Pleural effusion (Imaging) INTRODUCTION 1. Detection of pleural effusion(s) and creation of initial differential diagnosis are highly dependent upon imaging of pleural space. Conventional CXR and CT are primary imaging modalities that are used for evaluation of all types of pleural disease, but ultrasound and MRI have role in selected clinical circumstances. 2. The imaging of pleural effusions will be presented here. Imaging of pleural plaques, thickening, tumors, and pneumothorax are discussed separately. NORMAL PLEURAL ANATOMY 1. The term pleura is generally meant to encompass parietal pleura (lining inner surface of chest wall, including diaphragmatic pleura and cervical pleura also called dome of pleura or 2. 3. pleural cupola that covers lung apex and extends into cervical region), visceral pleura (lining outer surface of lung), and intervening pleural space. Both visceral and parietal pleural surfaces consist of mesothelial layer and 3 to 7 connective tissue layers, but visceral pleura is thicker than parietal pleura. Together, visceral and parietal pleural layers and lubricating liquid in interposed pleural space have combined thickness of 0.2 to 0.4 mm, while width of pleural space is 10 to 20 μm. Normal pleural anatomy can be displayed by CT. A 1 to 2 mm thick line of soft-tissue attenuation can be seen at point of contact between lung and chest wall, corresponding to visceral and parietal pleura and minimal amount of lubricating pleural liquid. Extrapleural fat and endothoracic fascia, each with thickness of 0.25 mm, are visible between pleural line and ribs (or subcostal and innermost intercostal muscles). The apical part of endothoracic fascia is thickened and is called Sibson's fascia. Outside this fascia is space filled with areolar tissue, called Semb's space. The anterior and posterior junction lines are well outlined by lung and contain 4 layers of pleura: 2 visceral and 2 parietal components (image 2A-B). The interlobar fissures and most accessory fissures in lungs are formed by 2 layers of visceral pleura, with exception of azygos vein fissure, which contains four layers of pleura, ie, two visceral and two parietal layers of pleura. CONVENTIONAL RADIOGRAPHY 1. 2. 3. 4. 5. Abnormalities of pleural space can easily be detected by conventional radiographic methods using frontal, lateral, oblique, and decubitus radiographs. Pleural effusions accumulate in the most dependent part of thoracic cavity because lung, which is physically less dense than liquid, floats on effusion. The otherwise normal lung will follow its intrinsic elastic recoil and decrease in volume while maintaining its shape during collapse. Because of gravity, initial accumulation of pleural liquid occurs in subpulmonic location, ie, between inferior surface of lower lobes and diaphragmatic leaflets. Up to 75 mL of pleural effusion can occupy subpulmonic space without spillover. As it accumulates, pleural liquid spills over into costophrenic sulcus posteriorly, anteriorly, and laterally. It surrounds lung and forms cloak, or cylinder, which looks like meniscoid arc in radiographic projections. The amount of pleural effusion can be estimated based on standard frontal and lateral radiographs. At least 75 mL are needed to obliterate posterior costophrenic sulcus, and a minimum of 175 mL is necessary to obscure lateral costophrenic sulcus on upright CXR. A pleural effusion of 500 mL will obscure diaphragmatic contour on upright CXR; if pleural effusion reaches level of 4th anterior rib, close to 1000 mL are present. On decubitus radiographs and CT, less than 10 mL, and possibly as little as 2 mL, can be identified (image 3). For quantitation on decubitus views, rind of layering pleural effusion is measured: small effusions are thinner than 1.5 cm, moderate effusions are 1.5 to 4.5 cm thick, and large effusions exceed 4.5 cm. Effusions thicker than 1 cm are usually large enough for sampling by thoracentesis, since at least 200 mL of liquid are already present. On supine radiographs, as little as 175 mL of effusion can be visible, sometimes forming apical caps which disappear on upright imaging. Mobile effusions also layer along posterior aspect of thorax in supine position and produce filter effect or pleural veil that overlies aerated lung; a gradient of decreasing opacity towards apex can be identified. The following features suggest that this appearance in supine patient is due to effusion, as opposed to parenchymal lung disease (such as pneumonia or pulmonary edema). A. Pulmonary vessels are clearly visible through added opacity created by effusion B. Air bronchograms are absent 6. Subpulmonic effusion A. Subpulmonic pleural effusions elevate lung base, mimicking elevated diaphragmatic leaflet. The apex of curvature at lung base is shifted laterally, and its slope slants sharply towards lateral costophrenic sulcus. This configuration has been dubbed “Rock of Gibraltar sign” and is particularly well seen on lateral CXR in patients with subpulmonic effusion. Large pleural effusions, especially on left side, can produce diaphragmatic inversion, making normally convex diaphragm appear concave. This configuration can lead to paradoxical breathing on affected side with inspiratory elevation of diaphragmatic leaflet and expiratory descent of hemidiaphragm. B. On left side, marked separation (> 2 cm) of lung from stomach bubble suggests subpulmonic effusion. This separation of stomach gas bubble from lung base, especially when bubble appears displaced inferomedially, is of particular significance on frontal and lateral views. C. Atypical localization of pleural effusion generally results from abnormality in underlying lung. When lung cannot expand to fill thoracic cavity, relative pleural pressure becomes more negative relative to atmospheric pressure. The increased negative pleural pressure enhances pleural liquid formation, leading to accumulation of pleural liquid. Pleural effusions accumulate in these areas subtended by lung with the greatest elastic recoil. 7. Loculated pleural effusion A. Pleural effusions can also loculate as result of adhesions. Loculation is most common when underlying effusion is due to hemothorax, pyothorax, chylothorax, or TB pleuritis. A typical configuration of loculation along chest wall, often described as pleural or extrapleural sign, has the following features. i. The angles of interface between pleural “mass” and chest wall are obtuse, and mass displays tapered borders ii. The surface of “mass” is usually smooth when seen in tangent, poorly marginated when seen “en face,” and only partially visualized when displayed in oblique projection (“incomplete margin sign”) also called “one-edged lesions” iii. The content is homogeneous iv. The “mass” droops on upright images owing to its liquid content and effect of gravity COMPUTED TOMOGRAPHY 1. CT detects small pleural effusions, ie, < 10 mL and possibly as little as 2 mL of liquid in pleural space. Thickening of the visceral and parietal pleura as well as enhancement of visceral and parietal pleura after injection of contrast material (“split pleura sign”) suggest presence of inflammation and thus exudative, rather than transudative, effusion. The administration of contrast material in patients with pleural abnormalities is important, since it facilitates differential diagnosis of pleural effusions. 2. Other uses of CT in evaluation of pleural disease. A. B. C. D. E. F. G. Facilitating measurement of pleural thickness Distinguishing empyema from lung abscess Visualization of small pneumothoraces in supine patients Visualization of underlying lung parenchymal processes that are obscured on CXR by large pleural effusion Determination of exact location of pleural masses and characterization Occasionally identifying peripheral bronchopleural fistulae Occasionally identifying a diaphragmatic defect in cirrhotic patient with hepatic hydrothorax H. Identification of lung parenchymal or upper abdominal abnormalities that may provide clue to etiology of pleural effusion (lung mass, apical cavities, aortic dissection, infradiaphragmatic abscess, liver cirrhosis with ascites leading to hepatic hydrothorax) I. Guidance for thoracentesis and tube thoracostomy of loculated empyema ULTRASONOGRAPHY 1. Ultrasonography permits easy identification of free or loculated pleural effusions, and it facilitates differentiation of loculated effusions from solid masses. The intrinsic characteristics of pleural effusion and its accompanying adhesions can be identified. 2. Thoracentesis of loculated pleural effusions is facilitated by ultrasound guidance. However, CT is method of choice for more complicated interventional procedures, such as empyema drainage or biopsy of pleural masses. MAGNETIC RESONANCE IMAGING 1. MRI can display pleural effusions, pleural tumors, and chest wall invasion. In selected cases, it can characterize content of pleural effusion. The role of MRI in imaging of hemothorax is discussed below; other aspects of thoracic MRI are presented separately. TRANSUDATIVE PLEURAL EFFUSION 1. The most common cause of transudative pleural effusion is HF. Pulmonary edema liquid permeates lung interstitium and visceral pleura, eventually accumulating in pleural space, in order to be resorbed by lymphatics of parietal pleural. Pleural effusions related to left ventricular failure are bilateral in nearly 90% of cases. Other causes of transudative pleural effusion include constrictive pericarditis, hepatic cirrhosis, and renal failure. In general, 2. 3. transudative pleural effusions are product of imbalanced hydrostatic forces. Occasionally these pleural effusions loculate and mimic masses, particularly in interlobar fissures; these have also been called pseudotumor or vanishing tumor. CT can sometimes determine true nature of such mass by showing its liquid content and its relationship to fissures, thereby excluding intrapulmonary origin. In rare instances, patients have bilateral pleural effusions with markedly different characteristics. This situation is called "Contarini's condition," named after 95th Doge of Venice, who died of cardiac decompensation with unilateral transudative pleural effusion and contralateral empyema caused by necrotizing pneumonia. CT in such situations can identify small collections of gas, loculations, or pleural thickening and pleural enhancement in an empyema, characteristics not found in a transudative pleural effusion. 4. Hepatic hydrothorax A. Hepatic hydrothorax is defined as pleural effusion, usually > 500 mL, in patients with cirrhosis, but without primary cardiac, pulmonary, or pleural disease. The majority occur in right hemithorax (85%). The evaluation of suspected hepatic hydrothorax is discussed separately. EXUDATIVE PLEURAL EFFUSION 1. The most common conditions leading to exudative pleural effusion are pneumonia (resulting in sterile parapneumonic effusion or empyema) and malignant tumors. Large unilateral exudative pleural effusions in young patients are suspicious for TB, whereas in older individuals they frequently indicate malignant process. 2. Empyema A. B. The vast majority of empyemas is due to pulmonary infections and occurs in post-pneumonic period; surgical procedures and trauma are other common causes. Empyemas are most often due to anaerobic bacteria or mixed aerobic-anaerobic flora. Aerobic bacteria, tuberculous mycobacteria, and fungi are less frequent causative agent. The radiologic diagnosis of empyema can be facilitated by CT. Three stages are recognized in evolution of empyema. i. Stage 1 consists of exudative pleural effusion that contains > 15,000 WBC/μL ii. Stage 2 is fibrinopurulent stage in which adhesions have already formed iii. Stage 3 is organizing stage, with development of thick pleural peel C. The effusion can be easily drained in stage 1; in contrast, decortication may be required in stages 2 and 3. Ultrasound is able to image early adhesions during fibrinopurulent stage of empyema. Linear, irregular, honeycomb-like adhesions predict difficulties in drainage. D. E. F. In early, exudative stage of empyema, pleural effusion appears on radiography to be freely layering. When effusion becomes loculated, it forms tapered borders with obtuse angles at its interface with chest wall, often showing gravity dependent changes in shape, such as "drooping" (image 13A-D) and on occasion the “incomplete margin” sign. In fibrinopurulent and organizing stages, contrast CT shows strong enhancement of visceral and parietal pleurae, producing "split pleura sign". The pleura is also frequently thickened, exceeding 3 to 5 mm. Empyemas tend to compress adjacent lung rather than destroy it, thereby allowing differentiation from large lung abscesses. In addition, empyemas typically have thinner, smoother walls than lung abscesses, which tend to have thicker walls and irregular luminal and exterior surfaces. Empyemas tend to form obtuse angle of interface with chest wall, compared with lung abscesses, which commonly have acute angle. However, wall thickness, uniformity, and crowding of adjacent vascular structures rather than their destruction or incorporation are more accurate for differentiation of these processes than chest wall angle of interface. G. The finding of gas-liquid level in empyema indicates presence of bronchopleural fistula (BPF). In this setting, gas-liquid levels in frontal and lateral projections on upright CXR characteristically have unequal, disparate linear dimensions and typically extend to chest wall. CT is also capable of identifying BPF. Central BPF occurs most often after surgical procedures or trauma and can be confirmed by bronchoscopy. In contrast, peripheral BPFs are often complication of necrotizing pneumonia. H. 3. Tuberculous empyemas tend to persist for decades and exhibit extensive calcification of pleura. They were seen more frequently in the past after pneumothorax for TB. Malignant pleural effusion A. The second most common cause of exudative pleural effusion is malignant tumor. Carcinoma of lung, breast, or ovary, and lymphoma account for about 80% of all malignant effusions. i. Increased pleural membrane and capillary permeability ii. Decreased clearance due to lymphatic obstruction iii. Bronchial obstruction leading to atelectasis and marked regional decrease in intrapleural pressure, which favors pleural liquid accumulation B. Findings on CT imaging that suggest malignant pleural effusion include irregular, nodular, or thickened pleura submerged in effusion. Enhancement of visceral pleura after administration of contrast suggests pleural inflammation or malignancy. C. 4. The size of malignant effusions varies, but metastatic malignancies are the most common cause of massive pleural effusion obliterating entire hemithorax. Malignant effusions can become loculated. D. The diagnosis and management of malignant pleural effusions are discussed separately. Hemothorax A. A hemothorax is defined as bloody pleural effusion with hematocrit exceeding half value in peripheral blood. It can be seen after trauma, pulmonary embolism, as result of metastatic disease, after anticoagulant therapy, or as sequela of leaking aortic aneurysm. B. CT of hemothorax shows effusion with relatively high attenuation, exceeding 35 HU when blood is fresh, and reaching 70 HU with clotted blood. A hematocrit effect with liquid-liquid level can become visible in subacute hematomas, due to the higher attenuation of sedimented RBC compared to that of supernatant, which contains serum of lower attenuation. C. 5. MRI is able to image blood and to determine age of hemorrhage. i. Oxyhemoglobin exists in fresh blood, which has low signal on T1W and high signal on T2W. ii. Deoxyhemoglobin exists in subacute bleeding (several hours to days old), which has low signal on T1W and T2W. iii. Methemoglobin can be seen when blood is several days to several weeks old. If it is intracellular, it displays high signal on T1W but low signal on T2W. When it is extracellular, methemoglobin exhibits high signal on both T1W and T2W. iv. Hemosiderin shows low signal on both T1W and T2W and usually indicates blood that is several weeks to several months old. Chylothorax A. Chylothorax is most likely result of mediastinal tumor involvement by lymphoma or bronchogenic carcinoma. These two neoplasms account for 54% of all chylothoraces, while trauma, including surgery, accounts for another 25%. Rare causes of chylothorax include filariasis, lymphangioleiomyomatosis, congenital anomalies of thoracic duct, and so-called idiopathic chylothorax. B. Disruption of thoracic duct leads to formation of chylous duct cyst, which can appear as posterior mediastinal mass. It can perforate, usually after interval of 10 days, leading to delayed development of pleural effusion. Radiologically, large pleural effusion is characteristic, and loculation can occasionally be seen. C. On CT, pleural accumulation of chyle can display lower attenuation values than other effusions. MRI can show high signal on T1W, due to high fat content. Traumatic right-sided chylothoraces indicate injury to lower third of thoracic duct, whereas left-sided chylothoraces indicate lesion in upper two-thirds of thoracic duct. SUMMARY AND RECOMMENDATION 1. Conventional CXR and CT are key to the detection and characterization of pleural effusions; pleural ultrasound and MRI play role in selected clinical circumstance. 2. 3. 4. 5. 6. 7. On conventional chest radiographs, frontal, lateral, and decubitus views are used to detect the presence of a pleural effusion and to differentiate pleural liquid from pleural thickening. Pleural effusions and thickening can both cause blunting of the costophrenic sulcus, but only freely mobile effusions will result in layering of liquid on the decubitus view. The amount of pleural effusion can be estimated based on decubitus chest radiographs; small effusions are thinner than 1.5 cm, moderate effusions are 1.5 to 4.5 cm thick, and large effusions exceed 4.5 cm. Effusions forming a rind thicker than 1 cm are usually large enough for sampling by thoracentesis, since at least 200 mL of liquid are already present. Subpulmonic pleural effusions elevate the lung base, mimicking an elevated diaphragmatic leaflet. The apex of the curvature at the lung base is shifted laterally, and its slope slants sharply towards the lateral costophrenic sulcus. On the left side, a marked separation (> 2 cm) of the lung from the stomach bubble suggests a subpulmonic pleural effusion. Loculated pleural effusions are differentiated from lung masses by certain characteristics: the angles of interface between a pleural loculation and the chest wall are obtuse with tapered borders; the surface of a loculated pleural effusion is usually smooth or displays the “incomplete border sign”, when not imaged in tangent; the content is homogeneous; and pleural loculations appear to droop on upright images owing to the liquid content and the effect of gravity. On CT, the visceral and parietal pleura and the minimal amount of lubricating pleural liquid between them appear as a line of soft-tissue attenuation 1 to 2 mm thick at the point of contact between the lung and the chest wall. Extrapleural fat and the endothoracic fascia, each with thickness of 0.25 mm, are visible between the pleural line and the ribs. CT scans can detect very small pleural effusions, ie, less than 10 mL and possibly as little as 2 mL of liquid in the pleural space. CT is helpful in evaluating complex pleural disease, such as empyemas, pleural liquid loculations, pleural masses associated with pleural effusions, and lung parenchymal processes obscured by pleural effusions. Intravenous administration of iodinated contrast material is important for optimal evaluation of pleural disease by CT scanning. In addition, CT guidance improves the accuracy of tube thoracostomy for drainage of loculated pleural effusion. 8. The presence of an exudative, rather than transudative, pleural effusion is suggested by thickening of the pleurae on CT scanning (> 3 to 5 mm) and by contrast enhancement of the visceral and parietal pleurae. 9. Thoracic ultrasonography is useful to identify free or loculated pleural effusions and to differentiate loculated effusions from solid masses. Thoracic ultrasound guidance for thoracentesis improves the accuracy and safety of the procedure. 10. Pleural effusions and tumors can also be delineated by MRI. The main roles for MRI in the evaluation of pleural effusion are to characterize a hemothorax and determine whether a pleural tumor extends into the surrounding soft tissues of the chest wall, mediastinum, supraclavicular region, or abdomen.