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Reversed halo sign in acute pulmonary embolism and infarction

Joseph Casullo and Alexandre Semionov Acta Radiol 2013 54: 505 originally published online 30 April 2013 DOI: 10.1177/0284185113475797 The online version of this article can be found at: http://acr.sagepub.com/content/54/5/505

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Original article

Reversed halo sign in acute pulmonary embolism and infarction

Joseph Casullo and Alexandre Semionov
Department of Diagnostic Radiology, Montreal General Hospital, McGill University Health Center, Montreal, Quebec, Canada Correspondence to: Joseph Casullo. Email: joseph.casullo@muhc.mcgill.ca

Abstract
Background: The reversed halo sign, originally described in cryptogenic organizing pneumonia, has been observed in a variety of pulmonary diseases, including pulmonary embolism (PE). Purpose: To describe the computed tomographic (CT) ndings in patients with the reversed halo sign and acute PE at initial presentation and in subsequent scans. Material and Methods: Contrast-enhanced CT examinations of 12 patients with the reversed halo sign and acute PE were analyzed retrospectively. The diagnosis of pulmonary embolism was made by CT angiography in 11 cases and by a routine contrast-enhanced scan of the chest in the other case. Follow-up scans of seven patients and follow-up radiographs of two patients were also examined retrospectively. The average age of the patients was 49 years (range, 21 80 years). Seven (58%) patients were women. Six patients had no signicant medical history, and six patients had deep venous thrombosis initially. Results: The reversed halo sign was observed as a single lesion in 10 patients; in two patients, two lesions were found. The lesions, all pleural-based, occurred more frequently in the lower lobes and were associated with acute thromboemboli in segmental and subsegmental pulmonary arteries of the corresponding segment. Ten (10/14, 71%) lesions displayed an ellipsoid conguration, two (2/14, 14%) had a pyramidal shape, and two involved an almost entire pulmonary segment. The average largest dimension was 3.9 cm (range, 2.1 6.7 cm). All lesions subtended one or more bronchovascular bundles; three (3/14, 21%) showed air-bronchograms, and a thromboembolus was identied in the subtended arteries in nine (9/14, 64%) lesions. In succeeding CT scans (eight lesions) and follow-up radiographs (three lesions), the lesions became smaller, and the majority evolved into pleural-based linear scars by 7 months. Conclusion: The reversed halo sign very likely corresponds to pulmonary infarction in patients with acute PE. Its recognition may have important clinical implications.

Keywords: Pulmonary CT angiography, pulmonary embolism, reversed halo sign, pulmonary infarction
Submitted April 24, 2012; accepted for publication December 4, 2012

The reversed halo sign refers to an area of ground glass opacication surrounded by a complete or almost complete rim of consolidation in computed tomographic (CT) images of the lungs. This unusual pattern of pulmonary opacication was originally described in patients with cryptogenic organizing pneumonia (1, 2), and the term reversed halo was coined by Kim et al. in 2003 (2). Later studies have shown that the sign is also associated with other pulmonary diseases, including pulmonary embolism (3). We have observed the reversed halo sign in 12 patients with acute pulmonary embolism and infer that the sign corresponds to pulmonary infarction based on the constellation of ndings in the initial and subsequent CT examinations. These ndings may be of relevance to the diagnosis of pulmonary infarction and are described in the present paper.

Material and Methods

The reversed halo sign was an incidental observation made in 12 patients with acute PE during routine reporting of chest CTs from June 2008 to September 2011. The CT examinations of the 12 patients were collected and then analyzed retrospectively. The diagnosis of pulmonary embolism was made by CT angiography in 11 cases, and in one patient the diagnosis was made incidentally by a routine contrast-enhanced scan of the chest. Subsequent scans of seven patients and follow-up chest radiographs of two patients were also examined retrospectively. The shortest interval between the initial and later scans was 13 days, and the longest was 2 years and 8 months. Three patients had two or three follow-up scans which were obtained
Acta Radiologica 2013; 54: 505 510. DOI: 10.1177/0284185113475797

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between 13 days and 12 months after the initial scan. The follow-up radiographs in the two patients were obtained at 2 weeks and 3 months, respectively. All studies were performed on 64-detector CT scanners (LightSpeed VCT, LightSpeed Discovery CT750 HD; GE Healthcare, Milwaukee, WI, USA). In 11 patients, a pulmonary embolism protocol was followed; patients received a bolus of 55 mL of non-ionic contrast (Iohexol [Omnipaque 300 mg/mL]; GE Healthcare Canada, Mississauga, ONT, Canada) followed by a 35 mL saline ush through the antecubital veins at a rate of 4.5 mL/s. The scan delay was predetermined by a test bolus (20 mL) using the pulmonary trunk as the region of interest. In the 12th patient, 90 mL of non-ionic contrast were administered intravenously at a rate of 2 mL/s, and the scan delay was 65s. Follow-up studies included pulmonary CT angiograms, contrast-enhanced CT scans of the chest and in a few cases, contrast-enhanced CT scans of the abdomen, in which patients received 85 100 mL of non-ionic contrast intravenously at a rate of 2 mL/s. The scan delay was also predetermined by a test bolus using the liver parenchyma as the region of interest. The pulmonary CT angiograms were obtained with 1.25 mm collimation at 0.9-mm intervals through the thorax; the standard studies were obtained with 5 mm collimation at 4-mm intervals and reconstructed at 1.25 1.25 mm. The scans of the abdomen were obtained with 1.25 1.25 mm collimation at 0.9-mm intervals from the base of the lungs, above the diaphragm, to the pelvis. The patients were between 21 and 80 years of age with a mean of 49 years; seven (58%) were women. Six patients had no signicant medical history. Three patients had underlying malignancy: metastatic adenocarcinoma of unknown primary, invasive urinary bladder transitional cell carcinoma, and metastatic pulmonary carcinoma. One patient, with paranoid schizophrenia and sickle cell anemia, was positive for anti-cardiolipin antibodies and had a history of pulmonary embolism and deep venous thrombosis (DVT). One patient had developed hypovolemic shock following laparoscopic cholecystectomy 30 days before the pulmonary CT angiogram was performed, and another patient had insulin-dependent diabetes. Six patients had evidence of DVT at the time of their initial scans. The presenting symptoms are summarized in Table 1.

Table 1 Clinical features of 12 patients with pulmonary embolism and infarction Mean age: 49 years (range, 21 80 years) Male/Female ratio: 5/7 (n 12) Clinical presentation (n 12) Chest pain Shortness of breath Calf tenderness Tachycardia Syncope Past medical history (n 12) None known Malignancy Sickle cell anemia Shock Insulin-dependent diabetes Distribution of thromboemboli (n 12) Right main pulmonary artery Left main pulmonary artery Right upper lobe arteries Right middle lobe arteries Right lower lobe arteries Left upper lobe arteries Lingular arteries Left lower lobe arteries Bilateral Site of lesion with reversed halo sign (n 14) Right upper lobe Right lower lobe Lingula Left lower lobe 1 7 1 5 (7%) (50%) (7%) (36%) 2 (17%) 1 (8%) 8 (67%) 5 (42%) 10 (83%) 5 (42%) 7 (58%) 11 (92%) 9 (75%) 6 3 1 1 1 (50%) (25%) (8%) (8%) (8%) 6 3 2 1 1 (50%) (25%) (17%) (8%) (8%)

Includes lobar, segmental, and subsegmental pulmonary arteries in a given lobe

Results
The reversed halo sign was observed as a single lesion in 10 patients; in two patients, two lesions were found. The incidence of the sign in all patients diagnosed with pulmonary embolism during the collection period was not determined. All lesions were pleural-based, and the majority (10/14, 71%) displayed a 3-dimensional shape resembling an ellipsoid with its longest diameter parallel to a pleural surface. In cross-sectional images, these opacities appeared oval or round depending on the plane of the image relative to their long (or short) diameters (Figs. 1, 2a, 3). Two (2/14, 14%) lesions had a pyramidal conguration with a broad pleural base and the apex directed towards the hilum. These appeared as triangular or wedge-shaped

areas of central ground-glass density bordered by consolidation in cross-sectional images (Fig. 4). The remaining two lesions involved a signicant portion of the inferior segment of the lingula (Fig. 2c) and almost the complete anterior segment of the left lower lobe, respectively. The average largest dimension of the opacities was 3.9 cm (2.1 6.7 cm) which was always along a pleural or ssural surface. All of the lesions subtended one or more peripheral bronchovascular bundles, and in 21% (3/14), the subtended bronchi could be followed a short distance within the zones of consolidation and ground-glass density forming air-bronchograms. A thromboembolus was identied in the subtended arteries in 64% (9/14) of the lesions (Fig. 4b); in the other cases, the vessels could not be reliably assessed. The lesions were located mainly in the lower lobes, occurring more frequently in the right lower lobe, and were associated with acute thromboemboli in the segmental and subsegmental pulmonary arteries of the corresponding segment in each case (Table 1). Except in one patient, in whom only the left lower lobe was involved, thromboemboli were multiple, being discovered in more proximal arteries and in the opposite lung. All of the lesions were associated with subtotal pulmonary embolism (i.e. obstruction of the segmental and subsegmental arteries as opposed to the lobar or main pulmonary arteries).

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Fig. 1 A 51-year-old woman with metastatic adenocarcinoma of unknown primary, deep venous thrombosis and incidental bilateral pulmonary embolism. (a, b) Transverse (a) and coronal (b) images demonstrate a 5.2-cm ellipsoid-shaped area of ground-glass density surrounded by a rim of consolidation (arrowheads) in the anterior segment of the right lower lobe which abuts the costal, ssural (white arrows), and diaphragmatic pleural surfaces. A second lesion is present in the adjacent lateral segment (black arrow in (a)). Note multiple subtended bronchovascular bundles at the medial margin of the lesions. (c) Transverse image of the right lower lung from an abdominal scan obtained at 19 days shows a slight decrease in the right lower lobe lesions and almost complete replacement by soft tissue density. There is retraction and enhancement of thickened visceral pleura (straight arrow) which adjoins a tiny loculated pleural effusion (curved arrow). (d) Coronal image of the right lung from a routine scan of the thorax obtained at 12 months shows a small residual pleural-based opacity (arrowhead) in the anterior segment of the right lower lobe corresponding to the previous lesion described in (a) and (b). Note the associated retraction of the adjacent lung and major ssure (single arrow). (The double arrows indicate the minor ssure)

The succeeding scans of seven patients (eight lesions) and the follow-up radiographs of two others (three lesions) showed a decrease in all 11 lesions. Five of the eight lesions followed by CT had evolved into pleural-based linear scars between 2 and 7 months (Fig. 2e). A follow-up scan of one patient at 2 years and 8 months also showed the formation of a linear scar (Fig. 2b), and in another patient, a small focal area of scarring was present at 12 months (Fig. 1d). In the remaining case, the lesion had developed into a smaller wedge-shaped opacity at 4 months with no further follow-up.

Discussion
Kim et al. (2) observed the reversed halo sign in six of 31 patients with cryptogenic organizing pneumonia and concluded that the sign appeared to be relatively specic for cryptogenic organizing pneumonia as they did not nd a similar pattern in any of their control cases. Previous radiologic-pathologic correlation (1) revealed that the central areas of ground-glass density corresponded to alveolar septal inammation and cellular debris in the alveoli with little granulation tissue, while the peripheral areas of

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Fig. 2 (a, b) A 47-year-old woman with insulin-dependent diabetes, acute shortness of breath, and bilateral pulmonary embolism. The pulmonary CT angiogram in the sagittal plane (a) demonstrates a 2.9-cm encapsulated area of ground-glass density (arrowhead) in the posterior costophrenic angle of the left lower lobe which subtends a bronchovascular bundle (curved arrow). Note the surrounding ground-glass opacication compatible with hemorrhage. Transverse image (b) of the left lower lobe from a CT angiogram performed at 2 years and 8 months shows the resulting linear scar (arrowhead). (c, d, e) A 67-year-old man with metastatic bronchogenic carcinoma, acute left pleuritic chest pain, and unilateral pulmonary embolism. Transverse image (c) of the left lung from a CT angiogram demonstrates ground-glass opacication (arrowhead) of a large portion of the inferior lingula which is encased by a thin layer of consolidation and bordered by the chest wall, the major ssure (arrow), and the epipericardial fat ( ). Transverse image (d) of the left lung from a routine scan of the thorax at 15 days shows a signicant reduction in the lingular opacication (arrowhead). At 7 months, the linear scarring (arrowheads) and the pleural and ssural thickening (curved arrow) that ensued are shown in a transverse image (e) from a routine scan of the thorax

consolidation corresponded to organizing pneumonia in the alveolar ducts and adjacent alveoli. The reversed halo sign was later described in 15 patients with paracoccidioidomycosis (4). Surgical biopsy specimens of the lungs from three infected patients showed no evidence of organizing pneumonia; the central area of the lesions was found to contain an inammatory inltrate within the alveolar septa, and the periphery consisted of a dense cellular inltrate within the alveoli. The reversed halo sign has since been observed in other pulmonary infections (e.g. invasive aspergillosis, histoplasmosis, cryptococcosis, pneumocystis jiroveci pneumonia, and tuberculosis), Wegener granulomatosis, sarcoidosis, bronchioloalveolar carcinoma, and pulmonary embolism. In a recent report, seven of 79 patients with the sign were found to have pulmonary embolism; the majority had either organizing pneumonia (18/79) or paracoccidioidomycosis (14/79) (3). In the present study, the sign was recognized in 12 patients with acute pulmonary embolism and likely

corresponded to an area of infarction. The shape of the lesions was typically ellipsoid (10/14 or 71%) rather than tetrahedral (2/14 or 14%). From pathological observations, infarcts can assume any shape, often being irregular or geographic (5 7). In their 1940 paper on pulmonary infarction, Hampton and Castleman correlated postmortem ndings and the changes in antemortem and postmortem radiographs and noted that none of the infarcts were pyramidal in shape or truly triangular (5). In a more recent pathological study of 23 surgical specimens of pulmonary infarcts, only six (26%) were triangular or wedge-shaped (7). Furthermore, a radiologic-pathologic correlative study of postmortem lung specimens utilizing CT found that peripheral wedge-shaped opacities were not specic for infarction (8). Hampton and Castleman observed that infarcts, especially those involving the costophrenic angles, produced opacities with a characteristic hump-shaped convexity directed towards the heart in radiographs of the

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Fig. 3 (a) A 75-year-old man with no signicant medical history, syncope, and bilateral pulmonary embolism. Sagittal image of the right hemithorax from a CT angiogram demonstrates a 3.5-cm encapsulated lesion with central lucency occupying the posterior costophrenic angle of the right lower lobe. Note the upper convex surface (curved arrow) and the bulging margins (arrowheads) outlined against a pleural effusion. (b, c) A 30-year-old woman with sickle cell anemia, acute chest pain, and bilateral pulmonary embolism. Coronal image of the right hemithorax from a CT angiogram shows a 2.2-cm encapsulated lesion with a rounded superior border (arrow in (b)) nestled in the lateral costophrenic angle of the right lower lobe. The same area of opacication in a frontal radiograph obtained the same day has a similar convex margin (arrow in (c)) directed centrally (Hamptons hump)

Fig. 4 A 29-year-old man with no signicant medical history, acute deep venous thrombosis, and bilateral pulmonary embolism. (a) Transverse image of the right upper lobe from a CT angiogram shows a 5.5-cm triangular opacity of ground-glass density and peripheral consolidation in the anterior segment. The consolidation is thickest along the pleural surfaces (curved arrows). (b) In an oblique transverse reformat, the anterior segmental artery and the arterial branch supplying the opacied area both contain thromboemboli which are separated by a tiny amount of contrast (arrow). (c) Detail of a frontal radiograph of the right upper lung obtained at 3 months shows a small linear opacity (arrow) very likely corresponding to a residual scar in the anterior segment of the right upper lobe

chest (5). In six of our patients, the lesions were nestled in the costophrenic angles of the lower lobes and also displayed a rounded margin facing centrally in coronal and sagittal CT images (Fig. 3; see also Figs. 1b and 2a). Air-bronchograms were observed in three (21%) of the 14 lesions, a higher frequency than previously reported (4/50) (10). In each case, one or more subtended bronchovascular bundles were seen at the medial margin of the opacities (vascular or vessel sign; (8 10)), and in at least 64% of the lesions, a thromboembolus was present in a subtended pulmonary artery. Thromboemboli were also found in other

pulmonary arteries of the corresponding segment, including the segmental arteries. In two CT studies on pulmonary infarcts, small lucencies within peripheral areas of consolidation were noted in 58% and 46% of cases, respectively (9, 10), and had a 98% specicity and a 46% sensitivity for infarction (10). Histologically, the lucencies represented viable lung among necrotic secondary pulmonary lobules (n 12) (9) or only coagulative necrosis and inammation (n 1) (10). The relatively larger areas of central ground-glass density observed in our cases probably reect a similar process of coagulative

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necrosis and lobular sparing (6) in a thromboembolized zone that still contained air. Pulmonary infarcts heal by organization. The granulation tissue begins at the periphery and progresses centripetally encapsulating the infarcted area (5, 7). Depending on the size of the infarct, this process may last for weeks to months resulting in gradual displacement of the air and replacement of the hemorrhagic and necrotic tissue with brous connective tissue. As healing continues, the infarcts become smaller, solidify and eventually form linear scars (5). In the seven patients with follow-up scans, shrinkage was evident by 13 days (the shortest interval between the rst and second scans), and residual air was present in all four lesions that were imaged within 25 days of the initial scan. A thin pleural-based linear scar was observed as early as 2 months, and the majority of the lesions had evolved into linear scars by 7 months. It seems very likely then that the peripheral consolidation in our cases corresponded to granulation and brous tissue. A component of inammation may have also been present at the margins of the lesions as previously described in some surgical specimens (7). Pulmonary thromboembolism does not commonly result in infarction; the incidence of infarction in autopsy subjects with pulmonary emboli ranges from 10% to 30% (6, 11). It is believed that the collateral bronchial circulation and reversal of ow through the pulmonary and bronchial veins prevent infarction after pulmonary embolism in the normal lung (6). On the other hand, pulmonary venous hypertension and systemic arterial hypotension favor the development of infarction (5, 6), and malignancy and hypercoagulable states may be other contributing factors (11). Seven (58%) of our patients did not have any known predisposing conditions at the time of the initial scans (which does not necessarily imply that none existed).

In conclusion, therefore, the recognition of the reversed halo sign in the context of acute pulmonary embolism could raise suspicion of pulmonary infarction and might also have important clinical implications in those individuals with no known risk factors for infarction. Conict of interest: None.
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