State of the Art Computed Tomography of Chronic Diffuse Infiltrative Lung Disease
NESTOR L. MULLER and ROBERTA R. MILLER Contents Introduction Technique Normal Anatomy Irregular Linear Pattern I.QtQ1?~thiL~ulm~ary"_Fi.QrQsis
Pulmonary !-YJ!1-Pl1a.!!&it!~.Carcinomatosis Asbestosis - Cystic Pattern Lymphangioleiomyomatosis NodularPattern" ". - . Silicosis and Coal Workers' Pneumoconiosis Sarcoidosis Histiocytosis X Extrinsic Allergic Alveolitis Ground-Glass Pattern Alveolar Proteinosis Chronic Eosinophilic Pneumonia Bronchiolitis Obliterans Conclusions
Introduction
A large number of chronic diseases may cause diffuse infiltration of the lungs. Although they are usually referred to as chronic interstitial lung diseases, the majority involve both the interstitium and the airspaces. Therefore, we prefer the term chronic infiltrative lung disease (CILD), as suggested by Carrington and Gaensler (1). The clinical and functional features of most of these diseases are similar. The chest radiograph may show patterns suggestive of a particular disease process but rarely allows a confident diagnosis. In a reviewof the radiographs of 365 patients, McLoud and colleagues (2) included the correct diagnosis in the first two radiologic choices in only 50% of cases. The chest radiograph may be normal even when there is severe disease clinically and pathologically. Of 458 patients with biopsy-proven CILD described by Epler and coworkers (3), 9.60/0 1206
had normal chest radiographs. Moreover, the severity of changes on the radiograph correlates poorly with functional impairment (4-7). Over the last five years, a number of studies have shown that computed tomography (CT) can playa major role in the assessment of patients with CILD. By eliminating superimposition of structures, CT allows a better assessment of the type, distribution, and severity of parenchymal abnormalities than is possible on the chest radiograph. It is currently the best method to assess gross pulmonary morphology, short of having the actual pathologic specimen. CT has the advantage of being noninvasive and allowing assessment of the entire lung rather than being limited to a small area as in open lung biopsy. It demonstrates well both the normal and the abnormal interstitium, including the secondary pulmonary lobule. Several chronic diffuse lung diseases have been shown to have a characteristic appearance on CT, even when the chest radiograph was normal or showed only nonspecific findings, Because many chronic diseases have a patchy distribution and the degree of disease activity may be variable in the different areas of involvement, CT can serve as a useful guide to the optimal biopsy site (8). This report will concentrate on the CT features of CILD and on the pathologic basis for the CT findings. The ability of CT to assess the lung parenchyma has been made possible by recent developments in scanner technology that allow scan times in the order of 1 to 2 s and that have the ability to perform high-definition, thin-section scans. Optimal assessment of the lung parenchyma requires the use of state-
of-the-art scanners and optimal CT technique. Technique
The CT image is a two-dimensional representation of a three-dimensional, cross-sectional slice, the third dimension being slice thickness. The slice thickness can vary from 1 to 10 mm by changing the width of the X-ray beam in the scanner. In CT terminology, the thickness of the slice is referred to as its collimation because the width of the X-ray beam is determined by collimators positioned between the X-ray tube and the patient. All structures within a unit volume of the slice, or voxel, are represented as a single unit on the image, or pixel. The X-ray characteristics of the structures within a given voxelare therefore averaged to produce an image. This volume averaging results in loss of spatial resolution. The thicker the slice, the lower the ability of CT to resolve small structures. Conventionally, CT scans of the chest are performed by obtaining 8- to 10-mm thick slices at 10-mm intervals (figure 1). The scans are performed during breathholding at end-inspiration with the patient in a supine position. These images are usually reconstructed using a matrix (This is Part 1 of two parts; the second part will appear in the next issue of the Review) 1 From the Departments. of Radiology and Pathology,Universityof BritishColumbia and Vancouver General Hospital, Vancouver, British Columbia, Canada. 2 Correspondence and requests for reprints should be addressed to Nestor L. Muller, M.D., Department of Radiology, University of British Columbia, 855W. 12thAvenue, Vancouver, BC V5Z IM9, Canada.
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Fig. 1. A. Normal , conventional collimat ion CT scan at the level of the right upper lobe bronchus . This scan was obtained using a 1G-mmcollimation (Le., slice thickness), a field-of-view of 37 cm to allow visual ization of both lungs and chest wall , and a standard reconstruction algorithm. B. High-resolut ion CT of right lung at same level allows belter visualizat ion of fine parenchymal detail . PUlmonary veins with in interlobular septa can be easily identified in the lung periphery (arrows). The centrilobular arteriole and bronch iole are seen as dots (arrowheads). This scan was obtained using a 1.5-mm collimat ion, a field-of-view of 25 cm targeted to the right lung, and a high-spat ial frequency reconstruction algor ithm .
of 512pixels, a 35-to 40-cm field-of-view, and a "standard" or "soft tissue" algorithm. These images allow assessment of the entire lung parenchyma, but the use of lO-mm collimation leads to volume averaging within the plane of section. Detailed analysis of the parenchyma requires the use of 1-to 2-mm collimation scans (9). The standard reconstruction algorithms smooth the image, thus reducing visible image noise and improving contrast resolution, but they decrease the spatial resolution. CT scanners also have high-spatial frequency algorithms that produce less smoothing at interfaces, making them sharply defined and enhancing resolution of small structures. They do, however, result in an increase in visible noise: image noise on the CT image can be reduced by increasing radiation dose. In practice, although increased noise is apparent, it does not significantly affect visualization of fme parenchymal detail (10, 11). The combination of thin-section CT (1- to 2-mm collimation) and the use of
a high-frequency resolution algorithm is referredto as high-resolution CT (HRCT) (figure 1). Further improvement in the image quality can be obtained by decreasing the field-of-view and targeting the image to one lung or to a portion of one lung (9-11). Reducing the field-of-view from 40 to 20 to 25 em reduces pixel size from 0.78 to 0.45 mrn, thus increasing spatial resolution approximately 40070. The spatial resolution is approximately 1.5 times the pixel size. Targeting to 12.8 cm givesthe smallest pixel size (0.25mm). Further decreases in field-of-view do not improve the image. Image targeting is helpful particularly when assessingsmall, localized abnormalities. Although HRCT provides optimal visualization of the lung parenchyma, it cannot be used to assess the entire chest. Abnormalities may be missed between scans unless conventional CT is also performed. Furthermore, HRCT images are often difficult to interpret unless they are compared to the corresponding conventional images . Therefore, at our institu-
tion, we routinely use both conventional CT and HRCT in the initial assessment of patients with diffuse lung disease. One-centimeter collimation scans are obtained through the lungs. HRCT is routinely obtained at three preselected levels: aortic arch, tracheal carina, and I em above the diaphragm. These levels give representative samples of each of the three lung zones. These are complemented by one or two images obtained in areas selected on the basis of findings on the conventional CT. We believe that the combination of conventional CT and HRCT provides the best overall assessment of disease pattern, extent, and distribution. It should be noted, however, that there is controversy as to what constitutes the optimal number of highresolution sections and the levelsat which these should be obtained (12, 13). The optimal HRCT technique is an area of ongoing study. In certain circumstances (e.g., in the assessment of patients with suspected asbestosis or in the follow-up of patients with known diagnosis), an
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in vivo (figure 1). However, in some patients, vascular distention and increased density in the dependent lung regions may obscure fine underlying parenchymal detail. This problem, if significant, can easily be solved by performing scans with the patient in supine and prone positions (16).
the lung periphery (17). The fibrosis in patients with sarcoidosis, on the other hand, is usually more severe centrally along the bronchovascular bundles (18). HRCT is superior to chest radiography and conventional CT in the assessment of thickening of the interlobular septa, a relatively common finding in CILD (9, 19-21). Thickening of interAbnormal Anatomy lobular septa of several secondarypulmonary lobules is seen on CT as a pattern A number of signs indicate the presence Normal Anatomy of CILD on conventional CT and HRCT. of multiple polygonal lines. In patients Excellent direct correlations between These include abnormal interfaces, pres- with interstitial fibrosis, the thickening HRCT of isolated, inflated lungs ob- ence of irregular linear opacities, thick- is irregular. In lymphatic spread of tutained at autopsy with macroscopic and ening of the interlobular septa, presence mor, the septa characteristically have a histologic sections werereported byMezi- of nodules, and ground-glass opacities nodular or beaded appearance (19). Alane and associates (14) and Webb and col- (i.e., airspace opacification). The dif- though a similar pattern may be seen in leagues (15). These studies showed the ferential diagnosis of chronic diffuse in- sarcoidosis, in most patients the thickfiltrative lung diseases on CT, like on the ening is less extensive, more irregular, and following: radiograph, is based on the type and dis- accompanied by distortion of the lobu(1) Pulmonary vessels as small as 0.5 mm can be seen as dots (in cross-section) tribution of the abnormalities. The most lar architecture (18, 20). Nodules 1 to 10 mm in diameter may or branching structures (when in the common patterns described on CT are be seen in a number of CILD. In patients plane of section). summarized in table 1. Abnormal interfaces between vessels, with sarcoidosis, most nodules are less (2) Bronchi can be visualized out to the peripheral three-quarters of the lung bronchi, and visceral pleura with the sur- than 5 mm in diameter. Their margins as smooth circles or tramlike lines adja- rounding parenchyma are the most com- may be smooth or irregular. Characcent to the pulmonary arterial branches. mon sign of CILD (9). The interfaces be- teristically they are located along the lym(3) Normal, secondary pulmonary lob- come thickened and irregular; they are phatics in the bronchovascular bundles, ules can be identified particularly in the better defined on HRCT than on con- subpleural regions, and interlobular septa lung periphery. These are outlined by in- ventional CT as long as the structures are (18, 22, 23). In silicosis, the nodules are terlobular septa that appear as thin, running parallel to the plane of section. usually more numerous in the posterior smooth lines extending to the pleural sur- Otherwise, they are easier to assess on region of the upper lung zones. A ground-glass density is a hazy inface or as polygonal lines located more conventional CT. centrally. The interlobular septa are more Irregular linear opacities may be seen crease in density seen in a variety of indeveloped in the anterior and lateral ill a number of lung diseases. In some terstitial and airspace processes. In IPF, aspects of the lung bases, and it is in these cases, the pattern and distribution on CT areas of ground-glass density have been areas that they may be seen normally with are virtually pathognomonic. For in- shown to correlate with the filling of the HRCT. However, it is important to note stance, idiopathic pulmonary fibrosis airspaces with histiocytes and with alvethat only a few thin, well-defined septa (lPF) is characterized by the presence of olar septal inflammation, the hallmarks are seen in normal lungs (15). The nor- reticular opacities and cysticairspaces lo- of disease activity (24). Hazy increase in mal pulmonary arterioles and bronchi- cated predominantly in the subpleural lung density on HRCT also seems to oles in the core of the secondary pulmo- lung regions and at the lung bases. Wheth- correlate with active alveolitis as assessed nary lobule are seen as small dots or short er the disease is mild or severe, early in by 67Ga scanning in patients wtih sarcoidbranching lines (14). the course or endstage, pathologically osis (22).Airspace opacification may also Comparable images may be obtained and on CT the process is most severe in be seen in desquamative interstitial pneumonia (DIP), alveolar proteinosis, and pulmonary edema. TABLE 1 Recentstudies haveshown a high degree CT PATIERNS OF CILD of accuracy in diagnosing specificchronic Irregular Linear Pattern lung diseases based on the CT findings -Idiopathic pulmonary fibrosis (25,26). Based on the pattern and distri- Lymphatic spread of tumor of abnormalities, Mathieson and bution - Asbestosis coworkers (25) recently compared the acCystic Pattern curacies of chest radiography and CT in - Lymphangioleiomyomatosis the prediction of specific diagnoses in 118 Nodular Pattern consecutive patients with chronic diffuse -Silicosis and coalworkers' pneumoconiosis infiltrate lung disease. The radiographs - Sarcoidosis and CT scans were independently' as-Histiocytosis X - Extrinsic allergic alveolitis sessed by three observers without knowledge of clinical or pathologic data. Based Ground-Glass Pattern -Alveolar proteinosis on the type and distribution of pulmo-Chronic eosinophilic pneumonia nary opacities, the three observers made - Bronchiolitis obliterans-organizing pneumonia a confident diagnosis with 23% of raadequate assessment may be obtained by limiting the study to 4 to 6 HRCT spaced at 2-cm intervals through the lower chest, without the concomitant use of any l-cm collimation scans. Such studies can be done at a much lower financial cost to the patient and result in lower radiation dose. Intravenous contrast is not necessary in the assessment of diffuse parenchymal lung disease.
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Fig. 2. High-resolution CT at level of tracheal carina in a 72-yr-old woman with Idiopathic pulmonary fibrosis shows reticular densities mainly in the subpleural lung regions. CT scan parameters: 1.5-mm collimation, fieldof-view of 20 cm targeted to right lung. and high-spatial frequency reconstruction algorithm .
diographic readings and 49010 of cr scan readings. This diagnosis was correct with 77 and 93% of those readings, respectively (p < 0.001). The CT scan interpretations were most accurate in silicosis (93%), usual interstitialpneumonia (89%), lymphangitic carcinomatosis (85%), and sarcoidosis (77%). The greater accuracy of diagnosis based on CT is not surprising because CT reflects the gross pathologic findings. Several studies have described the computed tomographic appearances of various diffuse lung diseases and the pathologic basis for this diagnosis. Although these studies include only a relatively small number of patients and disease entities, they demonstrate a role for CT in the diagnosis and management of CILD. The sequence of specific diseases being reviewed follows the outline of table 1. Irregular Linear Pattern
Idiopathic Pulmonary Fibrosis IPF (fibrosing alveolitis, usual interstitial pneumonia) is characterized on CT by the presence of reticular opacities located predominantly in the subpleural regions and in the lung bases (figure 2). These cause irregular pleural, vascular, and bronchial interfaces with normal parenchyma. The reticular opacities may be fine or coarse and are often associated with cystic airspaces measuring 2 to 20
mm in diameter. These cystic airspaces (honeycomb cysts) are seen in as many as 90% of cr scans as compared to 30% of radiographs (27). The peripheral predominance of IPF is present on CT and pathologically in the vast majority of patients, regardless of the stage of the disease (17, 25-28) (figure 3). Histologically, the reticular pattern corresponds to areas of irregular fibrosis (17).Pathologically and on CT, one of the hallmarks of IPF is the patchy distribution throughout the lung periphery. Areas of fibrosis are more clearly distinguished from normal parenchyma on HRCT than on conventional CT. Also, small honeycomb cysts amid areas of irregular fibrosis are better seen on HRCT. It has been repeatedly demonstrated that the severity of interstitial disease as assessed on the chest radiograph correlates poorly with the clinical and functional impairment in IPF (6, 29). Patients may have severe dyspnea and a normal chest radiograph or they may have extensive changes on the radiograph and minimal symptomatology. Staples and colleagues (27) compared CT with clinical, functional, and radiologic findings in 23 patients with IPF. CT scans gave a better estimate of disease extent and showed more extensive honeycombing than did the radiograph. There was good correlation between the extent of disease
as assessed with CT and the severity of dyspnea (r = 0.6, p < 0.001), as well as between CT and impairment in gas exchange as assessed by the carbon monoxide diffusing capacity (r = 0.64, p < 0.001). There was poor correlation between disease severity as assessed with chest radiography and the clinical and functional impairment (all r ~ 0.39). IPF has a progressive course, usually leading to death within 3 to 6 yr after the onset of symptoms (30). Both the long-term survival in IPF and response to treatment with corticosteroids correlate with the histologic changes. The best response to steroids is observed in patients with little fibrosis and marked disease activity as reflected by conspicuous mononuclear alveolitis, histiocytes within alveoli, and cellular granulation tissue in alveolar ducts and alveoli (24, 29-32). Open lung biopsy has been the only reliable method to determine disease activity in IPF. Muller and associates (24) have recently shown that disease activity may also be visualized by CT as patchy areas of airspace opacification that, like the reticular den sities, are predominantly in a subpleural distribution. In that study, the CT scans of 12 patients were assessed independently by two observers and then correlated with the level of disease activity as assessed by open lung biopsy. Both observers correctly identified the five patients with marked disease activity and five of seven patients with low disease activity (figure 4). These preliminary results suggest that CT may have a role in assessing disease activity by noninvasive means. DIP was originally described as a form of CILD distinct from IPF, although many investigators now view DIP as an early form of IPF in which the intraalveolar histiocytic component of disease activity is particularly conspicuous and the degree of fibrosis is relatively mild. Vedal and coworkers (33) described the CT appearance in a case of DIP as being one of patchy subpleural hazy densities with little fibrosis. In the report, they suggested that CT may be helpful in assessing response to treatment in patients with DIP.
Pulmonary Lymphangitic Carcinomatosis Pulmonary lymphangitic carcinomatosis (PLC) refers to tumor growth in the lymphatics of the lung. It is seen most commonly in carcinomas of the breast, lung, stomach, and colon, and in meta-
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Fig. 3. A. CT scan through upper lobes in 6O-yr-old man shows honeycombing in the subp leural lung regions with min imal involvement of the remaining lung parenchyma. Scan parameters: 1.5-mm collimation , tield-of-view of 40 em, and standard reconstruction algorithm . B. The macroscopic pathologic specimen of the right upper lobe cut in the same plane and at the same level as the CT scan mirrors the CT image. (Reproduced with permission from reference 17.)
static adenocarcinoma from an unknown primary tumor (34). The radiographic manifestations of PLC include reticular densities, KerleyB lines, and subpleural edema (35, 36). Hilar and mediastinal adenopathy may occur (35, 36); however, the findings are nonspecific, and many symptomatic patients have normal findings on the chest radiograph (19, 37-39). An accurate diagnosis with radiography was made in only 20 of 87 (23 %) patients in a report by Goldsmith and colleagues (39). In about 50070 of cases of pathologically proved PLC, the chest radiograph shows a normal appearance (35, 39). The major lymph vessels are located in the bronchovascular bundles, in the interlobular septa, and in the subpleural regions of the lung (40, 41). The distribution of tumor cells within these structures pathologically causes a virtually pathognomonic appearance on CT con-
sisting of uneven thickening of bronchovascular bundles and of interlobular septa, giving them a beaded chain appearance (9, 14, 19). Zerhouni and associates (9) were the first to demonstrate polygonal lines in the lungs of patients with PLC. Stein and coworkers (19)performed an extensive analysis of CT patterns and found localized or diffuse reticular densities and an increase in the number and thickness of peripheral lines in all patients with PLC. They demonstrated polygonal lines in approximately 50070 of patients. These polygonal structures, usually containing a central dot, represent peripheral secondary lobules seen in cross-section, with the central dot representing the lobular arteriole and associated connective tissue (figure 5). Munk and colleagues (41)demonstrated that the thickening of the interlobular septa and bronchovascular bundles
in patients with PLC was due mainly to tumor growth rather than to edema or fibrosis, as had been claimed previously (40). Thmor growth accounts for the nodular thickening. Edema causes smooth thickening ofthe interlobular septa (14). HRCT scans are necessary to assess adequately the lung parenchyma in patients with PLC. In particular, the characteristic polygonal lines cannot be seen on to-mm collimation scans. In approximately 50070 of patients, the disease process is focal, and CT is helpful in directing the clinician to the most productive biopsy sites. Characterisitc CT changes have been demonstrated even in patients with normal chest radiographs (figure 6). In these cases, the CT findings tended to be focal and were more pronounced in peripheral areas not well visualized on chest radiographs (19). In patients with neoplasms, interstitial lung disease may be due not only to PLC
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Fig. 4. High-resolution CT through right lung base shows reticular densities (arrowheads) and areas of airspace opacification (alTOws). The reticular densities represent interstitial fibrosis and the areas of airspace opacification reflect the presence of disease activity . Scan parameters: 1.5 mm collimation. zo-cm field-of-view targeted to the right lung, and high resolution reconstruction algorithm.
but also to drug reaction, infection, or pulmonary edema. Although the CT manifestations of PLC appear to be sufficiently characteristic to suggest the diagnosis, it is not known at the present time whether it will be possible to confidently distinguish PLC from other conditions on the basis of CT findings.
Asbestosis Asbestosis is defined as pulmonary interstitial fibrosis caused by asbestos exposure. It is usually diagnosed by a combination of clinical, functional, and radiographic findings in the presence of previous asbestos exposure. In the appropriate occupational setting, the chest radiograph has generally been accepted as sufficient evidence of the presence of asbestosis without histologic proof (42); however, the chest radiograph as an indicator of disease has several limitations. Considerable observer error is noted particularly in patients with a normal or near-normal chest radiograph (43). Some studies have shown a 10 to 200/0 incidence of histologic evidence of parenchymal fibrosis with a normal chest radiograph (3, 44).
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HRCT was considerably more sensitive than conventional CT in the detection of both pleural plaques and parenchymal fibrosis. HRCT may demonstrate pleural and parenchymal abnormalities even in patients with normal radiographs (50). HRCT findings characteristic of asbestosis include: (1)subpleural lines (linear densities of variable length within 1 em and parallel to the pleura); (2) parenchymal bands (linear densities 2 to 5 cm in length running through the lung, usu ally extending to a pleural surface); (3) thickened interlobular septal lines and thickening of structures within the secondary pulmonary lobule; (4) honeycombing (49-51) (figure 7). On CT and pathologically, the parenchymal changes may be indistinguishable from usual interstitial pneumonia. Aberle and associates (16) correlated the parenchymal abnormalities on HRCT scans with clinical diagnoses in 100 asbestos-exposed workers. The most distinctive HRCT features of asbestosis included thickened, nondependent interstitial short lines and parenchymal bands. Their study also showed a strong relationship between asbestosis and asbestosrelated pleural disease. Although pleural and parenchymal abnormalities may occur independently of one another, they found a significant correlation between the severity of pleural disease and the presence and severity of asbestosis. Recently, Staples and colleagues (50) Studies using conventional CT have yielded conflicting results (45-48). Ear- reviewed 169 asbestos-exposed subjects ly trials in subjects with asbestos exposure with no evidence of asbestosis on chest found that conventional CT was signifi- radiographs (ILO profusion < 1/0) and cantly more sensitive than were chest found that 57 (34%) had HRCT features radiographs in detecting pleural thicken- consistent with asbestosis. They found ing and parenchymal fibrosis (46, 47). In a significant difference in the pulmonary those CT studies, interstitial fibrosis ap- function profile between asbestos-expeared as areas of coarse honeycombing. posed workers with HRCT findings conLoss of normal gravity-dependent per- sistent with asbestosis and workers with fusion was also described in areas of normal or near-normal HRCT. The abfibrosis (46, 47). Begin and colleagues normal group had lower mean values of (48) analyzed the usefulness of conven- vital capacity and impairment in gas tional CT scans relative to posteroanteri- transfer, as assessed by the diffusing caor and four-view radiographs of the chest pacity, as well as a higher mean dyspnea for detecting asbestos-related pleuropar- score. As pointed out by McLoud (52), it is enchymal fibrosis in 127 workers. They found that the three methods yielded controversial whether the small irregular comparable results. However, CT scans opacities seen in an exposed population, did not recognize asbestosis in 19% of particularly if they are of low profusion 53 subjects in whom chest radiographs or severity, really indicate asbestosis. Irwere abnormal (lLO profusion ~ 1/0). regular opacities in exposed individuals Aberle and coworkers (49) compared may be related to age or smoking, alHRCT with standard CT in 29 subjects though this relationship also is controverwith occupational asbestos exposure. All sial. The lack of pathologic proof raises of the individuals studied had evidence questions regarding the specificity of the of mild to severe abnormalities consis- findings described. However, although tent with asbestosis on standard chest the information available is limited, it radiographs. They demonstrated that seems unlikely that the HRCT findings
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Fig. 5. A. CT scan in 51-yr-old man with Iymphang itic spread of adenocarcinoma shows bilateral polygonal lines (straight closed arrows) representing thickened interlobular septa. thickening of the major fissures (open arrows), and nodular thickening of the bronchovascular bundles (curved arrows) . CT scan parameters: t .s-mrn collimation , 40-cm field-of-view, and standard reconstruction algorithm. B. The patient underwent open lung biopsy of the lingula. Scanning micrograph of the open lung biopsy specimen shows thickening of the septa (straight arrows) and bronchovascular bundles due to tumor (curved arrows). (Reproduced with permission from reference 41.)
of asbestosis could be in any way related to cigarette smoking (53). In clinical practice, histologic confirmation is usually not required, the diagnosis being inferred from symptoms, physical findings, chest radiographic abnormalities, and evidence of lung restriction on pulmonary function tests . The technique recommended by Aberle and coworkers (16,49) and Staples and associates (50) for assessing asbestosis consists of HRCT scans acquired at full inspiration and obtained at five-spaced intervals through the lower thorax in both supine and prone positions. The pathologic changes of asbestosis are usually most marked at the posterior lung bases. In the supine position, this part of the lung is dependent, tends to be com-
pressed , and has a larger blood volume than does nondependent lung. When a patient is in the prone position, the HRCT scan is frequently critical in identifying fine structural abnormalities in the posterior lung and in confirming the fixed nature of septal thickening and subpleural lines. Cystic Pattern Lymphangioleiomyomatosis Lymphangioleiomyomatosis is a rare disease characterized by progressive proliferation of smooth muscle in the walls of bronchi, bronchioles, alveolar septa, pulmonary vessels, lymphatics, and pleura (54-56). It is seen only in women almost always of childbearing age. The radiologic manifestations include irregular
opacities, honeycombing, overinflation, recurrent pneumothoraces, and chylous pleural effusions (54-56). The characteristic findings on CT consist of numerous thin-walled, cystic airspaces of various sizessurrounded by relatively normal lung parenchyma (57-62). Individual cysts are much better seen on HRCT than on conventional CT. On CT, the cysts range from 2 mrn to 5 em in diameter (figure 8). The cystic airspaces are thought to be due to proliferation of muscle cells along the bronchioles, leading to air trapping. The cysts are partially surrounded by these cells. CT may demonstrate cysts in patients with apparently normal pulmonary parenchyma on chest radiographs (63, 64). 1\\'0 recent studies have also shown that the CT findings in lymphan-
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Fig. 6. A 50-yr-old woman withpreviouslyresected carcinoma ofthe breast presented withprogressive shortness of breath. Transbronchial biopsy was negative. CT scan through the upper lobes shows linear densities in the medial aspect of the left upper lobe representing thickened interlobular septa (arrows). The radiograph, even Inretrospect, was normal. Repeat transbronchial biopsyofthe leftupper lobe confirmedthe diagnosis of Iymphangitic carcinomatosis . CT scan parameters: 1Q-mm collimation, 37-
NESTOR L. MULLER and ROBERTA R. MILLER Contents Introduction Technique Normal Anatomy Irregular Linear Pattern I.QtQ1?~thiL~ulm~ary"_Fi.QrQsis
Pulmonary !-YJ!1-Pl1a.!!&it!~.Carcinomatosis Asbestosis - Cystic Pattern Lymphangioleiomyomatosis NodularPattern" ". - . Silicosis and Coal Workers' Pneumoconiosis Sarcoidosis Histiocytosis X Extrinsic Allergic Alveolitis Ground-Glass Pattern Alveolar Proteinosis Chronic Eosinophilic Pneumonia Bronchiolitis Obliterans Conclusions
Introduction
A large number of chronic diseases may cause diffuse infiltration of the lungs. Although they are usually referred to as chronic interstitial lung diseases, the majority involve both the interstitium and the airspaces. Therefore, we prefer the term chronic infiltrative lung disease (CILD), as suggested by Carrington and Gaensler (1). The clinical and functional features of most of these diseases are similar. The chest radiograph may show patterns suggestive of a particular disease process but rarely allows a confident diagnosis. In a reviewof the radiographs of 365 patients, McLoud and colleagues (2) included the correct diagnosis in the first two radiologic choices in only 50% of cases. The chest radiograph may be normal even when there is severe disease clinically and pathologically. Of 458 patients with biopsy-proven CILD described by Epler and coworkers (3), 9.60/0 1206
had normal chest radiographs. Moreover, the severity of changes on the radiograph correlates poorly with functional impairment (4-7). Over the last five years, a number of studies have shown that computed tomography (CT) can playa major role in the assessment of patients with CILD. By eliminating superimposition of structures, CT allows a better assessment of the type, distribution, and severity of parenchymal abnormalities than is possible on the chest radiograph. It is currently the best method to assess gross pulmonary morphology, short of having the actual pathologic specimen. CT has the advantage of being noninvasive and allowing assessment of the entire lung rather than being limited to a small area as in open lung biopsy. It demonstrates well both the normal and the abnormal interstitium, including the secondary pulmonary lobule. Several chronic diffuse lung diseases have been shown to have a characteristic appearance on CT, even when the chest radiograph was normal or showed only nonspecific findings, Because many chronic diseases have a patchy distribution and the degree of disease activity may be variable in the different areas of involvement, CT can serve as a useful guide to the optimal biopsy site (8). This report will concentrate on the CT features of CILD and on the pathologic basis for the CT findings. The ability of CT to assess the lung parenchyma has been made possible by recent developments in scanner technology that allow scan times in the order of 1 to 2 s and that have the ability to perform high-definition, thin-section scans. Optimal assessment of the lung parenchyma requires the use of state-
of-the-art scanners and optimal CT technique. Technique
The CT image is a two-dimensional representation of a three-dimensional, cross-sectional slice, the third dimension being slice thickness. The slice thickness can vary from 1 to 10 mm by changing the width of the X-ray beam in the scanner. In CT terminology, the thickness of the slice is referred to as its collimation because the width of the X-ray beam is determined by collimators positioned between the X-ray tube and the patient. All structures within a unit volume of the slice, or voxel, are represented as a single unit on the image, or pixel. The X-ray characteristics of the structures within a given voxelare therefore averaged to produce an image. This volume averaging results in loss of spatial resolution. The thicker the slice, the lower the ability of CT to resolve small structures. Conventionally, CT scans of the chest are performed by obtaining 8- to 10-mm thick slices at 10-mm intervals (figure 1). The scans are performed during breathholding at end-inspiration with the patient in a supine position. These images are usually reconstructed using a matrix (This is Part 1 of two parts; the second part will appear in the next issue of the Review) 1 From the Departments. of Radiology and Pathology,Universityof BritishColumbia and Vancouver General Hospital, Vancouver, British Columbia, Canada. 2 Correspondence and requests for reprints should be addressed to Nestor L. Muller, M.D., Department of Radiology, University of British Columbia, 855W. 12thAvenue, Vancouver, BC V5Z IM9, Canada.
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Fig. 1. A. Normal , conventional collimat ion CT scan at the level of the right upper lobe bronchus . This scan was obtained using a 1G-mmcollimation (Le., slice thickness), a field-of-view of 37 cm to allow visual ization of both lungs and chest wall , and a standard reconstruction algorithm. B. High-resolut ion CT of right lung at same level allows belter visualizat ion of fine parenchymal detail . PUlmonary veins with in interlobular septa can be easily identified in the lung periphery (arrows). The centrilobular arteriole and bronch iole are seen as dots (arrowheads). This scan was obtained using a 1.5-mm collimat ion, a field-of-view of 25 cm targeted to the right lung, and a high-spat ial frequency reconstruction algor ithm .
of 512pixels, a 35-to 40-cm field-of-view, and a "standard" or "soft tissue" algorithm. These images allow assessment of the entire lung parenchyma, but the use of lO-mm collimation leads to volume averaging within the plane of section. Detailed analysis of the parenchyma requires the use of 1-to 2-mm collimation scans (9). The standard reconstruction algorithms smooth the image, thus reducing visible image noise and improving contrast resolution, but they decrease the spatial resolution. CT scanners also have high-spatial frequency algorithms that produce less smoothing at interfaces, making them sharply defined and enhancing resolution of small structures. They do, however, result in an increase in visible noise: image noise on the CT image can be reduced by increasing radiation dose. In practice, although increased noise is apparent, it does not significantly affect visualization of fme parenchymal detail (10, 11). The combination of thin-section CT (1- to 2-mm collimation) and the use of
a high-frequency resolution algorithm is referredto as high-resolution CT (HRCT) (figure 1). Further improvement in the image quality can be obtained by decreasing the field-of-view and targeting the image to one lung or to a portion of one lung (9-11). Reducing the field-of-view from 40 to 20 to 25 em reduces pixel size from 0.78 to 0.45 mrn, thus increasing spatial resolution approximately 40070. The spatial resolution is approximately 1.5 times the pixel size. Targeting to 12.8 cm givesthe smallest pixel size (0.25mm). Further decreases in field-of-view do not improve the image. Image targeting is helpful particularly when assessingsmall, localized abnormalities. Although HRCT provides optimal visualization of the lung parenchyma, it cannot be used to assess the entire chest. Abnormalities may be missed between scans unless conventional CT is also performed. Furthermore, HRCT images are often difficult to interpret unless they are compared to the corresponding conventional images . Therefore, at our institu-
tion, we routinely use both conventional CT and HRCT in the initial assessment of patients with diffuse lung disease. One-centimeter collimation scans are obtained through the lungs. HRCT is routinely obtained at three preselected levels: aortic arch, tracheal carina, and I em above the diaphragm. These levels give representative samples of each of the three lung zones. These are complemented by one or two images obtained in areas selected on the basis of findings on the conventional CT. We believe that the combination of conventional CT and HRCT provides the best overall assessment of disease pattern, extent, and distribution. It should be noted, however, that there is controversy as to what constitutes the optimal number of highresolution sections and the levelsat which these should be obtained (12, 13). The optimal HRCT technique is an area of ongoing study. In certain circumstances (e.g., in the assessment of patients with suspected asbestosis or in the follow-up of patients with known diagnosis), an
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in vivo (figure 1). However, in some patients, vascular distention and increased density in the dependent lung regions may obscure fine underlying parenchymal detail. This problem, if significant, can easily be solved by performing scans with the patient in supine and prone positions (16).
the lung periphery (17). The fibrosis in patients with sarcoidosis, on the other hand, is usually more severe centrally along the bronchovascular bundles (18). HRCT is superior to chest radiography and conventional CT in the assessment of thickening of the interlobular septa, a relatively common finding in CILD (9, 19-21). Thickening of interAbnormal Anatomy lobular septa of several secondarypulmonary lobules is seen on CT as a pattern A number of signs indicate the presence Normal Anatomy of CILD on conventional CT and HRCT. of multiple polygonal lines. In patients Excellent direct correlations between These include abnormal interfaces, pres- with interstitial fibrosis, the thickening HRCT of isolated, inflated lungs ob- ence of irregular linear opacities, thick- is irregular. In lymphatic spread of tutained at autopsy with macroscopic and ening of the interlobular septa, presence mor, the septa characteristically have a histologic sections werereported byMezi- of nodules, and ground-glass opacities nodular or beaded appearance (19). Alane and associates (14) and Webb and col- (i.e., airspace opacification). The dif- though a similar pattern may be seen in leagues (15). These studies showed the ferential diagnosis of chronic diffuse in- sarcoidosis, in most patients the thickfiltrative lung diseases on CT, like on the ening is less extensive, more irregular, and following: radiograph, is based on the type and dis- accompanied by distortion of the lobu(1) Pulmonary vessels as small as 0.5 mm can be seen as dots (in cross-section) tribution of the abnormalities. The most lar architecture (18, 20). Nodules 1 to 10 mm in diameter may or branching structures (when in the common patterns described on CT are be seen in a number of CILD. In patients plane of section). summarized in table 1. Abnormal interfaces between vessels, with sarcoidosis, most nodules are less (2) Bronchi can be visualized out to the peripheral three-quarters of the lung bronchi, and visceral pleura with the sur- than 5 mm in diameter. Their margins as smooth circles or tramlike lines adja- rounding parenchyma are the most com- may be smooth or irregular. Characcent to the pulmonary arterial branches. mon sign of CILD (9). The interfaces be- teristically they are located along the lym(3) Normal, secondary pulmonary lob- come thickened and irregular; they are phatics in the bronchovascular bundles, ules can be identified particularly in the better defined on HRCT than on con- subpleural regions, and interlobular septa lung periphery. These are outlined by in- ventional CT as long as the structures are (18, 22, 23). In silicosis, the nodules are terlobular septa that appear as thin, running parallel to the plane of section. usually more numerous in the posterior smooth lines extending to the pleural sur- Otherwise, they are easier to assess on region of the upper lung zones. A ground-glass density is a hazy inface or as polygonal lines located more conventional CT. centrally. The interlobular septa are more Irregular linear opacities may be seen crease in density seen in a variety of indeveloped in the anterior and lateral ill a number of lung diseases. In some terstitial and airspace processes. In IPF, aspects of the lung bases, and it is in these cases, the pattern and distribution on CT areas of ground-glass density have been areas that they may be seen normally with are virtually pathognomonic. For in- shown to correlate with the filling of the HRCT. However, it is important to note stance, idiopathic pulmonary fibrosis airspaces with histiocytes and with alvethat only a few thin, well-defined septa (lPF) is characterized by the presence of olar septal inflammation, the hallmarks are seen in normal lungs (15). The nor- reticular opacities and cysticairspaces lo- of disease activity (24). Hazy increase in mal pulmonary arterioles and bronchi- cated predominantly in the subpleural lung density on HRCT also seems to oles in the core of the secondary pulmo- lung regions and at the lung bases. Wheth- correlate with active alveolitis as assessed nary lobule are seen as small dots or short er the disease is mild or severe, early in by 67Ga scanning in patients wtih sarcoidbranching lines (14). the course or endstage, pathologically osis (22).Airspace opacification may also Comparable images may be obtained and on CT the process is most severe in be seen in desquamative interstitial pneumonia (DIP), alveolar proteinosis, and pulmonary edema. TABLE 1 Recentstudies haveshown a high degree CT PATIERNS OF CILD of accuracy in diagnosing specificchronic Irregular Linear Pattern lung diseases based on the CT findings -Idiopathic pulmonary fibrosis (25,26). Based on the pattern and distri- Lymphatic spread of tumor of abnormalities, Mathieson and bution - Asbestosis coworkers (25) recently compared the acCystic Pattern curacies of chest radiography and CT in - Lymphangioleiomyomatosis the prediction of specific diagnoses in 118 Nodular Pattern consecutive patients with chronic diffuse -Silicosis and coalworkers' pneumoconiosis infiltrate lung disease. The radiographs - Sarcoidosis and CT scans were independently' as-Histiocytosis X - Extrinsic allergic alveolitis sessed by three observers without knowledge of clinical or pathologic data. Based Ground-Glass Pattern -Alveolar proteinosis on the type and distribution of pulmo-Chronic eosinophilic pneumonia nary opacities, the three observers made - Bronchiolitis obliterans-organizing pneumonia a confident diagnosis with 23% of raadequate assessment may be obtained by limiting the study to 4 to 6 HRCT spaced at 2-cm intervals through the lower chest, without the concomitant use of any l-cm collimation scans. Such studies can be done at a much lower financial cost to the patient and result in lower radiation dose. Intravenous contrast is not necessary in the assessment of diffuse parenchymal lung disease.
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Fig. 2. High-resolution CT at level of tracheal carina in a 72-yr-old woman with Idiopathic pulmonary fibrosis shows reticular densities mainly in the subpleural lung regions. CT scan parameters: 1.5-mm collimation, fieldof-view of 20 cm targeted to right lung. and high-spatial frequency reconstruction algorithm .
diographic readings and 49010 of cr scan readings. This diagnosis was correct with 77 and 93% of those readings, respectively (p < 0.001). The CT scan interpretations were most accurate in silicosis (93%), usual interstitialpneumonia (89%), lymphangitic carcinomatosis (85%), and sarcoidosis (77%). The greater accuracy of diagnosis based on CT is not surprising because CT reflects the gross pathologic findings. Several studies have described the computed tomographic appearances of various diffuse lung diseases and the pathologic basis for this diagnosis. Although these studies include only a relatively small number of patients and disease entities, they demonstrate a role for CT in the diagnosis and management of CILD. The sequence of specific diseases being reviewed follows the outline of table 1. Irregular Linear Pattern
Idiopathic Pulmonary Fibrosis IPF (fibrosing alveolitis, usual interstitial pneumonia) is characterized on CT by the presence of reticular opacities located predominantly in the subpleural regions and in the lung bases (figure 2). These cause irregular pleural, vascular, and bronchial interfaces with normal parenchyma. The reticular opacities may be fine or coarse and are often associated with cystic airspaces measuring 2 to 20
mm in diameter. These cystic airspaces (honeycomb cysts) are seen in as many as 90% of cr scans as compared to 30% of radiographs (27). The peripheral predominance of IPF is present on CT and pathologically in the vast majority of patients, regardless of the stage of the disease (17, 25-28) (figure 3). Histologically, the reticular pattern corresponds to areas of irregular fibrosis (17).Pathologically and on CT, one of the hallmarks of IPF is the patchy distribution throughout the lung periphery. Areas of fibrosis are more clearly distinguished from normal parenchyma on HRCT than on conventional CT. Also, small honeycomb cysts amid areas of irregular fibrosis are better seen on HRCT. It has been repeatedly demonstrated that the severity of interstitial disease as assessed on the chest radiograph correlates poorly with the clinical and functional impairment in IPF (6, 29). Patients may have severe dyspnea and a normal chest radiograph or they may have extensive changes on the radiograph and minimal symptomatology. Staples and colleagues (27) compared CT with clinical, functional, and radiologic findings in 23 patients with IPF. CT scans gave a better estimate of disease extent and showed more extensive honeycombing than did the radiograph. There was good correlation between the extent of disease
as assessed with CT and the severity of dyspnea (r = 0.6, p < 0.001), as well as between CT and impairment in gas exchange as assessed by the carbon monoxide diffusing capacity (r = 0.64, p < 0.001). There was poor correlation between disease severity as assessed with chest radiography and the clinical and functional impairment (all r ~ 0.39). IPF has a progressive course, usually leading to death within 3 to 6 yr after the onset of symptoms (30). Both the long-term survival in IPF and response to treatment with corticosteroids correlate with the histologic changes. The best response to steroids is observed in patients with little fibrosis and marked disease activity as reflected by conspicuous mononuclear alveolitis, histiocytes within alveoli, and cellular granulation tissue in alveolar ducts and alveoli (24, 29-32). Open lung biopsy has been the only reliable method to determine disease activity in IPF. Muller and associates (24) have recently shown that disease activity may also be visualized by CT as patchy areas of airspace opacification that, like the reticular den sities, are predominantly in a subpleural distribution. In that study, the CT scans of 12 patients were assessed independently by two observers and then correlated with the level of disease activity as assessed by open lung biopsy. Both observers correctly identified the five patients with marked disease activity and five of seven patients with low disease activity (figure 4). These preliminary results suggest that CT may have a role in assessing disease activity by noninvasive means. DIP was originally described as a form of CILD distinct from IPF, although many investigators now view DIP as an early form of IPF in which the intraalveolar histiocytic component of disease activity is particularly conspicuous and the degree of fibrosis is relatively mild. Vedal and coworkers (33) described the CT appearance in a case of DIP as being one of patchy subpleural hazy densities with little fibrosis. In the report, they suggested that CT may be helpful in assessing response to treatment in patients with DIP.
Pulmonary Lymphangitic Carcinomatosis Pulmonary lymphangitic carcinomatosis (PLC) refers to tumor growth in the lymphatics of the lung. It is seen most commonly in carcinomas of the breast, lung, stomach, and colon, and in meta-
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Fig. 3. A. CT scan through upper lobes in 6O-yr-old man shows honeycombing in the subp leural lung regions with min imal involvement of the remaining lung parenchyma. Scan parameters: 1.5-mm collimation , tield-of-view of 40 em, and standard reconstruction algorithm . B. The macroscopic pathologic specimen of the right upper lobe cut in the same plane and at the same level as the CT scan mirrors the CT image. (Reproduced with permission from reference 17.)
static adenocarcinoma from an unknown primary tumor (34). The radiographic manifestations of PLC include reticular densities, KerleyB lines, and subpleural edema (35, 36). Hilar and mediastinal adenopathy may occur (35, 36); however, the findings are nonspecific, and many symptomatic patients have normal findings on the chest radiograph (19, 37-39). An accurate diagnosis with radiography was made in only 20 of 87 (23 %) patients in a report by Goldsmith and colleagues (39). In about 50070 of cases of pathologically proved PLC, the chest radiograph shows a normal appearance (35, 39). The major lymph vessels are located in the bronchovascular bundles, in the interlobular septa, and in the subpleural regions of the lung (40, 41). The distribution of tumor cells within these structures pathologically causes a virtually pathognomonic appearance on CT con-
sisting of uneven thickening of bronchovascular bundles and of interlobular septa, giving them a beaded chain appearance (9, 14, 19). Zerhouni and associates (9) were the first to demonstrate polygonal lines in the lungs of patients with PLC. Stein and coworkers (19)performed an extensive analysis of CT patterns and found localized or diffuse reticular densities and an increase in the number and thickness of peripheral lines in all patients with PLC. They demonstrated polygonal lines in approximately 50070 of patients. These polygonal structures, usually containing a central dot, represent peripheral secondary lobules seen in cross-section, with the central dot representing the lobular arteriole and associated connective tissue (figure 5). Munk and colleagues (41)demonstrated that the thickening of the interlobular septa and bronchovascular bundles
in patients with PLC was due mainly to tumor growth rather than to edema or fibrosis, as had been claimed previously (40). Thmor growth accounts for the nodular thickening. Edema causes smooth thickening ofthe interlobular septa (14). HRCT scans are necessary to assess adequately the lung parenchyma in patients with PLC. In particular, the characteristic polygonal lines cannot be seen on to-mm collimation scans. In approximately 50070 of patients, the disease process is focal, and CT is helpful in directing the clinician to the most productive biopsy sites. Characterisitc CT changes have been demonstrated even in patients with normal chest radiographs (figure 6). In these cases, the CT findings tended to be focal and were more pronounced in peripheral areas not well visualized on chest radiographs (19). In patients with neoplasms, interstitial lung disease may be due not only to PLC
STATE OF THE ARr. CT OF ClLD
Fig. 4. High-resolution CT through right lung base shows reticular densities (arrowheads) and areas of airspace opacification (alTOws). The reticular densities represent interstitial fibrosis and the areas of airspace opacification reflect the presence of disease activity . Scan parameters: 1.5 mm collimation. zo-cm field-of-view targeted to the right lung, and high resolution reconstruction algorithm.
but also to drug reaction, infection, or pulmonary edema. Although the CT manifestations of PLC appear to be sufficiently characteristic to suggest the diagnosis, it is not known at the present time whether it will be possible to confidently distinguish PLC from other conditions on the basis of CT findings.
Asbestosis Asbestosis is defined as pulmonary interstitial fibrosis caused by asbestos exposure. It is usually diagnosed by a combination of clinical, functional, and radiographic findings in the presence of previous asbestos exposure. In the appropriate occupational setting, the chest radiograph has generally been accepted as sufficient evidence of the presence of asbestosis without histologic proof (42); however, the chest radiograph as an indicator of disease has several limitations. Considerable observer error is noted particularly in patients with a normal or near-normal chest radiograph (43). Some studies have shown a 10 to 200/0 incidence of histologic evidence of parenchymal fibrosis with a normal chest radiograph (3, 44).
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HRCT was considerably more sensitive than conventional CT in the detection of both pleural plaques and parenchymal fibrosis. HRCT may demonstrate pleural and parenchymal abnormalities even in patients with normal radiographs (50). HRCT findings characteristic of asbestosis include: (1)subpleural lines (linear densities of variable length within 1 em and parallel to the pleura); (2) parenchymal bands (linear densities 2 to 5 cm in length running through the lung, usu ally extending to a pleural surface); (3) thickened interlobular septal lines and thickening of structures within the secondary pulmonary lobule; (4) honeycombing (49-51) (figure 7). On CT and pathologically, the parenchymal changes may be indistinguishable from usual interstitial pneumonia. Aberle and associates (16) correlated the parenchymal abnormalities on HRCT scans with clinical diagnoses in 100 asbestos-exposed workers. The most distinctive HRCT features of asbestosis included thickened, nondependent interstitial short lines and parenchymal bands. Their study also showed a strong relationship between asbestosis and asbestosrelated pleural disease. Although pleural and parenchymal abnormalities may occur independently of one another, they found a significant correlation between the severity of pleural disease and the presence and severity of asbestosis. Recently, Staples and colleagues (50) Studies using conventional CT have yielded conflicting results (45-48). Ear- reviewed 169 asbestos-exposed subjects ly trials in subjects with asbestos exposure with no evidence of asbestosis on chest found that conventional CT was signifi- radiographs (ILO profusion < 1/0) and cantly more sensitive than were chest found that 57 (34%) had HRCT features radiographs in detecting pleural thicken- consistent with asbestosis. They found ing and parenchymal fibrosis (46, 47). In a significant difference in the pulmonary those CT studies, interstitial fibrosis ap- function profile between asbestos-expeared as areas of coarse honeycombing. posed workers with HRCT findings conLoss of normal gravity-dependent per- sistent with asbestosis and workers with fusion was also described in areas of normal or near-normal HRCT. The abfibrosis (46, 47). Begin and colleagues normal group had lower mean values of (48) analyzed the usefulness of conven- vital capacity and impairment in gas tional CT scans relative to posteroanteri- transfer, as assessed by the diffusing caor and four-view radiographs of the chest pacity, as well as a higher mean dyspnea for detecting asbestos-related pleuropar- score. As pointed out by McLoud (52), it is enchymal fibrosis in 127 workers. They found that the three methods yielded controversial whether the small irregular comparable results. However, CT scans opacities seen in an exposed population, did not recognize asbestosis in 19% of particularly if they are of low profusion 53 subjects in whom chest radiographs or severity, really indicate asbestosis. Irwere abnormal (lLO profusion ~ 1/0). regular opacities in exposed individuals Aberle and coworkers (49) compared may be related to age or smoking, alHRCT with standard CT in 29 subjects though this relationship also is controverwith occupational asbestos exposure. All sial. The lack of pathologic proof raises of the individuals studied had evidence questions regarding the specificity of the of mild to severe abnormalities consis- findings described. However, although tent with asbestosis on standard chest the information available is limited, it radiographs. They demonstrated that seems unlikely that the HRCT findings
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Fig. 5. A. CT scan in 51-yr-old man with Iymphang itic spread of adenocarcinoma shows bilateral polygonal lines (straight closed arrows) representing thickened interlobular septa. thickening of the major fissures (open arrows), and nodular thickening of the bronchovascular bundles (curved arrows) . CT scan parameters: t .s-mrn collimation , 40-cm field-of-view, and standard reconstruction algorithm. B. The patient underwent open lung biopsy of the lingula. Scanning micrograph of the open lung biopsy specimen shows thickening of the septa (straight arrows) and bronchovascular bundles due to tumor (curved arrows). (Reproduced with permission from reference 41.)
of asbestosis could be in any way related to cigarette smoking (53). In clinical practice, histologic confirmation is usually not required, the diagnosis being inferred from symptoms, physical findings, chest radiographic abnormalities, and evidence of lung restriction on pulmonary function tests . The technique recommended by Aberle and coworkers (16,49) and Staples and associates (50) for assessing asbestosis consists of HRCT scans acquired at full inspiration and obtained at five-spaced intervals through the lower thorax in both supine and prone positions. The pathologic changes of asbestosis are usually most marked at the posterior lung bases. In the supine position, this part of the lung is dependent, tends to be com-
pressed , and has a larger blood volume than does nondependent lung. When a patient is in the prone position, the HRCT scan is frequently critical in identifying fine structural abnormalities in the posterior lung and in confirming the fixed nature of septal thickening and subpleural lines. Cystic Pattern Lymphangioleiomyomatosis Lymphangioleiomyomatosis is a rare disease characterized by progressive proliferation of smooth muscle in the walls of bronchi, bronchioles, alveolar septa, pulmonary vessels, lymphatics, and pleura (54-56). It is seen only in women almost always of childbearing age. The radiologic manifestations include irregular
opacities, honeycombing, overinflation, recurrent pneumothoraces, and chylous pleural effusions (54-56). The characteristic findings on CT consist of numerous thin-walled, cystic airspaces of various sizessurrounded by relatively normal lung parenchyma (57-62). Individual cysts are much better seen on HRCT than on conventional CT. On CT, the cysts range from 2 mrn to 5 em in diameter (figure 8). The cystic airspaces are thought to be due to proliferation of muscle cells along the bronchioles, leading to air trapping. The cysts are partially surrounded by these cells. CT may demonstrate cysts in patients with apparently normal pulmonary parenchyma on chest radiographs (63, 64). 1\\'0 recent studies have also shown that the CT findings in lymphan-
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Fig. 6. A 50-yr-old woman withpreviouslyresected carcinoma ofthe breast presented withprogressive shortness of breath. Transbronchial biopsy was negative. CT scan through the upper lobes shows linear densities in the medial aspect of the left upper lobe representing thickened interlobular septa (arrows). The radiograph, even Inretrospect, was normal. Repeat transbronchial biopsyofthe leftupper lobe confirmedthe diagnosis of Iymphangitic carcinomatosis . CT scan parameters: 1Q-mm collimation, 37-
