema score only in patients with an of 1 L or more. mong patients with an less than 1 L, however, the correlation was much weaker. In only 10 of 35 patients with an less than 50% of predicted was the CT emphysema score greater than 40, indicating marked emphysema. Those authors concluded that CT visual emphysema score was not predominantly responsible for airflow limitation in COPD and that emphysema did not appear to be primarily responsible for severe expiratory airflow limitation in most patients with severe COPD. Zaporozhan et al. [12] also reported that no differences in inspiratory to 270 JR:192, January 2009

5 CT of Chronic Obstructive Pulmonary Disease Percentage Lung Volume at 950 HU expiratory emphysema index or changes in emphysema index and lung volume were found between patients with GOLD 3 and those with GOLD 4 disease. It remains unsettled whether inspiratory CT or expiratory CT is better for evaluating the severity of COPD. Studies [12 14] showed that the highest correlations between CT findings and physiologic variables consistent with emphysema were observed with CT measurements obtained at full expiration. Visual score correlates closely with morphologic emphysema and has better correlation with Dl c o as a percentage of predicted value. It does not reflect the site of small airways disease. Expiratory quantitative CT parameters are affected by peripheral airway obstruction and air trapping. In our study, mean lung density and lower attenuation volume measured from inspiratory MDCT scans Visual Score p = p = p = p = p = p = Fig. 4 Graph shows visual CT score according to Global Initiative for Chronic Obstructive Lung Disease stage in patients with chronic obstructive pulmonary disease. Percentage Lung Volume at 950 HU p = p = p = better correlated with as a percentage of predicted value and /FVC than did those values from expiratory scans when was 50% of predicted value or greater. In patients with less than 50% of predicted value, mean lung density and lower attenuation volume measured from expiratory MDCT scans better correlated with and RV/TLC than did the values from inspiratory scans. Fifth and 15th percentiles at both full inspiration and full expiration correlated well with /FVC and Dl c o but not well with whether was 50% of predicted value or greater or less than 50% of predicted value. The percentiles also correlated well with RV/TLC when was less than 50% of predicted value. Our study had limitations. The mean effective radiation dose to the chest for volumetric MDCT was 8 msv (range, 6 10 msv). Low-dose CT may be a clinically acceptable and diagnostically adequate technique for CT quantification of emphysema. Comparing standard-dose (effective tube current, ms) and low-radiation-dose (effective tube current, ms) techniques in the CT quantification of emphysema, Gierada et al. [15] found that low- and standard-dose emphysema indexes correlated at all attenuation thresholds. Mean emphysema indexes were higher on the low-dose scans, but the mean difference at all thresholds was less than 3%. Stolk et al. [16] using 4-MDCT imaged 10 patients with emphysema on two occasions 2 weeks apart. Scanning parameters were 140 kv, 20 ms, mm collimation, and effective thickness of 2.5 mm. The repeatability of the 15th percentile and the density-mask value of 910 HU was excellent with an estimated CT dose per examination of 0.7 msv for a chest 30 cm long. Fig. 3 Percentage lung volume at threshold of 950 HU according to Global Initiative for Chronic Obstructive Lung Disease stage in patients with chronic obstructive pulmonary disease., Graph shows results at full inspiration., Graph shows results at full expiration. Our study was different from other studies in materials and method. Zaporozhan et al. [12] obtained paired inspiratory and expiratory MDCT scans of 31 patients who had severe emphysema due to COPD (GOLD stages 3 and 4). They concluded that emphysema volumes measured from expiratory MDCT scans better reflect pulmonary function test abnormalities in patients with severe emphysema than do the values from inspiratory scans. Changes in relative emphysema volume were found between patients with GOLD stages 3 and 4 disease. t expiration, there was a change from the large emphysema cluster (3D volume class 4, > 120 mm 3 ) to the intermediate cluster (class 2, 8 65 mm 3 ; class 3, mm 3 ) and small cluster (class 1, 2 8 mm 3 ). The findings by Zaporozhan et al. were consistent with our findings in patients with GOLD stages 3 and 4 disease. Using paired inspiratory and expiratory volumetric MDCT scans of 36 patients with COPD, Matsuoka et al. [17] determined the attenuation threshold value from the detection and quantification of air trapping in COPD regardless of the degree of emphysema. In that study, a lung volume less than 950 HU was segmented as emphysema and eliminated. Changes in lung volume with attenuation values between 860 and 950 HU at inspiratory and expiratory CT significantly correlated with the results of pulmonary func tion tests, except for Dl c o in the moderate to severe emphysema group. In the minimal or mild emphysema group, all densitometric parameters correlated with pulmonary function test results. Mergo et al. [18] found that 3D volumetric reconstructions of hypoattenuating lung correlated well with pulmonary function test results and that inspiratory and expiratory data also were correlative. JR:192, January

6 kira et al. Fifth Percentile of Lung ttenuation Distribution Curve E/I Ratio , p = p = p = p = p = p = Fig. 6 Graph shows expiratory/inspiratory mean lung density ratio (E/I) according to Global Initiative for Chronic Obstructive Lung Disease stage in patients with chronic obstructive pulmonary disease. Visual score is useful in imaging of patients with less severe COPD. Measurements of lung attenuation obtained from 3D lung reconstructions at inspiration and expiration reflect different aspects of the severity of COPD. Measurements from inspiratory scans better reflect airflow limitation than do measurements from expiratory scans in mild or moderate COPD ( 50%). Measurements from expiratory scans better reflect airflow limitation than do measurements Fifth Percentile of Lung ttenuation Distribution Curve ,000 p = p = p = Fig. 5 Fifth percentile of lung attenuation distribution curve according to Global Initiative for Chronic Obstructive Lung Disease stage in patients with chronic obstructive pulmonary disease., Graph shows results at inspiration., Graph shows results at expiration. from inspiratory scans in severe COPD ( < 50%), apart from a predetermined percentile of the lung attenuation distribution curve. The combination of several measurements including visual score and expiratory measurements may be needed for assessing the severity of COPD. References 1. Coxson HO, Rogers RM. Quantitative computed tomography of chronic obstructive pulmonary disease. cad Radiol 2005; 12: Gevenois P, de Maertelaer V, De Vuyst P, Zanen J, Yernault JC. Comparison of computed density and macroscopic morphometry in pulmonary emphysema. m J Respir Crit Care Med 1995; 152: Gevenois P, De Vuyst P, de Maertelaer V, et al. Comparison of computed density and microscopic morphometry in pulmonary emphysema. m J Respir Crit Care Med 1996; 154: Müller NL, Staples C, Miller RR, bboud RT. Density mask : an objective method to quantitate emphysema using computed tomography. Chest 1988; 94: Global Initiative for Chronic Obstructive Lung Disease (GOLD) Update: GOLD workshop report, global strategy for diagnosis, management, and prevention of COPD. NIH publication GOLD Web site. ccessed May 3, [No authors listed]. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. merican Thoracic Society. m J Respir Crit Care Med 1995; 152[suppl]:S77 S83 7. [No authors listed]. Standardization of spirometry: 1987 update statement of the merican Thoracic Society. m Rev Respir Dis 1987; 136: Japanese Society of Chest Diseases. Standards of pulmonary function tests for Japanese. Jpn J Thorac Dis 1993; 31:appendix 9. Eda S, Kubo K, Fujimoto K, Matsuzawa Y, Sekiguchi M, Sakai F. The relations between expiratory chest CT using helical CT and pulmonary function tests in emphysema. m J Respir Crit Care Med 1997; 155: Park KJ, ergin CJ, Clausen JL. Quantitation of emphysema with three-dimensional CT densitometry: comparison with two-dimensional analysis, visual emphysema scores, and pulmonary function test results. Radiology 1999; 211: Gelb F, Hogg JC, Müller NL, et al. Contribution of emphysema and small airways in COPD. Chest 1996; 109: Zaporozhan J, Ley S, Eberhardt R, et al. Paired inspiratory/expiratory volumetric thin-slice CT scan for emphysema analysis. Chest 2005; 128: O Donnell R, Peebles C, Ward J, et al. Relationship between peripheral airway dysfunction, airway obstruction, and neutrophilic inflammation in COPD. Thorax 2004; 59: Camiciottoli G, artolucci M, Maluccio NM, et al. Spirometrically gated high-resolution CT findings in COPD: lung attenuation vs lung function and dyspnea severity. Chest 2006; 129: Gierada DS, Pilgram TK, Whiting R, et al. Comparison of standard- and low-radiation-dose CT for quantification of emphysema. JR 2007; 188: Stolk J, Dirksen, van der Lugt, et al. Repeatability of lung density measurements with low-dose computed tomography in subjects with alpha-1-antitrypsin deficiency-associated emphysema. Invest Radiol 2001; 36: Matsuoka S, Kurihara Y, Yagihashi K, Hoshino M, Watanabe N, Nakajima Y. Quantitative assessment of air trapping in chronic obstructive pulmonary disease using inspiratory and expiratory volumetric MDCT. JR 2008; 190: Mergo PJ, Williams WF, Gonzalez-Rothi R, et al. Three-dimensional volumetric assessment of abnormally low attenuation of the lung from routine helical CT: inspiratory and expiratory quantification. JR 1998; 170: JR:192, January 2009