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CT of pulmonary thromboembolism
CT of Pulmonary Thromboembolism S. Melanie Greaves, Eric M. Hart, and Denise R. Aberle Conventional incremental CT has for many years been useful in the fortuitous diagnosis of pulmonary thromboembolic disease, allowing for visualization of both the central occluding thrombus and the pleuroparenchymal sequelae. U nfortunately, the slow data acquisition times precluded the inclusion of conventional CT in diagnostic algorithms for the diagnosis of this disease. The development and increasing availability of fast scanning techniques, namely helical (spirall CT and electron-beam CT, now provide a noninvasive means of consistently and accurately demonstrating acute and chronic pulmonary arterial thrombus to the segmental level. CT has the added advantage over ventilation-perfusion scanning and pulmonary angiography of depicting unsuspected intrathoracic disease that may account for the patient's presenting illness.
Copyright© 1997by W.B. Saunders Company
ONTEMPORARY HELICAL (spiral) computed tomography (cT) and electron-beam CT (EBT) have made the detection of pulmonary thromboembolic disease practical, allowing for direct visualization of the obstructing emboli and associated parenchymal and pleural sequelae. ~-4 Reduced acquisition times and the potential to acquire volumetric data sets in a single breath-hold enable consistent, reproducible imaging of the central pulmonary vasculature and reliable detection of both acute and chronic thromboembolic phenomena, s,6 This article will illustrate the CT features of acute and chronic pulmonary thromboembolic disease, discuss the emerging role of CT in the diagnosis of thromboembolic disease, and address its potential limitations.
C
ACUTE PULMONARY EMBOLISM
Existing Diagnostic Algorithms and Clinical Practice Pulmonary embolism (PE) accounts for 10% of all hospital deaths and is a contributing factor in an additional 10%. 7 Historically, the diagnosis of acute PE has relied heavily on clinical assessment in conjunction with the radionuclide ventilationperfusion (V-P) scan. The V-P scan provides a probability of PE based on the Presence, size, morphology, and multiplicity of perfusion defects relative to ventilation. The multi-institutional Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study aimed to determine the sensitivity and specificity of the V-P scan for acute PE. 8-1°Using data from more than 1,400 patients, the PIOPED study showed that V-P scans of high probability have a positive predictive value of 88%, whereas normal or near normal V-P scans have a negative predictive value of 91%. Although the clinical presentation of acute PE
(including clinical history, signs, symptoms, and results of chest radiographs, arterial blood gases, and electrocardiograms) is highly variable and nonspecific, the PIOPED study found that concordance between clinical suspicion and V-P scan result improves the predictive value. H,12 Specifically, the combination of a high clinical suspicion and high probability scan have a positive predictive value of 96% for PE; a low clinical suspicion and low probability scan have a 96% negative predictive value for PE. Unfortunately, approximately 75% of hospitalized patients have indeterminate (intermediate or low probability) V-P scans or discordance between clinical suspicion and the V-P scan. 8 In these patients, the diagnosis cannot be conclusively established without additional tests. Compounding this problem is a 25% to 30% interobserver disagreement in the interpretation of low and intermediate probability V-P scans. 8 in patients in whom there is unresolved suspicion of PE, most diagnostic algorithms require pulmonary angiography, which allows for the direct visualization of thrombus within the pulmonary arteries. Unfortunately, this investigation is costly, requires special expertise, and is not always immediately available. Although pulmonary angiography is relatively safe (0.5% mortality) and highly accurate in the diagnosis of PE, there is continued reluctance by physicians to subject patients to this invasive procedure. Based on practices at a major teaching hospital, Schluger et al found
From the Department of Radiology, North Staffordshire Hospitals Trust, United Kingdom; and Radiological Sciences, University of California Los Angeles School of Medicine, CA. Address reprint requests to S. Melanie Greaves, Radiology Department, City General Hospital, Newcastle Road, Stoke-onTrent, Staffordshire, ST4 6QG, United Kingdom. Copyright © 1997 by W.B. Saunders Company 0887-2171/97/1805-000655.00/0
Seminars in Ultrasound, CT, and MR/, Vo118, No 5 (October), 1997: pp 323-337
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that 78% of patients with intermediate probability scans and 92% of patients with low probability scans had no further imaging. 13 In these patients, the decision to treat or not treat was based on clinical grounds. This practice of "best clinical guess" is typical of most medical practice. 14,15 In light of this, an accurate, noninvasive, readily available and cost-effective test for the assessment of PE is needed that will improve the diagnosis and management of patients with potential pulmonary thromboembolism.
tory misregistration. Moreover. rapid acquisition times permit optimal enhancement of the pulmonary circulation with intravenous contrast. Electron-beam CT is an elegant, although less widely available, tool for pulmonary vascular imaging. With EBT, transaxial exposures can be reduced to 100 ms, permitting the option of ECG-gating as well as single breath-hold sequences with optimal contrast enhancement. In patients unable to breathhold, ultrafast exposures minimize respiratory motion artifacts. Although EBT sequences are not true volumetric data sets, prospective overlapping transaxial images can be acquired. With both helical and electron-beam technologies, rapid scanmng speeds permit the use of narrow collimation ( 1- to 3-mm effective slice thickness) for the generation of sophisticated multiplanar and 3D vascular reformations. 20
HELICAL CT AND ELECTRON-BEAM CT PULMONARY ANGIOGRAPHY
Although the fortuitous observation of unsuspected pulmonary emboli has been described with conventional incremental CT, !6J7 an accurate and reproducible method has awaited the advent of helical CT and EBT. The advantages of helical CT for vascular imaging have been well-described. 5,6,1s,19 Helical technology allows for data acquisition during continuous movement of the patient through the scanning gantry. The result is a volumetric data set from which trar~saxial reconstructions can be generated at overlapping intervals: Acquisition times are reduced with helical CT, and the region (volume) of interest Can usually be scanned during a single inspiratory breath-hold. This eliminates missed diagnosis of Small structures, such as pulmonary thrombi, through respir a-
EFFICACY OF HELICAL CT
Several studies have shown that fast scanning CT techniques have both high sensitivity and specificity for the detection of thrombus to the segmental arterial level (Table 1). 5"6"21-25 In one of the first prospective studies using spiral CT. RemyJardin et al showed a sensitivity of 100%. specificity of 96%. positive predictive value of 95%, and negative predictive value of 100% for the detection of central pulmonary emboli (segmental or more proximal) in 42 patients. 5
Table 1. Published Accuracy of Computed Tomography in Pulmonary Embolism Authors (Year)
N
Sensitivity
Specificity
PPV
NPV
Remy-Jardin et al (1992) s Goodman et al (1995) 21 Central vessels All vessels Teigen et al (1995) 22 1" Central vessels All vessels van Rossum et al (1996) 23 van Ressum et al (1996) 24 ~ Central vessels All vessels Remy-Jardin et al (1996) 25 Central vessels All vessels
42 20
100%
96%
95%
100%
86% 63%
92% 89%
86% 88%
92% 67%
88% 65% 71%
98% 97% 97%
94% 94% 83%
95% 82% 95%
92% 88%
95% 95%
93% 93%
95% 91%
95% 91%
75% 78%
100% 100%
95% 89%
60
45 149
75
Abbreviations: N, number of patients studied; PPV, positive predictive value; NPV, negative predictive value. Note: Calculations include patients with acute PE, chronic PE, or both~ In all studies, truth was taken to be findings at conventional pulmonary angiography, except where otherwise noted. tTruth was based on conventional pulmonary angiography (58 patients), pathology (1 patient), or clinical history with all image data (1 patient). STruth was based on conventional pulmonary angiography (56 patients) or normal or high-probability scintigraphy (93 Patients). Percentages shown represent the mean of two readers.
CT OF PULMONARY THROMBOEMBOLISM
Teigen et al reported similarly impressive degrees of diagnostic accuracy for central clot detection using EBT. 22 In the latter study of 60 patients with suspected PE, the EBT scan and angiogram were discordant in nine cases. The single falsepositive EBT study involved segmental thrombus not observed on an angiogram in which there was patien t motion. Of eight false-negative EBT studies, four involved very peripheral (subsegmental) thrombi in patients with negative lower extremity ultrasound examinations and two involved patients with subtle chronic emboli. In two patients, angiograms suggested thrombi that actually were central tumor and radiation change, respectively, finding s which were correctly recognized on EBT scans. 22 None of the patients with false-negative EBT scans was treated for thromboembolic disease. These degrees of accuracy have been reproduced using a number of different commercial scanners, scan techniques, and methods of contrast administration. In addition, the few studies that have addressed intra- and interobserver variability in the interpretation of CT pulmonary angiograms suggest concordance in the range of 75% to 95% overall.6,21,24 A major advantage of CT angiography over both V-P scanning and pulmonary angiography is the ability to document nonthromboembolic abnormalities of the lung, heart, or mediastinum that provide alternative diagnoses in patients with unexplained symptoms and clinical signs. 23,24,26 CURRENT CONTROVERSIES IN CT ANGIOGRAPHY Although helical CT is reliable for demonstrating main, lobar and segmental clot, the accuracy of CT for the detection of subsegmental thrombus decreases considerably. Goodman et al prospectively compared helical CT an d pulmonary angiography in 20 patients with unresolved suspicion for PE based on clinical assessment and V-P scan criteria. 21 When only the central vessels were analyzed, CT was 86% sensitive and 92% specific for the detection of acute thrombus. When subSegmental arteries were included, CT sensitivity decreased to 63%, diagnosing only one of four isolated subsegmental thrombi. Similar Observations were made by van R0ssum et al in a prospecfive study of 45 patients with suspected acute PE in whom both helical CT and classical pulmonary angiography were performed. 23 The prevalence and significance of subsegmental
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thrombus have been questioned from several perspectives. Acute thromboembolism typically involves multiple vessels: an average of 8 thrombi per patient were observed in the Urokinase Pulmonary Embolism Trial (UPET), 27 Remy-Jardin observed 6.2 emboli per patient, 5 and Teigen et al observed 6.8 emboli per patient. 6 The prevalence of isolated subsegmental clot is a matter Of debate. with data from existing studies somewhat variable. The PIOPED study observed that 5.6% of patients (14/251) had emboli confined to the subsegmental or more distal pulmonary arteries. 8 Although similar prevalence rates have been observed more recently, 26 Goodman et al found a significantly higher prevalence of 36% in their study of 20 patients. 21 van Rossum observed a 20% lncidenceY and Oser et al observed isolated peripheral thrombus in 30% of patients on retrospective review of conventional pulmonary angiograms. % In addition, the detection of subsegmental thrombus on pulmonary angiography, the existing gold standard, is also problematic: the PIOPED study found 98% interobserver agreement for lobar thrombus using this technique, but only 66% agreement for subsegmental thrombus. 8 The significance of isolated subsegmental thrombus in patients without underlying cardiopulmonary disease is controversial. Some investigators have suggested that "mild clot" confined to the subsegmental circulation may not require specific treatment if there is no residual thrombus in the lower extremity veins. 29-~1 Stein et al reported on the !-year follow-up of 20 patients from the PIOPED trial who were not treated within 3 months of the initial event. 29 Of this cohort, all had low or intermediate probability V-P scans, and 84% had segmental or more peripheral clot. Among untreated and treated patients (the latter of whom had significantly different scintigrams and fewer peripheral clots on angiography), there was no difference in the frequency of fatal or recurrent PE, suggesting that there may be a category of "mild PE" that does not require specific treatment. Hull et al followed up patients with abnormal, but indeterminate V-P scans who had no significant cardiopulmonary disease and no evidence of deep vein thrombosis on serial lower extremity ultrasound examinations. 3° These patients received no anticoagulation and fewer than 3% suffered subsequent thromboembolic events. Novelline et al followed up 167 patients with suspected PE despite
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negative pulmonary angiograms for a minimum of 6 months. 31 No patient died from PE or suffered recurrent emboli, implying that if subsegmental or smaller emboli were present, they were not associated with significant morbidity or mortality. In contrast, in patients with severe cardiac or pulmonary disease, even subsegmental thrombus may be associated with significant morbidity and mortality, particularly if the occluded vessels supply areas of relatively normal lung: 25 TECHNICAL CONSIDERATIONS IN HELICAL CT In constructing an optimum protocol for CT pulmonary angiography, several parameters must be considered. These include adequate spatial resolution, the imaging volume, acquisition time (and therefore duration of suspended breath-hold), and peak vascular enhancement (Table 2). 4 Some invest!gators have found that fixed parameters PrOvide consistently good image quality in the majority of patients. 21 However, it may be necessary to individualize acquisition parameters in certain patients, and it is important to understand the influences of each of these parameters on the final image. High spatial resolution is importan t because of the deleterious effects of volume averaging on the conspicuity of thrombus in small vessels. With Table 2. Protocol Parameters for CT Pulmonary Angiography Image Sequence
Recommendation
Helical whole chest (noncontrast) 7-10 mm Collimation 1-2 Pitch 7-10 mm Reconstruction interval Timing injection Non-ionic iodinated (300-350 Contrast mg I/L) 20 mL at 3 mL/s (4-5 cc/s in Volume/rate individual patients) Initial delay: 6-8 seconds, then Acquisition timing every2s×26s Helical vascular sequence 12-15 cm (based on nonconScan volume trast sequence) Caudo-cranial direction 3 mm Collimation i-2 (pitch = 1 for non-breathPitch hold sequences) 2mm Reconstruction interval 15 seconds (or based On Scan delay timing injection + 3-5 seconds) 120-140 mL (based on scan Contrast volume length) >-3 mL/s Contrast flow rate
helical techniques, the spatial quality of the reconstructed image, the effective slice thickness, is dictated by three parameters: beam collimation. speed of table incrementation, and interpolation algorithm (usually 180 ° linear interpolation). The scan pitch defines the relationship between table mcrementation and beam collimation. In scanners with a 1-second gantry rotation, the following formula applies: Pitch = Table speed (cm/s)/ collimation (cm). For CT pulmonary angiography, collimations range from 3 to 5 m m with table speeds producing a pitch ranging from 1 to 2. Increasing the table speed (and therefore the pitch), produces a minor increase in effective slice thickness, but ensures coverage of the entire volume of interest in a single breath-hold. In patients unable to breath-hold, there will be varying, but unavoidable. degrees of respiratory misregistration. The acquisition time does not need to correspond to a breathhold in these patients and slower table speeds (eg, pitch of 1) ensure a greater sampling frequency through the region of interest. Image noise using 180 ° interpolation algorithms is somewhat increased compared with conventional CT and may be particularly evident with techniques using narrow beam collimation. Fortunately, CT x-ray tube generators with higher heat capacity have been introduced that may overcome this limitation of helical technology. The scan volume must encompass the main. lobar, and segmental pulmonary arteries of the upper and lower lobes, typically a 12- to 15-cm cephalocaudal distance. The scan volume is precisely determined by use of an initial noncontrast helical scan (7 to 10 mm collimation, pitch of 1 to 2), from which the pertinent vascular anatomy is localized. In addition to identifying anatomic landmarks, this initial scan provides a complete survey of the chest and may identify unsuspected pathology that is causing or contributing m the patient's symptoms and illness. N0n-ionic iodinated contrast material (300 m 350 mg I/mL) is usually administered by mechamcal injection through an upper extremity peripheral intravenous catheter. Flow rates from 3 to 7 mL/s have been reported, although a 3-mL/s flow rate normally provides adequate vascular enhancement. 4 In patients with poor cardiac function or very low systemic vascular resistance, higher flow rates (4 to 5 mL/s) may be necessary to achieve adequate vascular enhancement. Timing injections are used to establish the ideal
CT OF PULMONARY THROMBOEMBOLISM
delay between the initiation of bolus contrast injection and commencement of scanning. Using a small contrast bolus (usually 20 mL), serial scans are acquired at 1- to 2-second intervals at a single level through the central pulmonary arteries, from which a time-attenuation curve can be constructed. For the actual CT angiogram, it is prudent to add 3 to 5 seconds to the measured time of peak enhancement to ensure optimal enhancement of the peripheral pulmonary arteries. The scan delay from the start of bolus injection is typically 10 to 15 seconds in hemodynamically stable patients; this delay may increase to 30 seconds in patients with severe pulmonary hypertension or significantly compromised cardiac function. Failure to achieve opacification of the central pulmonary vessels with the timing injection should prompt a thorough search for possible technical causes such as local contrast extravasation at the catheter insertion site, venous obstruction of the raised arm at the thoracic inlet, or injector malfunction. In patients in whom the contrast injection has been "piggy-backed" into an existing intravenous line, retrograde filling of the primary solution must be avoided by completely occluding the primary circuit. In some patients with hemodynamic instability, it may be very difficult to achieve adequate opacification of the pulmonary artery circulation using peripheral intravenous access sites. In such patients, central venous catheters provide reliable access, but care must be taken to ensure that flow and pressure rates do not exceed manufacturer recommendations and that the catheter is meticulously cleaned. The contrast column (duration of contrast injection) should roughly parallel the scan acquisition time, although slightly increasing the length of the contrast column beyond the estimated scan time will ensure adequate vascular enhancement through the end of the sequence. Some investigators suggest using a bolus of normal saline immediately after the contrast injection to advance the entire contrast column into the central circulation. 32 ACUTE PULMONARY THROMBUS: VASCULAR APPEARANCES
Acute thrombus appears as a central filling defect in the vascular lumen or as complete occlusion of the vessel (Figs 1, 2). 5,22There is, typically, mild enlargement of the affected vessel at the site of thrombus (Fig 2). At the segmental level, the artery should always be seen in close proximity to its corresponding bronchus. In the upper lobes, the
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Fig 1. Acute pulmonary thromboemboli in a patient following surgery. (A) Helical CT shows a large filling defect within the left pulmonary artery, extending into the origin of the left upper lobe pulmonary artery (arrow). There is complete occlusion of the truncus anterior (arrowhead). (B) Additional thrombus extends into the basal segmental arteries of the right lower lobe (arrows).
arteries run medial to their corresponding bronchi while in the right middle lobe, lingula, and both lower lobes, the arteries run laterally. Technical failures and inconclusive scans are the main practical limitations of helical CT for the depiction of acute thrombi. 25 Technical failures occur in 1% to 4% of scans, and are usually the result of either motion artifact in patients with severe dyspnea or inadequate vascular opacification. 23,25 Poor vascular enhancement may result from faulty scanning techniques (see above) or from physiological conditions such as congenital cardiovascular disease with large right-to-left shunts, poor cardiac function, or low systemic vascular resistance. Inconclusive scans, in which findings are indeter-
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the lingular and right middle lobe vessels, 5,6,21 can be minimized by decreasing the effective slice thickness, using overlapping reconstructions, or performing multiplanar reconstructions. 2° Flow phenomena that produce central low density within vessels oriented perpendicular to the scan have been observed. This is often seen in vessels scanned either early or late in the sequence. The mechanisms responsible for this have not been elucidated, but likely relate to principals of laminar flow, fluid viscosity, and uneven mixing of the contrast column with unopacified blood from the lower extremities. Awareness of this phenomenon and careful interpretation of sequential images usually permit the distinction between flow artifact and true thrombus. Finally, a thorough knowledge of pulmonary vascular anatomy is required for the correct interpretation of spiral CT pulmonary angiograms. Intersegmental lymph nodes, unopacified veins, inspissated secretions in companion bronchi, or post-inflammatory injury may all be misinterpreted as segmental pulmonary emboli (Figs 3 through 5). 25As alluded to previously, a major advantage of CT over other pulmonary vascular imaging modalities is its ability to show other intrathoracic pathology that may be responsible for patient symptoms or morbidity (Figs 6, 7). Fig 2. Acute thromboembolic disease affecting the posterior basal segment of the right lower lobe. (A) Helical CT shows central intraluminal clot within the right posterior basal pulmonary artery (arrow). There is a small ipsilateral right pleural effusion. (B) On the corresponding lung window image, there is dilatation of the affected vessel relative to other arteries of corresponding size (arrow).
minate in a specific vascular territory, have been reported in up to 10% of CT pulmonary angiograms and are also multifactorial. 21'22'25In patients unable to sustain breath-holding for the duration of the scan, motion artifacts may obscure the terminal vascular territories. It is helpful to scan in a caudo-cranial direction in those patients unable to breath-hold to the very end of the acquisition, the upper thorax being less sensitive to the effects of respiratory motion. 21 Motion artifacts are considerably less problematic with EBT because of subsecond exposure times. However, regardless of scanner, motion may produce respiratory misregistration and inadequate sampling of the pulmonary vessels. Inadequate visualization of arteries that are obliquely oriented within the scan plane, such as
PARENCHYMAL CHANGES OF ACUTE PULMONARY EMBOLISM
It has been estimated that less than 10% of thromboembolic events result in lung infarction. 33 If vascular collaterals are sufficient to prevent pulmonary infarction, radiological findings may reflect oligemia or hemorrhage without necrosis. Infarction is particularly uncommon in otherwise healthy individuals, but becomes more likely in patients with cardiopulmonary disease who have impaired bronchial collateral circulation and/or pulmonary venous hypertension. On chest radiographs, the classical appearance of a pulmonary infarct, the Hampton's hump, is a well-defined region of consolidation with a broad pleural base and a truncated apex directed toward the hilum. This is observed in only about 10% of cases. In 1978, Sinner described the CT appearance of a triangular pulmonary density with a broad pleural base and its tip directed toward the hilum as suggestive of pulmonary infarction (Fig 8). 34 He predicted that the opacity could vary in morphology based on the anatomy of the secondary pulmo-
CT OF PULMONARY THROMBOEMBOLISM
329
immediately subtended by the embolus are perfused adequately by bronchial collaterals. Low attenuation regions without overt cavitation are frequently visible within the body of an infarct (Fig 9). I On HRCT, these appear as areas of ground-glass opacity with underlying reticulation. CT-pathologic correlation has shown that these areas represent viable lung intermixed with infarcted secondary pulmonary lobules. 35 Two reasons for this have been postulated: first, that the uninfarcted lobules are supplied by contiguous, non-embolized pulmonary arteries and, second, that the viable lobules were not being perfused at the time of the embolic shower. 33Although peripheral parenchymal opacities have a multitude of causes, the CT finding of a peripheral, irregularly polyhedral opacity with a truncated apex and central low attenuation is highly suggestive of infarction. The presence of a vascular sign, in which a thickened vessel extends to the apex,
Fig 3. Intersegmental lymph nodes simulating thrombus. (A) On the EBT transaxial image, lymphoid tissue along the under surface of the left upper lobe pulmonary artery can be confused with clot (arrow). (B) Multiplanar reformations may be helpful in distinguishing nodal tissue from the adjacent pulmonary artery (arrow).
nary lobule. The secondary pulmonary lobule, demonstrable on high-resolution computed tomography (HRCT), comprises three to five acini, is bounded by connective tissue septa, and is irregularly polyhedral in shape. Pulmonary arteries supplying the lobules are true end-arteries and the interlobular septa divide one terminal pulmonary bed from another. It is possible, therefore, to infarct isolated lobules. 37 Lobules are randomly organized and, because the configuration of an infarct depends on the number and location of affected lobules, infarcts are often irregularly shaped. Infarcts will have a truncated apex if the lobules
r
L Fig 4. Unopacified pulmonary vein simulating pulmonary artery thrombus. (A) Helical CT image acquired early in the contrast bolus shows low attenuation in a right upper lobe pulmonary vein (arrow). (B) The corresponding lung window shows that this vessel has no companion bronchus, confirming that it is a venous structure (arrow),
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GREAVES, HART, AND ABERLE
Fig 6. An 87-year-old female with hemoptysis and right pleuritic chest pain. Helical CT shows a large pleural-based opacity in the right upper lobe and right hilar lymphadenopathy. This was initially thought to represent thrombus with infarction. Overlapping reconstructions documented patency of the right upper lobe pulmonary artery; biopsy was remarkable for adenocarcinoma.
Fig 5. Mucous impaction simulating thrombus in an elderly patient with dyspnea and suspected pulmonary embolism. (A) Helical CT through the right lung base shows circular low density within the posterior basal segmental bronchus (arrow), which was initially confused with acute thrombus. (B) On the lung window image 2 mm cephalad, there is moderate peribronchial cuffing and mucous inspissation within the bronchus (arrow), The patient responded to vigorous pulmonary toilet.
tissue. The arterial supply is established by recanalization of the embolized artery or development of a systemic supply from the chest wall or diaphragm. 38 A vascular blush may be demonstrated on pulmonary angiography performed 2 or 3 weeks after the thromboembolic event. Contrast-enhanced CT performed at this time may show peripheral enhancement. McGoldrick et al reviewed serial chest radiographs in 32 patients with 58 angiographically proven infarcts; some decrease in size of the infarct was observed within 2 to 4 weeks and
increases the likelihood that it is an infarct (Fig 10). 36
Pulmonary hemorrhage invariably accompanies infarction; therefore, acute infarcts are typically surrounded by a hemorrhagic zone. The hemorrhage usually clears rapidly over the course of a few days and the infarct will become more precisely defined on CT (Fig 11). In contrast to pneumonic consolidation, which gradually becomes more heterogeneous in attenuation as it clears, an infarct decreases in size from the periphery while maintaining its original shape (Fig 9). 37 This appearance has been likened to that of a melting ice cube. As healing progresses, the necrotic parenchyma is demarcated from the surrounding lung by a hypervascular zone of organization
Fig 7. A 56-year-old female with dyspnea. On helical CT, large pleural effusions have effected considerable passive atelectasis of both lower lobes. Despite the consolidation and volume loss, the segmental arteries enhance normally. There was no pulmonary thromboembolism.
CT OF PULMONARY THROMBOEMBOLISM
Fig 8. A 26-year-old male with dyspnea, acute pulmonary embolus and infarction. Helical CT image through the left lower lobe shows discrete intraluminal thrombus in the posterior basal segmental artery {arrow). A triangular-shaped low density opacity within the subtended lung corresponds to pulmonary infarction, There is an incidental pericardial effusion.
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Fig 10. The vascular sign in a 48-year-old man with a left lower lobe infarct. Helical CT shows a left lower lobe Segmental vessel occluded by embolus (arrow) that subtends a wedge-shaped parenchymal infarct. (Reprinted with permission. 1)
Fig 9. Pulmonary infarction with partial resolution and secondary infection in a female with congestive cardiomyopathy. (A) Helical CT through the right lung base at the time of presentation demonstrates a characteristic pleural-based mass with mild peripheral enhancement. (B) The corresponding lung w i n d o w demonstrates central heterogeneous opacity and reticulation. (C) Follow-up CT 10 weeks after the acute event shows decreasing infarct size with residual local pleural thickening. (D) The patient later presented with bacteremia and secondary infection of the infarct. On repeat CT, there is now cavitation of the infarct.
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GREAVES, HART, AND ABERLE
originate from infected heart valves, indwelling venous catheters, and pacemaker leads or from peripheral Skin iesions. Kuhlman et al reviewed CT scans in 18 patients with documented pulmonary septic emboli. 4° Septic emboli were most commonly observed as multiple peripheral pulmonary nodule s that showed cavitation in 50% of patients and that were predominantly basal in distribution. Feeding veSSels were present in 67% of these lesions ~ indicating hematogenous spread (Fig 12). Also observed were wedge-shaped peripheral opacities~ air bronchograms within peripheral nodules, and involvement of the pleural spac e. PLEURAL EFFUSIONS Pleural effusions are commonly associated with pulmonary thromboembolism and develop soon after the onset of symptoms. They are typically Small and unilateral, reaching maximal size in the first 3 days. Pulmonary infarction is usually associi ated with larger effusions that may be hemorrhagic and are presumably related to the inflammatory response resulting from lung necrosis. Effusions that are delayed in onset or that progressively increase in size later in the course of the disease suggest recurrent PE or superimposed refection. •
"
'
41
Fig 11. A 64-year-old male with left ventricular dysfunction and right lower lobe infarction. (A) Initial helical CT shows airspace disease in the right 10we r lobe representing extensive pulmonary hemorrhage. (B)RePeat CT performed 2 weeks later shows resolution of much Of the initial hemorrhage revealing the underlying, more typical, features of pulmonary infarction. (Reprinted with permission,I)
resolution was well underway in all cases within 3 months. 39 Radiographic abnormalities persisting at one year usually remain unchanged and consist of linear fibrous scars, localized pleural thickening or diaphragmatic pleural adhesions. COMPLICATED INFARCTS AND SEPTIC EMBOLI Cavitation is rare in uninfected pulmonary infarcts and was not demonstrated in any of 58 infarcts followed for at least 3 months by McGoldrick et al. 39The development of cavitation usually implies secondary infection (Fig 9). Cavitation is commonly associated with septic emboli that may
Fig 12. A 2g-year-old female with infective endocarditis secondary to intravenous drug abuse; Helical CT shows t w o peripheral left lung nodules, one of which is cavitary. A feeding vessel can be seen extending to the )eft upper lobe lesion (arrow). iRePrinted with permission. 1)
CT OF PULMONARY THROMBOEMBOLISM
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CT IN CHRONIC THROMBOEMBOLIC DISEASE
Chronic pulmonary thromboembolic disease is a rare cause of pulmonary arterial hypertension and right ventricular failure. In this disease, pulmonary arterial thrombi fail to lyse completely and become organized, resulting in varying degrees of vascular occlusion. Chronic thromboembolic disease typically presents as exertional dyspnea; a history of deep venous thrombosxs or pulmonary embolism is unusual. Anticoagulant therapy is commonly ineffective and thrombi may continue to increase in size. Both the pulmonary vascular and right heart changes may, however, improve following successful pulmonary thromboendarterectomy.4243 Chest radiographs in chronic thromboembolic disease are often normal, or may show enlarged central pulmonary arteries, patchy oligemia, or pleuro-parenchymal scarring. Helical CT (or EBT) angiography may show chronic thromboemboli as eccentric filling defects with or without calcification. Complete arterial occlusions also occur, although in contrast to acute PE, the affected vessel is usually of reduced caliber (Fig 13). In a study by Schwickert et al, direct visualization of intraluminal thrombus on CT alone permitted the diagnosis of chronic thromboembolism in 53 of 75 patients. 42 Indirect signs that support chronic pulmonary thromboembolism include irregularity of the arterial walls, abrupt narrowing of vessel diameter, abrupt cutoff of distal lobar or segmental branches, vascular distortion, strictures, and webs (Fig 14). 42 Pulmonary thromboendarterectomy may be appropriate in those patients who have surgically accessible thrombus proximal to the lobar level. Conventional pulmonary angiography has limited utility in determining technical operability, because it is not sufficiently precise in detecting proximal thrombus which may be adherent to vessel walls. 44 In contrast, the sensitivity of CT in predicting technical operability, when correlated with surgery, was 77%. On the basis of these findings, Schwickert et al suggested that CT angiography be routinely used in the diagnosis and therapeutic assessment of chronic pulmonary thromboembolic disease. 42 PARENCHYMAL SEQUELAE OF CHRONIC THROMBOEMBOLIC DISEASE
With chronic thromboembolic disease, the occlusion of arterioles supplying secondary lobules produces geometric patterns of alternating low and normal or high lung attenuation. The subtending
Fig 13. A 27-year-old male with presumed primary pulmonary hypertension, found to have chronic pulmonary thromboembolic disease at CT angiography. (A) Helical CT image at the level of the right interlobar artery shows discrete thrombus (arrow). (B) Lung win¢low image at a slightly lower level shows marked diminution in size of the right interlobar artery and disproportionate enlargement of the proximal right middle lobe pulmonary artery (arrow), Additional thrombi were seen in other pulmonary arteries (not shown),
arteries in areas of low lung attenuation are typically diminutive, whereas enlarged pulmonary arteries subtend the higher attenuation parenchyma (Figs 13, 14). 43,45 This pattern of heterogeneous lung attenuation has been termed "mosaic oligemia" (or mosaic perfusion). King et al observed that the low attenuation regions correspond to perfusion defects on radionuclide SPECT scans, and therefore represent regional hypoperfusion.43 Focal peripheral linear and nodular opacities resulting from lung infarction also occur. There are potential difficulties in the CT evaluation of chronic thromboembolic disease. Small concentric thrombi adherent to the vessel wall may not be visualized; moreover, discrete stenoses and vascular webs are less well appreciated on CT than on conventional pulmonary angiography. Mosaic
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GREAVES, HART, AND ABERLE
oligemia secondary to vascular occlusive disease must be distinguiShed from other causes of low lung attenuation, such as emphysema and air trapping from bronchiolar diseases. 46 Emphysema is usually recognizable as regions of lung destruction. Identifying regional air trapping may be difficult unless there is associated bronchiectasis or other visible alteration of bronchial morphology, although expiratory CT sequences may produce attenuation patterns Characteristic of air trapping. Air trapping may also produce variations in vessel caliber, but these vascular alterations are frequently more dramatic in chronic thromboembolic disease, enabling differentiation of this disease from airflow obstruction.43, 45 PROPOSED CLINICAL PATHWAYS IN PULMONARY EMBOLISM
Cost Considerations
Fig 14. Vascular Webs and distortions in a 43-year-old female with chronic pulmonary thromboembolic disease. (A} Helical CT image shows a linear web within the left descending pulmonary artery (arrow), (B) On a lower section, there are linear filling defects within basal segmental bronchi Of both lower lobes (arrows). (C) Lung window image demonstrates there is a large, tortuous vessel supplying the superior segment of the left lower lobe. The subtending lung is of increased attenuation resulting in a mosaic attenuation pattern. Oligemia and vascular attenuation are evident in the Superior segment of the right lower lobe, representing a fixed perfusion defect.
There are a number of tests available for the diagnosis of PE, each with their own merits and limitations, making the design of a rational diagnostic algorithm challenging. Any comparison of algorithms must consider some measure of patient outcome and/or costs. The determining variables include the actual costs of each diagnostic examination, possible complications, the accuracy of the test, the prevalence of the disease in question, and the consequences of treatment or nontreatment. 4,47-49 A number of investigators have analyzed diagnostic algorithms for acute PE. 47'49 In a recent study, van Erkel et al eValuated the cost-effectiveness of 12 realistic diagnostic strategies that incorporated combinations of V-P scintigraphy, ultrasound of the lower extremities, D-dimer assay, conventional angiography, and helical CT angiography, using either of the latter two investigations as the final test. 49 To put these diagnostic strategies into perspective, three additional reference strategies were analyze& no treatment, anticoagulant treatment in all patients, and an ideal diagnostic strategy with 100% accuracy and no diagnostic costs. The values of baseline variables were derived from data pooled from the recent literature. In the experimental design, it was assumed that the appropriate therapeutic action was taken and no further diagnostic tests were performed under the following conditions: lower extremity ultrasound results were positive for deep venous thrombosis, the D-dimer test was negative, or V-P scans were interpreted as normal or high probability. The outcome measures were
CT OF PULMONARYTHROMBOEMBOLISM patient mortality at 3 months, morbidity at 3 months, and the average realistic costs of diagnosis and treatment of PE. When mortality was the primary outcome measure, the best diagnostic strategies all included helical CT angiography; lower extremity ultrasound followed by helical CT was the superior strategy. If cost per life saved was the primary outcome measure, helical CT angiography was again included in all of the best strategies. The use of the D-dimer assay before helical CT angiography improved the marginal cost-effectiveness (cost per life saved), but effected an increase in mortality. Interestingly, the inclusion of the V-P scan to limit the number of helical CT angiograms increased both mortality and cost per life saved. The sensitivity of helical CT for the detection of acute PE is critical to these cost analyses. 49 If this sensitivity decreases to less than 85%, then a strategy incorporating helical CT has a higher mortality than one using conventional pulmonary angiography. Sensitivities of 85% or greater with helical CT are supported by the literature if consideration is restricted to assessment of the segmental or more proximal arteries (Table 1). However, Remy-Jardin et al observed clinically significant subsegmental thrombus in four patients with underlying cardiopulmonary disease, and postulated that in these patients, conventional pulmonary angiography should be performed if lower extremity ultrasound and helical CT are negative. 25 The significance of isolated subsegmental clot will need to be addressed with longitudinal follow-up of affected patients. The prevalence of PE is also a consideration in diagnostic algorithms for acute PE. Gefter et al have suggested that algorithms using helical CT for the diagnosis and treatment of PE are more costeffective than traditional strategies that use V-P scans when the disease prevalence exceeds 10% to 30%, largely because of the frequency of nondiagnostic results. 4
335 published recommendations, the conventional pulmonary angiogram is heavily underused and most management decisions are based on "best clinical guess." Third, cost analyses suggest that V-P scans are not cost-effective in patient groups in which the prevalence of disease exceeds 10% to 30%, and they are seldom diagnostic in patients with underlying cardiopulmonary disease. Finally, the significance of peripheral clot (eg, clot isolated to the subsegmental or more distal pulmonary circulation) is controversial in patients without underlying cardiopulmonary disease in whom there is no evidence of residual clot burden in the lower extremities. Given the above considerations as well as the published accuracies of CT angiography for segmental or more proximal thrombus, the following diagnostic algorithm is proposed (Fig 15) for patients with suspected pulmonary thromboembolism. In patient groups with a low prevalence of PE (such as those presenting to the emergency room) in whom there is low clinical suspicion of PE and no significant underlying cardiopulmonary disease, scintigraphy is an acceptable first test. In most patients of this type, the study will be normal and no further evaluation is indicated. The prevalence and clinical suspicion of acute PE are much higher in hospitalized patients. In these patients, algorithms that include Doppler ultrasound of the lower extremities and CT pulmonary angiography are appropriate. If one test is negative, the other test should be performed. For example, a negative CT angiogram excludes throm-
Suspected/ PE
CTA ~ [+] TREAT-- STOP LE Doppler " ~ [.] 0 r ~ f I Angiogram F/U LE Doppler [High]---~ TREAT V-P [Normal]---I~STOP [Indet] ~ CTA / [ + ]
TREAT
or
ProposedAlgorithm There are a number of limitations in the historical diagnostic algorithm for acute PE. First, although normal and high-probability V-P scans offer reasonable certainty as to the absence or presence of thrombus, respectively, scintigraphy is nondiagnostic or discordant with clinical suspicion in the majority of hospitalized patients. Second, despite
LE Doppler'~ [-]
STOP
Fig 15. Proposed diagnostic algorithm for suspected pulmonary embolism. (1) High prevalence group; preexisting cardiopulmonary disease. (2) Low prevalence group; no underlying cardiopulmonary disease. (3) Contraindication to CTA (IV contrast allergy, etc.). Abbreviations: PE, pulmonary embolism; CTA, CT pulmonary angiography; V-P, ventilationperfusion scintigraphy; LE Doppler, lower extremity Doppler ultrasound; angiogram, conventional pulmonary angiogram.
336
GREAVES, HART, AND ABERLE
bus to the s e g m e n t a l arterial level, whereas a n e g a t i v e e x a m i n a t i o n o f the l o w e r extremities eliminates significant potential residual clot burden. In patients with severe underlying heart or lung disease, e v e n peripheral ( s u b s e g m e n t a l or distal) clot places these patients at risk o f m o r b i d or mortal complications. In these patients, p u l m o n a r y a n g i o g r a p h y should be p e r f o r m e d if the results o f both l o w e r e x t r e m i t y D o p p l e r ultrasound and C T p u l m o n a r y a n g i o g r a p h y are n e g a t i v e Y Finally, C T p u l m o n a r y a n g i o g r a m s are technically challenging examinations that should be super-
vised only by e x p e r i e n c e d radiologists. Just as with c o n v e n t i o n a l angiography, there is a learning curve in the p e r f o r m a n c e and interpretation of these studies. T h e efficacy of C T p u l m o n a r y angiography has been validated at institutions in which limited numbers o f radiologists p e r f o r m the examinations and there are rigorous quality control policies, such as w e e k l y case reviews, and m a n d a t o r y multiple readings. The C T p u l m o n a r y a n g i o g r a m should not replace traditional diagnostic tests unless there are e q u i v a l e n t m e c h a n i s m s in place to ensure proper training, experience, and quality control.
REFERENCES
1. Greaves SM, Brown K, Young DA, et al: Pulmonary thromboembolism: Spectrum of findings on CT. AJR 165:13591363, 1995 2. Goodman LR, Lipchik RJ: Diagnosis of acute pulmonary embolism: Time for a new approach. Radiology 199:25-27, 1996 3. Gurney JW: No fooling around: Direct visualization of pulmonary embolism. Radiology 188:618-619, 1993 4. Gefter WB, Hatabu H, Holland GA, et al: Pulmonary thromboembolism: Recent developments in diagnosis with CT and MR imaging. Radiology 197:561-574, 1995 5. Remy-Jardin M, Remy J, Wattinne L, et al: Central pulmonary thromboembolism: Diagnosis with spiral volumetric CT with single-breath-hold-technique: Comparison with pulmonary angiography. Radiology 185:381-387, 1992 6. Teigen CL, Maus TR Sheedy PF, et al: Pulmonary embolism: Diagnosis with electron-beam CT. Radiology 188: 839-845, 1993 7. Linblad B, Sternby WH, Berquist D: Incidence of venous thromboembolism verified by necropsy over 30 years. Br Med J 302:709-711, 1991 8. The PIOPED investigators: Value of the ventilation/ perfusion scan in acute pulmonary embolism: Results of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED). JAMA 263:2753-2759, 1990 9. Gottschalk A, Juni JE, Sostman HD, et al: Ventilationperfusion scintigraphy in the PIOPED study. Part I. Data collection and tabulation. J Nucl Med 34:1109- l 118, 1993 10. Gottschalk A, Sostman HD, Coleman RE, et al: Ventilation-perfusion scintigraphy in the PIOPED study. Part II. Evaluation of the scintigraphic criteria and interpretations. J Nucl Med 34:1119-1126, 1993 11. Stein PD, Terrin ML, Hales CT, et al: Clinical, laboratory, roentgenographic, and electrocardiographic findings in patients with acute pulmonary embolism and no preexisting cardiac or pulmonary disease. Chest 100:598-603, I991 12. Worsley DE Alavi A: Comprehensive analysis of the results of the PIOPED study. J Nucl Med 36:2380-2387, 1995 13. Schulger N, Henschke C, King T, et al: Diagnosis of pulmonary embolism at a large teaching hospital. J Thorac Imag 9:180-184, 1994 14. Sostman HD, Ravin CE, Sullivan DC, et al: Use of pulmonary angiography for suspected pulmonary embolism: Influence of scintigraphic diagnosis. AJR 139:673-677, 1982
15. Henschke CI, Mateescu I, Yankelevitz DF: Changing practice patterns in the workup of pulmonary embolism. Chest 107:940-945, 1995 16. Verschakelen JA, Vanwijck E, Bogaert J, et al: Detection of unsuspected central pulmonary embolism with conventional contrast-enhanced CT. Radiology 188:847-850, 1993 17. Chintapalli K, Thorsen K, Olsen DL, et al: Computed tomography of pulmonary thromboembolism and infarction. J Comput Assist Tomogr 12:553-559, 1988 18. Rubin GD, Date MD, Semba CP: Current status of three-dimensional spiral CT scanning for imaging the vasculature. Radiol Clin North Am 33:51-70, 1995 19. Brink JA, Heiken JR Wang G, et al: Helical CT: Principles and technical considerations. Radiographics 14:887893, 1994 20. Remy-Jardin M, Remy J, Cauvain O, et al: Diagnosis of central pulmonary embolism with helical CT: Role of twodimensional multiplanar reformations. AJR 165:1131-1138, 1995 21. Goodman LR, Curtin JJ, Mewissen MW, et al: Detection of pulmonary embolism in patients with unresolved clinical and scintigraphic diagnosis: Helical CT versus angiography. AJR 164:1369-1374, 1995 22. Teigen CL, Maus TR Sheedy PE et al: Pulmonary embolism: Diagnosis with contrast-enhanced electron-beam CT and comparison with pulmonary angiography. Radiology 194: 313-319, 1995 23. van Rossum AB, Treurniet FEE, Kieft GJ, et al: Role of spiral volumetric computed tomographic scanning in the assessment of patients with clinical suspicion of pulmonary embolism and an abnormal ventilation/perfusion lung scan. Thorax 51:2328, 1996 24. van Rossum AB, Pattynama PMT, Ton ERTA, et al: Pulmonary embolism: Validation of spiral CT angiography in 149 patients. Radiology 201:467-470, 1996 25. Remy-Jardin M, Remy J, Deschildre F, et al: Diagnosis of pulmonary embolism with spiral CT: Comparison with pulmonary angiography and scintigraphy. Radiology 200:699-706, 1996 26. Hull RD, Raskob GE, Carter CJ, et al: Pulmonary embolism in outpatients with pleuritic chest pain. Arch Intern Med 148:838-844, 1988 27. UPET: Urokinase pulmonary embolism trial: Phase 1 results--A cooperative study. JAMA 214:2163-2172, 1970
CT OF PULMONARY THROMBOEMBOLISM
28. Oser RF, Zuckerman DA, Gutierrez FR, et al: Anatomic distribution of pulmonary emboli at pulmonary angiography: Implications for cross-sectional imaging. Radiology 199:31-35, 1996 29. Stein PD, Henry JW, Relyea B: Untreated patients with pulmonary embolism. Outcome, clinical, and laboratory assessment. Chest 107:931-935, 1995 30. Hull RD, Raskob GE, Coates G, et al: Anew noninvasive management strategy for patients with suspected pulmonary embolism. Arch Intern Med 149:2549-2555, 1989 31. Novelline RA, Baltarowich OH, Athanasoulis CA, et aI: The clinical course of patients with suspected pulmonary embolism and a negative pulmonary arteriogram. Radiology 126:561-567, 1978 32. Hopper KD: The optimization of thoracic CT utilizing 50 cc of contrast power injected with a saline push and a patient-specific timed delivery technique. AJR 166:209, 1996 (abstr) 33. Heitzman ER, Markarian B, Dailey ET: Pulmonary thromboembolic disease: A lobular concept. Radiology 103:529537, i972 34. Sinner WN: Computed tomographic patterns of pulmonary thromboembolism and infarction. J Comput Assist Tomogr 2:395-399, 1978 35. Balakxishnan J, Meziane MA, Siegelman SS, et aI: Pulmonary infarction: CT appearance with pathologic correlation. J Comput Assist Tomogr 13:941-945, 1989 36. Ren H, Kuhlman JE, Hruban RH, et al: CT of inflationfixed lungs: Wedge-shaped density and vascular sign in the diagnosis of infarction. J Comput Assist Tomogr 14:82-86, 1990 37. Woesner ME, Sanders I, White GW: The melting sign in resolving transient pulmonary infarction. AJR 111:782-790, 1971 38. Groskin SA: Pulmonary embolism and infarction and pulmonary arterial hypertension, Groskin SA (ed): Heitzman's
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The Lung, Radiologic-Pathologic Correlations (ed 3). St. Louis, MO, Mosby-Year Book, 1993, pp 106-149 39. McGoldrick PJ, Rudd TG, Figley MM, et al: What becomes of pulmonary infarcts? AJR 133:1039-1045, 1979 40. Kuhlman JE, Fishman EK, Teigen C: Pulmonary septic emboli: Diagnosis with CT. Radiology 174:211-213, 1990 41. Bynum LJ, Wilson JE Ilk Radiographic features of pleural effusions in pulmonary embolism. Am Rev Respir Dis 117:829-834, 1978 42. Schwickert HC, Schweden F, Schild HH, et al: Pulmonary arteries and lung parencbyma in chronic pulmonary embolism: Preoperative and postoperative CT findings. Radiology 191:351-357, 1994 43. King MA, Bergin CJ, Yeung DWC, et al: Chronic pulmonary thromboembolism: Detection of regional hypoperfusion with CT. Radiology 191:359-363, 1994 44. Tardivon AA, Musset D, Maitre S, et al: Role of CT in chronic pulmonary embolism: Comparison with pulmonary angiography. J Comput Assist Tomogr 17:345-351, 1993 45. Bergin CJ, Rios G, King MA, et al: Accuracy of high-resolution CT in identifying chronic pulmonary thromboembolic disease. AJR 166:1371-1377, 1996 46. Stern EJ, Swensen SJ, Hartman TE, et al: CT mosaic pattern of lung attenuation: Distinguishing different causes. AJR 165:813-836, i995 47. Henschke CI, Yankelevitz DF, Mateescu I, et al: Evaluation of competing tests for the diagnosis of pulmonary embolism and deep vein thrombosis, part I. Clinical imaging 18:241-247, 1994 48. Henschke CI, Yankelevitz DF, Mateescu l, et al: Evaluation of competing diagnostic tests: Sequences for the diagnosis of pulmonary embolism, part II. Clinical Imaging 18:248-254, 1994 49. Van Erkel AR, van Rossum AB, Bloem JL, et al: Spiral CT angiography for suspected pulmonary embolism: A costeffective analysis. Radiology 201:29-36, 1996
Copyright© 1997by W.B. Saunders Company
ONTEMPORARY HELICAL (spiral) computed tomography (cT) and electron-beam CT (EBT) have made the detection of pulmonary thromboembolic disease practical, allowing for direct visualization of the obstructing emboli and associated parenchymal and pleural sequelae. ~-4 Reduced acquisition times and the potential to acquire volumetric data sets in a single breath-hold enable consistent, reproducible imaging of the central pulmonary vasculature and reliable detection of both acute and chronic thromboembolic phenomena, s,6 This article will illustrate the CT features of acute and chronic pulmonary thromboembolic disease, discuss the emerging role of CT in the diagnosis of thromboembolic disease, and address its potential limitations.
C
ACUTE PULMONARY EMBOLISM
Existing Diagnostic Algorithms and Clinical Practice Pulmonary embolism (PE) accounts for 10% of all hospital deaths and is a contributing factor in an additional 10%. 7 Historically, the diagnosis of acute PE has relied heavily on clinical assessment in conjunction with the radionuclide ventilationperfusion (V-P) scan. The V-P scan provides a probability of PE based on the Presence, size, morphology, and multiplicity of perfusion defects relative to ventilation. The multi-institutional Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study aimed to determine the sensitivity and specificity of the V-P scan for acute PE. 8-1°Using data from more than 1,400 patients, the PIOPED study showed that V-P scans of high probability have a positive predictive value of 88%, whereas normal or near normal V-P scans have a negative predictive value of 91%. Although the clinical presentation of acute PE
(including clinical history, signs, symptoms, and results of chest radiographs, arterial blood gases, and electrocardiograms) is highly variable and nonspecific, the PIOPED study found that concordance between clinical suspicion and V-P scan result improves the predictive value. H,12 Specifically, the combination of a high clinical suspicion and high probability scan have a positive predictive value of 96% for PE; a low clinical suspicion and low probability scan have a 96% negative predictive value for PE. Unfortunately, approximately 75% of hospitalized patients have indeterminate (intermediate or low probability) V-P scans or discordance between clinical suspicion and the V-P scan. 8 In these patients, the diagnosis cannot be conclusively established without additional tests. Compounding this problem is a 25% to 30% interobserver disagreement in the interpretation of low and intermediate probability V-P scans. 8 in patients in whom there is unresolved suspicion of PE, most diagnostic algorithms require pulmonary angiography, which allows for the direct visualization of thrombus within the pulmonary arteries. Unfortunately, this investigation is costly, requires special expertise, and is not always immediately available. Although pulmonary angiography is relatively safe (0.5% mortality) and highly accurate in the diagnosis of PE, there is continued reluctance by physicians to subject patients to this invasive procedure. Based on practices at a major teaching hospital, Schluger et al found
From the Department of Radiology, North Staffordshire Hospitals Trust, United Kingdom; and Radiological Sciences, University of California Los Angeles School of Medicine, CA. Address reprint requests to S. Melanie Greaves, Radiology Department, City General Hospital, Newcastle Road, Stoke-onTrent, Staffordshire, ST4 6QG, United Kingdom. Copyright © 1997 by W.B. Saunders Company 0887-2171/97/1805-000655.00/0
Seminars in Ultrasound, CT, and MR/, Vo118, No 5 (October), 1997: pp 323-337
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that 78% of patients with intermediate probability scans and 92% of patients with low probability scans had no further imaging. 13 In these patients, the decision to treat or not treat was based on clinical grounds. This practice of "best clinical guess" is typical of most medical practice. 14,15 In light of this, an accurate, noninvasive, readily available and cost-effective test for the assessment of PE is needed that will improve the diagnosis and management of patients with potential pulmonary thromboembolism.
tory misregistration. Moreover. rapid acquisition times permit optimal enhancement of the pulmonary circulation with intravenous contrast. Electron-beam CT is an elegant, although less widely available, tool for pulmonary vascular imaging. With EBT, transaxial exposures can be reduced to 100 ms, permitting the option of ECG-gating as well as single breath-hold sequences with optimal contrast enhancement. In patients unable to breathhold, ultrafast exposures minimize respiratory motion artifacts. Although EBT sequences are not true volumetric data sets, prospective overlapping transaxial images can be acquired. With both helical and electron-beam technologies, rapid scanmng speeds permit the use of narrow collimation ( 1- to 3-mm effective slice thickness) for the generation of sophisticated multiplanar and 3D vascular reformations. 20
HELICAL CT AND ELECTRON-BEAM CT PULMONARY ANGIOGRAPHY
Although the fortuitous observation of unsuspected pulmonary emboli has been described with conventional incremental CT, !6J7 an accurate and reproducible method has awaited the advent of helical CT and EBT. The advantages of helical CT for vascular imaging have been well-described. 5,6,1s,19 Helical technology allows for data acquisition during continuous movement of the patient through the scanning gantry. The result is a volumetric data set from which trar~saxial reconstructions can be generated at overlapping intervals: Acquisition times are reduced with helical CT, and the region (volume) of interest Can usually be scanned during a single inspiratory breath-hold. This eliminates missed diagnosis of Small structures, such as pulmonary thrombi, through respir a-
EFFICACY OF HELICAL CT
Several studies have shown that fast scanning CT techniques have both high sensitivity and specificity for the detection of thrombus to the segmental arterial level (Table 1). 5"6"21-25 In one of the first prospective studies using spiral CT. RemyJardin et al showed a sensitivity of 100%. specificity of 96%. positive predictive value of 95%, and negative predictive value of 100% for the detection of central pulmonary emboli (segmental or more proximal) in 42 patients. 5
Table 1. Published Accuracy of Computed Tomography in Pulmonary Embolism Authors (Year)
N
Sensitivity
Specificity
PPV
NPV
Remy-Jardin et al (1992) s Goodman et al (1995) 21 Central vessels All vessels Teigen et al (1995) 22 1" Central vessels All vessels van Rossum et al (1996) 23 van Ressum et al (1996) 24 ~ Central vessels All vessels Remy-Jardin et al (1996) 25 Central vessels All vessels
42 20
100%
96%
95%
100%
86% 63%
92% 89%
86% 88%
92% 67%
88% 65% 71%
98% 97% 97%
94% 94% 83%
95% 82% 95%
92% 88%
95% 95%
93% 93%
95% 91%
95% 91%
75% 78%
100% 100%
95% 89%
60
45 149
75
Abbreviations: N, number of patients studied; PPV, positive predictive value; NPV, negative predictive value. Note: Calculations include patients with acute PE, chronic PE, or both~ In all studies, truth was taken to be findings at conventional pulmonary angiography, except where otherwise noted. tTruth was based on conventional pulmonary angiography (58 patients), pathology (1 patient), or clinical history with all image data (1 patient). STruth was based on conventional pulmonary angiography (56 patients) or normal or high-probability scintigraphy (93 Patients). Percentages shown represent the mean of two readers.
CT OF PULMONARY THROMBOEMBOLISM
Teigen et al reported similarly impressive degrees of diagnostic accuracy for central clot detection using EBT. 22 In the latter study of 60 patients with suspected PE, the EBT scan and angiogram were discordant in nine cases. The single falsepositive EBT study involved segmental thrombus not observed on an angiogram in which there was patien t motion. Of eight false-negative EBT studies, four involved very peripheral (subsegmental) thrombi in patients with negative lower extremity ultrasound examinations and two involved patients with subtle chronic emboli. In two patients, angiograms suggested thrombi that actually were central tumor and radiation change, respectively, finding s which were correctly recognized on EBT scans. 22 None of the patients with false-negative EBT scans was treated for thromboembolic disease. These degrees of accuracy have been reproduced using a number of different commercial scanners, scan techniques, and methods of contrast administration. In addition, the few studies that have addressed intra- and interobserver variability in the interpretation of CT pulmonary angiograms suggest concordance in the range of 75% to 95% overall.6,21,24 A major advantage of CT angiography over both V-P scanning and pulmonary angiography is the ability to document nonthromboembolic abnormalities of the lung, heart, or mediastinum that provide alternative diagnoses in patients with unexplained symptoms and clinical signs. 23,24,26 CURRENT CONTROVERSIES IN CT ANGIOGRAPHY Although helical CT is reliable for demonstrating main, lobar and segmental clot, the accuracy of CT for the detection of subsegmental thrombus decreases considerably. Goodman et al prospectively compared helical CT an d pulmonary angiography in 20 patients with unresolved suspicion for PE based on clinical assessment and V-P scan criteria. 21 When only the central vessels were analyzed, CT was 86% sensitive and 92% specific for the detection of acute thrombus. When subSegmental arteries were included, CT sensitivity decreased to 63%, diagnosing only one of four isolated subsegmental thrombi. Similar Observations were made by van R0ssum et al in a prospecfive study of 45 patients with suspected acute PE in whom both helical CT and classical pulmonary angiography were performed. 23 The prevalence and significance of subsegmental
325
thrombus have been questioned from several perspectives. Acute thromboembolism typically involves multiple vessels: an average of 8 thrombi per patient were observed in the Urokinase Pulmonary Embolism Trial (UPET), 27 Remy-Jardin observed 6.2 emboli per patient, 5 and Teigen et al observed 6.8 emboli per patient. 6 The prevalence of isolated subsegmental clot is a matter Of debate. with data from existing studies somewhat variable. The PIOPED study observed that 5.6% of patients (14/251) had emboli confined to the subsegmental or more distal pulmonary arteries. 8 Although similar prevalence rates have been observed more recently, 26 Goodman et al found a significantly higher prevalence of 36% in their study of 20 patients. 21 van Rossum observed a 20% lncidenceY and Oser et al observed isolated peripheral thrombus in 30% of patients on retrospective review of conventional pulmonary angiograms. % In addition, the detection of subsegmental thrombus on pulmonary angiography, the existing gold standard, is also problematic: the PIOPED study found 98% interobserver agreement for lobar thrombus using this technique, but only 66% agreement for subsegmental thrombus. 8 The significance of isolated subsegmental thrombus in patients without underlying cardiopulmonary disease is controversial. Some investigators have suggested that "mild clot" confined to the subsegmental circulation may not require specific treatment if there is no residual thrombus in the lower extremity veins. 29-~1 Stein et al reported on the !-year follow-up of 20 patients from the PIOPED trial who were not treated within 3 months of the initial event. 29 Of this cohort, all had low or intermediate probability V-P scans, and 84% had segmental or more peripheral clot. Among untreated and treated patients (the latter of whom had significantly different scintigrams and fewer peripheral clots on angiography), there was no difference in the frequency of fatal or recurrent PE, suggesting that there may be a category of "mild PE" that does not require specific treatment. Hull et al followed up patients with abnormal, but indeterminate V-P scans who had no significant cardiopulmonary disease and no evidence of deep vein thrombosis on serial lower extremity ultrasound examinations. 3° These patients received no anticoagulation and fewer than 3% suffered subsequent thromboembolic events. Novelline et al followed up 167 patients with suspected PE despite
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GREAVES, HART, AND ABERLE
negative pulmonary angiograms for a minimum of 6 months. 31 No patient died from PE or suffered recurrent emboli, implying that if subsegmental or smaller emboli were present, they were not associated with significant morbidity or mortality. In contrast, in patients with severe cardiac or pulmonary disease, even subsegmental thrombus may be associated with significant morbidity and mortality, particularly if the occluded vessels supply areas of relatively normal lung: 25 TECHNICAL CONSIDERATIONS IN HELICAL CT In constructing an optimum protocol for CT pulmonary angiography, several parameters must be considered. These include adequate spatial resolution, the imaging volume, acquisition time (and therefore duration of suspended breath-hold), and peak vascular enhancement (Table 2). 4 Some invest!gators have found that fixed parameters PrOvide consistently good image quality in the majority of patients. 21 However, it may be necessary to individualize acquisition parameters in certain patients, and it is important to understand the influences of each of these parameters on the final image. High spatial resolution is importan t because of the deleterious effects of volume averaging on the conspicuity of thrombus in small vessels. With Table 2. Protocol Parameters for CT Pulmonary Angiography Image Sequence
Recommendation
Helical whole chest (noncontrast) 7-10 mm Collimation 1-2 Pitch 7-10 mm Reconstruction interval Timing injection Non-ionic iodinated (300-350 Contrast mg I/L) 20 mL at 3 mL/s (4-5 cc/s in Volume/rate individual patients) Initial delay: 6-8 seconds, then Acquisition timing every2s×26s Helical vascular sequence 12-15 cm (based on nonconScan volume trast sequence) Caudo-cranial direction 3 mm Collimation i-2 (pitch = 1 for non-breathPitch hold sequences) 2mm Reconstruction interval 15 seconds (or based On Scan delay timing injection + 3-5 seconds) 120-140 mL (based on scan Contrast volume length) >-3 mL/s Contrast flow rate
helical techniques, the spatial quality of the reconstructed image, the effective slice thickness, is dictated by three parameters: beam collimation. speed of table incrementation, and interpolation algorithm (usually 180 ° linear interpolation). The scan pitch defines the relationship between table mcrementation and beam collimation. In scanners with a 1-second gantry rotation, the following formula applies: Pitch = Table speed (cm/s)/ collimation (cm). For CT pulmonary angiography, collimations range from 3 to 5 m m with table speeds producing a pitch ranging from 1 to 2. Increasing the table speed (and therefore the pitch), produces a minor increase in effective slice thickness, but ensures coverage of the entire volume of interest in a single breath-hold. In patients unable to breath-hold, there will be varying, but unavoidable. degrees of respiratory misregistration. The acquisition time does not need to correspond to a breathhold in these patients and slower table speeds (eg, pitch of 1) ensure a greater sampling frequency through the region of interest. Image noise using 180 ° interpolation algorithms is somewhat increased compared with conventional CT and may be particularly evident with techniques using narrow beam collimation. Fortunately, CT x-ray tube generators with higher heat capacity have been introduced that may overcome this limitation of helical technology. The scan volume must encompass the main. lobar, and segmental pulmonary arteries of the upper and lower lobes, typically a 12- to 15-cm cephalocaudal distance. The scan volume is precisely determined by use of an initial noncontrast helical scan (7 to 10 mm collimation, pitch of 1 to 2), from which the pertinent vascular anatomy is localized. In addition to identifying anatomic landmarks, this initial scan provides a complete survey of the chest and may identify unsuspected pathology that is causing or contributing m the patient's symptoms and illness. N0n-ionic iodinated contrast material (300 m 350 mg I/mL) is usually administered by mechamcal injection through an upper extremity peripheral intravenous catheter. Flow rates from 3 to 7 mL/s have been reported, although a 3-mL/s flow rate normally provides adequate vascular enhancement. 4 In patients with poor cardiac function or very low systemic vascular resistance, higher flow rates (4 to 5 mL/s) may be necessary to achieve adequate vascular enhancement. Timing injections are used to establish the ideal
CT OF PULMONARY THROMBOEMBOLISM
delay between the initiation of bolus contrast injection and commencement of scanning. Using a small contrast bolus (usually 20 mL), serial scans are acquired at 1- to 2-second intervals at a single level through the central pulmonary arteries, from which a time-attenuation curve can be constructed. For the actual CT angiogram, it is prudent to add 3 to 5 seconds to the measured time of peak enhancement to ensure optimal enhancement of the peripheral pulmonary arteries. The scan delay from the start of bolus injection is typically 10 to 15 seconds in hemodynamically stable patients; this delay may increase to 30 seconds in patients with severe pulmonary hypertension or significantly compromised cardiac function. Failure to achieve opacification of the central pulmonary vessels with the timing injection should prompt a thorough search for possible technical causes such as local contrast extravasation at the catheter insertion site, venous obstruction of the raised arm at the thoracic inlet, or injector malfunction. In patients in whom the contrast injection has been "piggy-backed" into an existing intravenous line, retrograde filling of the primary solution must be avoided by completely occluding the primary circuit. In some patients with hemodynamic instability, it may be very difficult to achieve adequate opacification of the pulmonary artery circulation using peripheral intravenous access sites. In such patients, central venous catheters provide reliable access, but care must be taken to ensure that flow and pressure rates do not exceed manufacturer recommendations and that the catheter is meticulously cleaned. The contrast column (duration of contrast injection) should roughly parallel the scan acquisition time, although slightly increasing the length of the contrast column beyond the estimated scan time will ensure adequate vascular enhancement through the end of the sequence. Some investigators suggest using a bolus of normal saline immediately after the contrast injection to advance the entire contrast column into the central circulation. 32 ACUTE PULMONARY THROMBUS: VASCULAR APPEARANCES
Acute thrombus appears as a central filling defect in the vascular lumen or as complete occlusion of the vessel (Figs 1, 2). 5,22There is, typically, mild enlargement of the affected vessel at the site of thrombus (Fig 2). At the segmental level, the artery should always be seen in close proximity to its corresponding bronchus. In the upper lobes, the
327
Fig 1. Acute pulmonary thromboemboli in a patient following surgery. (A) Helical CT shows a large filling defect within the left pulmonary artery, extending into the origin of the left upper lobe pulmonary artery (arrow). There is complete occlusion of the truncus anterior (arrowhead). (B) Additional thrombus extends into the basal segmental arteries of the right lower lobe (arrows).
arteries run medial to their corresponding bronchi while in the right middle lobe, lingula, and both lower lobes, the arteries run laterally. Technical failures and inconclusive scans are the main practical limitations of helical CT for the depiction of acute thrombi. 25 Technical failures occur in 1% to 4% of scans, and are usually the result of either motion artifact in patients with severe dyspnea or inadequate vascular opacification. 23,25 Poor vascular enhancement may result from faulty scanning techniques (see above) or from physiological conditions such as congenital cardiovascular disease with large right-to-left shunts, poor cardiac function, or low systemic vascular resistance. Inconclusive scans, in which findings are indeter-
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the lingular and right middle lobe vessels, 5,6,21 can be minimized by decreasing the effective slice thickness, using overlapping reconstructions, or performing multiplanar reconstructions. 2° Flow phenomena that produce central low density within vessels oriented perpendicular to the scan have been observed. This is often seen in vessels scanned either early or late in the sequence. The mechanisms responsible for this have not been elucidated, but likely relate to principals of laminar flow, fluid viscosity, and uneven mixing of the contrast column with unopacified blood from the lower extremities. Awareness of this phenomenon and careful interpretation of sequential images usually permit the distinction between flow artifact and true thrombus. Finally, a thorough knowledge of pulmonary vascular anatomy is required for the correct interpretation of spiral CT pulmonary angiograms. Intersegmental lymph nodes, unopacified veins, inspissated secretions in companion bronchi, or post-inflammatory injury may all be misinterpreted as segmental pulmonary emboli (Figs 3 through 5). 25As alluded to previously, a major advantage of CT over other pulmonary vascular imaging modalities is its ability to show other intrathoracic pathology that may be responsible for patient symptoms or morbidity (Figs 6, 7). Fig 2. Acute thromboembolic disease affecting the posterior basal segment of the right lower lobe. (A) Helical CT shows central intraluminal clot within the right posterior basal pulmonary artery (arrow). There is a small ipsilateral right pleural effusion. (B) On the corresponding lung window image, there is dilatation of the affected vessel relative to other arteries of corresponding size (arrow).
minate in a specific vascular territory, have been reported in up to 10% of CT pulmonary angiograms and are also multifactorial. 21'22'25In patients unable to sustain breath-holding for the duration of the scan, motion artifacts may obscure the terminal vascular territories. It is helpful to scan in a caudo-cranial direction in those patients unable to breath-hold to the very end of the acquisition, the upper thorax being less sensitive to the effects of respiratory motion. 21 Motion artifacts are considerably less problematic with EBT because of subsecond exposure times. However, regardless of scanner, motion may produce respiratory misregistration and inadequate sampling of the pulmonary vessels. Inadequate visualization of arteries that are obliquely oriented within the scan plane, such as
PARENCHYMAL CHANGES OF ACUTE PULMONARY EMBOLISM
It has been estimated that less than 10% of thromboembolic events result in lung infarction. 33 If vascular collaterals are sufficient to prevent pulmonary infarction, radiological findings may reflect oligemia or hemorrhage without necrosis. Infarction is particularly uncommon in otherwise healthy individuals, but becomes more likely in patients with cardiopulmonary disease who have impaired bronchial collateral circulation and/or pulmonary venous hypertension. On chest radiographs, the classical appearance of a pulmonary infarct, the Hampton's hump, is a well-defined region of consolidation with a broad pleural base and a truncated apex directed toward the hilum. This is observed in only about 10% of cases. In 1978, Sinner described the CT appearance of a triangular pulmonary density with a broad pleural base and its tip directed toward the hilum as suggestive of pulmonary infarction (Fig 8). 34 He predicted that the opacity could vary in morphology based on the anatomy of the secondary pulmo-
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329
immediately subtended by the embolus are perfused adequately by bronchial collaterals. Low attenuation regions without overt cavitation are frequently visible within the body of an infarct (Fig 9). I On HRCT, these appear as areas of ground-glass opacity with underlying reticulation. CT-pathologic correlation has shown that these areas represent viable lung intermixed with infarcted secondary pulmonary lobules. 35 Two reasons for this have been postulated: first, that the uninfarcted lobules are supplied by contiguous, non-embolized pulmonary arteries and, second, that the viable lobules were not being perfused at the time of the embolic shower. 33Although peripheral parenchymal opacities have a multitude of causes, the CT finding of a peripheral, irregularly polyhedral opacity with a truncated apex and central low attenuation is highly suggestive of infarction. The presence of a vascular sign, in which a thickened vessel extends to the apex,
Fig 3. Intersegmental lymph nodes simulating thrombus. (A) On the EBT transaxial image, lymphoid tissue along the under surface of the left upper lobe pulmonary artery can be confused with clot (arrow). (B) Multiplanar reformations may be helpful in distinguishing nodal tissue from the adjacent pulmonary artery (arrow).
nary lobule. The secondary pulmonary lobule, demonstrable on high-resolution computed tomography (HRCT), comprises three to five acini, is bounded by connective tissue septa, and is irregularly polyhedral in shape. Pulmonary arteries supplying the lobules are true end-arteries and the interlobular septa divide one terminal pulmonary bed from another. It is possible, therefore, to infarct isolated lobules. 37 Lobules are randomly organized and, because the configuration of an infarct depends on the number and location of affected lobules, infarcts are often irregularly shaped. Infarcts will have a truncated apex if the lobules
r
L Fig 4. Unopacified pulmonary vein simulating pulmonary artery thrombus. (A) Helical CT image acquired early in the contrast bolus shows low attenuation in a right upper lobe pulmonary vein (arrow). (B) The corresponding lung window shows that this vessel has no companion bronchus, confirming that it is a venous structure (arrow),
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Fig 6. An 87-year-old female with hemoptysis and right pleuritic chest pain. Helical CT shows a large pleural-based opacity in the right upper lobe and right hilar lymphadenopathy. This was initially thought to represent thrombus with infarction. Overlapping reconstructions documented patency of the right upper lobe pulmonary artery; biopsy was remarkable for adenocarcinoma.
Fig 5. Mucous impaction simulating thrombus in an elderly patient with dyspnea and suspected pulmonary embolism. (A) Helical CT through the right lung base shows circular low density within the posterior basal segmental bronchus (arrow), which was initially confused with acute thrombus. (B) On the lung window image 2 mm cephalad, there is moderate peribronchial cuffing and mucous inspissation within the bronchus (arrow), The patient responded to vigorous pulmonary toilet.
tissue. The arterial supply is established by recanalization of the embolized artery or development of a systemic supply from the chest wall or diaphragm. 38 A vascular blush may be demonstrated on pulmonary angiography performed 2 or 3 weeks after the thromboembolic event. Contrast-enhanced CT performed at this time may show peripheral enhancement. McGoldrick et al reviewed serial chest radiographs in 32 patients with 58 angiographically proven infarcts; some decrease in size of the infarct was observed within 2 to 4 weeks and
increases the likelihood that it is an infarct (Fig 10). 36
Pulmonary hemorrhage invariably accompanies infarction; therefore, acute infarcts are typically surrounded by a hemorrhagic zone. The hemorrhage usually clears rapidly over the course of a few days and the infarct will become more precisely defined on CT (Fig 11). In contrast to pneumonic consolidation, which gradually becomes more heterogeneous in attenuation as it clears, an infarct decreases in size from the periphery while maintaining its original shape (Fig 9). 37 This appearance has been likened to that of a melting ice cube. As healing progresses, the necrotic parenchyma is demarcated from the surrounding lung by a hypervascular zone of organization
Fig 7. A 56-year-old female with dyspnea. On helical CT, large pleural effusions have effected considerable passive atelectasis of both lower lobes. Despite the consolidation and volume loss, the segmental arteries enhance normally. There was no pulmonary thromboembolism.
CT OF PULMONARY THROMBOEMBOLISM
Fig 8. A 26-year-old male with dyspnea, acute pulmonary embolus and infarction. Helical CT image through the left lower lobe shows discrete intraluminal thrombus in the posterior basal segmental artery {arrow). A triangular-shaped low density opacity within the subtended lung corresponds to pulmonary infarction, There is an incidental pericardial effusion.
331
Fig 10. The vascular sign in a 48-year-old man with a left lower lobe infarct. Helical CT shows a left lower lobe Segmental vessel occluded by embolus (arrow) that subtends a wedge-shaped parenchymal infarct. (Reprinted with permission. 1)
Fig 9. Pulmonary infarction with partial resolution and secondary infection in a female with congestive cardiomyopathy. (A) Helical CT through the right lung base at the time of presentation demonstrates a characteristic pleural-based mass with mild peripheral enhancement. (B) The corresponding lung w i n d o w demonstrates central heterogeneous opacity and reticulation. (C) Follow-up CT 10 weeks after the acute event shows decreasing infarct size with residual local pleural thickening. (D) The patient later presented with bacteremia and secondary infection of the infarct. On repeat CT, there is now cavitation of the infarct.
332
GREAVES, HART, AND ABERLE
originate from infected heart valves, indwelling venous catheters, and pacemaker leads or from peripheral Skin iesions. Kuhlman et al reviewed CT scans in 18 patients with documented pulmonary septic emboli. 4° Septic emboli were most commonly observed as multiple peripheral pulmonary nodule s that showed cavitation in 50% of patients and that were predominantly basal in distribution. Feeding veSSels were present in 67% of these lesions ~ indicating hematogenous spread (Fig 12). Also observed were wedge-shaped peripheral opacities~ air bronchograms within peripheral nodules, and involvement of the pleural spac e. PLEURAL EFFUSIONS Pleural effusions are commonly associated with pulmonary thromboembolism and develop soon after the onset of symptoms. They are typically Small and unilateral, reaching maximal size in the first 3 days. Pulmonary infarction is usually associi ated with larger effusions that may be hemorrhagic and are presumably related to the inflammatory response resulting from lung necrosis. Effusions that are delayed in onset or that progressively increase in size later in the course of the disease suggest recurrent PE or superimposed refection. •
"
'
41
Fig 11. A 64-year-old male with left ventricular dysfunction and right lower lobe infarction. (A) Initial helical CT shows airspace disease in the right 10we r lobe representing extensive pulmonary hemorrhage. (B)RePeat CT performed 2 weeks later shows resolution of much Of the initial hemorrhage revealing the underlying, more typical, features of pulmonary infarction. (Reprinted with permission,I)
resolution was well underway in all cases within 3 months. 39 Radiographic abnormalities persisting at one year usually remain unchanged and consist of linear fibrous scars, localized pleural thickening or diaphragmatic pleural adhesions. COMPLICATED INFARCTS AND SEPTIC EMBOLI Cavitation is rare in uninfected pulmonary infarcts and was not demonstrated in any of 58 infarcts followed for at least 3 months by McGoldrick et al. 39The development of cavitation usually implies secondary infection (Fig 9). Cavitation is commonly associated with septic emboli that may
Fig 12. A 2g-year-old female with infective endocarditis secondary to intravenous drug abuse; Helical CT shows t w o peripheral left lung nodules, one of which is cavitary. A feeding vessel can be seen extending to the )eft upper lobe lesion (arrow). iRePrinted with permission. 1)
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333
CT IN CHRONIC THROMBOEMBOLIC DISEASE
Chronic pulmonary thromboembolic disease is a rare cause of pulmonary arterial hypertension and right ventricular failure. In this disease, pulmonary arterial thrombi fail to lyse completely and become organized, resulting in varying degrees of vascular occlusion. Chronic thromboembolic disease typically presents as exertional dyspnea; a history of deep venous thrombosxs or pulmonary embolism is unusual. Anticoagulant therapy is commonly ineffective and thrombi may continue to increase in size. Both the pulmonary vascular and right heart changes may, however, improve following successful pulmonary thromboendarterectomy.4243 Chest radiographs in chronic thromboembolic disease are often normal, or may show enlarged central pulmonary arteries, patchy oligemia, or pleuro-parenchymal scarring. Helical CT (or EBT) angiography may show chronic thromboemboli as eccentric filling defects with or without calcification. Complete arterial occlusions also occur, although in contrast to acute PE, the affected vessel is usually of reduced caliber (Fig 13). In a study by Schwickert et al, direct visualization of intraluminal thrombus on CT alone permitted the diagnosis of chronic thromboembolism in 53 of 75 patients. 42 Indirect signs that support chronic pulmonary thromboembolism include irregularity of the arterial walls, abrupt narrowing of vessel diameter, abrupt cutoff of distal lobar or segmental branches, vascular distortion, strictures, and webs (Fig 14). 42 Pulmonary thromboendarterectomy may be appropriate in those patients who have surgically accessible thrombus proximal to the lobar level. Conventional pulmonary angiography has limited utility in determining technical operability, because it is not sufficiently precise in detecting proximal thrombus which may be adherent to vessel walls. 44 In contrast, the sensitivity of CT in predicting technical operability, when correlated with surgery, was 77%. On the basis of these findings, Schwickert et al suggested that CT angiography be routinely used in the diagnosis and therapeutic assessment of chronic pulmonary thromboembolic disease. 42 PARENCHYMAL SEQUELAE OF CHRONIC THROMBOEMBOLIC DISEASE
With chronic thromboembolic disease, the occlusion of arterioles supplying secondary lobules produces geometric patterns of alternating low and normal or high lung attenuation. The subtending
Fig 13. A 27-year-old male with presumed primary pulmonary hypertension, found to have chronic pulmonary thromboembolic disease at CT angiography. (A) Helical CT image at the level of the right interlobar artery shows discrete thrombus (arrow). (B) Lung win¢low image at a slightly lower level shows marked diminution in size of the right interlobar artery and disproportionate enlargement of the proximal right middle lobe pulmonary artery (arrow), Additional thrombi were seen in other pulmonary arteries (not shown),
arteries in areas of low lung attenuation are typically diminutive, whereas enlarged pulmonary arteries subtend the higher attenuation parenchyma (Figs 13, 14). 43,45 This pattern of heterogeneous lung attenuation has been termed "mosaic oligemia" (or mosaic perfusion). King et al observed that the low attenuation regions correspond to perfusion defects on radionuclide SPECT scans, and therefore represent regional hypoperfusion.43 Focal peripheral linear and nodular opacities resulting from lung infarction also occur. There are potential difficulties in the CT evaluation of chronic thromboembolic disease. Small concentric thrombi adherent to the vessel wall may not be visualized; moreover, discrete stenoses and vascular webs are less well appreciated on CT than on conventional pulmonary angiography. Mosaic
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GREAVES, HART, AND ABERLE
oligemia secondary to vascular occlusive disease must be distinguiShed from other causes of low lung attenuation, such as emphysema and air trapping from bronchiolar diseases. 46 Emphysema is usually recognizable as regions of lung destruction. Identifying regional air trapping may be difficult unless there is associated bronchiectasis or other visible alteration of bronchial morphology, although expiratory CT sequences may produce attenuation patterns Characteristic of air trapping. Air trapping may also produce variations in vessel caliber, but these vascular alterations are frequently more dramatic in chronic thromboembolic disease, enabling differentiation of this disease from airflow obstruction.43, 45 PROPOSED CLINICAL PATHWAYS IN PULMONARY EMBOLISM
Cost Considerations
Fig 14. Vascular Webs and distortions in a 43-year-old female with chronic pulmonary thromboembolic disease. (A} Helical CT image shows a linear web within the left descending pulmonary artery (arrow), (B) On a lower section, there are linear filling defects within basal segmental bronchi Of both lower lobes (arrows). (C) Lung window image demonstrates there is a large, tortuous vessel supplying the superior segment of the left lower lobe. The subtending lung is of increased attenuation resulting in a mosaic attenuation pattern. Oligemia and vascular attenuation are evident in the Superior segment of the right lower lobe, representing a fixed perfusion defect.
There are a number of tests available for the diagnosis of PE, each with their own merits and limitations, making the design of a rational diagnostic algorithm challenging. Any comparison of algorithms must consider some measure of patient outcome and/or costs. The determining variables include the actual costs of each diagnostic examination, possible complications, the accuracy of the test, the prevalence of the disease in question, and the consequences of treatment or nontreatment. 4,47-49 A number of investigators have analyzed diagnostic algorithms for acute PE. 47'49 In a recent study, van Erkel et al eValuated the cost-effectiveness of 12 realistic diagnostic strategies that incorporated combinations of V-P scintigraphy, ultrasound of the lower extremities, D-dimer assay, conventional angiography, and helical CT angiography, using either of the latter two investigations as the final test. 49 To put these diagnostic strategies into perspective, three additional reference strategies were analyze& no treatment, anticoagulant treatment in all patients, and an ideal diagnostic strategy with 100% accuracy and no diagnostic costs. The values of baseline variables were derived from data pooled from the recent literature. In the experimental design, it was assumed that the appropriate therapeutic action was taken and no further diagnostic tests were performed under the following conditions: lower extremity ultrasound results were positive for deep venous thrombosis, the D-dimer test was negative, or V-P scans were interpreted as normal or high probability. The outcome measures were
CT OF PULMONARYTHROMBOEMBOLISM patient mortality at 3 months, morbidity at 3 months, and the average realistic costs of diagnosis and treatment of PE. When mortality was the primary outcome measure, the best diagnostic strategies all included helical CT angiography; lower extremity ultrasound followed by helical CT was the superior strategy. If cost per life saved was the primary outcome measure, helical CT angiography was again included in all of the best strategies. The use of the D-dimer assay before helical CT angiography improved the marginal cost-effectiveness (cost per life saved), but effected an increase in mortality. Interestingly, the inclusion of the V-P scan to limit the number of helical CT angiograms increased both mortality and cost per life saved. The sensitivity of helical CT for the detection of acute PE is critical to these cost analyses. 49 If this sensitivity decreases to less than 85%, then a strategy incorporating helical CT has a higher mortality than one using conventional pulmonary angiography. Sensitivities of 85% or greater with helical CT are supported by the literature if consideration is restricted to assessment of the segmental or more proximal arteries (Table 1). However, Remy-Jardin et al observed clinically significant subsegmental thrombus in four patients with underlying cardiopulmonary disease, and postulated that in these patients, conventional pulmonary angiography should be performed if lower extremity ultrasound and helical CT are negative. 25 The significance of isolated subsegmental clot will need to be addressed with longitudinal follow-up of affected patients. The prevalence of PE is also a consideration in diagnostic algorithms for acute PE. Gefter et al have suggested that algorithms using helical CT for the diagnosis and treatment of PE are more costeffective than traditional strategies that use V-P scans when the disease prevalence exceeds 10% to 30%, largely because of the frequency of nondiagnostic results. 4
335 published recommendations, the conventional pulmonary angiogram is heavily underused and most management decisions are based on "best clinical guess." Third, cost analyses suggest that V-P scans are not cost-effective in patient groups in which the prevalence of disease exceeds 10% to 30%, and they are seldom diagnostic in patients with underlying cardiopulmonary disease. Finally, the significance of peripheral clot (eg, clot isolated to the subsegmental or more distal pulmonary circulation) is controversial in patients without underlying cardiopulmonary disease in whom there is no evidence of residual clot burden in the lower extremities. Given the above considerations as well as the published accuracies of CT angiography for segmental or more proximal thrombus, the following diagnostic algorithm is proposed (Fig 15) for patients with suspected pulmonary thromboembolism. In patient groups with a low prevalence of PE (such as those presenting to the emergency room) in whom there is low clinical suspicion of PE and no significant underlying cardiopulmonary disease, scintigraphy is an acceptable first test. In most patients of this type, the study will be normal and no further evaluation is indicated. The prevalence and clinical suspicion of acute PE are much higher in hospitalized patients. In these patients, algorithms that include Doppler ultrasound of the lower extremities and CT pulmonary angiography are appropriate. If one test is negative, the other test should be performed. For example, a negative CT angiogram excludes throm-
Suspected/ PE
CTA ~ [+] TREAT-- STOP LE Doppler " ~ [.] 0 r ~ f I Angiogram F/U LE Doppler [High]---~ TREAT V-P [Normal]---I~STOP [Indet] ~ CTA / [ + ]
TREAT
or
ProposedAlgorithm There are a number of limitations in the historical diagnostic algorithm for acute PE. First, although normal and high-probability V-P scans offer reasonable certainty as to the absence or presence of thrombus, respectively, scintigraphy is nondiagnostic or discordant with clinical suspicion in the majority of hospitalized patients. Second, despite
LE Doppler'~ [-]
STOP
Fig 15. Proposed diagnostic algorithm for suspected pulmonary embolism. (1) High prevalence group; preexisting cardiopulmonary disease. (2) Low prevalence group; no underlying cardiopulmonary disease. (3) Contraindication to CTA (IV contrast allergy, etc.). Abbreviations: PE, pulmonary embolism; CTA, CT pulmonary angiography; V-P, ventilationperfusion scintigraphy; LE Doppler, lower extremity Doppler ultrasound; angiogram, conventional pulmonary angiogram.
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bus to the s e g m e n t a l arterial level, whereas a n e g a t i v e e x a m i n a t i o n o f the l o w e r extremities eliminates significant potential residual clot burden. In patients with severe underlying heart or lung disease, e v e n peripheral ( s u b s e g m e n t a l or distal) clot places these patients at risk o f m o r b i d or mortal complications. In these patients, p u l m o n a r y a n g i o g r a p h y should be p e r f o r m e d if the results o f both l o w e r e x t r e m i t y D o p p l e r ultrasound and C T p u l m o n a r y a n g i o g r a p h y are n e g a t i v e Y Finally, C T p u l m o n a r y a n g i o g r a m s are technically challenging examinations that should be super-
vised only by e x p e r i e n c e d radiologists. Just as with c o n v e n t i o n a l angiography, there is a learning curve in the p e r f o r m a n c e and interpretation of these studies. T h e efficacy of C T p u l m o n a r y angiography has been validated at institutions in which limited numbers o f radiologists p e r f o r m the examinations and there are rigorous quality control policies, such as w e e k l y case reviews, and m a n d a t o r y multiple readings. The C T p u l m o n a r y a n g i o g r a m should not replace traditional diagnostic tests unless there are e q u i v a l e n t m e c h a n i s m s in place to ensure proper training, experience, and quality control.
REFERENCES
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15. Henschke CI, Mateescu I, Yankelevitz DF: Changing practice patterns in the workup of pulmonary embolism. Chest 107:940-945, 1995 16. Verschakelen JA, Vanwijck E, Bogaert J, et al: Detection of unsuspected central pulmonary embolism with conventional contrast-enhanced CT. Radiology 188:847-850, 1993 17. Chintapalli K, Thorsen K, Olsen DL, et al: Computed tomography of pulmonary thromboembolism and infarction. J Comput Assist Tomogr 12:553-559, 1988 18. Rubin GD, Date MD, Semba CP: Current status of three-dimensional spiral CT scanning for imaging the vasculature. Radiol Clin North Am 33:51-70, 1995 19. Brink JA, Heiken JR Wang G, et al: Helical CT: Principles and technical considerations. Radiographics 14:887893, 1994 20. Remy-Jardin M, Remy J, Cauvain O, et al: Diagnosis of central pulmonary embolism with helical CT: Role of twodimensional multiplanar reformations. AJR 165:1131-1138, 1995 21. Goodman LR, Curtin JJ, Mewissen MW, et al: Detection of pulmonary embolism in patients with unresolved clinical and scintigraphic diagnosis: Helical CT versus angiography. AJR 164:1369-1374, 1995 22. Teigen CL, Maus TR Sheedy PE et al: Pulmonary embolism: Diagnosis with contrast-enhanced electron-beam CT and comparison with pulmonary angiography. Radiology 194: 313-319, 1995 23. van Rossum AB, Treurniet FEE, Kieft GJ, et al: Role of spiral volumetric computed tomographic scanning in the assessment of patients with clinical suspicion of pulmonary embolism and an abnormal ventilation/perfusion lung scan. Thorax 51:2328, 1996 24. van Rossum AB, Pattynama PMT, Ton ERTA, et al: Pulmonary embolism: Validation of spiral CT angiography in 149 patients. Radiology 201:467-470, 1996 25. Remy-Jardin M, Remy J, Deschildre F, et al: Diagnosis of pulmonary embolism with spiral CT: Comparison with pulmonary angiography and scintigraphy. Radiology 200:699-706, 1996 26. Hull RD, Raskob GE, Carter CJ, et al: Pulmonary embolism in outpatients with pleuritic chest pain. Arch Intern Med 148:838-844, 1988 27. UPET: Urokinase pulmonary embolism trial: Phase 1 results--A cooperative study. JAMA 214:2163-2172, 1970
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