Chronic Pulmonary Emboli and Radiologic Mimics on CT Pulmonary Angiography

Chronic Pulmonary Emboli and Radiologic Mimics on CT Pulmonary Angiography

CHEST Special Features Chronic Pulmonary Emboli and Radiologic Mimics on CT Pulmonary Angiography A Diagnostic Challenge Shalini Wijesuriya, MBBS; L...

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CHEST

Special Features

Chronic Pulmonary Emboli and Radiologic Mimics on CT Pulmonary Angiography A Diagnostic Challenge Shalini Wijesuriya, MBBS; Ladli Chandratreya, MBBS; and Andrew R. Medford, DM, FCCP

Chronic pulmonary thromboembolism (CPE) is a challenging diagnosis for clinicians. It is an often-forgotten diagnosis and can be difficult to detect and easily misdiagnosed. The radiologic features on CT pulmonary angiography are subtle and can be further compounded by pathologic mimics and unusual findings observed with disease progression. Diagnosis is important because CPE can lead to progressive pulmonary hypertension, morbidity, and mortality. Moreover, chronic thromboembolic pulmonary hypertension is the only category of pulmonary hypertension with an effective curative treatment in the form of pulmonary endarterectomy. Therefore, CPE must be considered and recognized early. The features of chronic pulmonary emboli on CT scans can be categorized into vascular or parenchymal findings. Endoluminal signs include totally or partially occlusive thrombi and webs and bands. Parenchymal features such as mosaic attenuation and pulmonary infarction are also noted, in addition to features of pulmonary artery hypertension. Additional findings have been noted, including cavitation of infarcts, microbial colonization of cavities, and bronchopleural fistulae. As CPE can be diagnosed at different stages of its disease pathway, such findings may not necessarily arouse suspicion toward a causative diagnosis of chronic embolism. To aid diagnosis for clinicians, this article describes the characteristic vascular and parenchymal CT scan features of chronic emboli, as well as important ancillary findings. We also provide an illustrative case series focusing on CT pulmonary angiography specifically as an imaging modality to highlight the progressive nature of CPE and its sequelae, as well as important radiologic mimics to consider in the differential diagnosis. CHEST 2013; 143(5):1460–1471 Abbreviations: CPE 5 chronic pulmonary emboli; CTEPH 5 chronic thromboembolic pulmonary hypertension; CTPA 5 CT pulmonary angiography; IVC 5 inferior vena cava; PAH 5 pulmonary arterial hypertension; PEA 5 pulmonary endarterectomy

embolism represents a significant source Pulmonary of morbidity and mortality (30% in-hospital mor-

tality without treatment1) and is superseded only by stroke and myocardial infarction as the most common cause of acute cardiovascular disease.2 The underlying pathogenesis of chronic pulmonary emboli (CPE) is still unclear and several theories have been proposed.

Manuscript received June 2, 2012; revision accepted November 26, 2012. Affiliations: From the Department of Radiology (Drs Wijesuriya and Chandratreya), North Bristol Lung Centre (Dr Medford), Southmead Hospital, Westbury-on-Trym, Bristol, England. Correspondence to: Andrew R. Medford, DM, FCCP, North Bristol Lung Centre, Southmead Hospital, Westbury-on-Trym, Bristol BS10 5NB, England; e-mail: [email protected] © 2013 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.12-1384

A variety of imaging modalities have been used in the diagnosis of CPE and are discussed briefly, although the main focus of this article is on CT pulmonary angiography (CTPA). Natural History With treatment, most acute emboli undergo complete resolution. In some patients, for reasons that are unclear, the clot fails to resolve completely and may undergo organization and incorporation into the vessel wall. This may be due to underlying abnormalities in fibrinolysis or possibly recurrent embolism. The resulting thrombus is thought to trigger an arteriopathy in vessels distal to the occluded areas. A compensatory diversion of blood toward the patent vascular bed is also thought to occur, with remodeling noted

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within these vessels.3,4 The subsequent increase in pulmonary artery pressures leads to sequelae such as chronic thromboembolic pulmonary hypertension (CTEPH) and right ventricular dysfunction.5,6 Another hypothesis regarding the development of CTEPH is that it is not an embolic phenomenon but rather results from in situ thrombosis caused by alterations in the endothelium. The difficulties in estimating the true prevalence of CPE are largely due to the insidious nature of the presentation, clinically silent acute events, and the absence of long-term follow-up of all acute pulmonary emboli, although studies suggest an incidence of about one case per 1,000 people per year.1 CPE may go undetected for years, and may be diagnosed in patients presenting with severe CTEPH, the symptoms of which are nonspecific and include cough, progressive dyspnea, chest tightness, syncope, and hemoptysis.5,6 The key to the clinician making this diagnosis (as with all other challenging diagnoses) is to consider CPE in the first place and have a high index of suspicion, especially in cases of unexplained dyspnea out of proportion to lung function deficits, or unexplained ambulatory hypoxemia, hyperventilation, or impaired gas transfer. Only 45% of cases of CTEPH have a history of DVT, despite the association with thromboembolism.7 Early recognition of CPE is important because if CTEPH ensues, pulmonary endarterectomy (PEA) is a very effective treatment compared with any others available for CTEPH and other forms of pulmonary hypertension, and has low morbidity and mortality rates in experienced centers.5,6,8 Without PEA, the prognosis with CTEPH is as poor as that for idiopathic pulmonary arterial hypertension (PAH).9 Knowledge of the conventional and less common radiologic features, including mimics, is crucial to clinicians. Furthermore, an understanding of the protean findings that can occur secondary to progression of a chronic clot is vital to avoid misdiagnoses. These include cav-

itation of infarcts, secondary colonization of cavities (especially with Aspergillus), and bronchopleural fistulae. It is important not to attribute these findings to other disease processes.

Alternative Imaging Techniques The pros and cons of the two commonly used modalities, CTPA and perfusion scanning, are given in Table 1. Perfusion scanning is extremely useful when completely normal, as this excludes CPE by virtue of its high negative predictive value. As an initial test, perfusion scanning has a greater sensitivity than CTPA in diagnosing CPE (96% vs 51%10) with a very good, albeit slightly lower, specificity (90-95% vs 99%10). Of course, perfusion scanning has its own problems with false-positive scans, indeterminate findings, and an underestimation of clot burden, especially in large-vessel disease. More importantly, in the presence of effusions, atelectasis, or other common radiographic changes, perfusion scanning becomes indeterminate and unhelpful in this context. In addition, unlike CT scan, perfusion scan fails to detect other findings that are helpful in the diagnosis of CPE. This reason (and the inability to directly image the vessels and heart) probably accounts for the reason CTPA has replaced perfusion scanning for detection of CPE in most institutions. Diagnosis of acute thrombus in the setting of CPE is also superior if the first test is CTPA rather than perfusion scanning. CTPA is often easier to organize and is more accessible in many radiology departments than perfusion scanning. Finally, CTPA can detect other causes of dyspnea if there is no evidence of CPE, such as pericardial effusion, myocardial infarction, mucus plugging, and other underlying lung, pleural, or mediastinal disease. The traditional gold-standard investigation for CPE has been pulmonary angiography. While many centers

Table 1—Pros and Cons of CTPA and Perfusion Scan in Diagnosis of CPE CTPA Pros: Provides information on clot burden More specific for diagnosis of CPE Provides ancillary information on pulmonary vasculature Provides adjunctive information on cardiac chambers Provides additional information on pleural and pulmonary signs of CPE Provides further information on coexistent lung and/or mediastinal pathology Superior first test to diagnose acute thrombus in context of existing CPE Cons: Inferior sensitivity to perfusion scan as initial test Inferior negative predictive value to perfusion scan in CPE Need for IV contrast Radiation dose, issues in pregnancy

Perfusion Scan Pros: Higher initial sensitivity in diagnosis of CPE vs CTPA Superior negative predictive value to CTPA in CPE No need for IV contrast Cons: False-positive or indeterminate scans common when atelectasis, effusions, other radiographic changes are present Cannot estimate clot burden Provides no ancillary information on pulmonary vasculature, cardiac chambers, lung or mediastinal pathology Inferior to CTPA as first to diagnose acute PE in coexisting CPE

CPE 5 chronic pulmonary emboli; CTPA 5 CT pulmonary angiography; PE 5 pulmonary embolus. journal.publications.chestnet.org

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still use this technique, it is not without its problems for workup of patients with CTEPH prior to PEA.11 It is an invasive procedure and high-quality images are difficult to acquire. Interpretation of the images requires expertise, which is less prevalent given the predominance of noninvasive testing (especially CTPA) in recent years. It is also insensitive to detecting smooth thickening of the pulmonary arterial wall and now is largely confined to preoperative evaluation for PEA in CTEPH. Dual-energy CT scan is a newer technique of uncertain benefit in CPE that exploits the photoelectric absorption characteristics of iodine-based contrast media (Table 2).12 It involves simultaneous chest imaging at two different energy levels and results in a color-coded, iodine-surrogate perfusion map of the lung parenchyma at a single time point.13 This map can potentially improve the detection of segmental and subsegmental occlusions sometimes not seen on CTPA, assess the impact of CPE on the lung parenchyma, be used to monitor response to treatment, and provide information on segmental flow redistribution.14 The iodine map can be influenced by technical factors such as contrast flow rates, site of administration, and lung parenchymal disease, and, unlike perfusion scanning, “perfusion defects” on dualenergy CT scans may be missed in areas of lung distal to an occluded vessel because of collateralization. This is because iodine enters the collaterals, unlike 99mTc-macroaggregated albumin.

The role of contrast-enhanced, pulmonary, magnetic resonance angiography in the investigation of CPE is not well established. It is superior to CTPA for detecting poststenotic dilatations. A study reported sensitivity and specificity of 83% and 95%, respectively, at the lobar level and 72% and 94%, respectively, at the segmental level.15 More recent data from the larger, multicenter Prospective Investigation of Pulmonary Embolism Diagnosis III (PIOPED III) study indicated a sensitivity and specificity of 78% and 99%, respectively, for pulmonary embolism for those with technically adequate scans (75%).16 Concurrent magnetic resonance angiography and venography had a sensitivity and specificity of 92% and 96%, respectively, but only 48% had technically adequate scans. Other issues include the longer acquisition times compared with CTPA, making breath holding an issue. It is also unable to detect a thrombus adherent to the vessel wall. Furthermore, pulsation artifact in a non-ECG gated study may make interpretation of adjacent pulmonary vasculature difficult.17 The role of combined CT angiography with CT venography to image leg veins is not established in CTEPH and so it is unclear whether the potential increase in the diagnostic yield justifies the additional time, expense, and radiation dose involved.18 It is not routinely used, therefore, in clinical practice in the United Kingdom. The current modality of choice for the exclusion of DVT is Doppler ultrasound. Evidence from the PIOPED II study demonstrated that

Table 2—Pros and Cons of Less Common Imaging Techniques in CPE DE-CT Scan

CTA-CTV

CE-MRA

Pulmonary Angiography

Pros: Pros: Pros: Pros: Potential increase in diagnostic Allows visualization of local Can be superior to CTPA Gold standard diagnostic yield at one sitting by detection perfusion abnormalities, for detection of poststenotic test for CPE of concurrent pathology in deep allowing functional and dilatations Optimal investigation for leg veins anatomic data generation Cons: planning PEA simultaneously Some support that this is a viable Claustrophobia Can be performed at same Can detect segmental and alternative to existing imaging Unable to detect thrombus time as right-sided heart subsegmental occlusions not techniques in acute pulmonary adherent to vessel wall catheterization in the visible on CTPA emboli (from PIOPED II study19) Longer acquisition time appropriate setting Can provide sagittal imaging, Cons: compared with CTPA: breath Cons: which complements Additional time, expense, and holding becomes problematic Invasive cross-sectional imaging higher radiation dose Prone to pulsation artifact: need Difficult to acquire Cons: Unclear if this really does for ECG gating to resolve this high-quality images Role remains to be established improve yield and outcome Lower sensitivity than perfusion Declining expertise in image fully in CPE in CTEPH because there are scanning for CPE interpretation May not produce “perfusion no current data Difficult to obtain technically Insensitive to detection of defects” due to collaterals adequate scans smooth thickening of distal to occlusion (unlike pulmonary arterial wall perfusion scan) More time consuming Affected by changes in pulmonary vessel flow (contrast flow rate, site of administration, lung disease) CE-MRA 5 contrast-enhanced pulmonary magnetic resonance angiography; CTA-CTV 5 combined CT angiography and CT scan venography; CTEPH 5 chronic thromboembolic pulmonary hypertension; DE-CT 5 dual energy CT; PEA 5 pulmonary endarterectomy; PIOPED 5 Prospective Investigation of Pulmonary Embolism Diagnosis. See Table 1 legend for expansion of other abbreviations. 1462

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CT angiography with CT venography had similar sensitivity and specificity to that of combined CTPA and ultrasound in acute pulmonary embolism and is therefore a viable alternative here. Furthermore, it also showed that CT venography and ultrasound had similar results in the diagnosis of DVT.19,20 The radiation doses in this study to the chest, pelvis, and thighs were 3.8 mSv, 6 mSv, and 3.2 mSv, respectively.

Vascular Signs of CPE on CT Scan Filling Defects in the Arterial Bed CPE can result in complete occlusion of the vessel lumen. The angiographic appearance has been described as a “pouch defect” because the contrast material has a convex margin within the affected vessel.21 Contraction of the thrombus can cause retraction of the vessel wall, thereby reducing its diameter. On CT scans, the features to look for are (1) sudden truncation of occluded vessels, (2) affected vessels appearing smaller than the patent vessels on the opposite side, and (3) an inability to demonstrate contrast flow distal to the obstruction. These features are also noted in acute emboli. Organized clots can adhere to the arterial wall, causing intimal irregularities or focal areas of wall thickening.4 An eccentric, partially occlusive, chronic thrombus can appear as a crescentic, peripheral filling defect (Fig 1) within thickened or smaller vessels. In the axial plane, this defect forms an obtuse angle with the vessel wall. Recanalization of an occluded vessel may also occur (Fig 2). On CT scans, thin, irregular channels of contrast are noted passing through the thrombus. Poststenotic dilatation of affected vessels is also observed.4 Other recognized manifestations of CPE are endoluminal fibrous structures called bands and webs. A band is a linear defect anchored on either side to the intima with a freely mobile midsection.22 Bands are generally small, measuring ⱕ 0.3 cm wide, ⱕ 2 cm long, and aligned in the direction of blood flow. Many branching bands form a web (Fig 3). Webs are commonly bilateral and are unlikely to be observed in the main pulmonary trunk. Calcification of a thrombus is another feature of chronicity not demonstrated in acute clots.4 The vascular features of CPE are summarized in Table 3. Collateral Systemic Supply The bronchial arteries arise from the descending thoracic aorta.23 They do not usually participate in oxygen exchange and only represent ⱕ 2% of cardiac output.24 In CPE, there is a compensatory increase in blood flow through the bronchial arteries to reduce

Figure 1. Intraluminal features of chronic thrombus. Axial, contrast-enhanced CT scan demonstrating a crescentic, peripheral filling defect in the left lower lobe pulmonary artery (arrow), consistent with a chronic pulmonary embolus. The main pulmonary trunk (*) and central pulmonary arteries are dilated, consistent with pulmonary arterial hypertension. There is also asymmetric focal thickening of the wall of the anterolateral aspect of the right main pulmonary artery.

the risk of ischemia. When of normal size, the bronchial arteries are hardly visible on CT scan. In CPE, they may appear enlarged (diameter ⱖ 1.5 mm) and tortuous (Fig 4).25 Collateral flow can also arise from other systemic arteries. The most commonly hypervascularized, nonbronchial vessels are the intercostal, internal mammary, and inferior phrenic arteries.26

Figure 2. Intraluminal features of a chronic thrombus. Axial, contrast-enhanced CT scan demonstrates a large, partially occlusive thrombus in the right main pulmonary artery (arrow). A thin channel of contrast is noted within the thrombus, consistent with recanalization. A further embolus (arrowhead) is noted in the left lower lobe pulmonary artery; this is a small band in part of a web that also reflects chronic thrombus. This latter feature should not be confused with further, acute, superimposed thrombus.

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Figure 3. Intraluminal features of chronic pulmonary emboli: webs. A, Axial, contrast-enhanced CT scan demonstrates branching, linear filling defects (arrow) in the left main pulmonary artery, consistent with a web. B, Axial, contrast-enhanced CT scan demonstrates a web in the right main pulmonary artery extending into the upper and lower lobe arteries (arrow).

Cardiac Findings Dilatation of the chambers on the right side of the heart (due to elevation of pulmonary artery pressures) can occur in the setting of acute or chronic clot burden. On CT scans, the ratio of the diameters of right and left ventricles (greatest short-axis diameter in the axial plane) is . 1:1, with flattening or bowing of the interventricular septum toward the left.27 However, in chronic embolism, hypertrophy of the cardiac muscle occurs, a feature not noted in the acute setting. Right ventricular hypertrophy is suggested when the myocardial thickness is . 6 mm, normal being approximately 4 mm.28 Subsequent dilatation of the tricuspid valve annulus can occur, leading to tricuspid regurgitation.29 On CT scans, there is a reflux of contrast into the inferior vena cava (IVC) and hepatic veins (Fig 5). An important caveat is that reflux into the IVC may be noted in normal patients when the rate of contrast injection exceeds 3 mL/s.30 However, the presence of the contrast in the distal hepatic veins is unlikely to occur in the absence of tricuspid regurgitation or right-sided heart strain.27 Right ventricle function can deteriorate even in the absence of repeat embolic events, believed to be due to the formation of vascular lesions in the nonoccluded pulmonary vascular bed.30 Thrombus formation may occur within the dilated cardiac chambers Table 3—A Summary of the Intraluminal CT-Scan Features of Chronic Thrombus Features Complete occlusion partial occlusion: crescentic, peripheral Sudden truncation of vessels Disparity in vessel size Inability to demonstrate contrast flow distal to the obstruction Recanalization Bands and webs Calcification of thrombus

Figure 4. Systemic collateral formation in chronic pulmonary emboli. Axial, contrast-enhanced CT scan demonstrates dilated and tortuous bronchial artery collaterals (arrow) in a patient with chronic thromboembolic pulmonary hypertension.

and, with time, may calcify.29 Premature atherosclerotic calcification of the vessel walls can also occur.4 In severe PAH, pericardial effusions have also been described. These may manifest as either enlargement of the anterosuperior pericardial recess (. 15 mm), referred to as the “bikini bottom” sign, or diffuse pericardial thickening.31 In primary pulmonary hypertension, pericardial fluid, interventricular septal deviation, and right-sided chamber dilatation demonstrated on ECG have been associated with adverse patient outcomes.32 It is important to note that pericardial effusions are not specific to PAH and have been described in patients with connective tissue disease.33 Pulmonary Arterial Hypertension PAH is diagnosed when the mean pulmonary artery pressure is . 25 mm Hg at rest.34 It can be idiopathic or secondary to a myriad of other causes.35 CTEPH is one of the most important of these secondary causes as it is the most potentially treatable. It occurs in approximately 3.8% of patients in a 2-year period following an acute pulmonary embolus. Risk factors include a large perfusion defect and degree of clot burden, previous pulmonary embolism, young age, and idiopathic pulmonary emboli.6,36 It is rare for patients with organized CPE not to develop pulmonary hypertension, reflecting the fact that increasing clot burden increases likelihood of CTEPH.36 There are several features seen on CT scans that suggest PAH (Table 4). Regardless of the etiology, the central pulmonary arteries dilate. However, unlike idiopathic hypertension, enlargement of the pulmonary arteries secondary to thromboembolic disease may be asymmetric.29 Enlargement of the main pulmonary artery ⱖ 29 mm has a reported sensitivity and

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Table 4—A Summary of the CT-Scan Features of Pulmonary Artery Hypertension Features Dilatation of the central pulmonary arteries Enlargement of the MPA. MPA:AA ratio . 1 Dilatation and hypertrophy of the right-sided heart chambers Deviation of the interventricular septum to the left Tricuspid regurgitation Pericardial effusion Premature atherosclerotic calcification of the vessel walls Intracardiac thrombus, which may be calcified AA 5 ascending aorta; MPA 5 main pulmonary artery.

Figure 5. Features of right-sided heart strain in chronic pulmonary embolism. A, Axial, contrast-enhanced CT scan demonstrating enlargement of the main pulmonary trunk (arrow). The ratio of the diameters of the main pulmonary artery to that ascending aorta is . 1:1. B, Axial, contrast-enhanced CT scan demonstrating dilatation of the right ventricle. The ratio of the diameters of the right ventricle to that of the left ventricle is . 1:1. An incidental cyst in the right lobe of the liver is also noted. C, Axial, contrastenhanced CT scan demonstrating elevation of the pulmonary trunk (arrow) to the level of the aortic arch (“egg and banana” sign). D, Coronal, contrast-enhanced CT scan demonstrating reflux of contrast into a dilated inferior vena cava and hepatic veins (*), in keeping with tricuspid regurgitation. Eccentric chronic clot (arrow) is also noted in the right pulmonary artery.

specificity of 87% and 89%, respectively.37 In addition, a ratio of the diameters of the main pulmonary artery and ascending aorta . 1:1 is strongly suggestive of PAH, particularly in patients aged , 50 years.38 Measurement of the pulmonary artery is recommended in the axial plane at the bifurcation of the main trunk and perpendicular to its long axis. Furthermore, demonstration of the main pulmonary artery at the level of the aortic arch is specific to severe PAH (the “egg and banana” sign).27 Other cardiac features of PAH were described in the previous section. Pleural Signs Pleural effusions are estimated to be present in up to 61% of patients with pulmonary emboli.39 They tend to be small, are commonly unilateral, and generally occupy less than one-third of the involved hemithorax. However, large or bilateral effusions may occur. The fluid is usually an exudate. Loculated effusions have also been described and in some cases have shown improvement with systemic anticoagulant therapy.40 Common Parenchymal Signs Oligemia distal to occluded vessels causes a redistribution of blood away from the affected areas. These

irregularities in perfusion are demonstrated on CT scans as a sharply demarcated, mosaic pattern of attenuation (Fig 6).4 Hypoperfused areas are of low attenuation, with increased attenuation where the vessels have become larger and more prominent. Mosaic attenuation is nonspecific and can be caused by a variety of other pulmonary conditions, including small airways disease and primary disorders of the parenchyma.41 This sign is very important, however, as it can commonly be the first sign of CTEPH in patients referred for cross-sectional imaging for nonspecific cough, when contrast is not administered and therefore the scan is unenhanced. In small airways disease, air trapping usually occurs. This results in a mosaic pattern of normal and hyperlucent lung. In these hyperlucent areas, there is also a decrease in the caliber and number of the pulmonary vessels compared with the normal segments. The underlying pathology is possibly due to a vasoconstriction stimulated by local hypoxia or the compressive effect of air trapping on the vessels.42 In CPE, the decrease in caliber of vessels in abnormal areas is caused by underperfusion. In particular, the differential size of vessels in perfused areas is another key sign in CTEPH, unlike small airways disease. Paired inspiratory and expiratory CT scans can help distinguish between mosaic attenuation due to small airways disease and that caused by CPE. In normal lung, expiration should result in a decrease in lung volumes and increase in attenuation. In small airways disease, regions of the lung demonstrating air trapping will remain “black,” with very little decrease in lung volumes and, therefore, very little increase in attenuation. In CPE, the normal and oligemic portions of the lung will decrease on expiration, due to the absence of air trapping. Pulmonary infarction may also be noted in CPE. Because of the dual blood supply to the lungs (pulmonary and bronchial arteries), this is more likely to occur in patients with underlying comorbidities like congestive heart failure or severe pulmonary disease.43 Pulmonary infarctions characteristically present as peripheral, wedge-shaped areas with the apex

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Figure 6. A parenchymal feature in chronic pulmonary embolism: mosaic attenuation. Axial CT scan (lung windows) demonstrates a mosaic pattern of low and high attenuation within the lung parenchyma, which reflects areas of reduced and increased perfusion, respectively. The vessels in the high attenuation areas are more prominent (black arrows) than the smaller caliber vessels in the low attenuation areas (white arrows).

pointing toward the pulmonary hilum (Fig 7).4 They may also appear nodular. The infarcted tissue may constrict and eventually form a fibrotic scar, in which case they may appear as linear bands. They can be multiple and have a predilection for the lower lobes. A useful hint in the setting of multiple infarcts is that the intervening lung parenchyma is normal. Another helpful sign is that the edges of infarcts are frequently hyperemic with a reduced density in the middle of the infarct. Another feature that has been described is cylindrical bronchial airway dilatation adjacent to occluded pulmonary vessels.44 This was noted at the segmental and subsegmental level and found in approximately 64% of patients with CPE. An absence of a significant smoking or occupational history as well as normal pulmonary function testing can help distinguish between bronchial airway dilatation caused by CPE and that due to obstructive airways disease.44 Rare Parenchymal Findings Aseptic cavitation of large pulmonary infarcts secondary to chronic thrombus (Fig 8) has been occasionally documented in the literature; it is rare and more typically occurs in preexisting areas of infarction.45 Necrosis of infarcted tissue to form a cavity is usually initially aseptic, but secondary bacterial infection or microbial colonization (Fig 9) may occur. Alternatively, infection may be present at the time of cavitation. Cavitation can also be complicated by the formation of a pneumothorax.46

Figure 7. Chronic, extensive clot adherent to left pulmonary artery wall (thin white arrow) with obliteration and thrombus in the left, anterior, segmental upper lobe artery (thicker white arrow) with distal wedge-shaped infarction (black arrow). Smallvolume mediastinal lymphadenopathy is also noted. Note there is no contrast in the thoracic aorta, and the walls are heavily calcified.

Bronchopleural fistula is usually a complication of pulmonary resection or is caused by infection, trauma, malignancy, and radiotherapy.47 Rarely, it can complicate CPE. On chest radiography, the usual finding is a hydropneumothorax, the fistula itself being difficult to visualize. On CT scans, the diagnostic feature is a communication (single or multiple) between the peripheral airways and air within the pleural cavity, a finding that may not necessarily be clearly visible. Parenchymal features in CPE are summarized in Table 5. Radiologic Mimics There are a myriad of disorders that can mimic CPE radiologically, including a variety of types of thromboembolism (acute thromboembolism, tumor emboli, and in situ thrombus), and inflammatory (arteritis), malignant (primary sarcoma of the pulmonary artery), and developmental causes (proximal interruption of the pulmonary artery), as well as idiopathic pulmonary hypertension itself. Acute Thromboembolism Partially obstructing, acute emboli present as central, intraluminal filling defects.4 The appearances have been coined the “polo mint” and “railroad track” signs when viewed in the axial and longitudinal planes,

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Figure 8. Cavitation of a massive pulmonary infarct. A, Axial, contrast-enhanced CT scan demonstrates a large peripheral thrombus in the right pulmonary artery (*). There is a large area of consolidation in the right lower lobe (large area of infarcted lung parenchyma) with adjacent pleural thickening. B, Follow-up, axial, contrast-enhanced CT scan performed 4 months later demonstrates cavitation within the infarcted tissue (arrow). The peripheral thrombus in the right pulmonary artery (*) is again noted. C, Follow-up, axial CT scan (lung windows) demonstrates the transformation into a cavity (arrow).

respectively.2 If occupying an eccentric position, an acute thromboembolus forms an acute angle with the vessel wall, contrary to the obtuse angle noted in CPE. In complete obstruction, an acute thrombus can cause an increase in vessel diameter due to the effect of pulsatile flow on thrombus impaction. Right-sided ventricular dilatation and pulmonary infarction can be observed in both acute and chronic emboli. However, hypertrophy of the right ventricle and bronchial artery dilatation, due to a prolonged clot burden, are unlikely to be seen in the acute setting, and if noted, would favor a diagnosis of CPE. Chronic thrombus has a higher average attenuation value of about 87 Hounsfield units compared with acute clot (approximately 33 Hounsfield units).48 It is suggested that in CPE, organization of clot and higher concentrations of hemoglobin and iron, including the deposition of calcium, are the likely reasons for such differences. Although this is an interesting observation, its further significance is not currently known and requires further study. The differences between acute and chronic emboli are summarized in Table 6.

It is, of course, important to mention that it is entirely possible to encounter concurrent signs of both acute and chronic emboli in patients with recurrent thromboembolic disease. Idiopathic Pulmonary Hypertension A major diagnostic dilemma in patients with PAH is distinguishing between the idiopathic form and that resulting from chronic embolism. Both have the same clinical manifestations. However, the treatment of the former includes the use of prostanoids, phosphodiesterase inhibitors, and endothelin receptor antagonists, while CTEPH may be effectively treated with PEA.49 A higher frequency of dilated bronchial and nonbronchial systemic arteries has been noted in patients with thromboembolic hypertension compared with those with the primary, idiopathic form (73% vs 14%).26 Other discriminators include mosaic lung attenuation and variations in the caliber of the segmental vessels—findings that are uncommon in primary PAH.50

Figure 9. Cavitation of pulmonary infarcts with secondary colonization. A, A chest radiograph of an adult patient presenting with weight loss demonstrates multiple cavities in the lungs, the largest noted in the right middle zone (arrow). B, An axial, contrast-enhanced CT scan of the same patient demonstrates a thrombus in the right pulmonary artery (arrowhead), extending and occluding the right middle lobe artery. In the right middle lobe, there is a small cavitating infarct (arrow). C, Axial CT scan (lung windows) demonstrates a mass within the cavity along with an air crescent, the appearances of which are consistent with a mycetoma. It is acknowledged this is an unusual presentation in terms of location of the infarct. journal.publications.chestnet.org

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Table 5—A Summary of Pleuroparenchymal Findings on CT Scan in CPE Common

Very Rare

Mosaic attenuation: prominent vessels in perfused portions of the lung with differential size of vessels (can be only nonspecific sign in unenhanced CT scan) Pulmonary infarction: hyperemic infarct edges and reduced central oligemia Multiple/single bands of linear atelectasis (especially in lower lobes) Air trapping in hypoperfused areas Cylindrical bronchial dilatation Simple/loculated pleural effusion (small, unilateral)

Cavitation (usually occurs in preexisting infarct) Bronchopleural fistula

See Table 1 for expansion of abbreviations.

Primary Sarcoma of the Pulmonary Artery Sarcomas of the pulmonary artery are extremely uncommon. Their rarity and nonspecific presentation can cause confusion with CPE. Features on CT scan include a lobulated, enhancing mass, usually in the central arteries, which generally occludes and expands the entire lumen (Fig 10).51 Extravascular extension into the surrounding parenchyma or mediastinal structures is diagnostic. Furthermore, sarcomas avidly take up 18F-fluorodeoxyglucose on PET-CT scans.4 They also demonstrate high signal on short TI inversion recovery MRI sequences, including enhancement with IV gadolinium-based contrast—features absent in CPE. Primary sarcomas are usually unilateral and although unilateral chronic emboli have been described in the literature, they are uncommon.52 Tumor Emboli In patients with intraabdominal malignancies, tumor cells can embolize from the IVC to the pulmonary vasculature, causing intraluminal filling defects that mimic CPE. Common culprits include breast, liver, renal, and gastric carcinomas.53 These also can result in the so-called beaded vessel sign, reflecting the fact that medium to small pulmonary arteries have been distended by tumor.54

isolation. Left-sided anomalies are commonly associated with a right-sided aortic arch (Fig 11) or congenital cardiac diseases like tetralogy of Fallot.4,55 There is volume loss in the affected segment with blood supply to the lung parenchyma via systemic collaterals.55 The smooth, sharp narrowing of the pulmonary artery and the absence of intraluminal pathology help differentiate this congenital anomaly from chronic thromboembolic disease.4 Takayasu Arteritis This is an idiopathic, inflammatory arteritis affecting young women of Asian descent. There is concentric, mural thickening of the aorta and its major tributaries, with pulmonary artery involvement in 50% to 80% of cases.56 Systemic vessel involvement, collateral formation in vessels not supplying the lung parenchyma, and the absence of an intraluminal pulmonary thrombus point away from a diagnosis of CPE.4,56 Pulmonary Artery Stump In Situ Thrombosis Thrombi can form in the pulmonary artery stumps of patients who have undergone surgical resection for lung tumors. CT scan demonstrates an isolated thrombus in the stump with no evidence of thromboembolic disease or its ancillary findings elsewhere.2

Proximal Interruption of the Pulmonary Artery This is a vascular developmental anomaly in which the pulmonary artery ends abruptly at the hilum. It is more common on the right side, where it occurs in

Treatment The definitive treatment of thromboembolic hypertension is PEA, entailing removal (stripping) of the

Table 6—A Summary of the Differences Between Acute and CPE on CT Scan Acute Emboli Position is central or eccentric Acute angle with the vessel wall Impaction of thrombus can cause an increase in vessel diameter Lower attenuation Thrombus does not contain calcification Right ventricle may dilate but does not hypertrophy Bronchial artery collaterals are not present

Chronic Emboli Position usually is eccentric Obtuse angle with the vessel wall Affected vessels are usually smaller and appear thick walled Higher attenuation Calcification may be present Right ventricular dilatation and hypertrophy may be noted Bronchial artery collaterals usually noted

See Table 1 for expansion of abbreviations. 1468

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Figure 10. A rare mimic of chronic pulmonary embolus: pulmonary artery sarcoma. A, A chest radiograph in an adult patient demonstrates a large mass in the right middle zone (arrow). There is also some distal consolidation. B, An axial, contrast-enhanced CT scan demonstrates a large, unilateral, lowattenuation mass arising from the main pulmonary trunk. It extends into and expands the right lower lobe pulmonary artery (arrows). The degree of soft tissue expansion would be against a diagnosis of chronic pulmonary emboli. C, Axial short TI inversion recovery MRI demonstrates an abnormally high signal within this mass (arrows), which would not occur in chronic thrombus. The pathologic findings were in keeping with pulmonary artery sarcoma.

diseased intima in patients with proximal thromboembolic disease.57 Careful selection of patients for PEA is critical and requires multidisciplinary meetings with medical and surgical specialists and highquality imaging.58 PEA is not suitable if there is distal or microvascular thromboembolic disease (usually in 20% to 40% of cases), or significant comorbidities, especially COPD or severe left ventricle dysfunction.59 Mean pulmonary vascular resistance typically should be between 800 and 1,000 dyn/s/cm5 and , 1,200 dyn/s/cm5, as higher values are associated with higher mortality.5,60 Suitable patients are anticoagulated to prevent in situ thrombus and recurrent thromboembolism. Evidence is lacking for vasoactive therapies in CTPEH, but they are often used as bridging therapy until planned PEA.59 Postoperatively, patients are placed on lifelong anticoagulation and they may also undergo IVC filter implantation as an additional safety measure. Medical treatment is also available, particularly in those unsuitable for surgery or who develop recurrent hypertension postoperatively.

Figure 11. A rare differential diagnosis of chronic pulmonary embolus: proximal interruption of the pulmonary artery. A, An axial, contrast-enhanced CT scan demonstrates absence of the left pulmonary artery. There is a dilated intercostal artery on the left (arrows) that is contributing to the collateral supply. Of note, it is much larger than the corresponding intercostal artery on the right. Similar appearances were seen at multiple levels. Note also the right-sided aortic arch (*). B, An axial CT scan (lung windows) demonstrates a hypoplastic left lung with cystic changes in the parenchyma (arrow).

Conclusions There are several vascular and parenchymal CT scan features that aid the diagnosis of CPE. Some are less common than others. A high index of suspicion needs to be maintained because the nonspecific clinical presentation and pathologic mimics can create diagnostic dilemmas, potentially delaying definitive treatment. While unusual findings like cavitation of infarcts with or without secondary colonization and bronchopleural fistulae can occur in many other disease pathologies, their presence should also alert the clinician to look for chronic emboli. Acknowledgments Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

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