Transthoracic Ultrasound of Lung and Pleura in the Diagnosis of Pulmonary Embolism: A Novel Non-Invasive Bedside Approach

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1 Thematic Review Series Respiration 2003;70: DOI: / Received: May 27, 2003 Accepted: July 2, 2003 Transthoracic Ultrasound of Lung and Pleura in the Diagnosis of Pulmonary Embolism: A Novel Non-Invasive Bedside Approach Angelika Reissig Claus Kroegel Pneumology and Allergology Division, Department I, Medical University Clinics, Friedrich Schiller University, Jena, Germany Key Words Pulmonary embolism W Transthoracic sonography, lung, pleura W Ultrasound technique W Sonomorphology, embolic lung lesions W Differential diagnosis Abstract The diagnosis of pulmonary embolism (PE) presents a considerable challenge and requires a high index of clinical suspicion from the attending physician. In addition, diagnosing PE may require the use of one or more direct and indirect diagnostic methods. Here, transthoracic sonography (TS) provides an alternative and attractive bedside approach which is based on (1) detecting alterations in the lung parenchyma, (2) involvement of the pleura and (3) peripheral perfusion characteristics associated with thromboembolism. Using a 5 MHz or 3.5 MHz convex scanner, occasionally supplemented by a 7.5 MHz linear scanner or colour-flow Doppler mode, the intercostal areas are systematically examined by TS. Most of the PE-related lesions are localised in the lower lobes of the lung and are often associated with an area of pleuritic chest pain. The characteristic sonographic findings of TS in PE are multiple, hypoechoic, pleural-based parenchymal lesions which adopt a wedge-shape. In addition, a central echo may occasionally be detectable within the lesion. Another regular sonographic feature is the involvement of the pleura manifesting as either localised effusion, basal effusion or both. However, several differential diagnoses such as pneumonia, bronchogenic carcinoma, metastases of extra-pulmonary malignancies, and simple pleurisy need to be excluded. Since localisation of PE-associated lesions may occasionally escape sonographic detection, an inconspicuous sonographic result does not fully exclude PE. As detection of PE-associated lesions using chest ultrasonography has a high specificity and sensitivity, can be rapidly performed, is widely available, non-invasive, cost-effective, and avoids transport of critically ill patients to the investigation site, the technique may prove a valuable tool in the diagnosis of PE at bedside facilitating immediate treatment decision. Further, because the method focuses on detection of peripheral lesions it complements other diagnostic techniques employed when PE is suspected. Copyright 2003 S. Karger AG, Basel Previous articles in this series: 1. Kroegel C, Reissig A: Principle mechanisms underlying venous thromboembolism: Epidemiology, risk factors, pathophysiology and pathogenesis. Respiration 2003; 70: Meyer G, Roy PM, Sors H, Sanchez O: Laboratory tests in the diagnosis of pulmonary embolism. Respiration 2003; 70: Garg K, Macey L: Helical CT scanning in the diagnosis of pulmonary embolism. Respiration 2003;70: Schümichen C: V/Q-scanning/SPECT for the diagnosis of pulmonary embolism. Respiration 2003;70: ABC Fax karger@karger.ch S. Karger AG, Basel /03/ $19.50/0 Accessible online at: Angelika Reissig, MD Pneumology and Allergology, Medical Clinic I, Friedrich-Schiller-University Erlanger Allee 101 DE Jena (Germany) Tel , Fax , angelika.reissig@med.uni-jena.de

2 Introduction As signs and symptoms of pulmonary embolism (PE) may either be silent or non-specific, the diagnosis of PE presents a considerable challenge and requires a high index of clinical suspicion from the attending physician. In addition, for the diagnosis of PE, the physician usually relies on one or more elaborate imaging techniques of the pulmonary circulation vessels such as ventilation/perfusion scintigraphy (V/P), spiral computed tomography (sct), and pulmonary angiography (PA). However, diagnostic imaging methods are not always immediately accessible, are costly, and usually cannot be performed at short notice. Because PE is a potentially fatal disease needing immediate anticoagulant therapy, there is urgent demand for alternative diagnostic approaches. In the chest, the role of ultrasound (US) has traditionally been limited to evaluation of the pleural effusion and as a guidance for thoracentesis. However, in recent years US has emerged as a diagnostic tool in various pulmonary, pleural, and mediastinal conditions supplementing conventional radiographic techniques. A concise review of the employment of transthoracic ultrasound in malignancies, pneumothorax and pulmonary embolism, its potential diagnostic application in pleural and pulmonary processes as well as its use in critically ill patients has recently been published in this Journal [1]. Detection of thromboembolic lesions of the lung by sonography was first described both in animals (dogs) and humans some 30 years ago [2, 3]. However, the procedure has been disregarded for many years. Nevertheless, in the last decade technical advances together with the widespread availability of sonography has led to a number of clinical studies confirming the original observations have been published during the past decade [4 9]. In this review, we provide an in-depth assessment of the applicability of transthoracic ultrasound (TS) in the diagnosis of pulmonary embolism. Data available to date suggest that the diagnostic approach to PE employing TS is attractive, which is likely to change the diagnostic strategies in PE. History and Relevant Pathophysiology Sonographic examination of the pleura has long been recognised as a useful method for diagnosing pleural effusion and as a guide to thoracocentesis, pleural biopsy, as well as chest tube placement. However, most physicians believe that ultrasonography has a limited usage in disorders of the lung parenchyma. Nevertheless, as has been demonstrated by an increasing number of studies, chest ultrasound may reach much further into the thoracic cavity providing a valuable tool in the assessment of various lung diseases such as pneumonia, pulmonary malignancies, atelectasis, pulmonary fibrosis, pneumothorax, pleurisy, and even pulmonary embolism [6, 7, 9 21]. Under physiological conditions, the ultrasound beam penetrating a normal chest crosses the intercostal muscles, which are covered internally by the fascia endothoracica and the parietal pleura. The echogenic pleural line is caused by composite echoes from the inner visceral pleura and the total reflection of the ultrasound beam along the border between aerated lung and thoracic wall. If no pleural effusion is present the ultrasound beam reaches the visceral pleura and interacts in a complex manner with aerated parenchymal lung tissue resulting in poor sound transmission and rapid dissipation of the beam which precludes further exploration of the lung [22]. However, a collection of fluid within the pleural cavity or a pleural mass yielding an acoustic window for ultrasound exploration of the parietal and visceral pleura. The evacuation of intra-pulmonary air due to an airway-lock with atelectatic parenchymal tissue compression, the collection of intra-alveolar fluid or as a consequence of parenchyma infiltrating tumour growth, allows ultrasonic waves to penetrate deeper into the lung parenchyma resulting in a hypodense ultrasound image of the process or lung section, which sharply contrasts to the air-containing parenchymal lung tissue. As pointed out elsewhere in this series [23], in PE a sudden occlusion of pulmonary arteries by thromboemboli lead to a number of transient pathophysiologic consequences, involving both mechanical and reflex effects of vascular occlusion with a consecutive perfusion defect as well as to the release of vasoactive and other inflammatory mediators [23, 24]. As a consequence, the thromboembolic occlusion of a pulmonary artery may cause an intraalveolar haemorrhage without tissue destruction (incomplete infarction) or haemorrhage with necrosis of lung parenchyma (complete infarction) [25, 26]. In addition, the cessation of pulmonary arterial flow in the areas distal to the perfusion stoppage may result in atelectasis due to a rapid breakdown of the surfactant lining the inner surface of the airspace. Alternatively, the release of inflammatory mediators and the increase in the vascular pressure proximal to the thrombotic vessel occlusion causes an increase of alveolar-capillary permeability with a local pulmonary oedema accompanied by a consecutive filling of the alveolar lumen by an erythrocyte-containing exudate [23]. Irre- 442 Respiration 2003;70: Reissig/Kroegel

3 spective of the pathophysiologic sequelae, these processes essentially involve the terminal air spaces and result in the evacuation of air from the affected parenchymal area creating an ultrasonic window, allowing ultrasound waves to travel further into the lung (table 1). In order to be detectable by TS, the lesions need to extend to the pleural surface of a fully extended lung which usually is the case. In addition, parenchymal alterations may also be detectable in lung detached from the chest wall when an acoustic window such as for instance atelectasis or pleural effusion is present, allowing the ultrasound to penetrate into deeper tissue regions (fig. 1). On the basis of these alterations, thromboembolic lesions become visible to sonographic examination both in the presence or absence of pleural effusion. A further consequence of PE-associated alterations is that the pleural line corresponding to the PE-related areas may loose its echogenicity and become irregular or fragmented. In addition, mechanical alterations associated with atelectatic lung tissue, and increased capillary pressure as well as a raised vessel wall permeability due to the release of inflammatory mediators also causes increased exudation of fluid into the pleural space [27] leading to localised pleural fluid collection adjacent to the affected pulmonary region eventually giving rise to a basal pleural effusion. Technique of Sonographic Examination Technical Requirements For the sonographic examination of the lung and pleura, a 5 MHz or 3.5 MHz convex scanner is usually employed. In addition, a 7.5 MHz linear scanner can be applied when a linear representation of the superficial parenchymal or pleural area is required. In addition, when a colour-flow Doppler mode can be used the perfusion properties are to be examined. Patient Examination Sonographic examination of the chest is usually performed with the patient either seated (dorsal application) or in a prone position (ventral application). The scanner is first applied in the intercostal areas where the patient localises the pain, which is then followed by a systematic evaluation of the remaining intercostal spaces. Examination is performed during tidal breathing. However, maximal inspiration and exhalation may also be required to gain access to areas covered by overlying bones of the thoracic cage (rips, clavicle, transverse pro- Fig. 1. Ultrasonic approaches in transthoracic sonography: direct (A) or indirect (B, C) through an ultrasonic window like atelectasis (B) or a pleural effusion (C). Table 1. Essential diagnostic questions and answers in transthoracic sonography Question to be asked 1 What is the size of the alteration? 2 Which shape does the lesion have? 3 How is the lesion bordered? 4 Which echo pattern has the lesion? Diagnostic criteria size measured in the longitudinal and transverse axes wedge-shape, oval, rounded, polygonal sharp, well-demarcated versus blurred homogeneous versus heterogeneous 5 Is the lesion perfused? perfusion versus no perfusion detectable 6 Is the pleura involved? pleura line fragmentation, localised effusion, basal effusion cess of the thoracic vertebrae, scapulae). If a pulmonary process is not completely accessible, the intercostal space may be widened by placing the patient s hands behind the head and elevating the elbows [12]. In addition, breathholding by the patient may be useful. This manoeuvre may be particularly helpful in determining the features of a discovered lesion which is otherwise is distorted by breathing motion. It may also help to exclude breath motion-related artefacts, especially for detecting the vascular sign which can only accurately be identified during breath-holding. Transthoracic Ultrasound in the Diagnosis of Pulmonary Embolism Respiration 2003;70:

4 Fig. 3. Pulmonary embolism sonogram. 47-year-old man with CTproven pulmonary embolism. The sonogram reveals one triangular, hypoechoic, pleural-based parenchymal lesion (+) measuring 24.4! 26.1 mm. Fig. 2. Schematic representation of the parenchymal, pleural and vascular features associated with pulmonary embolism. Description of Lung Alterations Once a suspicious lesion is detected, its localisation with respect to chest wall (intercostal space) and the body side (anterior, posterior or lateral) needs to be determined. Further, the lesion should be assessed along the longitudinal and transverse axes with respect to the size and the sonomorphology of the parenchymal lesion. In order to fully characterise the alteration, six essential questions need to be answered (table 1). Diagnostic Features of Pulmonary Embolism-Associated Alterations There are a number of criteria which can be applied in the diagnosis of PE. For reasons of clarity the sonographic findings associated with pulmonary thromboembolism (fig. 2) are classified according to the anatomic structures involved [7] as follows: (1) parenchymal criteria; (2) pleural criteria and (3) vascular criteria. The individual criteria will be discussed in detail below. Parenchymal Criteria The most regular and characteristic sonographic finding in PE is a hypoechoic, pleural-based parenchymal alteration. The majority of these lesions are localised in an area of pleuritic chest pain and adopt a wedge-shape (185%) [7]. The remainder have a rounded or a polygonal configuration. Irrespective of the shape, the lesions are hypoechoic, have a homogeneous sonomorphology, and by definition, extend to the pleural surface (fig. 3). In approximately one fifth of the patients [7] a single echo typically localised at the centre of the lesion (fig. 4) may be detected. Characteristically, the size of these lesions exceeds 2 cm in diameter. The central hyperechoic structure indicates the presence of air occupied by the bronchiole affected and is considered as a sign of segmental involvement [28]. This may correspond to CT-findings where an area of low attenuation within an infarction reflects normal lung tissue within it [29]. PE-related parenchymal lesions detected by transthoracic sonography vary considerably among patients with PE, both in number and size. Up to 9 subpleural lesions can be found per patient with an average number of 2.6 lesions [6, 7]. In addition, the majority of the lesions are located within the lower lobes (79.7%) with a preference to the right lung [30]. Most consolidations associated with PE have a size ranging from 5 to 20 mm in diameter. However, their size may on occasion extend to 7 8 cm measured in the longitudinal and transverse axes, respectively [6, 7]. Interestingly, multiple consolidations and lesions within an area of breath-dependent thoracic pain increases the likelihood of PE as the cause of the alterations. The early subpleural and reperfusionable lesion may resolve within hours possibly indicating incomplete infarction [23]. However, if no or incomplete lysis occurs, the lesion persists and adopts a more echoic, non-homogeneous sonomorphology in a wedge-shaped configuration with well-demarcated, irregular or serrated margins. If PE-related complications, such as post-infarction pneumonia and pulmonary abscess do not develop, pulmonary 444 Respiration 2003;70: Reissig/Kroegel

5 Fig. 4. Pulmonary embolism. A Sonogram. Sonogram of a 69-yearold woman with breathlessness on exertion and at rest. A polygonal hypoechoic pleural-based parenchymal lesion with a single echo localised within the centre. B Corresponding spiral computed tomogram. Lung window imaging shows the corresponding pleura-based consolidation. C Corresponding computed tomogram. A filling defect within the left lower pulmonary artery is demonstrated confirming the diagnosis of pulmonary embolism. Fig. 5. A Pulmonary embolism sonogram. A 39-year-old woman with increasing dyspnoea on exertion suffered from CT-proven pulmonary embolism. The sonogram reveals one triangular, hypoechoic, well-demarcated, pleura-based parenchymal lesion (+) in the right lower lobe measuring 24.2! 18.2 mm. B Pulmonary embolism control-sonogram five months later. The lesion has lost its clear and well-demarcated margins. It appears as an irregular shaped, hypoechoic, pleura-based parenchymal lesion (+) of a smaller size of 9.13! 11.3 mm. embolic lesions slowly decreasein size (fig. 5) and normalise over several weeks or even months. Irregularities of the corresponding pleural surface are likely to be the result of a local fibrotic scarring tissue, maybe the only remainder of the lesion. Pleural Criteria Pleural involvement in PE initially leads to localised fluid collection adjacent to the affected pulmonary region and may eventually develop into a basal pleural effusion. Localised effusions are characterised by a circumscript dehiscence between the pleura visceralis and pleura parietalis and are most likely caused by an accompanying inflammatory process of the pleura adjacent to affected lung parenchyma. In addition, the pleural line corresponding to a subpleural lesion may become convexshaped and bulge outwards. Further, the pleural line appears less echogenic and fragmented [7]. Therefore, a regular feature of pleural involvement are both localised and basal effusions suggesting that the pleural space is often affected in PE [6, 7]. The frequency of pleural effusion in PE has been recorded at 51% on chest radiographs [31], 57% on CT [32], and 61% using transthoracic sonography [7]. A localised effusion characteristically corresponding to the peripheral lesion (fig. 6) is seen in about 40% of the patients with confirmed pulmonary embolism, whereas localised and/or basal effusions can be found in approximately two thirds of the patients using sonography [7]. Vascular Criteria Exploration of the lesions by colour Doppler imaging may provide additional diagnostic information. In pulmonary infarction, areas of pulmonary arterial flow cannot be detected on colour Doppler ultrasound, a phenomenon referred to as consolidation with little perfusion [33]. On the other hand, recanalization of incomplete infarction resulting from anticoagulation treatment or intrinsic lysis can be demonstrated by the reappearance of a blood flow signal on follow-up. In addition, a congested thromboembolic vessel ( vascular sign ) may on occasion be visible [34, 35], corre- Transthoracic Ultrasound in the Diagnosis of Pulmonary Embolism Respiration 2003;70:

6 Fig. 6. Pulmonary embolism sonogram. 29-year-old woman suffering from breath-dependent pleuritic chest pain and haemoptysis following pulmonary embolism. The sonogram shows two wedgeshaped, subpleural lesions (+) with a size of 10.2! 11.0 mm and 9.92! 11.6 mm and a small corresponding localised pleural effusion (+) of 1.86 mm. Table 2. Sensitivity and specificity of the various methods used in diagnosing pulmonary embolism (data summarized are taken from [6, 7, 9, 37 44]) Sensitivity (%) Specificity (%) Combined transthoracic and transesophageal echocardiography Ventilation/perfusion scan Transthoracic sonography Spiral computed tomography MR-angiography Pulmonary angiography sponding to the vascular sign at the apex of a subpleural hypodense lesion as can be demonstrated in patients with PE on high resolution computed tomography [36]. As shown by radiological-pathological correlation studies, the vascular sign corresponds to a pulmonary artery with thickened vessel walls around an intraluminal organising embolus [36]. Sensitivity and Specificity of Transthoracic Sonography There are only few investigations that report on the specificity and the sensitivity of TS. Moreover, data available to date are based on studies with a small number of patients only. The sensitivity of transthoracic sonography for pulmonary embolism has been estimated to vary between 80 and 94%, while the specificity varies between 84 and 92% [6, 7, 9]. These values are comparable to those calculated for sct with a specificity of % and a sensitivity of 76 95% [6, 7, 9, 37 44] (table 3). The positive and negative predictive values of transthoracic sonography for the detection of pulmonary embolism were 92 97% and 72 91%, respectively. Finally, the accuracy of the technique has been calculated to range from 82 to 91% [6, 7, 9], which is again comparable to that obtained by sct. Differential Diagnosis A number of differential diagnoses of peripheral PE have to be considered including pneumonia, bronchogenic carcinoma, lung metastases and pleurisy (table 2 and fig. 7). Pneumonia Pneumonia characteristically presents as a hypoechoic, and what is most important, non-homogenous consolidation with an essentially irregular shape which contrasts to the regular margin of embolic pulmonary lesions, usually allowing easy differentiation. In addition, a bronchoaerogram featuring as a branching echogenic structure as well as multiple lentil-sized air inclusions are typical characteristics of a lung infiltration due to pneumonia. Occasionally, a pneumonic parenchymal infiltration may reveal a fluid bronchogram sign, which is an anechoic tubular shadow within the hypoechoic area relating to fluidfilled bronchial structures. In this context, it should be kept in mind that the sonographic features of end-stage post-infarction pneumonia may adopt features resembling that of pneumonia making it impossible to differentiate the aetiology on sonographic features alone. Bronchogenic Carcinoma Bronchogenic carcinoma characteristically presents as an echo-poor area with a polycyclic shape. The lesions are not sharply demarcated as found in PE-related lesions and occasionally infiltrating growth into the adjacent tissue is visible, providing some additional diagnostic clues. Unimpaired breath-dependent motion of the lesion indicates a strictly intrapulmonary localisation while failing breathdependent motion indicate tumour growth crossing the border of the lung and infiltrating into the chest wall. Distal of the solid lesions, an area of increased echogenicity with amplification artefacts is usually visible. 446 Respiration 2003;70: Reissig/Kroegel

7 Fig. 7. Schematic representation of the sonomorphology of conditions to be considered in the differential diagnoses when pulmonary embolism is suspected. Table 3. Differential diagnostic criteria for sonography to distinguish between pulmonary embolism, pneumonia, bronchogenic carcinoma and lung metastases (modified after [15]) Pulmonary embolism Pneumonia Bronchogenic carcinoma Lung metastases Echogenicity hypoechoic hypoechoic hypoechoic hypoechoic Echotexture homogeneous (early PE) inhomogeneous (late PE) non-homogeneous mostly homogeneous homogeneous Shape triangular 1 round irregular polycyclic round or oval Bordering well-demarcated, sharp margins (late PE) blurred edges infiltrating growth sharp and smooth Broncho-aerogram none a regular feature none none Vascularity vascular sign regularly present; enhanced signal Characteristic features occasionally, a single central echo may be present fluid bronchogram may be visible irregular neo-vascularisation tissue necrosis (echo-free zones within the tumour) may occur irregular (if demonstrable) unimpaired breathdependent motion Transthoracic Ultrasound in the Diagnosis of Pulmonary Embolism Respiration 2003;70:

8 Fig. 8. Pulmonary embolism. A Sonogram. A 33-year-old man was admitted to hospital because of tachycardia, breathlessness and sweat exudation. Two wedge-shaped, hypoechoic pleural-based parenchymal lesion with a size of 11.7! 6.1 and 25.8! 9.4 mm are demonstrated on sonogram. The right lesion contains an echoic reflex within the triangle. B Corresponding spiral computed tomogram. Lung window imaging shows one dorsal, oval pleural-based consolidation and two lateral, triangular subpleural lesions. The latter correspond to the consolidations shown on sonogram. C Corresponding computed tomogram. Filling defects within the pulmonary arteries on both sides confirm the diagnosis of pulmonary embolism. Lung Metastases Lung metastases are typically less echogenic, round or oval in shape and are well demarcated structures which contrasts to the findings associated with a bronchogenic carcinoma. Due to the sharp margin, metastatic consolidations may occasionally resemble PE-caused lesions. Simple Pleurisy Simple pleurisy has also to be considered in the differential diagnosis of sonographic examination. Pleurisy may cause an irregular and broken echogenic pleural line, occasionally accompanied by localised pleural effusion. However, small hypoechoic subpleural and blurred bordered consolidations may occasionally be detected [21]. Advantages of Transthoracic Sonography in Diagnosing Pulmonary Embolism Due to recurrent embolism, an endogenous lytic system, or anticoagulant-induced lysis, PE represents an extremely dynamic process with constantly changing features [23]. The dynamic course is best visible by TS, which can be repeatedly applied. Further, TS is non-invasive, thus avoiding complications deriving from the administration of ionising radiation or contrast-medium [45]. Moreover, the advantages of TS in diagnosing PE also include the identification of minor peripheral events as well as the opportunity of repeated controls during the treatment period. In addition, the early detection of possible PE-related complications such as post-infarction pneumonia is advantageous. Finally, TS allows real-time imaging and can be performed immediately at the patient s bedside. The sensitivity of TS for the detection of emboli in subsegment vessels is better than that of CT. The poorer sensitivity may be caused by the limited spatial resolution of the CT. In addition, small subsegment vessels of both the upper and lower lobes lie outside the imaging range of CT. However, with new imaging techniques, such as multidetector spiral CT the depiction of subsegmental emboli will improve [46, 47]. It has been demonstrated that in PE, peripheral lesions and central obstruction of pulmonary artery branches occur simultaneously in about 80% of the cases [6, 7] (fig. 8). The thromboemboli may disintegrate mechanically or under the influence of intrinsic fibrinolytic activity into smaller fragments which continue to travel distally, resulting in multiple small emboli causing peripheral thromboembolisms. Therefore, TS offers the possibility depicting peripheral lesions and thus supplements other methods detecting central emboli. Thus, to date TS represents the most sensitive technique for detecting pleural effusion. Moreover, in contrast to other imaging techniques, TS also allows the detection of small localised effusions as well as the differentiation between localised and basal effusions. Although the causes of pleural effusion are multifold, detection of pleu- 448 Respiration 2003;70: Reissig/Kroegel

9 ral fluid collection in patients with suspected PE may represent an additional diagnostic feature. Limitations of Transthoracic Sonography in Diagnosing Pulmonary Embolism As with other diagnostic techniques, there are a number of limitations associated with TS-based exploration that occasionally limit the diagnostic potential of the method and have to be taken into consideration. First, only thromboembolic lesions extending up to the lung periphery can be detected although, this is often the case. However, on occasion, centrally located embolic alterations restricted to the central pulmonary arteries and to surfaces of a pulmonary lobe not adjoining to the chest wall escape sonographic detection, causing false-negative results of the sonographic exploration. Because of this, an inconspicuous sonographic exploration does not fully exclude pulmonary embolism. Second, only about two thirds of the peripheral lung areas are accessible to sonographic examination, the remainder being covered by bony structures of the thoracic cage. However, most peripheral emboli occur in the lower lobes which are readily accessible to TS. In addition, some lesions covered by overlying bones of the thoracic cage become accessible by performing special manoeuvres (see above). Moreover, as with all sonographic methods, the results obtained using TS are operator-dependent and the attending physician needs to be experienced and comfortable with the performance of TS-based thoracic exploration. Even in pulmonary angiography the inter-observer agreement for subsegmental emboli was only 66% [48]. Finally, to date, only data evidence grade B (US Agency for Health Care Policy and Research). Therefore, large multicentre studies to evaluate TS in diagnosing PE are under way. Comparison to Other Methods Diagnosing Pulmonary Embolism Diagnosing PE often requires the combination of several diagnostic methods. The sensitivities and specificities of various methods used when PE is suspected are demonstrated in table 3. For PE affecting the central pulmonary arteries a sensitivity of sct up to 100% has been reported [49]. Limitations of CT scanning include the poor visualisation of the subsegmental areas. Usually, pulmonary angiography is considered to be the diagnostic gold standard for PE. However, as the technique has never been evaluated against an independent reference standard it does not fulfil the criteria of a gold standard [50]. Thus, histological exploration has to be considered as the only true gold standard. The Significance of Peripheral Thromboembolism TS is based on detecting peripheral PE-caused lesions. However, to date, the diagnostic significance of small peripheral embolic lesions has not been clearly defined and continues to be a matter of debate. Thus, the question arises, which diagnostic significance these lesions have. Indeed, the clinical significance of small emboli in subsegmental vessels remains uncertain. Follow-up in the PIOPED study [51] showed that the sequelae of pulmonary embolism did not develop in patients with negative pulmonary angiograms, even though small emboli may have been missed in these patients. Thus, the early mortality of treated minor PE appears to be very low, supporting the belief of some that subsegmental emboli may not be clinically important. However, although there is little information on the risk of recurrence of PE in untreated patients one study showed fatal pulmonary embolism in 5% and recurrent non-fatal PE in a further 5% of untreated patients within 3 months of the initial PE [52]. The principle problem with these data is that the vast majority of small thromboembolic lesions escape detection due to the indifferent presentation and little or minor cardiopulmonary symptoms. In addition, peripheral thromboembolic lesions are mostly associated with central embolism. These epidemiological data testify to the fact that even small emboli may be of clinical significance in the course of the disease. Since mortality associated with pulmonary embolism has not changed throughout the past 40 years [23, 53] a different approach which also includes small peripheral lesions should be taken into consideration. Further, since the disease course including the recurrence of embolism is not predictable, all thromboembolic events have to be taken seriously and should be considered as a signum mali ominis [23]. Thromboemboli of a smaller size may indicate the presence of a hidden risk factor and may precede further thromboembolic events. To emphasise the potential significance of minor or small PE s without cardiopulmonary dysfunction, the term signal embolism has been coined [6, 23]. Transthoracic Ultrasound in the Diagnosis of Pulmonary Embolism Respiration 2003;70:

10 Outlook A number of important technical breakthroughs have been made in the past decade. Technical progress in ultrasonography is especially rapid now, due to continuing advances in transducer design, signal processing techniques, and Doppler technology. Among these, multidimensional array transducers, harmonic imaging, miniaturised transducers, extended field-of-view imaging, hand-carried ultrasound units, three-dimensional ultrasound, and new ultrasound contrast agents are the most important innovations. An extended field-of-view imaging provides a larger field for demonstration of pathology in certain anatomic locations. Hand-carried sonographic units are used widely in a physician s office or in remote areas, and bring high-quality medical imaging to the bedside. Together, these techniques provide improved spatial and contrast resolution allowing delineation of anatomic details and increasing diagnostic accuracy and confidence [54]. The recent introduction of tissue harmonic imaging may resolve the problems related to ultrasound in technically difficult patients by providing a marked improvement in image quality. Tissue harmonics are generated during the transmit phase of the pulse-echo cycle, that is, while the transmitted pulse propagates through tissue. Tissue harmonic images are formed by utilising the harmonic signals that are generated by tissue and by filtering out the fundamental echo signals that are generated by the transmitted acoustic energy. This imaging mode could be used in different organs with a heightening of low-contrast lesions through artefact reduction, allowing more powerful anatomic and functional evaluation of human organs [55] which may be particularly relevant in chest sonography. Advances in computer technology is expected to lead to more important breakthroughs in the next years which may further improve the potential of chest sonography. In addition to harmonic imaging, amplitude codedcolour Doppler sonography (ACDS), extended field of view, echo-enhanced, and three-dimensional ultrasound may be successfully applicable to pulmonary disorders such as PE. They amend sonographic diagnosis in many conditions, such as lung parenchymal lesion volume assessment, comprehensive visualisation of sonomorphology and complex pathology, evaluation of the perfusional characteristics of pulmonary alteration, superior documentation with improved comparability for follow-up, or simply by offering clearer tissue delineation and differentiation. Taken together, modern US techniques are successfully applicable to various organs including the lung, further boosting the value of US in the pulmonary conditions. As handling becomes more sophisticated, modern sonography will develop not only into a more powerful, but also a more demanding method, with the need for expert knowledge and dedicated training [56]. Concluding Remarks In the chest, the role of US has traditionally been limited to the evaluation of pleural effusion and guidance for thoracentesis, although its role in the diagnosis of pulmonary, pleural, and mediastinal masses has been emphasised for some years. As illustrated by an increasing number of recently published articles, TS is also gaining acceptance as an effective non-invasive diagnostic modality in PE. The results published to date using TS for detection of PE-associated thoracic lesions are encouraging and emphasises the potential role of TS in the diagnosis of pulmonary disorders. Ultrasound-based exploration of the thorax is be an attractive and safe alternative to other diagnostic techniques, with a high success rate in lesions that abut the chest wall, including apical, anterior mediastinal, and juxtadiaphragmatic lesions, as well as in parenchymal alterations with adjacent pleural effusions that may be present in PE. This technique is particularly well suited for very sick patients who are less able to cooperate. Thus, the TS-based procedure should be added to the armamentarium of diagnostic techniques employed when PE is suspected. Although TS has been compared with other diagnostic techniques large prospective, multicentre studies are urgently warranted. Acknowledgment The authors are indebted to Nasim Kroegel, BSc, for reviewing the manuscript. 450 Respiration 2003;70: Reissig/Kroegel

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