834 AJR:191, September 2008trol measures as well as for ensuring the ap-propriatetherapyforinfectedpatients.Un-fortunately, acid-fast bacilli are found in the sputum in a limited number of patients with active pulmonary TB [6]. Therefore, the im-agingdiagnosiswouldprovideanappropri-atetherapyforinfectedpatientsbeforethe denitive diagnosis by the bacteriology. The aimofthisarticleistoelaboratenewcon-ceptsinthediagnosisandtreatmentofpul-monary TB in the 21st century, to review the characteristicimagingndingsofvarious formsofpulmonaryTB,andtoassessthe role of CT in the diagnosis and management of pulmonary TB.Development of Infection and PathogenesisM.tuberculosisisanaerobic,nonmotile, non-spore-formingrodthatishighlyresis-tant to drying, acid, and alcohol. It is trans-mitted from person to person via droplet nu-cleicontainingtheorganismandisspread mainlybycoughing.Apersonwithactive butuntreatedTBinfectsapproximately 1015 other people per year. The probability oftransmissionfromonepersontoanother depends on the number of infectious droplets Pulmonary Tuberculosis: Up-to-Date Imaging and ManagementYeon Joo Jeong1 Kyung Soo Lee2Jeong YJ, Lee KS1Department of Diagnostic Radiology, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Pusan, Korea.2Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Ilwon-Dong, Kangnam-Ku, Seoul 135-710, Korea. Address correspon-dence to K. S. Lee (kyungs.lee@samsung.com).ChestI magi ngRevi ewCMEThis article is available for CME credit.See www.arrs.org for more information.AJR 2008; 191:8348440361803X/08/1913834 American Roentgen Ray SocietyTuberculosis(TB)isanairborne infectious disease caused by My-cobacteriumtuberculosisandis amajorcauseofmorbidityand mortality,particularlyindevelopingcoun-tries [13]. In 2005, 8.8 million people devel-opedactiveTBand1.6milliondiedofthe disease[4].MostcasesoccurinSoutheast Asia and Africa.Patients with active pulmonary TB may be asymptomatic, have mild or progressive dry cough,orpresentwithmultiplesymptoms, includingfever,fatigue,weightloss,night sweats,andacoughthatproducesbloody sputum.IfTBisdetectedearlyandfully treated,peoplewiththediseasequicklybe-comenoninfectiousandeventuallycured. However, multidrug-resistant (MDR) and ex-tensivelydrug-resistantTB,HIV-associated TB, and weak health systems are major chal-lenges.TheWorldHealthOrganizationis making an effort to dramatically reduce the burdenofTBandtohalveTBdeathsand prevalenceby2015,throughitsStopTB StrategyandsupportingtheGlobalPlanto Stop TB [5].ThepromptdiagnosisofTBisessential forcommunitypublichealthinfectioncon-Keywords: lung CT, lung disease, lung infection, tuberculosis, pulmonaryDOI:10.2214/AJR.07.3896Received February 24, 2008; accepted after revisionApril 11, 2008.Supported by the SRC/ERC program of MOST/KOSEF (grant no. R11-2002-103).OBJECTIVE. Pulmonary tuberculosis (TB) is a common worldwide infection and a med-ical and social problem causing high mortality and morbidity, especially in developing coun-tries. The traditional imaging concept of primary and reactivation TB has been recently chal-lenged, and radiologic features depend on the level of host immunity rather than the elapsed time after the infection. We aimed to elaborate the new concept of the diagnosis and treatment of pulmonary TB, to review the characteristic imaging ndings of various forms of pulmo-nary TB, and to assess the role of CT in the diagnosis and management of pulmonary TB. CONCLUSION. Fast and more accurate TB testing such as bacterial DNA ngerprint-ing and whole-blood interferon- assay has been developed. Miliary or disseminated primary pattern or atypical manifestations of pulmonary TB are common in patients with impaired immunity. CT plays an important role in the detection of TB in patients in whom the chest radiograph is normal or inconclusive, in the determination of disease activity, in the detection of complication, and in the management of TB by providing a roadmap for surgical treatment planning. PET scans using 18F-FDG or 11C-choline can sometimes help differentiate tubercu-lous granuloma from lung malignancy. Jeong and LeePulmonary TuberculosisChest ImagingReviewDownloaded from www.ajronline.org by 36.70.231.113 on 08/09/15 from IP address 36.70.231.113. Copyright ARRS. For personal use only; all rights reserved AJR:191, September 2008835Pulmonary Tuberculosisexpelled by a carrier, the duration of exposure, and the virulence of the M. tuberculosis. The risk of developing active TB is greatest in pa-tientswithalteredhostcellularimmunity, including extremes of age, malnutrition, can-cer, immunosuppressive therapy, HIV infec-tion, end-stage renal disease, and diabetes.TB infection begins when the mycobacte-ria reach the pulmonary alveoli, where they invadeandreplicatewithinalveolarmacro-phages.Inhaledmycobacteriaarephagocy-tized by alveolar macrophages, which interact with T lymphocytes, resulting in differentia-tionofmacrophagesintoepithelioidhistio-cytes [7]. Epithelioid histiocytes and lympho-cytesaggregateintosmallclusters,resulting ingranulomas.Inthegranuloma,CD4T lymphocytes(effectorTcell)secretecyto-kines,suchasinterferon-,whichactivate macrophagestodestroythebacteriawith which they are infected. CD8 T lymphocytes (cytotoxicTcell)canalsodirectlykillin-fected cells [8]. Importantly, bacteria are not alwayseliminatedfromthegranuloma,but can become dormant, resulting in a latent in-fection. Another feature of human TB granu-lomasisthedevelopmentofnecrosisinthe center of the tubercles.The primary site of infection in the lungs is calledtheGhonfocus[9].Iteitherenlarges asdiseaseprogressesor,muchmorecom-monly,undergoeshealing.Healingmayre-sultinavisiblescarthatmaybedenseand contain foci of calcication. During the early stageofinfection,organismscommonly spread via lymphatic channels to regional hi-lar and mediastinal lymph nodes and via the bloodstream to more distant sites in the body. ThecombinationoftheGhonfocusandaf-fectedlymphnodesisknownastheRanke complex. The initial infection is usually clini-cally silent. In approximately 5% of infected individuals, immunity is inadequate and clin-ically active disease develops within 1 year of infection,aconditionknownasprogressive primary infection [10]. For most infected in-dividuals,however,TBremainsclinically and microbiologically latent for many years.In approximately 5% of the infected popu-lation,endogenousreactivationoflatentin-fectiondevelopsmanyyearsaftertheinitial infection(thishasalsobeencalledpostpri-mary TB) [10]. The reactivation TB tends to involve predominantly the apical and posteri-or segments of the upper lobes and the supe-rior segments of the lower lobes. This location islikelyduetoacombinationofrelatively higher oxygen tension and impaired lymphat-icdrainageintheseregions[11].Asdistinct from primary infection site, in which healing istherule,reactivationTBtendstoprog-ress. The main abnormalities are progressive extension of inammation and necrosis, fre-quently with development of communication withtheairwaysandcavityformation.The endobronchialspreadofnecroticmaterial fromacavitymayresultinTBinfectionin thesameorinotherlobes.Hematogenous dissemination may result in miliary TB.DiagnosisAdenitivediagnosisofTBcanonlybe made by culturing M. tuberculosis organisms fromaspecimentakenfromthepatient. However, TB can be a difcult disease to di-agnose,mainlybecauseofthedifcultyin culturingthisslow-growingorganisminthe laboratory.AcompleteevaluationforTB must include a medical history, a chest radio-graph, a physical examination, and microbio-logic smears and cultures. It may also include a tuberculin skin test and a serologic test.The treatment of latent TB infection to pre-vent progression to active disease has been an essentialcomponentofpublichealthefforts to eliminate TB [12]. Currently, latent infec-tion is diagnosed in a nonimmunized person by a tuberculin skin test (TST), which yields adelayed-hypersensitivity-typeresponseto puried protein derivatives of M. tuberculo-sis.However,theTST,whichhasbeenused for years for the diagnosis of latent TB infec-tion,hasmanylimitations,includingfalse-positivetestresultsinindividualswhowere vaccinatedwithbacilleCalmette-Gurin (BCG)andinindividualswhohaveinfec-tions not related to M. tuberculosis [13, 14].DiscoveryoftheroleofTlymphocytes andinterferon-intheimmuneprocesshas led to the development of an in vitro assay for cell-mediatedimmunereactivitytoM.tu-berculosis[15].Recently,thiswhole-blood interferon-assayhasbeenintroducedfor the diagnosis of latent TB infection and has shown a higher diagnostic accuracy than the TST [13, 16]. These new TB tests are being developedwiththehopeofcheap,fast,and moreaccurateTBtesting.Thesenewtests usepolymerasechainreactiondetectionof bacterial DNA and whole-blood interferon- assay [17]. Individuals with a positive TST or whole-bloodinterferon-assay,especially HIV-infectedpersonsorthosewhohave chest radiographic or CT ndings consistent with TB, should be considered for treatment of a latent infection [18].New Concept of RadiologicManifestations of TuberculosisPatientswhodevelopdiseaseafterinitial exposure are considered to have primary TB, whereaspatientswhodevelopdiseaseasa resultofreactivationofapreviousfocusof TBareconsideredtohavereactivationTB. Traditionally,itwasbelievedthattheclini-cal,pathologic,andradiologicmanifesta-tionsofreactivationTBwerequitedistinct from those of primary TB. This concept has beenrecentlychallengedonthebasisof DNA ngerprinting.DNAngerprintpatternwithrestriction fragment length polymorphism (RFLP) anal-ysis of M. tuberculosis isolates can give clini-ciansaninsightintothetransmissionofTB [19]. Isolates from patients infected with epi-demiologicallyunrelatedstrainsofTBhave different RFLP patterns, whereas those from patients with epidemiologically linked strains generallyhaveidenticalRFLPpatterns. Therefore,clusteredcasesofTB,denedas thoseinwhichtheisolateshaveidenticalor closely related genotypes, have usually been transmittedrecently.Incontrast,casesin which the isolates have distinctive genotypes generallyareareactivationofinfectionac-quired in the distant past [20, 21].ArecentstudybasedongenotypingM. tuberculosis isolates with RFLP showed that the radiographic features are often similar in patients who apparently have a primary dis-easeandthosewhohaveareactivationTB [22, 23]. Therefore, time from acquisition of infection to the development of clinical dis-ease does not reliably predict the radiograph-icappearanceofTB.Theonlyindependent predictor of radiographic appearance may be integrityofthehostimmuneresponse; namely,severelyimmunocompromisedpa-tientsshowatendencytohavetheprimary form of TB, whereas immunocompetent pa-tients tend to have the reactivation form [22, 23].Becausethisresultispreliminaryand mostpublisheddataarebasedonthetradi-tionalconceptofprimaryandreactivation disease,wefollowthetraditionaloutlinein this article.Radiologic Manifestations inImmunocompetent HostsPrimary TuberculosisThe initial parenchymal focus of TB may enlarge and result in an area of airspace con-solidation or, more commonly, undergo heal-ingbytransformationofthegranulomatous tissue into mature brous tissue. Primary TB Downloaded from www.ajronline.org by 36.70.231.113 on 08/09/15 from IP address 36.70.231.113. Copyright ARRS. For personal use only; all rights reserved 836AJR:191, September 2008Jeong and Leeoccurs most commonly in children but is be-ing seen with increasing frequency in adults [24]. The most common abnormality in chil-drenislymphnodeenlargement,whichis seenin9095%ofcases[25,26].The lymphadenopathyisusuallyunilateraland locatedinthehilumortheparatrachealre-gion.OnCT,theenlargednodestypically showcentrallowattenuation,whichrepre-sentscaseousnecrosis,andperipheralrim enhancement, which represents the vascular rimofthegranulomatousinammatorytis-sue [27, 28] (Fig. 1).Airspaceconsolidation,relatedtoparen-chymalgranulomatousinammationand usually unilateral, is evident radiographical-lyinapproximately70%ofchildrenwith primaryTB[26].Itshowsnopredilection for any particular lung zone [26]. On CT, the parenchymal consolidation in primary TB is most commonly dense and homogeneous but may also be patchy, linear, nodular, or mass-like [29] (Fig. 2).Pleuraleffusionisusuallyunilateraland on the same side as the primary focus of TB. Theeffusionmaybelargeandoccurinpa-tients without evidence of parenchymal dis-ease on chest radiographs [30].Reactivation TuberculosisThemostcommonradiographicmanifes-tation of reactivation pulmonary TB is focal orpatchyheterogeneousconsolidationin-volving the apical and posterior segments of the upper lobes and the superior segments of thelowerlobes[29,31].Anothercommon nding is the presence of poorly dened nod-ulesandlinearopacities,whichareseenin approximately 25% of patients [31]. Cavities, theradiologichallmarkofreactivationTB, areevidentradiographicallyin2045%of patients [2931]. In approximately 5% of pa-tientswithreactivationTB,themainmani-festation is a tuberculoma, dened as a sharp-ly marginated round or oval lesion measuring 0.54.0cmindiameter[29,31].Histologi-cally, the central part of the tuberculoma con-sists of caseous material and the periphery, of epithelioid histiocytes and multinucleated gi-antcellsandavariableamountofcollagen. Satellitenodulesaroundthetuberculoma maybepresentinasmanyas80%ofcases [32].Becauseofactiveglucosemetabolism causedbyactivegranulomatousinamma-tion, tuberculomas sometimes have been re-ported to accumulate 18F-FDG and to cause PET scans to be interpreted as false-positive for malignancy [33] (Fig. 3). Unlike 18F-FDG AFig. 1Primary tuberculosis manifesting primarily as lymphadenopathy in 26-year-old woman.A, Posteroanterior chest radiograph shows right hilar mass (arrow). Note smaller nodule (arrowhead) in right upper lung zone.B, Contrast-enhanced transverse CT scan (5.0-mm section thickness) obtained at level of basal trunk using mediastinal window setting shows enlarged right hilar and subcarinal lymph nodes (arrows), central necrotic low attenuation, and peripheral rim enhancement.BAFig. 2Primary tuberculosis presenting with consolidation and lymphadenopathy in 21-year-old woman.A, Posteroanterior chest radiograph shows airspace consolidation in right middle lung zone.B, Contrast-enhanced transverse CT scan (5.0-mm section thickness) obtained at level of right middle lobar bronchus using mediastinal window setting shows airspace consolidation in right middle lobe. Note enlarged right hilar and subcarinal lymph nodes (arrows). Hilar node has necrotic low attenuation.BFig. 3Tuberculous granulomas in 58-year-old man. 18F-FDG PET/CT scan shows increased FDG uptake in noduleswell-dened predominant nodule (arrow) and surrounding smaller satellite nodules (arrowheads)in right upper lobe with maximum standard uptake value of 6.1.Downloaded from www.ajronline.org by 36.70.231.113 on 08/09/15 from IP address 36.70.231.113. Copyright ARRS. For personal use only; all rights reserved AJR:191, September 2008837Pulmonary TuberculosisPETscans, 11C-cholinePETscanscanhelp differentiate between lung cancer and tuber-culoma[34].Thestandarduptakevalueof tuberculoma is low in 11C-choline PET scans.Hilarormediastinallymphadenopathyis uncommon in reactivation TB, being seen in approximately510%ofpatients[30,31]. Pleural effusion, typically unilateral, occurs in 1520% of patients [35].The most common CT ndings of reacti-vation pulmonary TB are centrilobular small nodules, branching linear and nodular opaci-ties(tree-in-budsign),patchyorlobularar-eas of consolidation, and cavitation [24, 36, 37].Thecentrilobularsmallnodulesand tree-in-bud sign reect the presence of endo-bronchial spread and are due to the presence ofcaseousnecrosisandgranulomatousin-ammation lling and surrounding terminal andrespiratorybronchiolesandalveolar ducts[36,38](Fig.4).Thesetree-in-bud signs are considered a reliable marker of the activity of the process [6]. Cavitation is also a sign of an active disease process and usu-ally heals as a linear or brotic lesion.Although it is usually accompanied by pa-renchymalabnormalities,pleuraleffusion maybethesoleimagingmanifestationof TB. In this particular situation, the determi-nationofpleuraluidadenosinedeaminase (ADA) level (elevated in TB pleurisy) can be helpful for the characterization of the pleural uid; the ADA assay has a sensitivity of 92% (95% CI, 9093%) and a specicity of 90% (8991%)fordiagnosingTBpleurisy[39]. Newsubpleurallungnodulesmaydevelop during medication for TB pleural effusion. It shouldnotberegardedastreatmentfailure. Theseparadoxicalsubpleuralnoduleswill eventuallyshowimprovementwithcontin-ued medication [40].Miliary TuberculosisMiliaryTBreferstowidespreaddissemi-nation of TB by hematogenous spread. It oc-curs in 26% of primary TB and also occurs somewhat more frequently in reactivation TB [41]. In the latter situation, miliary TB may be seen in association with typical parenchymal changes or may be the only pulmonary abnor-mality. Each focus of miliary infection results inlocalgranulomasthat,whenwelldevel-oped,consistofaregionofcentralnecrosis surrounded by a relatively well-delimited rim of epithelioid histiocytes and brous tissue.The characteristic radiographic and high-resolution CT ndings consist of innumera-ble, 1- to 3-mm diameter nodules randomly AB CD EFig. 4Reactivation tuberculosis in 55-year-old man.A, Anteroposterior chest radiograph shows cavitary consolidation in right upper lung zone and multiple ill-dened nodules in both lungs.B and C, High-resolution CT scans (1.0-mm section thickness) obtained at levels of aortic arch (B) and proximal ascending aorta (C) show consolidation and acinus-sized nodules containing several cavities in both upper lobes. Note branching nodular and linear opacities (tree-in-bud signs) (arrows) and centri-lobular small nodules (arrowheads, C) in both lungs.D, Photograph of gross specimen obtained at lobectomy from different patient shows multiple foci of nodules and consolidation that are distinctly white, consistent with caseous necrosis. Most have nodular appearance and some appear to be branching (arrows), suggestive of airway-centered nature of lesions.E, Photomicrograph of surgical specimen discloses multiple granulomas, each related to small membra-nous bronchiole (arrows). Some granulomas show central caseous necrosis (arrowhead). (H and E, 40)distributedthroughoutbothlungs[4144] (Fig.5).Thickeningofinterlobularsepta and ne intralobular networks are frequently evident[37].Diffuseorlocalizedground-glass opacity is sometimes seen, which may heraldacuterespiratorydistresssyndrome [4345] (Fig. 6).Airway TuberculosisThemostcommoncauseofinammatory strictureofthebronchusisTB.Tracheobron-chialTBhasbeenreportedin1020%ofall patients with pulmonary TB [24, 46]. The prin-cipal CT ndings of airway TB are circumfer-ential wall thickening and luminal narrowing, withinvolvementofalongsegmentofthe bronchi [46, 47]. In active disease, the airways areirregularlynarrowedintheirluminaand havethickwalls,whereasinbroticdisease, theairwaysaresmoothlynarrowedandhave thin walls [46, 47]. The left main bronchus is involvedmorefrequentlyinbroticdisease, whereasbothmainbronchiareequallyin-volved in active disease [46] (Fig. 7).Radiologic Manifestations inImmunocompromised HostsImpaired host immunity has been regard-edasapredisposingfactorinTB.Known riskfactorsfordevelopmentofactiveTB Downloaded from www.ajronline.org by 36.70.231.113 on 08/09/15 from IP address 36.70.231.113. Copyright ARRS. For personal use only; all rights reserved 838AJR:191, September 2008Jeong and LeeAFig. 5Miliary tuberculosis in 70-year-old man.A, Posteroanterior chest radiograph shows evenly distributed, discrete, uniformly sized, millet-sized nodular opacities in both lungs.B, High-resolution CT image (1.0-mm section thickness) at level of right upper lobar bronchus shows uniform-sized small nodules randomly distributed throughout both lungs. Note subpleural and subssural nodules (arrows).BFig. 6Miliary tuberculosis presenting as acute respiratory distress syndrome in 47-year-old man.A, Posteroanterior chest radiograph shows innumerable millet-sized nodular opacities and ground-glass opacities in both lungs.B, High-resolution CT image (1.0-mm section thickness) obtained at ventricular level shows randomly distributed small nodules and extensive bilateral ground-glass opacity. Note interlobular septal (arrows) and intralobular interstitial thickenings in both lungs.C, Photomicrograph of pathologic specimen obtained with transbronchial lung biopsy discloses granuloma (arrows) in alveolar wall. Diffuse alveolar wall thickening and intraalveolar brin deposition (not shown) suggesting early stage of diffuse alveolar damage were also observed. (H and E, 400)C A BAFig. 7Actively caseating bronchial tuberculosis in 42-year-old woman.A and B, Contrast-enhanced transverse CT scans (5.0-mm section thickness) using mediastinal window setting obtained at levels of thoracic inlet (A) and main bronchi (B) show luminal narrowing of trachea and proximal left main bronchus and irregular wall thickening. Note lymph nodes (arrows, A) in mediastinum.C, Bronchoscopy shows narrowed left main bronchial lumen with its mucosa swollen and covered diffusely with whitish cheeselike substance (arrow).C Bincludeconditionsthatareassociatedwith defectsincell-mediatedimmunity,suchas HIV infection; malnutrition; drug and alco-hol abuse; malignancy; end-stage renal dis-ease;diabetesmellitus;andcorticosteroid orotherimmunosuppressivetherapy[48]. Iniximab and etanercept (used in the treat-ment of Crohns disease and rheumatoid ar-thritis) are human antibodies against tumor necrosisfactor-(TNF-),whichisin-volvedinthehostdefenseagainstTBkillingofM.tuberculosisbymacrophage, granuloma formation, or apoptosis and pre-ventionofdisseminationofinfectionto other sites. Active TB may develop soon after Downloaded from www.ajronline.org by 36.70.231.113 on 08/09/15 from IP address 36.70.231.113. Copyright ARRS. For personal use only; all rights reserved AJR:191, September 2008839Pulmonary Tuberculosisthe initiation of treatment with such drugs. Therefore,beforeprescribingthesedrugs, assessment of TB infection risk factors and a TST or interferon- assay are strongly rec-ommended to determine the patients latent TBinfectionstatusandtheriskofactive disease [49, 50].TB is a major cause of death among peo-plelivingwithHIVinfectionorAIDS.In 2005, the World Health Organization (WHO) estimatedthat12%ofHIVdeathsglobally were due to TB and that there were 630,000 new coinfections with TB and HIV [51]. Im-munerestorationinducedbyhighlyactive anti-retroviraltherapy(HAART)indevel-opedcountrieshasconsiderablyimproved the outcome of HIV-positive patients and re-duced the prevalence of opportunistic infec-tion and TB in these patients. However, HIV-associatedTBstillcontinuestooccurin countries where HAART is widely used [52]. Furthermore,HAARTmayresultinpara-doxicalworseningorTBmanifestationsin patients with immune reconstitution inam-matory syndrome [53, 54] (Fig. 8).TheradiographicmanifestationsofHIV-associatedpulmonaryTBarethoughttobe dependent on the level of immunosuppression atthetimeofovertdisease[5557].OnCT, HIV-seropositive patients with a CD4 T lym-phocyte count < 200/mm3 have a higher prev-alence of mediastinal or hilar lymphadenopa-thy, a lower prevalence of cavitation, and often AFig. 8Paradoxical worsening of tuberculous lymphadenitis associated with immune reconstitution inammatory syndrome in 40-year-old woman with AIDS.A, Contrast-enhanced transverse CT scan (5.0-mm section thickness) using mediastinal window setting obtained at level of aortic arch just before highly active antiretroviral therapy, shows multiple enlarged lymph nodes (arrows) with central necrotic low attenuation in prevascular and right paratracheal areas. Patients HIV RNA viral load and CD4 counts were more than 1 million copies/mL and 35 cells/L, respectively.B, Follow-up CT image obtained 3 months after A shows increased extent of necrotic lymph nodes (arrows). Patients HIV RNA viral load and CD4 counts at this time were 433 copies/mL and 142 cells/L, respectively.BA BC DFig. 9Pulmonary tuberculosis with lymphadenopathy and extrapulmonary involvement in 42-year-old man with AIDS. His CD4 count was 64 cells/L.A, Posteroanterior chest radiograph shows multiple small nodular opacities in both lungs, especially in upper lung zones.B, High-resolution CT scan (1.0-mm section thickness) obtained at level of aortic arch shows randomly distributed small nodules and interlobular septal thickenings in both lungs.C and D, Contrast-enhanced transverse CT scans (5.0-mm section thickness) using mediastinal window setting obtained at levels of mandible (C) and thoracic inlet (D) show enlarged lymph nodes (arrows), central necrotic low attenuation, and peripheral rim enhancement in right neck and left axilla.Downloaded from www.ajronline.org by 36.70.231.113 on 08/09/15 from IP address 36.70.231.113. Copyright ARRS. For personal use only; all rights reserved 840AJR:191, September 2008Jeong and Leeextrapulmonaryinvolvementascompared with HIV-seropositive patients with a CD4 T lymphocyte count equal to or 200/mm3 [58] (Figs. 9 and 10). Miliary or disseminated dis-easehasalsobeenreportedtobeassociated with severe immunosuppression [58] (Fig. 9).Unusual or atypical manifestations of pul-monary TB are common in patients with im-paired host immunity. In cases of active pulmo-naryTB,diabeticandimmunocompromised patients have a higher prevalence of multiple cavities in a tuberculous lesion and of nonseg-mentaldistributionthandopatientswithout underlying disease [48]. The incidence of TB in patients with idiopathic pulmonary brosis (IPF) is more than four times higher than that of the general population. Atypical manifesta-tions such as subpleural nodules or a lobar or segmentalairspaceconsolidationarecom-moninpatientswithIPF,whichmaymimic lung cancer or bacterial pneumonia [59]. Pul-monaryTBinpatientswithsystemiclupus erythematosus(SLE)hasahigherincidence and prevalence because of abnormal function of alveolar macrophages and exposure to cor-ticosteroid and cytotoxic drugs. TB in patients with SLE tends to show radiologic ndings of miliary dissemination, diffuse consolidation, or primary TB [60].Radiologic Manifestations ofMultidrug-Resistant TuberculosisAnti-TB drug resistance is a major public health problem that threatens the success of globalTBcontrol.Themajorconcernsof drug resistance are fear regarding the spread of drug-resistant organisms and the ineffec-tiveness of chemotherapy in patients infected withtheresistantorganisms.Inaddition, MDRTBisafataldiseasebecauseofthe high mortality rate, depending on the under-lyingdiseases,particularlyinHIV-infected patients [61, 62].Imaging ndings of MDR TB do not basi-callydifferfromthoseofdrug-sensitiveTB. However,multiplecavitiesandndingsof chronicity, such as bronchiectasis and calcied granulomas,aremorecommoninpatients with MDR TB [63, 64] (Fig. 11). A strong cor-relation seems to exist between the radiologic features of MDR TB and the mode of acquisi-tion of drug-resistance. Patients with primary drug resistance, who develop MDR TB with-outahistoryofanti-TBchemotherapyora therapyhistoryoflessthan1month,were foundtopresentwithnoncavitaryconsolida-tion, pleural effusion, and a primary tubercu-losis pattern of disease [65]. On the other hand, those who acquired MDR TB with a chemo-therapyhistoryoflongerthan1monthoften showcavitaryconsolidationsandingeneral show a reactivation pattern of the disease.Extensively-drug-resistantTBisdened as TB that has evolved resistance to rifampin andisoniazid,aswellastoanymemberof the quinolone family and at least one of the followingsecond-lineTBtreatments:kana-mycin,capreomycin,oramikacin[66].Ex-tensively-drug-resistantTBisassociated AFig. 10Pulmonary tuberculosis in 51-year-old man with AIDS. His CD4 count was 4 cells/L.A, Posteroanterior chest radiograph shows multifocal masslike airspace consolidation in bilateral upper lung zones.B and C, High-resolution CT scans (1.0-mm section thickness) obtained at levels of left innominate vein (B) and azygos arch (C) show masslike airspace consolidation with air bronchograms, centrilobular small nodules (arrows, C), and ground-glass opacity in both upper lobes.C BAFig. 11Multidrug-resistant tuberculosis in 36-year-old man.A, Posteroanterior chest radiograph shows multiple small nodules, patchy consolidation containing several cavities, and linear opacities in both lungs. Note decreased volume in right lung and apical pleural thickening.B, High-resolution CT scan (1.0-mm section thickness) obtained at level of left basal trunk shows consolidation containing several cavities in right middle lobe and right lower lobe. Note small cavitary nodule and centrilobular nodules in left upper lobe.BDownloaded from www.ajronline.org by 36.70.231.113 on 08/09/15 from IP address 36.70.231.113. Copyright ARRS. For personal use only; all rights reserved AJR:191, September 2008841Pulmonary Tuberculosiswith a much higher mortality rate than MDR TB because of a reduced number of effective treatmentoptions.Theepidemiologyand imagingndingsofextensively-drug-resis-tant TB have not been well studied, but it is believed that the spread of extensively-drug-resistant TB is closely associated with a high prevalence of HIV and poor infection control [67]. There has been no report on radiologic ndings of extensively-drug-resistant pulmo-naryTB;butinourexperience,thedisease manifestsanadvancedpatternofprimary TB (extensive consolidation with or without lymphadenopathy)inAIDSpatientsandan advanced pattern of MDR TB (multiple cavi-tarylesionsinconsolidativeornodularle-sions) in non-AIDS patients.Complications and Sequelaeof TuberculosisA variety of thoracic sequelae and compli-cationsfrompulmonaryTBmayoccurand may involve the lungs, airways, vessels, me-diastinum,pleura,orchestwall[47,6871] (Appendix 1, Figs. 12 and 13).The radiologic manifestations of acute re-spiratory distress syndrome secondary to TB includeextensivebilateralareasofground-glass opacity or consolidation superimposed onndingsofmiliaryorendobronchial spread of TB. Multiple cystic lesions may de-velopinpatientsrecoveringfromacutere-spiratorydistresssyndromeorinpatients with extensive consolidation due to TB [71]. Thecysticlesionsmayresemblepneumato-celes or bullae, which may resolve over sev-eral months or persist [71].Rasmussen aneurysm is a pseudoaneurysm that results from weakening of the pulmonary artery wall by adjacent cavitary TB (Fig. 12). Empyemanecessitatis(Fig.13)resultsfrom leakage of tuberculous empyema through the parietalpleuraanddischargeofitscontents into the subcutaneous tissues of the chest wall or, less commonly, into the pericardium, ver-tebral column, or esophagus [69].CT in TuberculosisChest radiographs play a major role in the screening,diagnosis,andresponsetotreat-mentofpatientswithTB.However,thera-diographs may be normal or show only mild or nonspecic ndings in patients with active disease[30].Commoncausesofamissed diagnosis of TB are failure to recognize hilar and mediastinal lymphadenopathy as a man-ifestation of primary disease in adults, over-lookingofmildparenchymalabnormalities inpatientswithreactivationdisease,and failure to recognize that an upper lobe nod-uleormasssurroundedbysmallnodular opacities or scarring may represent TB [30].CT is more sensitive than chest radiography inthedetectionandcharacterizationofboth subtle localized or disseminated parenchymal disease and mediastinal lymphadenopathy [37, 42, 72, 73]. The radiographic diagnosis of TB isinitiallycorrectinonly49%ofallcas-es34% for the diagnosis of primary TB and 59% for the diagnosis of reactivation TB [30]. WithCT,thediagnosisofpulmonaryTBis correct in 91% of patients and TB is correctly excluded in 76% of patients [74]. CT and high-resolutionCTareparticularlyhelpfulinthe detection of small foci of cavitation in areas of conuentpneumoniaandinareasofdense nodularity and scarring [37]. In one study of 41 patientswithactiveTB[37],high-resolution CT showed cavities in 58%, whereas chest ra-diographs showed cavities in only 22%.InadditiontothediagnosisofTB,high-resolution CT is useful in determining disease activity. A tentative diagnosis of active TB on CT could be based on the pattern of parenchy-mal abnormalities and the presence of cavita-tion or evidence of endobronchial spread, such as the presence of centrilobular nodules or a tree-in-bud pattern. In the series by Lee et al. [74],80%ofpatientswithactivediseaseand 89% of those with inactive disease were cor-rectly differentiated on high-resolution CT.CTisalsohelpfulintheevaluationof pleural complications, including tuberculous effusion,empyema,andbronchopleurals-tula, and may show pleural disease that is not evident on chest radiography [75].In addition to its major role in the diagno-sis of TB, CT plays an important role in the management of TB, especially in complicat-ed or MDR TB. MDR TB often shows mul-tiple cavities, which lead to the expectoration ofalargenumberofbacilliandendobron-chialspreadtopreviouslyunaffectedareas of the lung. Limited drug penetration into the cavities that harbor large numbers of myco-AFig. 12Rasmussen aneurysm in chronic destructive pulmonary tuberculosis in 62-year-old man.A, Contrast-enhanced transverse CT scan (2.5-mm section thickness) obtained at level of main bronchi using mediastinal window setting shows cavitary consolidation with air-crescent sign (low-attenuation lesion and surrounding air) (arrow) in left upper lobe.B, CT scan obtained 15 mm inferior to A shows contrast-enhancing round vascular structure (arrow) in consolidative lesion.C, Left pulmonary angiogram shows contrast material lling aneurysm (arrow).C BDownloaded from www.ajronline.org by 36.70.231.113 on 08/09/15 from IP address 36.70.231.113. Copyright ARRS. For personal use only; all rights reserved 842AJR:191, September 2008Jeong and Leebacteria is believed to contribute to the drug resistance. Therefore, surgery may be an ad-juvanttreatmentforMDRTB,although present-dayTBtreatmentreliesonchemo-therapy [76]. CT can locate the site of cavita-tionandtheextentofactivediseaseand therefore can be a roadmap for the planning of surgical treatment.ConclusionAlthoughtheslowreductionoftheinci-denceofTBhasbeenseenindeveloped countries,TBisstillamajorchallenge amonginfectiousdiseases,eveninthe21st century.FastandaccurateTBtesting,such asbacterialDNAanalysisandwhole-blood interferon-assay,hasbeendevelopedfor detectinglatentinfection.Thetraditional imaging concept of primary and reactivation TB has recently been challenged on the basis ofDNAngerprinting,andradiologicfea-turesdependonthelevelofhostimmunity rather than the elapsed time after the infec-tion.PETscansusing 18F-FDGor 11C-cho-linecansometimeshelpdifferentiateatu-berculous nodule from lung malignancy. CT is an effective diagnostic method when chest radiographs are normal or inconclusive, and it provides valuable information for the diag-nosis and management of TB.References1. 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For personal use only; all rights reserved 844AJR:191, September 2008Jeong and LeeAPPENDIX 1:Complications and Sequelae of Thoracic Tuberculosis Parenchymal complicationsAcute respiratory distress syndromeExtensive lung destruction and cicatrizationMultiple cystic lung lesionsAspergillomaAirway complicationsBronchiectasisBronchiolitis obliteransTracheobronchial stenosisBroncholithiasisVascular complicationsPulmonary and bronchial arteritis and thrombosisBronchial artery pseudoaneurysmPulmonary artery pseudoaneurysm (Rasmussen aneurysm)Mediastinal complicationsEsophagomediastinal stulaEsophagobronchial stulaFibrosing mediastinitisConstrictive pericarditisPleural complicationsPleurisyEmpyemaFibrothoraxPneumothoraxBronchopleural stulaChest wall complicationsOsteomyelitisChondritisSpondylitisEmpyema necessitatis 70. Choi D, Lee KS, Suh GY, et al. Pulmonary tuber-culosis presenting as acute respiratory failure: ra-diologic ndings. J Comput Assist Tomogr 1999; 23:107113 71. Ko KS, Lee KS, Kim Y, Kim SJ, Kwon OJ, Kim JS. Reversible cystic disease associated with pul-monary tuberculosis: radiologic ndings. Radiol-ogy 1997; 204:165169 72. KimWS,MoonWK,KimIO,etal.Pulmonary tuberculosis in children: evaluation with CT. AJR 1997; 168:10051009 73. Pastores SM, Naidich DP, Aranda CP, McGuinnes G, Rom WN. Intrathoracic adenopathy associated with pulmonary tuberculosis in patients with hu-manimmunodeciencyvirusinfection.Chest 1993; 103:14331437 74. LeeKS,HwangJW,ChungMP,KimH,Kwon OJ. Utility of CT in the evaluation of pulmonary tuberculosisinpatientswithoutAIDS.Chest 1996; 110:977984 75. HulnickDH,NaidichDP,McCauleyDI.Pleural tuberculosis evaluated by computed tomography. Radiology 1983; 149:759765 76. TakedaS,MaedaH,HayakawaM,SawabataN, Maekura R. Current surgical intervention for pul-monarytuberculosis.AnnThoracSurg2005; 79:959963F O R Y O U R I N F O R M AT I O NThis article is available for CME credit. 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