Thorax 1991;46:77-84

THORAX

Review

The role of high resolution computed tomographyin the diagnosis of interstitial lung disease

DavidM Hansell, Ian H Kerr

Until recently the chest radiograph has beenthe only imaging technique used in the assess-ment of patients with suspected diffuse lungdisease. In this context the chest radiograph isless than ideal. Problems arise with both falsenegative and false positive results. It is wellestablished that the chest radiograph mayappear entirely normal in up to 10% ofpatients with biopsy proved diffuse lung dis-ease of various causes,1 and a poor qualitychest radiograph, especially of an obesepatient, may misleadingly raise the spectre ofdiffuse lung disease. The two dimensionalnature of a chest radiograph dictates that thereis superimposition of structures over the lungsand it has been estimated that up to 40% ofthe lungs is obscured in normal subjects. Thisobscuration will be further compounded bythe presence of pleural thickening or aneffusion. Even when the chest radiographshows definite evidence of diffuse lung diseaseMcCloud has pointed out that "the chestradiograph is often non-specific. Variousradiographic patterns, together with theirpredominant location, correlate statisticallywith their pathologic entities but in individualcases the chest roentgenogram is rarely diag-nostic. "'

Until recently the main use for computedtomography has been detection of pulmonarynodules and, despite some pioneering work byKreel in the early 1980s,3 it has had a limitedrole in the investigation of diffuse lung dis-ease. Improvements in computed tomographyscanner technology, notably in terms of spatialresolution and shorter scan times, have led torenewed interest in the application of com-puted tomography to show the fine morpho-logical detail of the lung. Research in this areais particularly active and is reflected in thelarge volume of descriptive work on the com-puted tomographic appearances of many dif-fuse lung diseases that has appeared over thelast five years4; there are no signs that thisperiod of research is over. The technique ofhigh resolution computed tomography, usedto show the lung parenchyma,' is sufficientlydifferent from conventional computed tomo-graphy to warrant a brief description.

Conventional computed tomography of thethorax uses contiguous 1 cm sections; in thisway the entire lungs are included in one

study. This protocol is widely used when acomprehensive examination of the lungs isrequired-for example, in the search formetastases. The volume averaging that occurswithin the 1 cm thickness of the scan,however, substantially reduces the ability ofconventional computed tomography to resolvesmall structures. For high resolution com-puted tomography the section thickness isreduced to 1-3 mm and a different softwarereconstruction of the image is used to improvespatial resolution (figs la and lb). These scansare interspaced by at least 1 cm. Where 3 mmsections are taken 1 cm apart the radiationdose to the breast is reduced to about half thatof conventional computed tomography. Nonethe less, the radiation burden inherent in highresolution computed tomography is con-siderable and in a complete study using 3 mmsections every 1 cm the dose is roughly 40times that received from a single chest radio-graph.6

Because high resolution computed tomo-graphy includes only very short segments ofpulmonary vessels these narrow sections maybe misinterpreted as showing a nodular pat-tern. For this reason some radiologistsadvocate conventional computed tomographybefore high resolution computed tomographybut this obviously adds to the radiation dose.Because, by definition, diffuse lung disease iswidespread many radiologists now perform alimited number of high resolution computedtomography scans, perhaps as few as six, insuch patients. In this way not only is theradiation dose restricted but the cost of theexamination is not much more than that of aposteroanterior and lateral chest radiograph.It has been estimated in the United States thathigh resolution computed tomography used inthis way costs $180, compared with $90 for aposteroanterior and lateral chest radiograph.In the same comparison a transbronchialbiopsy with bronchoalveolar lavage costs$1500 and an open lung biopsy $5000 (R AWebb, personal communication). Computedtomography is becoming more widely avail-able throughout the United Kingdom andmost computed tomography machines instal-led over the last three years are able to providehigh resolution images.The spatial resolution of the latest gener-

Department ofRadiology, RoyalBrompton NationalHeart and LungHospital, LondonSW3 6HPD M HansellI H KerrReprint requests to:Dr Hansell

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Figure 1 ( a(Conventional 10 niniwidth co-mputedtomographic sectionthrough the upper lobesnlormtial). (b High

resolution 3 mmil widthcomputed tomographicsectiotn at the santie level.Note the differentappearanice of the bloodzvssels anid brotichi.

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ation of computed tomography scanners

cnables structures as small as 200 pm to beresolved.7 As a result the outline of the basicunit of the lung, the secondary pulmonarylobule, can often be identified. The inter-lobular septum measures 100 pm across innormal individuals and is therefore more oftenidentified in pathological states when there isthickening of the interstitium (fig 2). Thesesepta, analogous to the Kerley B septal linesseen in a different plane on the chestradiograph, are seen most frequently in theperiphery of the anterolateral parts of the lungand over the surface of the diaphragm. Thesecondary pulmonary lobule itself is an

irregular polyhedron and contains a connec-

tive tissue sheath that surrounds thebronchovascular bundle. This core may bevisible as a small dot in the centre of thelobule (fig 3).

Attempts to discriminate so called "air-space" from "interstitial" disease by inferences

from the pattern on a chest radiograph havelargely been discredited."M This is partlybecause the abnormal shadowing on a radio-graph results from summation of numerousfoci; the chest radiograph has been fancifullydescribed as "the two-dimensional projectionalsum of several thousand histologic slices.""'Another compelling reason is the over-whelming frequency with which interstitialand airspace lesions coexist in any given disease(see fig 2). Nevertheless, high resolution com-puted tomography does show interstitial thick-ening precisely in the few diseases in which thepathological process is largely confined to theinterstitium. An example is shown in figure 4;the chest radiograph of this patient showednon-specific shadowing in the right upperzone. Despite extensive investigation a diag-nosis was not reached. High resolution com-puted tomography through the upper lobesshows unilateral thickening of the bronchovas-cular bundles and interlobular septa, features

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The role of high resolution computed tomography in the diagnosis of interstitial lung disease

Figure 2 a) Polygonaloutlines representitngthickened interlobularsepta (arrowheads) insilicosis. The backgroundnodularity is more obviouson sections through theupper zones. (b)Thickening of theinterlobular septa in areasof airspace consolidationdue to alveolar proteinosis.

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characteristic of lymphangitis carcinomatosa."From the pathological descriptions of lym-phangitis the high resolution computedtomography appearances can be predicted andthe same applies to pulmonary sarcoidosis.'There are subtle but definite features thatdifferentiate the high resolution computedtomography appearances of sarcidosis fromlymphangitis carcinomatosa: in sarcoidosis thenodular thickening of the bronchovascularbundles is more pronounced and thickening ofthe interlobular septa less obvious (fig 5).Nevertheless, as with chest radiography, pul-monary sarcoidosis has many guises and a widerange of high resolution computed tomographyappearances has been reported'3 (fig 6). Fibros-ing alveolitis, whether "lone" or associatedwith other diseases, has been shown to have a

characteristic computed tomographic appear-

ance. The crescentic subpleural distributionconcentrated in the posterobasal segments ofthe lower lobes is virtually pathognomonic'4 15

(fig 7). Not surprisingly, given this basal dis-tribution, high resolution computed tomo-graphy will show disease despite a normal chestradiograph.'" Scans taken in the prone positionmay be helpful in distinguishing parenchymalopacification due to increased perfusion of thedependent parts of the lung from minimalfibrosing alveolitis. As the fibrosis progresses a

widespread, coarse reticular pattern super-

venes, resulting in a non-specific appearance ofend stage pulmonary fibrosis. In the clinicalcontext of unexplained deterioration of a

patient with fibrosing alveolitis high resolutioncomputed tomography may be of value as itmay reveal other disease-for example, a bron-chogenic carcinoma. High resolution com-

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Hansell, Kerr

Figure 3 Intralobularbronchovascular bundlesvisible as minute centraldots (arrows) in this caseof subacute extrinsicallergic alveolitis.

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Figure 4 Lymphangitiscarcinomatosa: in the rightlung there is thickening ofthe bronchovascularbundles and prominentsubpleural interlobularsepta. There is a pleuralplaque posteriorly in theleft chest.

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puted tomography may also show coexistingemphysema,'7 which may be impossible todetect by chest radiography. There is increas-ing evidence of a high degree of correlationbetween high resolution computed tomo-graphy appearances and the amount of diseaseactivity in fibrosing alveolitis in terms of theproportion of cellular infiltrate to established

fibrosis found histologically. The observationthat amorphous parenchymal opacificationrepresents increased cellularity, in both theairspaces and the interstitium (fig 8), whereasthe reticular pattem is the result offibrosis (fig 7)appears, with some provisos, to be true.'8 1' Noother diagnostic technique (including lungfunction tests20) short of biopsy allows this

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The role of high resolution computed tomography in the diagnosis of interstitial lung disease

Figure 5 Sarcoidosis,with nodulespredominantlyconcentrated aroundbronchovascular bundles.

Figure 6 Sarcoidosis: aless common pattern withirregular areas ofconfluent parenchymalopacification (pronescan).

distinction to be made reliably.The superior sensitivity of high resolution

computed tomography for detecting asbestosisis now undisputed, particularly in thosepatients with extensive pleural disease, whichobscures the underlying lung.2 22 High resolu-tion computed tomography, however, has

opened a window on minor degrees of pleuro-parenchymal abnormality whose long termsignificance is as yet unknown. It will be someyears before the natural history of thesechanges is established. Other conditions inwhich high resolution computed tomographyfrequently shows parenchymal abnormality in

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Hansell, Kerr

Figure 7 Cryptogenicfibrosing alveolitis: thetypical subpleuraldistribution of the reticularpattern of establishedfibrosis (prone scan).

Figure 8 Crytogenicfibrosing alveolitis: poorlydefined parenchymalopacificationcorresponding to apredominantly cellularinfiltration in theinterstitium and airspaces(prone scan).

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the face of a normal chest radiograph includesubacute extrinsic allergic alveolitis23 (fig 9)and drug induced lung damage.24 The highresolution computed tomography patterns ofmost ofthe rarer diffuse lung diseases have nowbeen described in detail. These include thepulmonary manifestations of lymphangio-leiomyomatosis,25 26 histiocytosis X,27 and

tuberous sclerosis.28 Although these patternsmay not in themselves be unerringly diagnos-tic, in a given clinical context they will oftenconfirm the diagnosis and at the same timeexclude other suspected diseases, such asemphysema. The example of lymphangio-leiomyomatosis shown in figure 10 demon-strates numerous cystic air spaces of uniform

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The role of high resolution computed tomography in the diagnosis of interstitial lung disease

Figure 9 Slbacuttecxtrilsic allergicalzeolitis: globalpareuchymal opacificationdute to infiltration of theIuterstitium and airspaces.A concurrent chestradiograph was uiornial.

Figure 10Lymphangioleiomyomatos-is: well defined cysticairspaces. Note thepreservation of a normalvascular pattern. Thechest radiograph showedminimal and non-specificchanges.

size with fine but definable walls (in contra-distinction to the areas of lung destruction seenin emphysema, which do not have discerniblemargins). This woman with lymphangioleio-myomatosis had a spontaneous pneumothoraxduring pregnancy; the underlying lungs ap-peared questionably abnormal on the chestradiograph. In this instance a definite diagnosiswas made from the high resolution computedtomography appearances without resorting toan open lung biopsy.Although the sensitivity of high resolution

computed tomography in detecting minordegrees of diffuse lung disease is not seriously

challenged by any other imaging techniquecurrently available, its precise role in thedyspnoeic patient with a normal chestradiograph and abnormal results in lung func-tion tests remains to be determined. It seemslikely that high resolution computed tomo-graphy will obviate the need for lung biopsy byproviding a specific diagnosis in some of thesepatients. In patients needing a biopsy highresolution computed tomography should beused to provide guidance to the site most likelyto yield satisfactory histological material.The utility of high resolution computed

tomography compared with chest radiography

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Hansell, Kerr

in predicting a specific diagnosis of diffuse lungdisease has been elegantly demonstrated in astudy from Vancouver.29 The radiographs andcomputed tomograms of 118 patients, withwidely varying diagnoses proved by biopsy,were assessed by three observers withoutknowledge of any clinical data apart from theage of the patient. The observers listed thethree most likely diagnoses in order ofprobability and rtcorded their level of con-fidence for the first diagnosis. Overall, regard-less of confidence levels, the correct diagnosiswas made in 57% of cases with chest radio-graphy and 76% of cases with high resolutioncomputed tomography. High confidence wasachieved in 23% of chest radiograph readingsand 49% of high resolution computed tomo-graphy readings; of these readings the correctdiagnoses were made in 77% and 93% respec-tively. The implications are that high resolu-tion computed tomography will allow a con-fident and specific diagnosis of diffuse lungdisease to be made considerably more often andmore accurately than with chest radiography.As an aside to the main purpose of this study,Mathieson et al showed that HRCT correctlypredicted whether transbronchial or open lungbiopsy was more appropriate in 87% of cases,compared with 65% when chest radiographywas used (the criterion being that if sarcoidosisor lymphangitis carcinomatosa was thefavoured diagnosis transbronchial biopsy wasindicated). This is an important study, whichshould be repeated in the light of increasingexperience with high resolution computedtomography.Now that the correlations between the high

resolution computed tomography appearancesand the pathological features of most diffuselung diseases have been thoroughly studied,other areas receiving attention are functionalcorrelations between the extent of disease asshown by high resolution computed tomo-graphy and the results of lung function tests.Longitudinal studies of the rate of change bydiffuse lung disease detected by high resolutioncomputed tomography compared with thatshown by other monitoring techniques, bothimaging and functional, are also needed.The availability and sophistication of com-

puted tomography machines capable. of pro-ducing high resolution images continues toincrease, but skill in interpreting these imagesis not increasing at the same rate and remainslimited to a few centres. Given the obviousutility of high resolution computed tomo-graphy in diffuse lung disease (summarised inthe table), chest physicians and radiologistsshould now consider high resolution computed

Summary of the role of high resolution computedtomography in the assessment of interstitial lung disease

1 Confirming or excluding questionable shadowing on achest radiograph

2 Investigation of a dyspnoeic patient with abnormal lungfunction test values and an apparently normal chestradiograph

3 Characterisation of disease-may provide specificdiagnosis

4 Disclosing coexisting disease-for example, emphysema5 Providing a guide to the type and site of lung biopsy

tomography a routine and indispensable part ofthe investigation and assessment of a patientwith suspected diffuse lung disease.

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