Computed tomography, magnetic resonance imaging and PET imaging in tuberculosis

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Computed tomography, magnetic resonance imaging and PET imaging in tuberculosis Adelard I De Backer, Filip M Vanhoenacker, and Paul van den Brande

PULMONARY TUBERCULOSIS INTRODUCTION The presentation of pulmonary TB is still frequently determined by the age of the individual: neonates and children develop primary TB and adults develop postprimary TB with infiltrates in the apicoposterior segments of the lungs and formation of cavities. Because of the changing epidemiology, this strict age-related distinction is fading, resulting in possible atypical and ‘mixed’ radioclinical patterns in adults and immunocompromised patients.1 It is very difficult to draw distinct lines between primary and postprimary radiographic patterns, and there is considerable overlap in the radiological manifestations. The disease and its imaging patterns should be interpreted in light of the interaction between the patient’s immune status and Mycobacterium tuberculosis.2 This chapter will focus on the specific use of computed tomography (CT) in the diagnostic setting of pulmonary TB. It is emphasized that the different radiological patterns may present as isolated, combined or successive in the same patient; therefore, a specific subsection is dedicated to imaging patterns that can be seen in both primary and postprimary pulmonary TB.

PRIMARY PULMONARY TUBERCULOSIS Classically, four entities have been described: 1. gangliopulmonary TB; 2. tuberculous pleuritis; 3. miliary TB; and 4. tracheobronchial TB. Only gangliopulmonary TB will be discussed in this subsection. It is characterized by the presence of mediastinal and/or hilar adenopathy and less conspicuous parenchymal abnormalities (Ghon focus) (Fig. 26.1). Because of its preferential occurrence in children, it has been designated as ‘childhood’-type pulmonary TB; however, in regions with low incidence of TB, it is now a rare entity in children, except for non-indigenous children, and has been increasingly encountered in adults and elderly patients. Right paratracheal and hilar localizations are the most common sites of nodal involvement in primary pulmonary TB, although other combinations have been described. The prevalence of adenopathy decreases with age.3 On contrast-enhanced CT, tuberculous adenopathy, often measuring more than 2 cm, shows a very characteristic, but not

pathognomonic, ‘rim sign’ consisting of a low-density centre surrounded by a peripheral enhancing rim (Fig. 26.2). Associated parenchymal infiltrates are encountered on the same side as nodal enlargement in approximately two-thirds of paediatric cases of primary pulmonary TB.3 Parenchymal opacities are typically located in the periphery of the lung, especially in the subpleural areas. They are usually difficult to see on conventional radiographs, because of their small volume; therefore, CT is often necessary to detect these subtle parenchymal infiltrates.2 Generally, the disease is self-limiting and the only radiological or CT evidence is the so-called Ranke complex: the combination of a parenchymal scar (whether calcified or not) – the Ghon lesion – and calcified hilar and/or paratracheal lymph nodes. Gangliopulmonary TB may be complicated by perforation of a node in a bronchus, retro-obstructive pneumonia, and/or atelectasis (epituberculosis; Fig. 26.3). A retro-obstructive infiltrate in primary TB most commonly appears as an area of homogeneous consolidation. Obstructive atelectasis or overinflation may result from compression by an adjacent enlarged node. Distribution is typically right sided, with obstruction occurring at the level of the right lobar bronchus or bronchus intermedius.2 Retro-obstructive inflammation may resorb and evolve to a fibrotic and/or calcified lesion. Destruction and fibrosis of the lung parenchyma result in formation of traction bronchiectasis within the fibrotic region. Evolution to cavitary disease is rare in children. Primary infection in adults most frequently results in parenchymal consolidation without adenopathy. These infiltrates may excavate and lead to phtysis. Immunodeficient and elderly patients may present with the childhood type (hilar/mediastinal adenopathy and parenchymal abnormalities), frequently combined with formation of cavities (mixed type).

POSTPRIMARY PULMONARY TUBERCULOSIS OR PHTYSIS Postprimary pulmonary TB is one of the many terms (reactivation TB, secondary TB, ‘adulthood’ TB, etc.) applied to the form of TB which develops and progresses under the influence of acquired immunity. It results from the reactivation of dormant residual foci, spread at the time of the primary infection. It is usually, but not always, a disease of adults.4 Phtysis defines a form of respiratory TB characterized by: 1. liquefaction of caseous necrosis; 2. formation of cavities; and 3. progressive fibrosis and lung destruction.

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Fig. 26.1 Primary TB. Contrast-enhanced chest CT shows a well-delineated, solitary nodular lesion (Ghon focus) in the apical segment of the right upper lobe (large arrow) and right hilar lymphadenopathy (small arrow).

Fig. 26.2 Tuberculous adenopathy. Contrast-enhanced CT demonstrates enlarged tuberculous lymph node in the mediastinum characterized by peripheral enhancement and low-density centre (arrow).

Fig. 26.3 Epituberculosis. Contrast-enhanced CT shows hilar adenopathy and associated retro-obstructive consolidation in the lingula.

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Fig. 26.4 Postprimary TB with cavity formation. CT obtained with lung windowing demonstrates irregular defined cavities accompanied by mural bronchial wall thickening and endobronchial spread of tuberculous disease in both lungs.

Typically, lesions are located in the apicoposterior lung segments and to a lesser degree in the apical segments of the lower lobes.5 In the first stage of disease, regions of caseous necrosis liquefy and communicate with the tracheobronchial tree to form cavities. CT may show extensive abnormalities, such as apicoposterior infiltrates, cavities, pleural exudates, fibro-productive lesions causing distortion of lung parenchyma, elevation of fissures and hila, pleural adhesions and formation of traction bronchiectasis. Cavitation in one or multiple sites is evident in 40% of cases of postprimary disease (Fig. 26.4). The cavity walls may range from thin and smooth to thick and nodular. It can be difficult to distinguish thin-walled cavities from bullae, cysts or pneumatoceles. When multiple apical cavities are encountered, the possibility that cystic bronchiectases are present in addition to necrotic cavities must be considered.6 Air-fluid levels in the cavity may occur in 10% of cases and may represent superimposed bacterial or fungal infection of the cavity.2 High-resolution (HR) CT is the imaging technique of choice to reveal early bronchogenic spread.7 Typical findings are 2- to 4mm centrilobular nodules and sharply marginated linear branching opacities, which have been shown to represent caseous necrosis containing bacilli within and around terminal and respiratory bronchioles (‘tree-in-bud’ sign; Fig. 26.5). Cicatrization atelectasis is a common finding after postprimary TB. Up to 40% of patients with postprimary TB have a marked fibrotic response, which manifests as atelectasis of the upper lobe, retraction of hilum, compensatory lower lobe hyperinflation and mediastinal shift towards the fibrotic lung (Fig. 26.6). Apical pleural thickening associated with fibrosis may reveal proliferation of extrapleural fatty tissue and peripheral atelectasis on CT.7 Complete destruction of a whole lung or a major part of a lung is not uncommon in the end stage of TB; such damage results from a combination of parenchymal and airway involvement. Secondary pyogenic or fungal infection may supervene. Once the lung is destroyed, the activity is difficult to assess with imaging.2 Diagnosis of postprimary TB is made bacteriologically. After antituberculous therapy, radiographs show disappearance of infiltrates and fibrosis develops. Fibrosis may be stable or regress. When sputum culture is negative, but CT findings suggest bronchogenic spread, a guided fibroscopy to assess the correct diagnosis of active

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Computed tomography, magnetic resonance imaging and PET imaging in tuberculosis

Fig. 26.5 Endobronchial spread of TB (same patient as in Fig. 26.3). CT obtained with lung windowing shows severe changes of bronchiolar dilatation and impaction. Bronchiolar wall thickening (small arrow) and mucoid impaction of contiguous branching bronchioles produce a tree-in-bud appearance (large arrow).

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Exudative pleuritis Exudative pleuritis is seen most frequently in older children and adolescents as a complication of primary TB. Contrast-enhanced CT and MRI with exudative tuberculous pleuritis typically shows smooth thickening of visceral and parietal pleura (‘split-pleura’ sign; Fig. 26.7).9 Tuberculous pleurisy may become localized, causing a tuberculous empyema. This empyema may break through the parietal pleura to form a subcutaneous abscess, so-called empyema necessitatis.9 In chronic tuberculous empyema, CT shows a focal fluid collection with pleural thickening and calcification with or without extrapleural fat proliferation. Fibrothorax with diffuse pleural thickening, but without pleural effusion on CT, suggests inactivity.2 Empyema may also communicate with the bronchial tree by bronchopleural fistula. Diagnosis of bronchopleural fistula is based on an increasing amount of sputum production, air in the pleural space, a changing air-fluid level and contralateral spread of disease. CT demonstrates directly the communication between the pleural space and bronchial tree or lung parenchyma in patients with bronchopleural fistula.10 Tracheobronchial tuberculosis Tracheobronchial TB occurs in 2–4% of patients with pulmonary TB. Plain radiographs may be normal. On HRCT, acute tracheobronchial TB manifests as irregular or smooth circumferential bronchial narrowing associated with mural thickening.11 Enhancement

Fig. 26.6 Lung destruction in postprimary TB. CT demonstrates a fibrotic, shrunken left lung with compensatory overexpansion of the right lung. Bronchiectasis is noted in the left lung with areas of emphysema and atelectasis. Bilateral symmetrical interstitial nodules, typical of miliary TB, are also present.

TB may be proposed. If staining and/or culture remain negative and the imaging features remain stable, the process may be considered as ‘inactive’ TB.

IMAGING PATTERNS ENCOUNTERED IN BOTH PRIMARY AND/OR POSTPRIMARY PULMONARY TUBERCULOSIS Several imaging patterns are not seen exclusively in either primary or postprimary TB. These patterns are discussed separately.

Miliary tuberculosis Computed tomography may demonstrate miliary disease before it becomes radiographically apparent. At thin-section CT, a mixture of both sharply and poorly defined 1- to 4-mm nodules are seen in a diffuse, random distribution often associated with intra- and interlobular septal thickening (Fig. 26.6).2 The more widespread location of these micronodules, including subpleural location, excludes the diagnosis of lymphangitis carcinomatosa and bronchiolitis.8

Fig. 26.7 Exudative tuberculous pleuritis demonstrated on MRI. Contrast-enhanced T1-weighted image shows a right-sided pleural effusion with enhancement of both visceral and parietal pleura.

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and enlarged adjacent mediastinal nodes are common findings in the active stage of stenosis. After healing of this focal infection of the bronchial wall, cicatricial bronchostenosis may occur. The left main bronchus is most frequently involved in fibrotic disease. In the chronic fibrotic stage, CT findings include concentric narrowing of the lumen, uniform thickening of the wall and involvement of a long bronchial segment.

Tuberculoma Although pulmonary tuberculomas are most often the result of healed primary TB, they are seen in 3–6% of cases of postprimary TB as the main or only abnormality on chest radiographs.2 Lesions range in size from 0.4 to 5 cm in diameter and are solitary or multiple. Small lesions are more conspicuous on CT. The majority of lesions remains stable in size and may calcify. Calcification is found in 20–30% of tuberculomas and is usually nodular or diffuse. In 80% of cases, small round opacities (‘satellite lesions’) are observed in the immediate vicinity of the main lesion. COMPLICATIONS OF PULMONARY TUBERCULOSIS, DOCUMENTED BY CT A residual tuberculous cavity may be colonized by Aspergillus species and present as an ‘aspergilloma’. CT scan shows a spherical nodule or mass separated by a crescent-shaped area of decreased opacity or air from the adjacent cavity wall. On supine and prone positions, it is obvious that the nodule is often mobile. Bronchogenic carcinoma and pulmonary TB often coexist, creating a difficult diagnostic problem. Manifestations of carcinoma may mimic or may be misinterpreted as progression of TB. Tuberculosis may favour the development of bronchogenic carcinoma by local mechanisms (scar cancer), or TB and carcinoma may be coincidentally associated. In addition, carcinoma may lead to reactivation of TB, both by eroding into an encapsulated focus and by affecting the patient’s immunity; therefore, any predominant or growing nodule should be suspicious for coexisting lung cancer in patients with TB. Pulmonary arteries and veins in an area of active TB may demonstrate vasculitis and thrombosis. Bronchial arteries may be enlarged in bronchiectasis associated with TB or

in parenchymal TB itself. In patients with bronchiectasis, nodular and tubular structures therefore are suggestive for hypertrophied bronchial arteries on HRCT scan. Spiral-CT angiography may be a useful technique for confirming these hypertrophied arteries.2 A Rasmussen aneurysm is a pseudoaneurysm of a pulmonary artery caused by erosion from an adjacent tuberculous cavity.12 Broncholithiasis is an uncommon complication, caused by rupture of a calcified pulmonary peribronchial node into an adjacent bronchus. Right-sided lobar or segmental bronchi are most frequently involved.13 CT scan shows a calcified lymph node that is either endobronchial or peribronchial and is associated with findings of bronchial obstruction, such as atelectasis, obstructive pneumonitis, branching opacities in V- or W-shaped configuration (obstructive bronchoceles), focal hyperinflation or bronchiectasis. Tuberculous pericarditis may be caused by extranodal extension of tuberculous adenitis into the pericardium due to the close anatomical relationship between the lymph nodes and the posterior pericardial sac. The pericardium may also be involved in miliary spread of the disease. On CT, adenopathies and a pericardial thickening (with or without effusion) may be seen. Constrictive pericarditis with fibrous or calcified constrictive thickening of the pericardium of more than 3 mm occurs as a delayed complication (Fig. 26.8).14 Pneumothorax secondary to TB occurs in approximately 5% of patients with postprimary TB, usually in severe cavitary disease. Tuberculous fibrosing mediastinitis is an uncommon complication and progresses insidiously without significant clinical symptoms. CT findings include a mediastinal or hilar mass, calcification in the mass, tracheobronchial narrowing, pulmonary vessel encasement and sometimes a superior vena cava syndrome.15

MAGNETIC RESONANCE IMAGING (MRI) The use of MRI for the evaluation of intrathoracic tuberculous lesions is limited because of technical restrictions, as well as the limited availability in countries where TB is endemic. MRI has been used for the demonstration of intrathoracic lymphadenopathy, pericardial thickening (with or without effusion) (Fig. 26.8) and pleural effusions (Fig. 26.7).16

Fig. 26.8 CT and MRI findings in a patient with postprimary tuberculous pericarditis resulting in calcific pericarditis. (A) On CT pericardial thickening with extensive, coarse calcifications are noted. (B) Black blood MR image shows calcifications as areas with low signal intensities. A localized pericardial fluid collection along the wall of the left ventricle is noted.

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EXTRAPULMONARY TUBERCULOSIS INTRODUCTION Although the predominant form of TB is pulmonary disease, infection with M. tuberculosis may be seen in any organ system. Extrapulmonary TB mainly results from haematogenous dissemination or lymphogenous spread from a primary, usually a pulmonary, focus.17 An increasing incidence has been noted both in developing countries and in developed countries since the mid-1980s,18 especially in HIV-infected patients.19 The more widespread use of cross-sectional imaging modalities may also explain why extrapulmonary TB is more commonly diagnosed. The most common sites of extrapulmonary TB consist of lymphatic, genitourinary, bone and joint, and central nervous system involvement followed by peritoneal and other abdominal organ involvement.

ABDOMEN Gastrointestinal tuberculosis Pathologically, the most active inflammation takes place in the submucosal lymphoid tissue of the intestine, resulting in wall thickening due to the formation of epithelioid tubercles, cellular infiltration and lymphatic hyperplasia.20 Within 2–4 weeks, caseous necrosis of the tubercle begins, which eventually leads to ulceration of overlying mucosa. Further extension within the bowel wall and regional lymph nodes occurs by lymphatic spread. Granuloma formation, fibrosis and scarring develop in a later stage.17 Regional lymphadenopathy may adhere to the diseased bowel wall, forming an inflammatory mass.21 The gross appearance of the intestinal tuberculous lesions has led to its traditional categorization into three forms: 1. The more common ulcerative form is characterized by the presence of multiple small ulcers, usually 3–6 mm in diameter, with an irregular margin; they usually present as transverse lesions located parallel to each other. This orientation is related to the arrangement of the submucosal lymphatic structures. 2. In the less common hypertrophic form, extensive inflammatory response and reactive tissue produce a multinodular mucosal pattern resembling a neoplastic process. 3. The ulcero-hypertrophic pattern consists of a combination of both types and may result in a cobble-stone appearance.17 The ileum and ileocaecal region are the most commonly involved sites, followed by the ascending colon, which is commonly affected in direct continuity with ileocaecal involvement.22 This is related to the abundance of lymphoid tissue and relative stasis. Other sites in which the disease occurs are, in descending order of frequency, the ascending colon, jejunum, other parts of colon, rectum, duodenum and stomach.23 Usually one segment of the colon, the ascending, transverse or descending colon, is involved. Pancolitis is rare and is difficult to differentiate from ulcerative colitis.24 On barium enema, spiculation, spasm and rigidity in the early stage, and short or long stenosis in the advanced stage, may be seen.17 On CT and MRI, associated lymphadenopathy and manifestations of tuberculous peritonitis may be demonstrated. CT has become an important imaging modality in demonstrating gross morphological changes of the tuberculous bowel wall as well as extraluminal ancillary features, such as adenopathy and

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mesenteric changes. When inflammation is mild, CT shows only slight and symmetrical wall thickening, slight haziness of the pericaecal fat and an enlarged ileocaecal valve with a few regional lymph nodes. Features may be indistinguishable from Crohn’s disease or ileocaecal lymphoma. With severe and advanced involvement, caecal wall thickening and adjacent lymph nodes form a soft-tissue mass centred at the ileocaecal valve, resulting in asymmetric wall thickening. The tuberculous mass may result in engulfment of the terminal ileum (Fig. 26.9). On CT and MRI, the inflammatory mass may have a heterogeneous appearance on contrast-enhanced images.21 On MRI, the tuberculous lesion may show intermediate signal intensity and increased, slight heterogeneous signal intensities on T1- and T2-weighted images, respectively. Associated regional lymph nodes are usually multiple, ranging between 0.5 and 3.5 cm in size. Gastric TB is exceedingly rare. The antrum is the commonest site of involvement, and findings include benign ulcer in the ulcerative form, mass lesion simulating malignancy in the hypertrophied form and gastric outlet obstruction due to the formation of fibrosis.17 CT and MRI are useful for demonstrating associated regional lymphadenopathy. Duodenal involvement is also extremely rare and occurs in only 2% of patients with gastrointestinal TB.25,26 The third and fourth part of the duodenum is usually involved. Adjacent lymphadenopathy may result in narrowing with duodenal obstruction and is sometimes complicated by fistula formation.17 Cross-sectional imaging is useful for demonstrating thickening of the duodenal wall, associated regional lymphadenopathy and a thickened mesenteric root. Jejunal or ileal involvement, except for the terminal ileum, occurs infrequently and is usually associated with peritonitis.17,26 Imaging characteristics are non-specific and include non-stenotic ulcers, girdle ulcers with strictures, and mucosal fold thickening.17

Peritoneal tuberculosis The incidence of tuberculous peritonitis is low in western countries and immunocompetent patients, although in developing countries it may account for 30% of all non-pulmonary TB and for at least 20% of all cases of ascites.25 It is commonly associated with tuberculous adenopathy and gastrointestinal TB. Tuberculous peritonitis is traditionally divided into three types according to the amount of ascitic fluid:17,27 1. The ‘wet’ type is the most common and is associated with large amounts of ascitic fluid that may be either diffusely distributed or loculated. 2. The ‘fibrotic-fixed’ type is less common and characterized by omental masses, matted loops of bowel and mesentery and occassionally loculated ascites. 3. The ‘dry-plastic’ type is uncommon and consists of caseous nodules, fibrous peritoneal reaction and dense adhesions. There is considerable overlap between the first two types,26 and this classification does not seem accurate enough to reflect all combinations of radiological features demonstrated by imaging modalities; therefore, the radiological features of the peritoneum and its reflections are better discussed separately.26

Ascites A variable amount of ascites is usually seen in tuberculous peritonitis and can be free, localized or loculated. Ultrasound is a sensitive technique for imaging very small quantities of ascites, but its value is limited in the presence of overlying bowel gas. Usually, multiple

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Fig. 26.9 Ileocaecal TB. (A) Contrast-enhanced CT shows concentric caecal wall thickening (large arrow). Some blurring in the pericaecal fat is present. Note the presence of associated regional lymphadenopathy (small arrow). Lymphadenopathy is characterized by heterogeneous and peripheral contrast enhancement. (B) Coronal and (C) axial 18F-fluoro-2-deoxyglucose–positron emission tomography (FDG-PET) image shows a marked FDG uptake in the right lower quadrant. Patient was initially suspected for intestinal malignancy. Positive mycobacterial cultures from biopsy material obtained by colonoscopy proved abnormalities corresponded to intestinal TB.

fine, complete or incomplete and mobile strands of fibrin and debris are seen within the ascites. This results in a lattice-like appearance.25,28 On CT, the fluid typically has high attenuation values (25– 45 HU), higher than that of water, which probably reflect the high

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protein and cellular content of the fluid;17,26 however, the ascitic fluid may be of similar density to that of water in some patients.29 This may be due to a transudative phase of the immune reaction.29 A fat–fluid level is rarely seen in chylous ascitic fluid, resulting from lymphatic obstruction.30

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Computed tomography, magnetic resonance imaging and PET imaging in tuberculosis

CT, unlike ultrasound, is not limited by bowel gas but fails to demonstrate the internal septa. The combination of the two imaging modalities has been advocated for obtaining the correct diagnosis of tuberculous peritonitis.28 On contrast-enhanced MRI ascites may demonstrate delayed enhancement 15–20 minutes after intravenous administration of gadolinium contrast medium.31

Peritoneum Ultrasound may demonstrate diffuse hypoechoic peritoneal thickening of 2–6 mm, or irregular nodular thickening with tiny nodules of less than 5 mm only if a considerable amount of ascites is present.17,26 CT and MRI demonstrate smooth, mild peritoneal thickening and/or pronounced enhancement (Fig. 26.10).17,26,32 Omentum and small bowel mesentery CT is the modality of choice for demonstrating tuberculous omental and small bowel mesentery involvement. Involvement of the omentum in tuberculous peritonitis has a smudged or caked appearance.33 The differential diagnosis of tuberculous peritonitis consists of disseminated peritoneal malignancy, mesothelioma, non-tuberculous peritonitis and occasionally lymphoma.17,26,34 Extension of the inflammation through the peritoneum into the extraperitoneal compartment suggests TB and can be helpful in the differential diagnosis from peritoneal carcinomatosis. In mesothelioma, the ascites is disproportionately minimal in relation to the degree of tumour dissemination. Furthermore, the presence of a smooth peritoneum with minimal thickening and pronounced enhancement supports the diagnosis of tuberculous peritonitis, whereas nodular implants and irregular peritoneal thickening rather suggest peritoneal carcinomatosis. Other features in favour of tuberculous peritonitis include the presence of mesenteric macronodules, relative regularity of infiltrated omentum and lymph nodes with low-density centre or calcification.17,26 Tuberculous lymphadenopathy Tuberculous lymphadenopathy is the most common manifestation of abdominal TB.35 It may occur as an isolated manifestation without other evidence of abdominal involvement; however, associated involvement of the gastrointestinal tract, peritoneum and solid viscera (e.g. liver and spleen) is often seen. Commonly involved lymph node groups are the upper para-aortic region, the lesser omentum, the mesentery and the anterior pararenal space.35 This preferential distribution is explained by lymphatic drainage from main areas of infection: small bowel, ileocaecum, right side of the colon, liver and spleen. The lower

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para-aortic lymph nodes may be involved through systemic haematogenous spread or from direct spread from the reproductive organs.17,26 Tuberculous lymphadenopathy is usually multiple. A wide spectrum of patterns ranging from increased number of normal-sized nodes to massive nodal conglomerates has been described.35,36 Tuberculous lymphadenopathy is usually not responsible for invasion or obstruction of the common bile duct, blood vessels and urinary or gastrointestinal tracts.35,36 The CT findings of abdominal tuberculous lymphadenopathy include circular or ovoid lesions showing peripheral enhancement with low-density centre; heterogeneous or homogeneous enhancement on contrast-enhanced CT has also been described.35 The involved lymph nodes may occasionally show calcification.37 On MRI tuberculous lymphadenopathy is mostly hyperintense on T2-weighted images (Fig. 26.11), although hypointense lymphadenopathy on T2-weighted images has been reported.35,36 Similar to the T2-weighted appearance of an intracranial tuberculoma, the signal intensity may differ, depending on the stage of evolution, with central hyperintensity on T2-weighted images corresponding to liquefaction necrosis, and central hypointensity resulting from the presence of paramagnetic free radicals secreted from active phagocytic cells.38 Obliteration of the perinodal fat, characterized by increased signal intensities on T2-weighted images, has been suggested to reflect capsular disruption.35 On T1-weighted fat-suppressed images, lymphadenopathy is iso- or hypointense and shows a variety of patterns of enhancement, even within the same nodal group, after intravenous administration of gadolinium. This finding reflects the different stages of the pathological process.35 Enhancement patterns include peripheral enhancement visible as a uniform, thin or thick, complete or incomplete rim; and conglomerate group of nodes showing peripheral and central areas of enhancement. Heterogeneous enhancement and, less frequently, homogeneous enhancement or no enhancement may also be seen.35–38 The peripheral enhancing portion has been proposed to correspond to a perinodal highly vascular inflammatory response or granulation tissue within the nodes, whereas the central non-enhancing portion corresponds to caseation or liquefaction necrosis within the nodes.38 This appearance, especially when found in young people, is highly suggestive but not pathognomonic of TB. A similar pattern may also be seen with metastatic malignancy, lymphoma after treatment, inflammatory conditions, such as Crohn’s disease, pyogenic

Fig. 26.10 Tuberculous peritonitis. (A) Contrast-enhanced CT demonstrates ascites with thickening of the peritoneum, omental thickening and lymphadenopathy in the mesentery and retroperitoneum. (B) Contrast-enhanced T1-weighted fat-suppressed MR image at another level shows diffuse infiltration of the mesentery, thickening and enhancing of the peritoneum (black arrow) and rim-enhancing retroperitoneal lymphadenopathy (white arrow).

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Fig. 26.11 Tuberculous lymphadenopathy. (A) T2-weighted MR image shows a 5-cm-large mass in the porta hepatis. The lesion is heterogeneous, and shows central areas of high signal intensity and a peripheral, irregular hypointense rim (arrow). (B) On the gadolinium-enhanced T1-weighted image, lymphadenopathy shows heterogeneous enhancement due to the presence of focal enhancing and non-enhancing intranodal areas (large arrow). A smaller lesion is demonstrated in the lesser omentum showing predominant peripheral contrast enhancement (small arrow).

infection and Whipple’s disease.27 In untreated lymphoma, the enhancement pattern of lymphadenopathy is usually homogeneous; however, after treatment the enlarged lymph nodes may show decreased density and mesenteric stranding.39 The presence of calcification within enlarged lymph nodes is not pathognomonic of TB and may rarely be seen in metastases from teratomatous testicular tumours and non-Hodgkin’s lymphoma after treatment.39 However, nodal calcification in patients from endemic areas in the absence of known primary malignancy suggests a tuberculous aetiology.

Tuberculosis of the solid organs Liver, spleen and gallbladder On imaging, two main types of hepatosplenic TB have been described: the micronodular and the macronodular form.17 The more common micronodular form manifests usually only as moderate hepatosplenomegaly. The individual lesions typically are below the resolving capability of imaging modalities, but may appear on CT as tiny low-density foci throughout the spleen. The macronodular form is rare, and may be seen as solitary or multiple rounded or oval lesions measuring between 1 and 3 cm, rarely exceeding 3 cm in size (Fig. 26.12).40 However, a few giant lesions

Fig. 26.12 Splenic TB. Contrast-enhanced CT demonstrates widespread low-attenuation nodules within the spleen.

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have been reported with a diameter up to 17 cm.41 CT findings of the macronodular form are considered variable and non-specific. Findings vary from a non-calcified low-density lesion to a calcified high-density lesion with or without rim enhancement. On MRI, a solitary tuberculoma may also show non-specific features. A tuberculoma has been described on T1-weighted images as an isointense lesion compared with adjacent splenic tissue and may become visible on T2-weighted images as a hypointense mass with hyperintense areas. On gadolinium-enhanced images, slight peripheral rim enhancement may be seen.40 On MRI, tuberculous focal hepatosplenic lesions may show variable signal intensities and enhancement patterns after intravenous administration of gadolinium (Fig. 26.13). This spectrum of variable imaging findings may represent different phases of disease progression corresponding to different degrees of fibrosis, granuloma formation, caseation and liquefaction necrosis.40 Lesion hypointensity on T2-weighted images, thought to be due to the presence of free radicals produced by macrophages during active phagocytosis, may be associated with increased fibrosis and granulomatous tissue, or may reflect the presence of calcifications.17 The finding of lesion hypointensity on T2-weighted images may be a helpful characteristic for differentiating splenic tuberculoma from other neoplastic or inflammatory lesions.42 Furthermore, a hypointense nodule with a less hypointense rim on T1-weighted images, and a hyperintense central area with a less intense rim on T2-weighted images have also been reported.42 These findings may reflect caseating granuloma with a liquid centre and peripheral reactive fibrosis.43 Finally, a hyperintense mass without rim hypointensity on T2-weighted images may also be noted. The latter finding may reflect extensive central liquefaction necrosis with only minimal peripheral granuloma formation and/or fibrosis. Dynamic contrast-enhanced MRI most often shows a central unenhancing lesion with peripheral enhancement. This finding probably represents central caseation or liquefaction necrosis with peripheral granulation tissue. Recently, a less common pattern consisting of a peripheral enhancing lesion with, on delayed images, complete fill-in has been described. The latter finding probably represents a granuloma with minimal or absent caseation necrosis.44 The differential diagnosis of the miliary form includes metastases, lymphoma, sarcoidosis and fungal infection. The macronodular form mimics metastases, primary malignant tumour or pyogenic abscess.17

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Fig. 26.13 Macronodular hepatic TB. (A) T2-weighted MR image shows a heterogeneous lesion within the left lobe of the liver (arrow). (B) On the gadolinium-enhanced T1-weighted MR image, heterogeneous enhancement due to the presence of non-enhancing intralesional areas is noted (arrow).

Because of the non-specific and wide spectrum of imaging appearances, ultrasound- or CT-guided biopsy with subsequent staining for acid-fast bacilli, culture and histology will be mandatory for obtaining a definitive diagnosis. The value of the histological and microbiological examination depends on a very careful technique, with multiple passes through the periphery and the centre of the lesion; the periphery of the lesions contains caseating granulomas and aspiration of material from the necrotic centre is more likely to yield viable tubercle bacilli.17 Fine needle aspiration biopsy of the spleen has recently been reported to be of diagnostic value with a low complication rate.45 The gallbladder is a very rare site of infection, because the normal mucosa and gallbladder wall are resistant to M. tuberculosis.46 It is usually associated with severe abdominal TB affecting the peritoneum, mesentery and lymph nodes. Extension from adjacent foci is the usual route of infection. Imaging is non-specific and reveals an enlarged, thick-walled gallbladder and/or an internal soft-tissue mass. The differential diagnosis from gallbladder carcinoma or adenomyomatosis must be made.17

Fig. 26.14 Tuberculous involvement of head of pancreas and tuberculous spondylitis. Gadolinium-enhanced T1-weighted MR image with fat suppression shows a sharply delineated heterogeneous mass with multiloculated appearance (arrow).

Pancreas Pancreatic TB is extremely rare and is usually due to miliary spread.47 Focal tuberculous involvement of the pancreas occurs most frequently in the pancreatic head.48 Diffuse pancreatic involvement is exceedingly rare.48 On contrast-enhanced CT and MRI, focal involvement is characterized by a well-defined mass showing irregular margins and peripheral enhancement. Areas of central enhancement may result in a multiloculated appearance (Fig. 26.14). On MRI, the lesion is hypointense and mixed (hypo- and hyperintense) on T1-weighted, fat-suppressed images and T2-weighted images, respectively. The common bile duct and main pancreatic duct are normal. These features are nonspecific and may resemble inflammatory or neoplastic cystic lesions of the pancreas.47 Rarely, diffuse enlargement of the pancreas along with hypodense areas may be seen.49 On MRI, diffuse involvement is characterized by pancreatic enlargement with narrowing of the main pancreatic duct and heterogeneous enhancement. Signal intensity abnormalities include hypointensity and hyperintensity on T1-weighted, fat-suppressed images and T2-weighted images, respectively.47 The latter morphological abnormalities are also non-specific and may be seen with pancreatitis and lymphoma. Diffuse enlargement of the gland with pancreatic duct narrowing may also be seen in patients with autoimmune pancreatitis.17

Genitourinary tuberculosis Renal Renal TB typically occurs secondary to haematogenous spread from the lungs when bacilli lodge in periglomerular capillaries. When host immunity prevails, cortical granulomata form and remain stable for many years. Renal TB usually does not manifest before 10–15 years later when reinfection/reactivation of bacilli results in spread of organisms into the collecting system. The end result is destruction, loss of function and calcification of the entire kidney (autonephrectomy). Spread beyond the kidney to involve perinephric and retroperitoneal tissues may occur and fistulae may form with the gastrointestinal tract or skin.50 CT accurately detects calcifications, and may demonstrate perinephric extension. Coalescence of granulomas to form a tuberculoma may mimic tumour. In advanced disease CT may show cavities communicating with the collecting system, large caseating granulomas, focal or diffuse cortical scarring, non-function and dystrophic amorphous calcifications. In end-stage disease a nonfunctioning small calcified renal remnant may be seen. Collecting system involvement leads to ulceration, wall thickening and fibrosis with stricturing involving the infundibulum, renal pelvis and ureter; various patterns of hydronephrosis, including hydrocalyx, are

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demonstrated, depending on the site of stricture. Bladder involvement is seen in one-third of genitourinary TB. Tuberculous cystitis appears as a shrunken bladder with wall thickening, and occasionally granulomas present as filling defects in the bladder and mimic carcinoma. Bladder wall calcification is rare and should raise the possibility of other diseases such as schistosomiasis in appropriate clinical settings.50

Adrenal tuberculosis Adrenal gland TB is rare. It is usually bilateral, but unilateral disease may occur.17 Imaging is non-specific and reveals enlargement of the adrenal glands with areas of central necrosis. The gland may undergo atrophy and calcification in the end stage of the disease.34 Male genital tuberculosis Tuberculosis of the prostate is characterized by non-specific imaging findings.17 On contrast-enhanced CT, foci of caseous necrosis and inflammation present as non-specific hypoattenuating areas. On contrast-enhanced T1-weighted MR images peripheral enhancement is seen in areas of caseous necrosis, whereas T2weighted images reveal diffuse, radiating, streaky areas of low signal intensity in the periphery of the prostate (‘watermelon skin’ sign).51 Healing results in prostate calcification. Unilateral or bilateral tuberculous epididymal involvement may occur. In the more advanced stages, testicular involvement caused by direct extension of a tuberculous abscess in the epididymis may be seen.52 Tuberculous epididymo-orchitis manifests on ultrasound as focal or diffuse areas of decreased echogenicity.17 If calcification or central necrosis is present, the lesion may have a more heterogeneous echotexture.52

Female genital tuberculosis Female genital TB is an uncommon disease in developed countries but is not infrequently reported in patients from developing countries.32 Female genital TB may be primary, but is usually secondary to haematogenous dissemination during the time of active extragenital disease.53 The initial infection in female genital TB probably begins in the fallopian tubes and subsequently involves, with decreasing frequency, the endometrium, the cervix, the myometrium and the ovaries.32 With tuberculous involvement, the fallopian tubes may become enlarged and distended with multiple constrictions and a beaded appearance. The fimbriae, in contrast to other forms of salpingitis, may be patent. With further disease progression, a more pronounced enlargement of the tubes and occasionally pyosalpinges and even tubo-ovarian abscesses may be seen. Peritubal adhesions are common findings and may, especially in the presence of ascites, attach the adjacent viscera and pelvic walls to the anterior abdominal wall. When uterine involvement occurs, the endometrial cavity may become filled. In some cases dilatation as a consequence of obstruction of the cervix may be seen. In the presence of tuberculous peritonitis, the serosal surfaces of the fallopian tubes may become covered with miliary tubercles. Contrast-enhanced CT and MRI may demonstrate heterogeneous tubo-ovarian masses, dilatation of the fallopian tubes with wall thickening and marked enhancement (Fig. 26.15).32 Extrapelvic spread with involvement of the peritoneum, omentum, mesentery and bowel may be seen.17 Tuberculous tubo-ovarian abscesses may calcify.25 Imaging findings of female genital TB are non-specific and differential diagnosis includes pelvic inflammatory disease, chlamydial

Fig. 26.15 Tuberculous salpingitis. (A) On a left parasagittal gadolinium-enhanced, T1-weighted MR image, a hypointense dilatated tubular structure with peripheral enhancement, representing the left salpinx, is seen (arrow). There is associated infiltration of the mesentery. (B) Axial gadoliniumenhanced, T1-weighted MR image demonstrates fluid within the pouch of Douglas with nodular thickened and enhancing peritoneum, a diffuse mass-like appearance of the mesentery and a dilated left and right tube with peripheral enhancement (arrows). Note rim-enhancing iliac lymph nodes.

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salpingitis, sarcoidosis, fungal infections, tertiary syphilis, lymphogranuloma venerium, brucellosis, lymphoma and primary tumour and metastatic disease of the fallopian tubes.54

TUBERCULOSIS OF THE AORTA AND ITS BRANCHES Tuberculous involvement of blood vessels is a rare phenomenon.55 Of the vascular structures that may be involved, aortic involvement is the rarest.56 Aortic involvement may take the form of stenosing arteritis or an aneurysm. Most tuberculous aneurysms are pseudoaneurysms (87%) and rarely true (9%) or dissecting (4%). They are usually saccular in shape.56 They result from haematogenous dissemination or from direct extension of a contiguous tuberculous focus, usually lymphadenitis. One should consider the possibility of tuberculous aetiology of an aneurysm in cases of known disseminated TB or the presence of an aneurysm with an adjacent focus with suspicion of TB. Unlike atherosclerotic aneurysms, calcification is conspicuously absent in tuberculous aneurysms.56

TUBERCULOSIS OF THE SPINE Tuberculosis of the spine results from haematogenous dissemination of tubercle bacilli from a primary or reactivated focus. Rarely, vertebral TB may result by extension from a paraspinal infection or from lymphatic drainage from an adjacent affected area.57 Once in the vertebra, a granulomatous lesion develops. The inflammatory reaction, with the formation of granulation tissue, may cause bone expansion with gradually trabecular destruction, progressive demineralization, bone destruction and, eventually, cartilage destruction with involvement of the adjacent disc space. The margins of the bony, lytic lesions are distinct and usually there is no bone regeneration or periosteal reaction. Fibrosis, bone sclerosis and a resulting ankylosis occur when the disease has chronically faded out. Paraosseous abscesses (so-called ‘cold abscesses’), erosion and sinus tract formation may develop.58

Radiological features Vertebral TB is most often found in the lower thoracic and upper lumbar regions. Cervical and sacral involvement is uncommon. Two distinct patterns of vertebral osteomyelitis may be seen. The classic finding of spondylodiscitis is characterized by destruction of two or more contiguous vertebrae and opposed end plates, disc infection and commonly a paraspinal mass or collection; the increasingly more common atypical form of spondylitis without disc involvement is the second pattern.59 The infection typically commences at the superior or inferior anterior vertebral body corner adjacent to the discovertebral junction, and spreads by subligamentous extension and penetration of the subchondral plate. With further disease progression, the lateral and anterior cortices of the vertebral body may become destroyed, leading to collapse, kyphosis and vertebral instability. Because the disc is avascular, disc infection is seen late, and results in disc interval narrowing secondary to herniation of the disc into the undermined, collapsed vertebral body. Collapse and wedging of multiple vertebral bodies because of intraosseus cavitation result in the characteristic gibbus deformity. Paravertebral and/or epidural soft-tissue infection with subsequent abscess formation may track for considerable distances beneath the anterior or posterior longitudinal ligament, and may discharge by sinus tracts in unusual locations, such as groin, buttock or chest. Advanced disease may

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demonstrate abscesses tracking along fascial planes. Paraspinal infection may involve the iliopsoas muscle, resulting in psoas abscess and may extend into the groin and thigh. The paravertebral collection in a high cervical infection may be seen as a retropharyngeal collection. Calcification within the abscess is virtually pathognomonic of TB.39 CT is of great importance in demonstrating small, early foci of bone infection and the extension of the bone and soft-tissue involvement. End plate destruction, fragmentation of the vertebrae and paravertebral calcifications are adequately demonstrated. After administration of intravenous iodinated contrast paravertebral and/or epidural abscesses may show thick, nodular wall enhancement and a sinus tract may adequately be delineated.60 However, beam hardening may impair detection of more subtle epidural involvement. CT-guided fine needle aspiration has become widely accepted for both culture and histological diagnosis. Multiplanar capability and superior tissue contrast make MRI the modality of choice in the evaluation and follow-up of spondylodiscitis. A major advantage of MRI, compared with CT, is the higher sensitivity for detection of early inflammatory bone marrow changes and infiltrative end plate changes in the vertebra. MRI is mostly useful in delineating paravertebral, epidural and intraosseous abscesses and in evaluating the extent of cord compression and the presence of intramedullary lesions (Fig. 26.16).60 MRI findings in tuberculous osteomyelitis may be non-specific and consist of low signal intensity on T1-weighted images and heterogeneous increased signal intensity on T2-weighted images. With intraosseous abscess, low signal intensity on T1-weighted images and very high signal intensity on T2-weighted images may be seen located centrally in the vertebral body.57 However, characteristic findings of MRI in vertebral TB include decreased signal intensity on T1-weighted images of both vertebral bodies and disc spaces, but a signal intensity that is increased in the vertebral disc and markedly decreased in the vertebral bodies on T2weighted images.60 With late chronic vertebral TB, signal intensity is variable; T1-weighted images may show decreased or increased signal intensity. Hyperintense signal intensity on T1-weighted images in the setting of chronic infection may be specific to TB and shows normalization with treatment.61 The intravenous administration of gadolinium chelates allows better delineation of epidural abscesses and masses, and cord and nerve root compromise. Peripheral enhancement is seen in abscesses and represents granulomatous infectious tissue while central low signal intensity on T1-weighted contrast-enhanced images represents central necrosis. With tuberculous spondylodiscitis, the disc shows signal characteristics seen with pyogenic discitis in at least 75% of cases: bright signal on T2-weighted images, decreased signal on T1-weighted images and enhancement after contrast administration.57 Disc space preservation, normal signal intensity and lack of enhancement may also been seen.60

Differential diagnosis of vertebral tuberculosis Many infectious processes may have imaging findings similar to those of vertebral spondylodiscitis. These include low-grade pyogenic infections, such as brucellosis, and other bacterial and fungal infections. Granulomatous diseases (sarcoidosis), traumatic and osteoporotic fractures, and primary and metastatic neoplasms may have features comparable to those of vertebral TB. The diagnosis of TB is favoured if a calcified paravertebral mass and absence of sclerosis or new bone formation are noted. Conversely, a reduced height of an intervertebral disc is only rarely seen

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Fig. 26.16 Tuberculous spondylodiscitis of the thoracic spine. (A) Sagittal T2-weighted MR image shows extensive spondylodiscitis of T8–T10 characterized by destruction of vertebral bodies and disc spaces. Large paravertebral and epidural abscesses of high signal intensity are noted. (B) Sagittal gadolinium-enhanced T1-weighted MR image shows peripheral enhancement of paravertebral abscess and marked enhancement of epidural involvement. Epidural involvement results in displacement and compression of spinal cord.

in neoplastic forms, and a rapid loss of height in the disc with destruction, along with extensive sclerosis, the absence of gibbus deformities and the absence of calcified paravertebral masses are in favour of a pyogenic spondylodiscitis. Characteristic features of brucellar spondylitis include gas within the disc, a minimal associated paraspinal mass, absence of kyphosis and a predilection for the lower lumbar spine.34,58

EXTRASPINAL MUSCULOSKELETAL TUBERCULOSIS Musculoskeletal tuberculous lesions mainly result from haematogenous dissemination or lymphogenous spread from a primary or reactivated infected focus. Rarely, mycobacterial disease may be the result of direct inoculation. Injuries may result in reactivation of pre-existing tuberculous foci.62 Tuberculous involvement of the joint space may result from haematogenous dissemination through the subsynovial vessels, or indirectly from epiphyseal (more common in adults) or metaphyseal (more common in children) lesions, which erode into the joint space. A granulomatous lesion develops within the bone at the site of deposition of the mycobacterium. This lesion becomes a caseating focus which expands, causing trabecular destruction. Cortical destruction may then occur with subsequent development of a periosteal reaction and a soft-tissue mass.63

Tuberculous arthritis As in most infectious joint diseases, tuberculous arthritis is usually monoarticular. In approximately 10% of patients multiple joints may be involved.62 Most commonly involved joints are the hip

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and knee, followed by, in order of frequency, the sacroiliac joint, shoulder, elbow and ankle. Radiographic features include joint effusion, cortical irregularity, lytic lesions, joint space narrowing and periosteal new bone formation.63 Peripherally located osseous erosions are characteristic features of TB in ‘tight’ or weight-bearing articulations, such as the hip, knee and ankle. A triad of radiological abnormalities (Phemister triad) consisting of periarticular osteoporosis, peripherally located osseous erosion and gradual diminution of the joint space suggests the diagnosis of TB.62,63 Occasionally, wedge-shaped areas of necrosis (kissing sequestra) may be present on both sides of the affected joint. Bone sclerosis and periostitis occur late in the disease, except for children, in whom a layered periosteal reaction may be seen. The end stage of tuberculous arthritis is characterized by severe joint destruction and eventually sclerosis and fibrous ankylosis when the active infectious stage has slowly extinguished. In contradiction to pyogenic arthritis, the development of bone ankylosis is an uncommon finding. Ultrasonography may demonstrate the presence of joint effusions. It may also be helpful for aspiration of these effusions for microbiological and histopathological examination. CT is useful for evaluating the degree of bone destruction, sequestrum and surrounding soft-tissue extension.62 Although conventional radiography is the appropriate initial imaging test for the evaluation of musculoskeletal TB, plain films may be negative early in the disease. Therefore, in case of a high index of suspicion of tuberculous arthritis, MRI should be considered. On MRI, focal areas of cartilaginous destruction interspersed with areas of relatively normal-appearing chondral elements may be

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Computed tomography, magnetic resonance imaging and PET imaging in tuberculosis

demonstrated. Chondral and subchondral bone erosions may be visible at a stage when the joint space is well preserved. Bone marrow changes may reflect either osteomyelitis or bone marrow oedema. Hypertrophied synovial lining and joint effusion with mixed high and intermediate signal intensity on T2-weighted images rather than pure signal intensity is seen.40 Therefore, it is often difficult to clearly differentiate between the synovial abnormalities and joint effusion on unenhanced images. On contrast-enhanced images, acute synovitis often produces moderate-to-marked enhancement, whereas chronic synovitis may show no enhancement.63 Suh et al.64 reported invariably intermediate signal intensity in synovial abnormalities on T2weighted images corresponding to haemorrhage, inflammatory debris, fibrosis and caseation necrosis. Associated soft-tissue abnormalities, such as para-articular collections, myositis, tenosynovitis, bursitis and sinus tract formation, may be seen. Sinus tracts are characterized by a linear, high signal intensity on T2-weighted images with marginal ‘tram-track enhancement’ on gadoliniumenhanced images.62 Para-articular abscesses mostly show a thin and smooth enhancing wall.62 The differential diagnosis of tuberculous arthritis includes pyogenic and fungal arthritis, subacute or chronic pyogenic arthritis, traumatic arthritis and even pauci-articular rheumatoid arthritis and juvenile idiopathic arthritis.

Extra-axial tuberculous osteomyelitis Tuberculous osteomyelitis is less common than tuberculous arthritis. Previously, tuberculous osteomyelitis was more often multifocal and disseminated.62 However, recent reports indicate that solitary lesions are now more commonly seen.63 Tuberculous osteomyelitis occurs most commonly in bones of the extremities, including the small bones of the hands and feet, although virtually any bone may be affected. The bacillus implants in the medulla of the metaphysis with subsequent formation of a granulomatous lesion. As the infected focus enlarges, caseation and liquefaction necrosis occurs with resorption of bone trabeculae. Further disease progression may result in macroscopic visible bone destruction, transphyseal spread of disease and joint involvement.62 Rarely, lesions involve the diaphysis. Tuberculous infection may erode through the cortex to form a paraosseous mass or collection. Findings of tuberculous osteomyelitis include soft-tissue swelling, minimal periosteal reaction, osteolysis with little or no reactive change, periarticular osteoporosis and erosions. Sclerosis is less frequently seen. Tuberculous sequestration is uncommon and less extensive than with pyogenic osteomyelitis.63 Multifocal tuberculous osteomyelitis is also known as osteitis cystica tuberculosa multiplex. The lesions are found at different stages of development owing to the haematogenous spread by which bacilli are seeded at different times to the flat and long bones. Multiple sites of involvement are usually seen in children; in adults involvement is more often confined to a single bone. The radiographic appearance may be somewhat different in children compared with adults. In children, the lesions usually are lytic and well defined, are without sclerosis and may show a variable size. Lesion growth may cause metaphyseal expansion. In adults, the lesions are smaller, are located in the long axis of bone and may show well-defined sclerotic margins.62,64,65 MRI may demonstrate intraosseous involvement earlier than with other imaging modalities. Marrow changes are demonstrated as areas of low and high signal intensity on T1- and T2-weighted images, respectively, and show enhancement after the intravenous administration of gadolinium chelates. Areas of necrosis appear hyperintense

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on T2-weighted images. Deep soft-tissue fistulae, sinus tracts and abscesses are better delineated on gadolinium-enhanced images (Fig. 26.17).62 The differential diagnosis of a monostotic tuberculous lesion includes pyogenic and fungal osteomyelitis, Brodie’s abscess and rarely neoplasm such as bone cyst, non-ossifying fibroma, enchondroma and even sarcoma. In an epiphyseal-located lesion, a chondroblastoma may be considered. Involvement of the metatarsophalangeal joint of the great toe may be misdiagnosed as gout. The differential diagnosis of multifocal tuberculous osteomyelitis includes eosinophilic granulomas, sarcoidosis, multiple myeloma, cystic angiomatosis, lymphoma and even metastases.

Soft-tissue tuberculosis Tuberculous tenosynovitis and bursitis Primary tuberculous tenosynovitis, a rare condition, most commonly involves the flexor tendon sheaths of the dominant hand.66 It may result from haematogenous spread or from periarticular extension of tuberculous arthritis. Either tendon or synovium, or both, may be infiltrated and thickened. Tubercle formation may result in caseation necrosis and secondary effusion within the tendon sheath. Disease progression may lead to thinning of the tendon and tendon rupture. As in other forms of chronic tenosynovitis, tendon and synovial thickening predominate with relatively little synovial sheath fluid as opposed to acute suppurative tenosynovitis where synovial sheath fluid is the predominant feature. Ultrasound is an ideal first-line investigation of tenosynovitis to confirm the diagnosis and reveal the degree and extent of tendon and tendon sheath involvement. In more advanced cases, MRI may be helpful to delineate the precise extent of soft-tissue involvement and associated osseous or joint involvement. Three forms of tuberculous tenosynovitis are described: the hygromatous, serofibrinous and fungoid stage.67 The hygromatous stage is characterized by the presence of fluid inside the tendon sheath without associated sheath thickening. The serofibrinous stage is characterized by thickening of flexor tendons and synovium with multiple tiny hypointense nodules within the hyperintense synovial fluid on T2-weighted images. These tiny nodules correspond to the rice bodies previously reported in the literature. Finally, a soft-tissue mass involving the tendon and tendon sheath is a characteristic feature in the fungoid stage. Secondary tuberculous involvement of synovial bursa membranes is a well-known condition, but primary bursitis is rarely reported.62,66 The trochanteric bursa, subacromial, subgluteal and radioulnar wrist bursae are most commonly affected. Two patterns of involvement have been reported on MRI: a uniform distended bursa and a bursa containing multiple small abscesses.68 Low signal intensity material on T2-weighted images within the fluid-filled bursa corresponds to caseous necrosis and fibrotic material.69 The wall of the distended bursa may contain calcifications. Long-standing bursitis is usually complicated by local osteopenia due to hyperaemia. Local pressure of the enlarged bursa may result in focal lytic bone destruction (e.g. greater trochanter, humeral head). The differential diagnosis of tuberculous tenosynovitis and bursitis includes pyogenic and fungal infection and post-traumatic lesions. Imaging does not reliably differentiate tuberculous and non-tuberculous bursitis. TUBERCULOSIS OF THE CENTRAL NERVOUS SYSTEM Central nervous system TB is the most hazardous type of systemic TB.43,67 A central nervous system infection with M. tuberculosis may

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Fig. 26.17 Tuberculous osteomyelitis of second metatarsal bone, tenosynovitis and tuberculous abscess. (A, B) Axial and coronal T1-weighted image shows bone marrow oedema, endosteal erosion, periosteal thickening, soft-tissue oedema and tenosynovitis. (C) Coronal T2-weighted image with fat suppression shows bone marrow oedema, cortical destruction and soft-tissue involvement characterized by increased signal intensities. A tuberculous abscess is noted at the dorsal aspect of metatarsal bone (arrow). (D) Contrast-enhanced, T1-weighted image with fat suppression shows marked enhancement of tuberculous changes. Soft-tissue swelling and thickening of the tendon sheath of the second toe and central necrosis in metatarsal bone is noted. Peripheral enhancement of tuberculous abscess is noted (arrow).

present either as a diffuse form (e.g. basal exudative leptomeningitis) or as a localized form (e.g. tuberculoma, abscess or cerebritis). Coexistence of extraneural TB is reported amongst 50% of cases of neuro-TB,70 which may be a clue to the diagnosis of central nervous system TB. Contrast-enhanced MRI is considered to be superior to CT in the detection and assessment of central nervous system TB. Neuroimaging procedures should include both the brain and spine, as concomitant intracranial and intraspinal involvement is common.43

Meningeal tuberculosis Tuberculous leptomeningitis Tuberculous meningitis is the most common presentation of neuro-TB and occurs predominantly in young children and

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adolescents.43 The common triad of neuroradiological findings in tuberculous meningitis is: (1) basal meningeal enhancement, (2) hydrocephalus and (3) infarctions in the supratentorial brain parenchyma and brainstem. Basal meningeal enhancement is the most consistent feature, caused by the ‘leaky’ inflammatory neovessels.67 On non-contrast CT, obliteration of the basal cisterns is observed. After contrast administration, there is typically diffuse enhancement of the basal subarachnoid cisterns and occasionally meningeal enhancement is seen over the cerebral convexities, the Sylvian fissures and the tentorium.67 In the early stages, MRI without the use of a paramagnetic contrast agent may show little or no abnormalities. In a later stage, distension of the affected subarachnoid spaces occurs with associated

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mild shortening of T1 and T2 relaxation times compared with normal cerebrospinal fluid. Gadolinium-enhanced T1-weighted imaging demonstrates abnormal meningeal enhancement and is generally considered to be more sensitive than CT.67 Some authors have reported minimal or absent meningeal enhancement on CT or MR images in patients with acquired immunodeficiency syndrome-related neuro-TB, supposedly due with an impaired immunological response resulting in the absence of basal meningeal exudates;71 however, other reports have not shown major imaging differences compared with immunocompetent patients.72 Extension of the inflammatory response to the ventricular system through the cerebrospinal fluid pathways resulting in ependymitis or choroid plexitis can cause ependymal or choroid plexus enhancement.43 Hydrocephalus is the most frequent complication of tuberculous meningitis and is usually more prominent in children. In addition to the dilatation of lateral ventricles, an increased periventricular signal may be seen on T2-weighted images as a sign of interstitial oedema due to increased intraventricular pressure with transependymal migration of cerebrospinal fluid.43 Cerebral infarction is another common complication of basal meningitis.73 The inflammatory exudate involves the adventitia and progresses to affect the entire vessel wall, leading to panarteritis with secondary thrombosis and occlusion.67 The majority of the infarcts are seen in the basal ganglia and internal capsule related to the encasement of the basal perforating arteries by the extensive basal meningeal exudates that characterize tuberculous meningitis. The large vascular distribution territories of the anterior and middle cerebral arteries are less commonly involved.43 A high proportion of these infarctions are haemorrhagic and this may lead to cavitation. Following infarction, CT shows ill-defined hypodense areas with mass effect and variable peripheral, sometimes diffuse, intravenous contrast enhancement. These lesions progress to circumscribed hypodensities. MRI is more accurate than CT in depicting basal ganglia infarctions. A hyperintense lesion on T2weighted images with mass effect and variable enhancement pattern after intravenous administration of gadolinium of a recent infarct will progress to a cavitated infarct, which is typically hypointense on T1-weighted images and hyperintense on T2weighted images.43 Fluid-attenuated inversion-recovery (FLAIR) imaging may even be more useful for defining the exact extent of the lesion and for differentiating old cerebral infarctions with cystic appearance from the surrounding tuberculous border zone encephalitis. On FLAIR imaging the old infarcts are characterized by a central area of low signal intensity (cavity due to tissue loss), surrounded by a hyperintense rim (presumably reflecting gliotic scar tissue). Conversely, T2-weighted images demonstrate both areas as equally hyperintense. MR angiography has also been reported to be a useful and non-invasive technique for assessment of vascular involvement in tuberculous meningitis.43,73 Involvement of cranial nerves is common with tuberculous meningitis. Cranial nerves II, III, IV, VI and VII are most frequently affected. Cranial nerve impairment can be due to vascular compromise resulting in ischaemia of the nerve or entrapment of the nerve in the basal exudates.67,73 Cranial nerve involvement may also be due to direct mass effect of a tuberculoma within the subarachnoid course of the cranial nerves or by direct involvement of the cranial nerve nuclei in the brain.67 Late-stage fibrotic changes can cause permanent loss of function in these nerves.43 The proximal portion of the nerve at the root entry zone is most vulnerable, and on contrast-enhanced MRI this portion of the nerve may be thickened and enhancing.67

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The brain tissue immediately underlying the tuberculous exudate shows various degrees of oedema, perivascular infiltration and microglial reaction, a process called ‘border zone encephalitis’.43,67 Recognition of border zone encephalitis is difficult, as the bright signal on MR T2-weighted images in these border zones merges with the high signal of the leptomeningeal exudate.43 Meningeal, parenchymal and ependymal tuberculoma formation is common during the course of tuberculous meningitis.43 Potential sequelae of tuberculous meningitis include meningeal or ependymal calcifications, focal areas of atrophy secondary to infarcts and hydrocephaly, encephalomalacia in the areas of cerebral infarction and occasionally syringomyelia or syringobulbia.67

Pachymeningeal tuberculosis Pachymeningeal TB consists of either isolated dural involvement or a predominantly dural-based lesion with secondary pial or parenchymal involvement. Focal and diffuse patterns of tubercular pachymeningitis exist. Most focal lesions of pachymeningeal TB are seen as en plaque, homogeneous, uniformly enhancing, duralbased masses; lesions appear hyperdense on plain CT scans, isointense to brain parenchyma on T1-weighted MR images and isointense to hypointense on T2-weighted MR images. Parenchymal tuberculosis Parenchymal TB is more common in HIV-infected patients and can occur with or without meningitis.74 The most common parenchymal form of central nervous system TB is tuberculous granuloma (tuberculoma). Other presentations of parenchymal diseases are tuberculous abscesses, focal cerebritis and ‘allergic’ tuberculous encephalopathy. Parenchymal tuberculomas Parenchymal tuberculomas may occur at any age. They are commonly found in patients with miliary pulmonary TB who are neurologically asymptomatic.43 Tuberculomas may involve the brain, spinal cord, subarachnoid, and subdural or epidural space, and may be solitary or multiple. The frontal and parietal lobes are the most commonly affected regions.70 Occasionally, tuberculomas have been described in the intrasellar region, brainstem, thalami, basal ganglia, cerebellopontine angle, optic pathways, pineal region and ventricles.43 Most tuberculomas occur at the corticomedullary junction. This supports the hypothesis of haematogenous spread in their pathogenesis, for there is a dramatic narrowing of the arterioles supplying the cortex as they enter the white matter.74 A small number of tuberculomas develop from extension of cerebrospinal fluid infection into the adjacent parenchyma via cortical veins or perivascular Virchow–Robin spaces around small penetrating arteries.74 These lesions originate as a conglomerate of microgranulomata in an area of tuberculous cerebritis that join to form a mature non-caseating tuberculoma. In most cases subsequent solid central caseous necrosis will develop, which may eventually liquefy.67 The radiological presentation depends on whether the granuloma is non-caseating (homogeneous enhancement), caseating with a solid centre (heterogeneous enhancement centrally and ring enhancement of the capsule) or caseating with a liquid centre (rim enhancement).67,74 The degree of surrounding oedema is variable and is thought to be inversely proportional to the maturity of the lesion. The non-caseating granuloma is usually slightly hypodense or isodense to the surrounding brain tissue on CT studies. On contrast-enhanced CT, these solid lesions are characteristically round, oval or lobular, and they enhance homogeneously. On MRI, these lesions are hypointense relative to brain tissue on T1-weighted images and hyperintense on T2-weighted acquisitions. On

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contrast-enhanced MR studies, homogeneous enhancement is seen. In the early stage of these lesions, they are frequently surrounded by a halo of contiguous vasogenic white matter oedema, which can be demonstrated by CT and MRI.67,74 In the solid, caseating granuloma the central portion enhances heterogeneously, whereas the capsule presents a ring-enhancing pattern. This ring enhancement tends to be unbroken and is usually of uniform thickness. This type of lesion appears relatively hypointense or isointense on T1-weighted images and isointense to

hypointense on T2-weighted images. The rim of a caseating tuberculoma is often strikingly hypointense on T2-weighted images and enhances on T1-weighted gadolinium-enhanced MRI. The reason for shortening of the T2 signal in some tuberculomas is not clear but may be the result of the presence of paramagnetic free radicals in the enclosed macrophages.43 In the next stage, central liquefaction of the tuberculoma develops. This granuloma with central liquefaction of caseous material (Fig. 26.18) is seen as a hypodense core surrounded by a dense ring

Fig. 26.18 Cerebral tuberculoma. (A) Axial T2-weighted MR image shows a subcortical lesion within the right lobe, with surrounding vasogenic oedema. (B, C) Axial and coronal gadolinium-enhanced, T1-weighted MR image shows strong enhancement of the lesion. Areas of ring-like enhancement are seen within the lesion with central areas of absence of enhancement, and correspond to caseating granuloma with central liquefaction of caseous material.

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of enhancement on contrast-enhanced CT. The central signal is hypointense on T1-weighted images and hyperintense on T2weighted images. T1-weighted gadolinium demonstrates intense rim enhancement of the lesion. In this stage, lesions may be indistinguishable on MRI from true tuberculous or pyogenic abscess formation.42,74 According to McGuinness,74 the target sign, defined as a central nidus of calcification or central enhancement surrounded by a ring of enhancement, is a pathognomonic finding of central nervous system TB; however, recent studies have suggested that only the target sign with central calcifications is pathognomonic of tuberculoma, whereas the target sign with a central enhancing dot does not necessarily correspond to tuberculoma.75 Such cases may represent reactivation of chronic calcified parenchymal lesions.43 Miliary central nervous system tuberculomas usually are associated with tuberculous meningitis and many of these patients have a primary pulmonary focus of TB.67,74 The contrast-enhanced CT and T1-weighted images after gadolinium administration may show numerous enhancing foci which are hyperintense on T2-weighted images.43,74 The activity of a tuberculoma may be judged by the degree of contrast enhancement on follow-up CT or MRI studies.74 Occasionally, newly developing or enlarging intracranial tuberculomas may be observed despite appropriate anti-TB therapy.43,74 Therefore, patients on anti-TB therapy who develop signs of raised intracranial pressure or new neurological signs should have urgent neuroimaging to exclude the development of new lesions or the enlargement of existing granulomas located in close proximity to strategic points of possible cerebrospinal fluid obstruction.76 Late changes include calcifications and regional atrophy, although many lesions leave no radiological traces following successful medical treatment.74

Tuberculous abscess Tuberculous abscess formation is a rare complication of central nervous system TB.43 A tuberculous abscess develops from parenchymal tuberculous granulomas or the spread of tuberculous foci in the meninges to the brain substance in patients with tuberculous meningitis.74 In contrast to a tuberculoma, which contain few bacilli, a tuberculous abscess is formed by semiliquid pus teeming with tubercle bacilli. Tuberculous abscesses may be indistinguishable from caseating granulomas with a liquid centre. They are usually larger (often > 3 cm in diameter), multiloculated and solitary, with thin walls.43 Spinal tuberculosis Spinal TB may take a variety of forms, including tuberculous radiculomyelitis, myelitic tuberculoma, epidural phlegmon and abscess. MRI should be the primary imaging modality in the screening of patients with suspected intraspinal TB, since MRI better delineates the extent of leptomeningeal disease than CT myelography and allows direct evaluation of intramedullary lesions and associated epidural or osseous pathology of the spine.77,78 Tuberculous radiculomyelitis Tuberculous leptomeningitis in the spinal canal frequently involves the spinal cord and nerve roots. This condition is known as tuberculous radiculomyelitis. It frequently accompanies intracranial disease. The thoracic cord is most commonly affected, followed by the lumbar and the cervical regions.43 Although the contents of the spinal canal may be difficult to see on CT, some CT findings have been reported in tuberculous

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radiculomyelitis, such as gross volume changes of the myelum, pear-shaped cross-section in the lower thoracic region, related extra-axial mass lesions and associated spinal tuberculous osteomyelitis. Administration of intravenous contrast may be of value in enhancing epidural tuberculous granulation tissue or any paravertebral abscess.43 The MRI features of spinal tuberculous meningitis include cerebrospinal fluid loculations, obliteration of the spinal subarachnoid space with loss of outline of the spinal cord in the cervicothoracic spine and thickened, clumped nerve roots in the lumbar region. The spinal cord can be directly or indirectly affected, with diffuse high signal intensity changes on T2-weighted images representing oedema, cord infarction or myelitis. Contrastenhanced MRI reveals a linear or nodular enhancement coating the nerve roots and spinal cord or a thick intradural enhancement completely filling the subarachnoid space. Contrast-enhanced MRI is helpful in differentiating active tuberculous granulomatous disease from chronic fibrotic adhesions and in separating tuberculoma from surrounding oedema, as areas of both fibrotic tissue and oedema fail to enhance.43,67 Syringomyelia is a well-known complication of tuberculous radiculomyelitis. Inflammatory oedema and spinal cord ischaemia appear to be the underlying mechanisms in the early cases, whereas chronic arachnoiditis underlies late-onset cases.43 Indeed, focal scarring in the subarachnoid spaces impedes free circulation of cerebrospinal fluid, thus forcing cerebrospinal fluid into the central canal of the spinal cord via Virchow–Robin spaces. Focal cystic dilatations in the cord eventually coalesce to form a syrinx. On MRI syringomyelia presents as a central cavity that is isointense to cerebrospinal fluid on both pulse sequences and does not enhance.43

Myelitic tuberculomas Myelitic tuberculomas are very rare. They arise from haematogenous dissemination. The MRI findings are similar to the characteristic appearance of intracranial tuberculomas.43 Infrequent cases of intramedullary tuberculous abscesses have been reported.79 Extrinsic tuberculous involvement Extrinsic tuberculous involvement of the spinal cord is usually secondary to epidural abscess formation. They often extend directly from infections of the spinal column (Fig. 26.16).

POSITRON EMISSION TOMOGRAPHY IN PULMONARY AND EXTRAPULMONARY TUBERCULOSIS Metabolic imaging with positron emission tomography (PET) has become an important new technique in the diagnosis and differential diagnosis of malignant lesions. PET is also used in the prognosis, management and follow-up of malignant diseases.80 The most frequently used tracer in PET is 18F-fluoro-2-deoxyglucose (FDG). Its effect is based on a higher rate of glucose metabolism of cancer cells, but also on other pathological non-tumoral conditions, such as infectious diseases, radiation pneumonitis, postoperative surgical conditions and inflammatory diseases. Furthermore, FDG accumulates in various organs with high glucose metabolism, such as brain, muscles, myocardium, thyroid gland, gonadal tissue, gastrointestinal and urogenital tract, and the brown adipose tissue in the neck.80,81 The mechanism by which FDG uptake takes place is due to the promotion of glycolysis by an increased expression of glucose transport proteins and an upregulation of the intracellular

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GENERAL CLINICAL FEATURES AND DIAGNOSIS

hexokinase and phosphofructokinase activity in tumour cells. This results in accumulation of FDG in the neoplastic cells, a process called ‘metabolic trapping’, since structural changes prevent FDG from being catabolized and transported back into the extracellular space once FDG is phosphorylated.82 The distribution of the tracer, using positron-emitting isotopes such as 18fluorine, can be measured in vivo using a PET camera, resulting in whole-body imaging; FDG-PET also provides semiquantitative data in the form of standardized uptake value (SUV) or standardize uptake ratio (SUR). A SUV of 2.5 or more has generally been used as the cut-off value indicative for malignancy. However, FDG uptake is not specific for malignancy; positive findings may also be found in infectious diseases (mycobacterial, fungal, bacterial) and in inflammatory conditions (sarcoidosis). With infectious lesions, the increase of FDG uptake is attributed to an increase in granulocytic and/or macrophage activity (Fig. 26.9).80

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Tuberculosis is one of the examples of granulomatous disease together with sarcoidosis, histoplasmosis, Wegener’s disease and coal miner’s lung. A large number of case reports have been published with positive FDG-PET in pulmonary and extrapulmonary TB.83,84 However, in tuberculous disease, FDG-PET shows a low specificity, and, as a consequence, makes investigation not appropriate for its diagnosis. 11 C-choline is another tracer that can be used for imaging malignancies. An increased activity of choline transporter and choline kinase corresponds to an increased cell membrane synthesis and tumour cell proliferation. Unlike the macrophages in malignancy, the macrophages in the chronic phase of TB do not proliferate and do not need 11C-choline, resulting in low 11 C-choline uptake. Therefore, the combination of a high FDG and low 11C-choline SUV may be useful in directing the diagnosis towards TB.82

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