EXPIRATORY HIGH-RESOLUTION CT SCAN

IMAGING OF OBSTRUCTIVE PULMONARY DISEASE

0033-8389/98 $8.00

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EXPIRATORY HIGH-RESOLUTION CT SCAN Hiroaki Arakawa, MD, and W. Richard Webb, MD

High-resolution CT (HRCT) is invaluable in the diagnosis and management of patients with diffuse lung disease, providing anatomic detail comparable with gross pathology. Although HRCT has proved most useful in the diagnosis of diffuse infiltrative lung diseases, its application to the diagnosis of airway and obstructive lung diseases has recently been emphasized.68,Io2 Expiratory HRCT techniques as an adjunct to inspiratory are particularly useful in assessing patients with obstructive lung diseases, providing physiologic information in regard to regional lung function. In patients with obstructive lung diseases, morphologic abnormalities visible on inspiratory scans can be subtle or nonspecific in some patients. CT or HRCT obtained during forced exhalation (dynamic expiratory CT),93,lo3 during suspended respiration after forced exhalation (postexpiratory CT), or at a user-selected respiratory level controlled during exhalation using a spirometer (spirometrically triggered expiratory CT)41,42, 4y have all been shown to be useful in the diagnosis of diseases characterized by airflow limitation or air-trapping. Focal, multifocal, or diffuse air-trapping visible using these expiratory or postexpiratory CT techniques as areas of abnormally low attenuation can confirm the presence of obstructive physiology in patients with airway abnormalities visible on inspiratory scans, allow the diagnosis of obstructive abnormali-

ties in some patients with normal inspiratory scans, and help in distinguishing between obstructive disease and infiltrative disease as a cause of inhomogeneous lung opacity seen on inspiratory scans. Air-trapping on expiratory CT has been recognized in patients with various obstructive or airway diseases, such 46, 93 asthma,74constrictive as emphy~erna,4~, bronchiolitis (CB),6, 26, 60, 64, 76, 93, 97 and bronchiectasis.36,y3 EXPIRATORY CT TECHNIQUES Dynamic Expiratory HRCT Scans obtained dynamically during forced expiration can be obtained using an electronbeam scanner or a helical scanner. Dynamic scanning with an electron-beam scanner has been termed dynamic ultrafast high-resolution CT (DUHRCT)?', y3 DUHRCT is performed using a scanner capable of obtaining a series of images with a 100-millisecond scan time (500-millisecond interscan delay, 3-mm collimation, 150 kVp, 650 mA).53,y2-y4 In general, when using this technique, a series of 10 scans is performed at a single level during a 6-second period as the patient first inspires and then forcefully exhales (Fig. 1). Patients are instructed to breathe in deeply and breathe out as rapidly as possible. Usually, dynamic CT sequences

From the Department of Radiology, University of California-San Francisco, San Francisco, California

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Figure 1. Dynamic expiratory HRCT (3-mm collimation) obtained using an electron beam scanner in a patient with cystic fibrosis. A, A sequence of six scans from a 10-scan series, obtained with a 100-millisecond scan time and a 500-msec interscan delay during forced expiration. The sequence begins with the middle image in the top row and proceeds clockwise, with the last scan being in the top left-hand corner. During expiration, the anterior lung significantly increases in attenuation in a normal fashion. Lateral and posterior lung remains lucent because of air-trapping. Note the increased size of vessels in the dense lung regions. 6,Time attenuation curve plotted for the 10 images in this sequence for the region of interest (ROI) showmin the image. The ROI has been positioned within a region of lucent lung. Elapsed time during the scan sequence is indicated on the horizontal axis, and the Hounsfield unit on the vertical axis. Little attenuation change is noted for the ROI during expiration, indicative of air-trapping.

are obtained at three selected levels through the lungs (e.g./ the level of the aortic arch, carina, and at the lung bases), although the protocol can be varied in individual cases or imaging targeted to a specific region. During expiration, the diaphragm ascends

and the lungs move cephalad. Lung motion is most significant on scans through the lung bases. Although slightly different regions of the lung are imaged on sequential scans obtained at the same level, the effect of diaphragmatic motion on the assessment of lung

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attenuation has been regarded as inconsequential.92,93, lo3 Little motion-related image degradation is visible on DUHRCT because 94 of the very rapid scan time Dynamic scans can also be obtained using a spiral or helical CT scanner with a gantry rotation time of 1 second or less. If a 180degree linear interpolation reconstruction algorithm is used with a l-second rotation time, individual images represent a scan period of about 0.5 seconds. Because of the continuous

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scanning, which is possible with helical technique, scans can be reconstructed at any point in time during the scan sequence, thus providing a temporal resolution roughly equivalent to that of the DUHRCT technique described previously. Because of the longer time required to obtain each image, however, some degradation of anatomic detail can be expected on individual images. Dynamic helical scans can be obtained without table motion (Fig. 2) to show dy-

Figure 2. Dynamic expiratory CT (5-mm collimation) obtained using a spiral scanner in a patient with polychondritis and bronchomalacia. Stents have been positioned in the proximal main bronchi. A, An inspiratory scan shows a patent right bronchus intermedius. Lung attenuation is symmetric, measuring - 804 H for the ROI placed in the posterior right lung and - 773 H for the ROI placed in the posterior left lung. 6,Scan obtained 6 seconds after the start of forced expiration. The anterior right lung and left lung show a normal increase in attenuation. The bronchus intermedius is collapsed, and the right lower lobe remains lucent because of air-trapping; with anterior bowing of the major fissure. ROI in the normal left lower lobe measures -590 H, an increase of 183 H as compared with the inspiratory scan. The ROI placed in the right lower lobe measures -801 H, a change of only 3 H as compared with inspiration, and indicative of air-trapping.

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namic airway or lung function at one level, or scanning can be done with table motion to show a volume of lung during the expiratory maneuver. Collimation can be varied from 1 to 7 mm or more depending on the area of interest. Using either technique, the images can be evaluated quantitatively or qualitatively with measurement of lung attenuation during different phases of the respiratory maneuver (see Fig. 2), calculation of time-attenuation curves (see Fig. lB), or simple viewing of the serial scans in sequence or in cine mode. Postexpiratory CT

Postexpiratory HRCT, obtained during suspended respiration following a forced exhalation, is easily performed with any scanner. The postexpiratory scans are invariably obtained in conjunction with a routine HRCT examination obtained at full inspiration, with scans at spaced intervals from the lung apices to bases. Postexpiratory scans can be performed at several predetermined levels (e.g., aortic arch, carina, and at the lung bases) or at levels appearing abnormal on the inspiratory images. Scans at two to five levels have been used by different author^.^, 74, 78 Although targeting postexpiratory scans to lung regions

appearing abnormal on the inspiratory scans would seem to be advantageous, using preselected scans allows the same lung regions to be imaged routinely on follow-up examinations, and in some patients can show airtrapping when inspiratory scans are normal. Each of the postexpiratory scans is compared with the inspiratory scan that most closely duplicates its level in order to detect air-trapping (Fig. 3). Anatomic landmarks, such as pulmonary vessels, bronchi, and fissures, are most useful for localizing corresponding levels. Because of diaphragmatic motion occurring with expiration, attempting to localize the same scan levels by using the scout view is difficult and sometimes misleading.

Spirometrically Triggered Expiratory CT

Spirometrically triggered expiratory CT is a technique by which expiratory scanning can be done at specific, reproducible, user-selected lung volumes.41,42, 49 With this technique, the patient breathes through a small hand-held spirometer while positioned on the CT scan table. Before scanning, a spirometric measurement of the vital capacity is obtained

Figure 3. Normal postexpiratory HRCT. An expiratory scan at the level of the carina (A) has been matched with the inspiratory scan that most closely represents the same level (B). Lung appears significantly denser on the expiratory scan, with posterior lung increasing more in density than anterior lung.

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and trigger level (e.g., 90% of vital capacity) is chosen. During exhalation, the spirometer and associated microcomputer measure the volume of gas expired and trigger CT after a specific volume is reached. When the trigger signal is generated, air flow is inhibited by closure of a valve attached to the spirometer and scanning starts. Two or three different levels in the chest are typically selected and evaluated with respect to lung attenuation at specific lung volumes. Using this method, quantitative assessment of CT images with respect to lung attenuation can be performed with excellent precision.4l.42 NORMAL FINDINGS ON EXPIRATORY CT Lung Attenuation

In normals, lung attenuation at full inspiration appears relatively homogeneous, ranging from -700 to -900 H.2,loo An attenuation gradient is typically present, however, with the most dependent lung regions being the densest, and the most nondependent lung regions being the least dense. This gradient is largely due to regional differences in blood and gas volume that, in turn, are determined by gravity, mechanical stresses on the lung, and intrapleural pressures.7o,looDifferences in attenuation between anterior and posterior lung have been measured in supine patients, and values generally range from 50 to 100 H128,82, looalthough gradients of more than 200 H have been reported?* The anteroposterior attenuation gradient is nearly linear, and is present regardless of whether the subject is supine or prone.82,Io3 With expiration, lung density and attenuation increase, due to a reduction in gas volume within the lung. The mean attenuation difference between full inspiration and expiration ranges from 150 to 300 H regardless of the expiratory technique used (Figs. 2 and 4).99, loo,lo3,Io6 According to Kalender et a1,42 using spirometrically triggered CT scan, a 10% change in vital capacity resulted, on average, in a change of about 16 H, and estimates of lung attenuation at 0% and 100% of vital capacity were -730 H and -895 H, respectively. In another study,61 the physical density of lung at full inspiration and expiration was calculated based on the assumption that physical density had linear relation to radiographic density (physical density = 1-

Figure 4. Time density curve in a normal subject measured using dynamic expiratory HRCT. On expiration, lung attenuation for the ROI indicated increases from -860 to -640 H, a change of 220 H. Note that the image shows anterior bowing of the posterior tracheal membrane, a finding useful in confirming an adequate expiration.

CT attenuation in Hounsfield units/1000).21 Using this method, peripheral lung tissue density was measured as 0.0715 g/cm3 (SD, 0.017) at full inspiration and 0.272 g/cm3 (SD, 0.067) at end expiration. Usually, dependent lung regions show a greater increase in lung attenuation during expiration than do nondependent lung regions irrespective of the patient’s position (Figs. 3 and 5).81,82, 92, 99, lo3,lo6 As a result, the anteroposterior attenuation gradients normally seen on inspiration are significantly greater on expiratory scans.81,99, loo Furthermore, the expiratory lung attenuation increase in dependent lung regions is greater in the lower lung zones than in the middle and upper zones, probably due to greater diaphragmatic movement or greater basal blood volume.1o3 In children, the CT attenuation of lung parenchyma is higher than in adults, and decreases with age?2, loo Attenuation increases seen with expiration are similar to those found in adults. Ringertz et a1,8O using ultrafast CT, measured the CT attenuation of children under the age of 2.5 years during

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Figure 5. Preexpiratory and postexpiratory HRCT in a normal patient. On the inspiratory scan (A), lung appears homogeneously lucent. Following expiration (B),lung increases in attenuation with posterior lung showing the greatest increase. Note, however, that lung posterior to the major fissures (arrows) appears slightly more lucent than lung anterior to the fissures. This appearance is normal.

quiet respiration; the average CT lung attenuation was -551 (SD, 106) on inspiration and -435 H (SD, 103) on expiration. Vock et allo* measured the lung attenuation changes in children ranging from 9 to 18 years old. Mean lung attenuation at full inspiration and full expiration measured -804 and -646 H, respectively. The anteroposterior attenuation differences were similar to those seen in adults, averaging 56 H at the subcarinal level, and increased with maximal expiration and increased during expiration.loO Although there are several reports that the anteroposterior attenuation gradient is linear or curvilinear,6l*82 Webb et all" reported in their study using dynamic ultrafast CT that the anteroposterior lung attenuation gradient can have a lobar component on expiratory scans. Often, the posterior aspect of the upper

lobe, anterior to the major fissure, appears denser than the anterior aspect of the lower lobe, behind the major fissure (see Fig. 5). Changes in Airways

The intrathoracic trachea shows significant changes in cross-sectional area, anteroposterior diameter, and transverse diameter from full inspiration to full expiration. In a study using ultrafast dynamic CT in 10 healthy menpo the mean cross-sectional area of the trachea decreased 35% during forced vital capacity (FVC) maneuver (range, ll%to 61%; SD, 18). The anteroposterior diameter decreased from a mean of 19.6 mm (range, 16.1 to 23.2 mm; SD, 2.3) to 13.3 mm (range, 8.3 to 18 mm; SD, 3.5) for a mean decrease of 32%.

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This change is largely due to an anterior bowing of the posterior tracheal membrane, a finding that is useful in confirming that an adequate expiration has occurred on expiratory CT (see Fig. 4). The transverse diameter shows less change with expiration; in this study it decreased from a mean of 19.4 mm (range, 15.2 to 25.3 mm; SD, 2.7) to a mean of 16.9 mm (range, 12.3 to 20.5 mm; SD, 2.6) for a mean decrease of 13%. The change of crosssectional area correlated well with the changes in the anteroposterior and transverse diameters of the trachea (r = 0.88 and 0.92 and I',= 0.0018 and 0.0002, respectively). The shape of the normal trachea is round or elliptical on inspiration and horseshoe-shaped during and at the end of a full expiration, because the posterior tracheal membrane bows anteriorly. The cross-sectional area of larynx also decreases with decreasing lung volume. In one study using dynamic ultrafast CT,ll mean cross-sectional area decreased 69% (SD, 14) from full inspiration to functional residual capacity and decreased an additional 17% (SD, 7) from functional residual capacity to residual volume. In children, changes in airway cross-section may be larger than in adults. In a study that evaluated 12 children (mean age, 6.5 years) during quiet re~piration;~mean expiratory narrowing of the cross-sectional areas of the laryngeal airway, cervical trachea, and intrathoracic trachea were 64% (range, 49% to 73%), 19% (range, 4% to 38%), and 15% (range 1% to 42%), respectively. Morphologic changes in the appearances of bronchi during respiration have not been studied systematically. In our experience, the cross-sectional area of main and lobar bronchi appears slightly reduced on full expiration; some invagination of the posterior wall of the right main bronchus or bronchus intermedius sometimes occurs during forced expiration. Because slightly different levels are usually imaged on the inspiratory and expiratory scans, comparing individual bronchi or specific bronchial levels is often difficult. ABNORMAL FINDINGS ON EXPIRATORY CT Lung Attenuation

Areas of air-trapping are seen as relatively low in attenuation on expiratory scans. Areas

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of air-trapping can be patchy and nonanatomic; can correspond to individual secondary pulmonary lobules, segments, lobes (see Fig. 2); or may involve an entire lung.80,92 Pulmonary vessels within the low-attenuation areas of air-trapping often appear small relative to vessels in the more opaque normal lung (see Fig. l)?, Although abnormal areas can often be identified subjectively because of their relatively low attenuation, there are two objective methods of identifying abnormal lung regions. First, areas of air-trapping are reported to show an increase in attenuation of less than 100 H on dynamic expiratory scans, a value that is significantly lower than that of normal lung6 As mentioned previously, the normal mean attenuation difference between full inspiration and expiration ranges from 150 to 300 H. On dynamic scans, a lung attenuation change of less than 70 to 80 H between full inspiration and full exhalation may be regarded as abnormal (see Figs. 1 and 2), but on simple postexpiratory scans, lung attenuation change of less than 70 may sometimes be normal. Lung attenuation change is most simply measured using a small (1 to 2 cm) region of interest. Measuring the change in overall lung attenuation from inspiration to expiration may be used in patients with diffuse air-trapping, but is clearly less sensitive in patients with patchy disease. A second method of quantitating air-trapping is to compare equivalent areas in each lung. In healthy subjects, the mean difference in attenuation change between symmetric regions of the right and left lungs during exhalation was measured as 36 H (SD, 14).lo3From this, a right-left difference in attenuation increase during exhalation exceeding 78 H (>3 SD) can be considered abnormal [see Fig. 2B1). This method is especially useful when air-trapping is unilateral. Occasionally, lung attenuation decreases during expiration in regions of air-trapping; a decrease of attenuation by as much as - 258 H has been reported during dynamic expirati0n.9~Although there is no definite explanation for this phenomenon, several suggestions have been made.93 The most likely is that during exhalation, lung units trapping air compress small pulmonary vessels, squeezing blood out of the lung and decreasing lung perfusion. Another possible explanation is socalled pendelluft, in which air may pass from a normally ventilated lung unit to a partially

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obstructed lung unit during rapid expiration, resulting in an increased gas volume?* Although measurement of lung attenuation can be used to diagnose air-trapping, except in patients with diffuse air-trapping (e.g., emphysema, large bronchial obstruction), the extent of air-trapping rather than the lung attenuation better predicts pulmonary function test findings of obstruction?2,93 Air-Trapping Score

Air-trapping in a lobe or lung is usually associated with large airway or with generalized small airway abnormalities, whereas lobular or segmental air-trapping is associated with diseases that produce small airway abn~rmalities.~~ The extent of air-trapping present on expiratory scans can be measured using a semiquantitative scoring system, which estimates the percent of lung that appears abnormal on each scan.36,93, lo3 These systems have the advantage of being simple, quick, and easy to perform. For example, in the scoring system proposed by Stern et al,” estimates of air-trapping are made at three levels scanned using expiratory technique: (1) the level of aortic arch, (2) carina, and (3) 5 cm below the carina. At each level and for each lung, a four-point scale is used to estimate the extent of airtrapping visible subjectively: 0 = no air-trapping, 1 = 1%to 25% of cross-sectional area of lung affected, 2 = 26% to 50% of affected lung, 3 = 51% to 75% of affected lung, and 4 = 76% to 100% of affected lung. The airtrapping score is the summation of these numbers for the three levels studied, and thus ranges from 0 to 24. Other methods of visually scoring the extent of air-trapping on expiratory scans have also been used and validated.% In a study of DUHRCT in nine patients with a variety of obstructive diseases, Stern et a193found a high correlation between the air-trapping score and forced expiratory volume in 1 second (FEV,); percent predicted (r = -0.92, P < 0.0004); percent predicted Values of peak flow rate (r = -0.91, P = 0.004); FVC (r = -0.92, P = 0.0005); and the mean forced expiratory flow rate during the middle of the FVC (r = -0.90, P = 0.003). The airtrapping score ranged from 7 to 24 (mean, 18.2). In patients studied using postexpiratory CT, the correlations between air-trapping score and pulmonary function test findings

of obstruction have proved somewhat lower, approximating r = -0.6.7 In a study of 70 patients with chronic purulent sputum production,36 the air-trapping score defined at a lobar level significantly correlated with Values of FEV, and FEVJFVC. Air-trapping can also be seen in normal subjects. Air-trapping in one or more secondary pulmonary lobules is not uncommon. Also, focal areas of relative lucency can be seen on expiratory scans in the lingula and superior segments of the lower lobes in healthy subjects and in the lingula or middle It is postulated that the slender segments may be less well ventilated than adjacent lung, having a tendency to trap air during e ~ h a l a t i o n .In ~ ~their study of 10 young normal subjects, Webb et allo3found that the air-trapping score never exceeded a total of two at any level. In subsequent experience with normal subjects, a n air-trapping score of up to six has been found in subjects with no known disease.

Pixel Index

The pixel index (PI) is defined as the percentage of pixels in both lungs on a single scan that shows an attenuation lower than a predetermined threshold value (usually - 900 to - 950 H).46,74 Although the inspiratory PI has wide normal range, the expiratory PI is relatively constant. The normal PI at full inspiration ranges from 0.6 to as much as 58 when the threshold is -900 H,2 although the mean value ranges from 10 to 25 depending on the level scanned and on the CT collimat i ~ n At . ~full ~ expiration, with a threshold value of -900 H, the normal range of PI is rather small with a mean of less than 1.04 (SD, 1.30) (Fig. 6).74Thus, in normals, the area of lung having an attenuation of less than -900 H at full expiration can generally be regarded as less than a few percent. The expiratory PI can be used to assess quantitatively the area of low attenuation lung in patients with air-trapping or emphysema (Fig. 7). For example, in one study:6 64 patients underwent both inspiratory and expiratory CT correlated with pulmonary physiology. There were 28 patients with an inspiratory PI of more than 40, and 14 of these had an expiratory PI of more than 15. This group showed markedly abnormal pulmonary function test values suggestive of em-

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Figure 6. Pixel index (PI) measured in a patient with bilateral lung transplantationand normal lung function. An expiratory scan (A) and scan with pixels measuring less than -900 H highlighted (6) are shown. The low-attenuation pixels shown in B represent 0.6% of lung area (PI 0.6).

physema, whereas other patients showed preserved lung function. Also, an expiratory PI over 15 accurately reflected and quantitated the degree of emphysema estimated by various pulmonary function tests. The expiratory PI has also been used to discriminate quantitatively asthmatic patients from normal subjects. In a study of both asthmatic and normal both inspiratory and expiratory PI were obtained at two levels (one at the transverse aorta and one just superior to the diaphragm) and compared with pulmonary function tests. Using collimations of 10 and 1.5 mm, the expiratory PI at a level immediately superior to the diaphragm was significantly higher in asthmatic subjects (4.45 and 10.03 for the two collimations, respectively) than in normal subjects (0.16 and 1.04) and provided the best separation between the groups.74

Lung Volume Changes

Robinson and KreeP have shown that there is a significant correlation between changes in cross-sectional lung area measured using CT and lung volume (r = 0.569). The percentage decrease in lung cross-sectional area that occurred during exhalation also correlates In a study with the attenuation increase.81,’03 using DUHRCT,lo3a significant correlation between cross-sectional lung area and lung attenuation was found for each of three lung regions evaluated (upper lung: r = 0.51, P = 0.03; midlung: r = 0.58, P = 0.01; lower lung: r = 0.51, P = 0.05). Usually, areas of air-trapping show little or no area and volume change during exhalation, which can help to identify areas of airtrapping. In one study of nine cases of SwyerJames syndrome,6° expiratory CT in areas of

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Figure 7. lnspiratory and postexpiratory images in a patient with left lung transplantationfor panlobular emphysema. A, lnspiratory HRCT. B, Postexpiratory HRCT shows extensive right-sided emphysema. The attenuation increase in the right lung measured from inspiration to expiration, using ROI, was only 3 H. Although the transplanted left lung is much denser than the right, patchy air-trapping is visible as inhomogeneous opacity. This finding suggests small airway obstruction and is consistent with constrictive bronchiolitis. This was confirmed on transbronchoscopic biopsy. Illustration continued on opposite page

abnormal lung showed no significant lung volume change, and mediastinal shift toward the normal lung was also seen.

structive physiology, and the extent of such abnormalities correlates with the degree of ventilatory impairment.

EXPIRATORY CT FINDINGS IN SPECIFIC LUNG DISEASES

Large Airway Obstruction

Expiratory CT has been shown to be valuable in the diagnosis of a variety of obstructive diseases. It can allow a diagnosis of airtrapping in some patients with normal inspiratory scans; this is most often the result of CB or asthma. In patients with evidence of airway abnormalities on inspiratory CT, expiratory CT can reveal the presence of ob-

In patients with large airway abnormalities, expiratory CT can show (1) airway collapse during exhalation and (2) air-trapping in a lobe or lung (Figs. 2 and 8)?, Such patients are best evaluated using conventional spiral CT with 5- to 10-mm collimation rather than HRCT, with dynamic spiral CT being used to demonstrate the site, degree, and mode of bronchial obstruction. We have found this

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Figure 7 Continued. C, Pixels having a value of less than -900 H in the postexpiratory image have been highlighted. The PI for the emphysematous right lung measures 72 and is markedly abnormal. PI for the left lung measures 0.7 and is within normal limits.

technique of most value in the diagnosis of focal bronchial narrowing or malacia associated with inflammatory disease (e.g., polychondritis, Wegener’s granulomatosis) or stricture, rather than in the diagnosis of neoplasms. Using dynamic expiratory spiral CT, the site of bronchial narrowing can be clearly defined prior to placement of airway stents,

and the effectiveness of treatment monitored (see Fig. 8). In a series of pediatric patients with airway obstruction studied by Ringertz et alm using dynamic ultrafast CT, time-attenuation curves in obstructed lung regions and normal regions were compared. In this study, there was a high correlation between time-density

Figure 8. Tracheomalacia in a patient with polychondritis and airway obstruction on pulmonary function tests (also shown in Fig. 2). Spiral dynamic expiratory CT (3-mm collimation) at inspiration (A) and 9 seconds after the stalt of a forced expiration (B). There is marked tracheal narrowing during expiration. Dynamic expiratory CT following stent placement (C) shows no evidence of collapse; symptoms were markedly improved.

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curves obtained from normal lung regions (r > 0.79). On the contrary, a negative correlation was found between the lung attenuation in normal and abnormal lung regions (r < - 0.58). Emphysema and Chronic Obstructive Pulmonary Disease

Inspiratory HRCT has proved to be sensitive and accurate in diagnosing emphysema. The pathologic extent of emphysema correlates well with the CT visual scores47,62 and quantitative measurements of emphysema extent using a density mask 69 HRCT is more sensitive than pulmonary function tests in the diagnosis of emphysema and is considered the best method to evaluate the presence and extent of emphysema in vivo. The utility of expiratory HRCT in the quantitative diagnosis of emphysema is somewhat controversial. In a study of patients with emphysema by Knudson et al," the expiratory PI consistently showed better correlation with pulmonary function indices of emphysema and airflow limitation than did inspiratory PI (see Fig. 7). In this study% of 64 subjects, many of whom had airflow obstruction, inspiratory and expiratory PI (threshold value - 900 H) were correlated with various pulmonary function tests. The authors found that the expiratory PI had higher correlations with specific pulmonary function test findings of emphysema than inspiratory PI (YODLco per alveolar volume: r = -0.716, P < 0.001 versus r = -0.427, P < 0.001; loss of lung recoil: r = 0.398, P < 0.001 versus r = 0.091, P < 0.243). Expiratory PI also correlated better with functional indices of airflow limitation than inspiratory PI (% FEV1: r = -0.676, P < 0.001 versus r = -0.430, P < 0.001; FEVI/FVC: r = -0.748, P < 0.001 versus r = -0.536, P < 0.001; residual volume/total lung capacity: r = 0.608, P < 0.001 versus r = 0.350, P = 0.002). In other studies of emphysema patients, however, the expiratory PI correlated better with pulmonary function indices of airflow limitation than did inspiratory PI, but the expiratory PI did not show better correlation with pulmonary function findings specific to e m p h y ~ e m a ?In ~ ,one ~ ~ studyz9the PI of inspiratory and expiratory HRCT was correlated with the microscopic and macroscopic extent of emphysema. Results of stepwise multiple

regression analysis showed that an inspiratory PI of - 950 H was superior to expiratory PI for both macroscopically and microscopically quantified emphysema. On the other hand, the expiratory PI correlated better than inspiratory PI with functional measurements of airflow obstruction and air-trapping, such as FEV, and residual volume. In patients with emphysema, airflow limitation may be due to (1) a decrease in lung elastic recoil, (2) a decrease in support of intrapulmonary airways, or (3) smoking-related bronchitis and bronchiolitis. Even if expiratory CT shows a close correlation with pulmonary function test indices of airflow limitation in patients with emphysema, this finding may reflect airway abnormalities associated with cigarette smoking rather than the extent of emphysema. In a recent study of patients with chronic obstructive pulmonary disease and fixed expiratory airflow limitation, there was poor correlation between the extent of emphysema and FEV, (r = -0.20) or FEVJFVC (r = -0.36).27 Spirometrically triggered CT with images obtained at 90% and 10% of vital capacity have been of some value in the differentiation of emphysema and chronic bronchitis in patients with chronic destructive pulmonary disea~e.4~ Patients with emphysema have significantly lower lung attenuation on inspiration (900/, of vital capacity) than normals or patients with chronic bronchitis. On the other hand, on expiration (10% of vital capacity) patients with emphysema and chronic bronchitis had significantlylower lung attenuation than normals." Bronchiectasis

Bronchiectasis is defined as localized irreversible bronchial dilatation. Although the etiology of bronchiectasis varies, pulmonary function tests usually reveal obstructive pulmonary physiology,50and resected specimens in patients with severe bronchiectasis consistently show the coexistence of CB.16**O Inspiratory HRCT is highly accurate in the diagnosis of bronchiectasis.3z,72, lffi Areas of air-trapping on expiratory CT are commonly seen in patients with bronchiectasis, and the extent of expiratory air-trapping correlates well with both pulmonary function tests and In a study of 70 the extent of bronchie~tasis.~~ patients with chronic purulent sputum pro-

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duction,36 the air-trapping score defined at a lobar level on expiratory CT was inversely related to the values FEV, (P < 0.002) and FEVJFVC (P < 0.004), independent of age, sex, and smoking history. The air-trapping score also correlated positively with the total bronchiectasis scores (r = 0.49, P < 0.001). Furthermore, evidence of air-trapping was noted in 40% of areas without CT evidence of bronchiectasis. The authors of this study postulate that small airway disease may precede the development of bronchiectasis. Cystic Fibrosis

Pathologically, in patients with cystic fibrosis (CF), bronchiectasis and mucus plugging are consistently seen and small airway disease is a relatively early finding.88,98 Adults with very mild pulmonary involvement are being increasingly recognized and HRCT can play an important role in their diagnosis. One of the earliest HRCT findings in CF is the presence of sharply defined lobular areas of decreased attenuation, presumably representing lobular or subsegmental air-trapping, which can be seen only on expiratory HRCT.53 Other early findings include thickening of the walls of the proximal right upper lobe bronchi, bronchiectasis, and the appearance of bronchiolar impaction or "tree-in-bud.'18, 57, 96 Commonly, areas of air-trapping are seen in association with abnormal bronchi (see Fig. 1).The visual CT score of CF correlates well with pulmonary function tests (PFTs), such as FEV,, FEV,/FVC, and maximum expiratory flow at 50%, which are indices of small airway abnormality and airflow limitation.57,96 CB

CB, also referred to as bronchiolitis obliterans or obliterative bronchiolitis, is characterized by bronchiolar narrowing or obstruction due to submucosal and peribronchiolar inflammation and fibrosis, primarily involving respiratory bronchioles, and is associated with airflow l i m i t a t i ~ n . ~Usually, ~ pulmonary involvement in CB is patchy and histologic proof can be difficult to obtain. CB may be idiopathic, but most cases are secondary to infection (bacterial or viral); toxic-fume inhalation (nitrogen dioxide, sulfur dioxide, ammonia, chlorine, phosgene, and ozone); collagen vascular diseases and drug therapy

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(penicillamine, gold); and organ (lung and bone marrow) transplantation. Inspiratory HRCT often shows patchy areas of decreased attenuation with decreased vessel size (mosaic perfusion) that reflect poor ventilation and reflex oligemia (Fig. 9).13,*', 53* 76, 97 Bronchial or bronchiolar dilatation53,76 may be associated. Although these abnormalities are often seen on inspiratory HRCT, the extent of abnormalities does not correlate well with pulmonary function On expiratory CT, areas of air-trapping are commonly seen, and expiratory CT better delineates the presence and the extent of airtrapping than do inspiratory scans (see Fig. 9).6 Furthermore, expiratory CT may reveal the presence of air-trapping in patients with normal scans (Fig. 10). In a series of 24 patients with CB associated with consumption of Sauropus androgynus, a leafy vegetable, Yang et allo4 reported that nine patients showed inhomogeneous opacity only on expiratory scans, indicating the presence of airtrapping. Interestingly, in this series those patients with abnormalities visible only on expiratory scans had significantly better FEV, than those with mosaic perfusion visible on inspiratory scans.

Swyer-James Syndrome

Swyer-James syndrome (Macleod syndrome) is considered to be a variant of postinfectious CB in which abnormalities are predominantly or solely ~ n i l a t e r a l .In ~ ~this condition, viral infection in infancy or childhood results in obliteration of small airways while leaving the lung parenchyma relatively unaffected; collateral ventilation results in airtrapping. Usually, the affected lung is smaller than the contralateral lung, probably because the insult retards lung growth. On HRCT, evidence of air-trapping is extensive on the affected side and sometimes is identified in the contralateral lung." Abnormalities are more dramatic and sometimes more extensive on the expiratory CT. The normal anteroposterior gravitational CT attenuation gradient is absent.6O The volume of abnormal lung shows no significant change during exhalation. Other CT findings are bronchiectasis, atelectasis, and small foci of abnormal opacities representing chronic infection or residual scarring.

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Figure 9. lnspiratory and postexpiratory HRCT in constrictive bronchiolitis. The inspiratory scan (A) shows inhomogeneous lung attenuation due to mosaic perfusion, but this finding is subtle on the right. Postexpiratory HRCT (6) shows patchy bilateral airtrapping. Note that the extent of the abnormality is better shown on the postexpiratory image.

Asthma

Asthma is defined as a clinical syndrome characterized by increased responsiveness of the tracheobronchial tree to a variety of stimUsuuli and reversible airway obstr~ction.~ ally the diagnosis is made on clinical grounds, and HRCT is not indicated. One indication for CT in patients with asthma is the clinical suspicion of allergic bronchopulmonary aspergillosis, in which proximal bronchiectasis is a common finding.73Common HRCT findings of asthma include bronchial wall thickening, bronchiectasis, small centrilobular opacities, decreased lung attenuation, and mucoid impaction.33,54, Although decreased lung attenuation due to abnormal ventilation is thought to be an uncommon finding in asthmatic patients, a series of 50 patients showed decreased lung attenuation in 31% on inspiratory HRCT.33

Expiratory HRCT can show air-trapping in asthma patients who have normal inspiratory scans (Fig. 11).Recent studies regarding the usefulness of expiratory HRCT in patients with asthma support the utility of this technique, but differ somewhat in their concl~sions.~~~ 78 In one of 18 asthmatic patients and 22 control subjects, the PI (threshold value -900 H) was calculated at two preselected levels. The postexpiratory CT through the lower lung zones provided the best distinction between the normal and asthmatic patients. Furthermore, the postexpiratory PI significantly correlated with the degree of air-trapping and airflow limitation in the asthmatic group. In another series with 39 asthmatic patients and 14 healthy subjects, postexpiratory HRCT obtained at five preselected levels were subjectively evaluated for the presence of airtrapping and the frequency was correlated

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Figure 10. lnspiratory and postexpiratory HRCT in constrictive bronchiolitis secondary to lung transplantation. Although the inspiratory scan (A) appears normal, patchy bilateral air-trapping is visible on the postexpiratory image (6).

with PFT pararneter~.~~ In this study, air-trapping involving more than a segment was present in 50% of asthmatic patients and 14% of healthy subjects ( P < 0.001). There was no significant difference in the prevalence of airtrapping in patients with an FEV, of less than 60% of predicted, however, compared with patients with normal airflow and with mild airflow obstruction (FEV, 60% to 80%). One limitation of this latter study is that only the frequency and not the extent of air-trapping was evaluated and was correlated with PFT parameters. Hypersensitivity Pneumonitis

Hypersensitivity pneumonitis, or extrinsic allergic alveolitis, is an immunologically mediated disorder in response to various inhaled organic antigens and is characterized by granulomatous, interstitial, and alveolar infiltration.I5 The clinical, pathologic, and radiographic features are quite similar regardless of the causative antigens. Clinically, exposure

of susceptible individuals to high concentrations of antigen leads to recurrent episodes of fever, chills, cough, and dyspnea, whereas continuous exposure to lower concentrations results in gradually progressive dyspnea. Pathologically, chronic inflammatory infiltrates involving small airways (cellular bronchiolitis), diffuse interstitial infiltrates of chronic inflammatory cells, and scattered small nonnecrotizing granulomas are the hallmark of this disease.I7In the chronic stage the cellular infiltration and granulomas become less prominent and peribronchial fibrosis and honeycombing ensue.86Bronchiolitis obliterans organizing pneumonia is also a relatively common finding in the subacute and chronic stages.17,86 Pulmonary function tests can show both restrictive and obstructive patterns. In the acute phase, reduction in lung volume, diffusing capacity, and static lung compliance are the most common fb1dings.3~.lol An obstructive pattern is frequent in the subacute and chronic phases as indicated by increased residual volume and total lung capacity and

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Figure 11. A, Postexpiratory HRCT in a patient with uncomplicated asthma shows patchy bilateral air-trapping. 8, Dynamic expiratory HRCT in a patient with asthma and allergic bronchopulmonary aspergillosis shows extensive bilateral air-trapping in association with bronchiectasis.

slowing on forced expiration, and can be seen lol in combination with a restrictive pattern.37* In one study, the pulmonary function of 19 patients with hypersensitivity pneumonitis was compared with 28 nonsmoking healthy Nonventilated lung volume (trapped air) was significantly increased in patients with hypersensitivity pneumonitis (mean, 0.73 L) relative to normal subjects (mean, 0.32 L, P < 0.01). The HRCT findings of hypersensitivity pneumonitis depend on the phase of the disease. In the acute phase, HRCT shows airspace con~olidation.~~ In the subacute phase, the most common HRCT findings are the presence of extensive ground-glass opacity or small (usually less than 5 mm) ill-defined nodules that are characteristically located in the centrilobular regions.*,34, 55, 79, 87 In the chronic phase, irregular linear areas of scar-

ring, architectural distortion, and honeycombing are seen in addition to findings seen in patients with subacute di~ease.~, l2 These abnormalities are equally distributed in the three lung zones or slightly predominant in 79 Evidence of air-trapthe lower lung z0ne.3~’ ping is also a common HRCT finding in both the subacute and chronic stage of hypersensitivity pneumonitis (Fig. 12), although its pathologic basis is not clearly understood.l2, 34, 35,79 In one series of 22 patients with hypersensitivity pneumonitis, HRCT with limited number of expiratory images were correlated with pulmonary function tests.35Areas of decreased attenuation, mosaic perfusion, and air-trapping were seen in 19 patients and were the most frequent abnormalities. In addition, the extent of decreased attenuation correlated well with severity of functional index of air-trapping as indicated by increased

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Figure 12. Air-trapping in a patient with hypersensitivity pneumonitis. A, lnspiratory HRCT shows mild lung inhomogeneity, which is difficult to characterize. 6,Patchy air-trapping is visible on the postexpiratory scan.

residual volume (r = 0.58, P C 0.01). The authors concluded that areas of decreased attenuation and mosaic perfusion are important CT findings and probably related to pathologic findings of bronchiolitis. Sarcoidosis Pathologically, pulmonary involvement in sarcoidosis is most prominent in the peribronchovascular, interlobular septal, and pleural interstitium and less frequent in the parenchymal i n t e r ~ t i t i u mGranulomas .~~ are also common in the airway mucosa, particularly in small bronchi. The granulomas are discrete in the early stage, and may become confluent, result in fibrosis, or regress spontaneously. Extensive fibrosis with bronchiectasis or, less often, honeycombing occurs later in the course of the disease, predominantly in the upper lobes. Although pulmonary function tests usually reveal restrictive dysfunction, obstruction may also be present. In fact, recent studies show that airway dysfunction is seen in some patients with stage I sarcoidosis, becoming more evident in disease of longer dura-

tion.48, It is postulated that bronchial obstruction in sarcoidosis may result from five different mechanisms: (1) airways compression by enlarged lymph nodes; (2) endobronchial lesions with narrowing, occlusion, bronchial wall destruction, and bronchiectasis; (3) fibrotic scarring of endobronchial lesions with resultant narrowing of bronchi, as well as bronchial distortion by peribronchial, hilar, or perihilar fibrosis; (4)extension of the granulomatous process into the bronchial wall from an extrabronchial location; and ( 5 ) small airway hyperactivity seen in some patients with stage I sarcoidosis with airflow limitation.52,58 HRCT findings may be characteristic?, 56, 66, 67, 75 The number of sarcoidosis patients evaluated with expiratory CT has been limited,3O but it is clear that air-trapping can be seen. In three cases in one report,% postexpiratory HRCT revealed widespread patchy areas of air-trapping, and in two, inspiratory HRCT did not show any typical signs of parenchymal sarcoidosis. As stated previously, small airway abnormalities are seen in some patients with early sarcoidosis and this may result in widespread patchy areas of air-trapping. The exact frequency of air-trapping, however, is unknown. Whether the air-trap-

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ping regresses as granulomas resolve or whether it is irreversible and thus is of prognostic significance is uncertain. Cystic Lung Diseases

Lymphangiomyomatosis (LAM) and Langerhans' cell histiocytosis are two common diseases associated with the presence of lung cysts. Although these diseases differ significantly, cyst formation and air-trapping are common denominators of both diseases.94 Air-trapping camalso be seen in some patients with intralobar seq~estration.~~ LAM results in proliferation of smooth muscle along the lymphatic vessels. Bronchiolar obstruction results in air-trapping and cyst formation.'* Pulmonary function test results are inconsistent and may show airflow limitation, restrictive dysfunction, or bothI4; a reduction of FEV,/ FVC ratio is a poor prognostic fact0r.4~The HRCT extent of abnormalities correlates well with the degree of airflow limitation and re51, 65 The expiratory CT, howduced DLCO.~, ever, appears more accurate in the evaluation of pulmonary functional impairment. In one study,19 expiratory CT was used to evaluate 10 patients with LAM and 10 normal subjects and CT extent of the disease was quantitatively correlated with the functional abnormalities using PI (threshold value -900 H). The summation of PI at two levels (areas of lung attenuation less than -900 H in two slices, one at the aortic arch and another just above the diaphragm) discriminated the patients with LAM from normal subjects in all the cases. The PI also correlated significantly with airflow limitation (FEV1: r = -0.90, P = 0.0005; FEV,/FVC: r = -0.71, P = 0.217); air-trapping (residual volume: r = 0.70, P = 0.02); DLco (r = -0.76, P = 0.01); gas exchange (alveolar to arterial oxygen gradient at rest, r = 0.69, P = 0.007 and at maximum exercise, r = 0.79, P = 0.007); and exercise performance (maximum workload: r = -0.84, P = 0.002). Langerhans' cell histiocytosis is an idiopathic disease usually occurring in young adults. More than 90% of the patients are smokers. Pathologically, multiple granulomatous lesions locate in the interstitiurn, especially close to small bronchioles, in the early stage of the disease. These granulomatous nodules subsequently undergo fibroblastic proliferation and fibrotic scarring results, which causes encroachment upon bronchioles

and interstitial fibrosis.59Pulmonary function test results are inconsistent and show airflow limitation, restrictive dysfunction, or both.25,59 In most of the cases, HRCT shows cysts with various wall thicknesslo Less frequently, centrilobular nodules with or without cavity formation are seen and can be the only abnormality.63There is no correlation between the CT score of abnormality and air flow limitation, although in one study DLco correlated well with CT score (r = 0.71).'j3In only one study has the utility of expiratory CT been described in a patient with Langerhans' cell histio~ytosis.~ In~ this study, DUHRCT showed focal and diffuse air-trapping and a distribution of air-trapping paralleled that of the cystic lung disease. Intralobar sequestration is usually well demarcated from adjacent normal lung and consists of cystic spaces with variable quantity of air, mucus, and pus and intervening parenchyma.84Pathologically, the cysts resemble dilated bronchi and the parenchyma, which varies from scanty to abundant, shows various degrees of differentiation.4O The parenchyma is often emphysematous. CT findings of sequestration include lucent lung surrounding cysts or soft-tissue nodules or masses, cysts containing air or fluid or softtissue masses, and dilatation of or an excess number of lung vessels connecting to a systemic In a study of 24 cases of intralobar and extralobar seque~tration,3~ 13 cases showed emphysema or lucent lung surrounding lung cysts. In a patient with intralobar sequestration studied using dynamic ultrafast CT:5 evidence of air-trapping was seen on expiration, not only in the sequestrated lung but also in adjacent normal-appearing lung. EXPIRATORY CT IN THE DIAGNOSIS OF INHOMOGENEOUS LUNG OPACITY

Inhomogeneous lung opacity visible on inspiratory HRCT may represent (1) groundglass opacity, (2) mosaic perfusion resulting from air-trapping, (3) mosaic perfusion resulting from vascular obstruction, or (4) a combination of these. In the presence of mosaic perfusion, vessel caliber is often reduced in areas of low attenuation, whereas this is not the case in the presence of ground-glass opacity. Expiratory CT can also help to discriminate these causes of inhomogeneous lung opacity

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seen on inspiratory scan^.^,^^ In patients with mosaic perfusion due to airway disease, lung inhomogeneity is accentuated on expiration (see Fig. 12), whereas in patients with mosaic perfusion due to vascular obstruction, this is not the case. In a study of 53 patients with inhomogeneous opacity visible on inspiratory scans: patients were classified as having (1)groundglass opacity due to infiltrative disease, (2) mosaic perfusion due to airway disease, (3) mosaic perfusion due to vascular disease, or (4) a mixed pattern, and the degree of confidence indicated. Patients were then reclassified with expiratory scans available. A correct diagnosis was made more often (93% versus 79%, P < 0.05), and a correct high confidence level interpretation was reached more often (93% versus 45%, P < O.OOOl), when expiratory scans were used. In patients with airway disease, accuracy increased from 84% to 100% with the use of expiratory scans. References 1. Aberle DR, Hansell DM, Brown K, et al: Lymphan-

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