Pulmonary embolism (PE) is protean in nature, continues

Transcription

1 Review: Current Perspective Spiral Computed Tomography for Acute Pulmonary Embolism U. Joseph Schoepf, MD; Samuel Z. Goldhaber, MD; Philip Costello, MD There is still considerable debate about the optimal diagnostic imaging modality for acute pulmonary embolism. If imaging is deemed necessary from an initial clinical evaluation such as D-dimer testing, options include nuclear medicine scanning, catheter pulmonary angiography, and spiral CT. In many institutions, spiral CT is becoming established as the first-line imaging test in daily clinical practice. With spiral CT, thrombus is directly visualized, and both mediastinal and parenchymal structures are evaluated, which may provide important alternative or additional diagnoses. However, limitations for the accurate diagnosis of small peripheral emboli, with a reported miss rate of up to 30% with single-slice spiral CT so far, have prevented the unanimous embrace of spiral CT as the new standard of reference for imaging pulmonary embolism. The clinical significance of the detection and treatment of isolated peripheral pulmonary emboli is uncertain. Evidence is accumulating that it is safe practice to withhold anticoagulation in patients with suspected pulmonary embolism on the basis of a negative spiral CT study. Remaining concerns about the accuracy of spiral CT for pulmonary embolism detection may be overcome by the introduction of multidetector-row spiral CT. This widely available technology has improved visualization of peripheral pulmonary arteries and detection of small emboli. The most recent generation of multidetector-row spiral CT scanners appears to outperform competing imaging modalities for the accurate detection of central and peripheral pulmonary embolism. In this review, we assess the current role and future potential of CT in the diagnostic algorithm of acute pulmonary embolism. (Circulation. 2004;109: ) Key Words: diagnosis embolism imaging thrombosis Pulmonary embolism (PE) is protean in nature, continues to masquerade as other illnesses, and is frequently overlooked and misdiagnosed, at times even by experienced clinicians. Noninvasive imaging tests for PE are increasingly sophisticated and provide previously unimaginable fine resolution of peripheral pulmonary arteries. Despite technical progress, imaging the pulmonary arteries has remained costly and potentially harmful, even with noninvasive approaches. Therefore, imaging tests cannot be ordered on every patient who presents with a remote possibility of PE. Accordingly, diagnostic algorithms have been developed to rationalize the use of noninvasive imaging tests. Ideally, there is a progression from clinical assessment to fundamental nonimaging tests before imaging of the pulmonary arteries ensues (Table 1). The diagnostic process can identify other important illnesses (such as myocardial infarction on ECG or pneumonia or pneumothorax on chest radiograph). Bedside tests have been refined to assess the clinical likelihood of PE. The test developed by Wells and colleagues, 1 for example, is a simple questionnaire for patients with possible PE. With 7 basic questions, the test can rapidly assess the clinical probability of PE. Arterial blood gas analysis 2 and calculation of alveolar-arterial oxygen tension difference 3 are not reliable tools to detect patients who have PE. The principal blood-screening test has become the D-dimer assay. D-dimer testing is highly sensitive and has a very high negative predictive value, so it is an excellent screening test for emergency department patients. At Brigham and Women s Hospital s Emergency Department, with 1106 consecutive assays for suspected PE, the sensitivity was 97% and the negative predictive value was 99.6%. 4 Similar results have been obtained in other emergency departments. 5 Initial evaluation and testing should be completed within several hours in the emergency department setting. At that point, the decision to proceed with direct chest imaging for PE must ensue. D-dimer is less useful for patients who are already hospitalized because the levels are elevated in many illnesses that mimic PE, such as pneumonia and myocardial infarction. D-dimer levels are also elevated in patients with cancer and sepsis, those who are pregnant, and those in the postoperative state. To increase the precision of the diagnostic workup, the standardized clinical assessment and D-dimer test result can be used together to help decide which patients warrant further workup. 6 8 Ordinarily, the workup for PE can stop if the D-dimer ELISA is normal. While awaiting results of the D-dimer, most patients should undergo ECG and chest radiography. The ECG may be normal in patients with massive PE. Sometimes, there are signs of right-side heart strain such as negative T waves in the precordial leads, 9 right bundle-branch block, the classic S1Q3T3 pattern, 10 and the recently described Qr in lead V The chest radiograph may be normal, even in From the Department of Radiology (U.J.S., P.C.) and Cardiovascular Division, Department of Medicine (S.Z.G.), Brigham and Women s Hospital, Harvard Medical School, Boston, Mass. Correspondence to U. Joseph Schoepf, MD, Department of Radiology, Brigham and Women s Hospital, Harvard Medical School, 75 Francis St, Boston, MA schoepf@bwh.harvard.edu (Circulation 2004;109: ) 2004 American Heart Association, Inc. Circulation is available at DOI: /01.CIR

2 Schoepf et al Spiral CT for Acute Pulmonary Embolism 2161 TABLE 1. Diagnostic Approaches to Acute PE: Strengths and Weaknesses Test Strengths Weaknesses Wells questionnaire 1 Rapid bedside stratification of likelihood of PE Influenced by one subjective question: whether alternative diagnoses are more likely than PE Arterial blood gases: hypoxemia 2 Rapid; widely available Does not discriminate well between patients with and without PE Arterial blood gases: A-A gradient 3 Rapid; widely available Normal gradient present in as many as 20% of patients with PE D-dimer 4,5 Rapid; widely available; high negative predictive value Not specific; low positive predictive value Electrocardiogram 9 11 Universally available; may indicate right heart strain Not specific; may be normal despite PE Chest x-ray 12 May identify mimics of PE: pneumonia, pneumothorax, congestive heart failure May be normal despite PE; patients may have concomitant PE and pneumonia or PE and congestive heart failure Venous ultrasound May identify DVT, thus establishing the presence of venous thrombosis May be normal despite PE (because DVT embolized) CT venography 17,18 May obviate venous ultrasonography if DVT is detected Low sensitivity for calf DVT; radiation exposure Echocardiography 20 Identifies patients at high risk if right ventricular dysfunction is Usually normal despite PE detected; on rare occasions will visualize the PE Lung scanning 30,31 Avoids contrast injection; useful if normal or high probability Often nondiagnostic Pulmonary angiography Classically considered the gold standard ; detailed display of pulmonary vascular morphology, oligemic areas of perfusion, manifestations of antecedent, chronic emboli (webs, pouches, laminated clot, vessel fenestrations), and venous drainage Invasive; labor intensive; costly; high interobserver variability for detection of subsegmental emboli Spiral CT 29,33,37,38,40,51 60 De facto first line imaging test in clinical practice; widely available; direct visualization of thrombus and of alternative or additional diagnoses; cost effective; high negative predictive value for clinically relevant PE Requires use of iodinated contrast material; radiation exposure patients with massive PE. The most common radiographic abnormality is cardiomegaly. 12 The utility of venous ultrasonographic screening of patients without leg symptoms who have suspected PE is controversial If a diagnosis of deep venous thrombosis (DVT) can be established in a patient with symptoms of PE, the course of therapy is most often predetermined. However, this approach may miss more than half of patients with PE, 15 probably because the DVT has often completely embolized to the lungs. Also, venous ultrasonography is notoriously insensitive for diagnosing DVT in asymptomatic patients. 13,14,16 If CT is used as the primary imaging test for suspected PE, the feasibility of combining CT angiography of the pulmonary arteries with CT venography of the deep venous system for a comprehensive evaluation for venous thromboembolism has been demonstrated. 17,18 Finally, echocardiography is not recommended as a routine imaging test to diagnose suspected acute PE. Instead, echo- Figure 1. Contrast-enhanced 16-slice CT examination of 72-year-old man with extensive, acute central PE with saddle embolus (arrows) extending into both central pulmonary arteries. Colored volume-rendering technique seen from an anterior (A) and anteriocranial (B) perspective allows intuitive visualization of location and extent of embolism.

3 2162 Circulation May 11, 2004 Figure 2. Contrast-enhanced 16-slice CT examination of patient with acute disseminated pulmonary emboli (arrows). As an incidental finding, examination also reveals focal lung lesion (open arrow) in left upper lobe that was later confirmed to be stage I small-cell lung cancer. cardiography is most useful for risk stratification and prognostication after the diagnosis of PE has been established. 19,20 Imaging Acute PE Pulmonary Angiography, Nuclear Medicine Lung Scanning, and MRA Catheter pulmonary angiography has been hailed as the gold standard technique for PE diagnosis and has the advantage of providing simultaneous hemodynamic information that may be useful for patient management. In reality, however, this test is infrequently performed. 21,22 The morbidity and mortality rates for this invasive test are reported to range from 3.5% to 6% and 0.2% to 0.5%, respectively Use of nuclear medicine imaging, once the first imaging study for suspected PE, is in decline 26,27 because of the high Figure 3. Patient status after acute PE. Wedge-shaped area of consolidation (arrows) in epidiaphragmal portion of lower lobe of left lung represents infarction of lung parenchyma secondary to acute PE. Shown is contrast-enhanced 16-slice multidetectorrow spiral CT examination with multiplanar reformation in midcoronal (left) and left sagittal (right) plane. Figure 4. Sixteen-slice multidetector-row spiral CT angiogram in patient with recurrent thromboembolic disease. Displays are coronal maximum-intensity projection (A), coronal minimumintensity projection (B), and volume-rendered technique seen from posterior (C). Pulmonary arteries (PA) in right lower lobe are most affected by PE and appear obliterated, with normalsized pulmonary veins returning to left atrium (LA). Lung perfusion in lower lobes of lung is diminished but maintained in upper lobes (B). Blood flow to right lower lobe is maintained via bronchial arteries (BA), which are hypertrophied (arrow in A and C) and have formed collaterals bypassing occluded and obliterated pulmonary arteries. PV indicates pulmonary veins.

4 Schoepf et al Spiral CT for Acute Pulmonary Embolism 2163 TABLE 2. Patient Outcome if Anticoagulation Is Withheld on the Basis of a Negative Spiral CT Study in Patients With Suspected PE: Peer-Reviewed Publications Reference Year Journal Patients Without Anticoagulation Based on Normal CT, n Follow-Up Period Documented DVT/PE in Patients Without Anticoagulation, n Negative Predictive Value of Normal CT for Ruling out PE, % Garg AJR Am J 78 6 mo 1 99 Roentgenol Lomis J Vasc Interv Radiol mo Goodman Radiology mo 2 99 Blachere AJR Am J d Roentgenol Gottsater Eur Radiol mo Ost Am J Med 71 6 mo 3 96 Tillie-Leblond Radiology mo 3 98 Swensen Mayo Clin Proc mo 8 99 Nilsson Acta Radiol mo Musset Lancet mo Van Strijen Ann Intern Med mo percentage of indeterminate studies (73% of all performed 28 ) and poor interobserver correlation. 29 Revised criteria for the interpretation of ventilation-perfusion examinations 30,31 and novel technologies in nuclear medicine such as SPECT 32 can decrease the proportion of indeterminate scintigraphic studies but cannot offset the limitations inherent to a functional imaging test. 33 Different from other imaging tests, ventilation-perfusion scintigraphy is an indirect test for PE based on assessment of pulmonary perfusion. This differs from imaging modalities that allow direct visualization (Figure 1) of PE and other thoracic pathology. Contrast-enhanced MRA 34,35 has acquisition protocols that lack sufficient spatial resolution for reliable evaluation of peripheral pulmonary arteries. 35,36 More important, this modality has not seen widespread use in the acutely ill patient with suspected PE because of a lack of general availability, relatively long examination times, and difficulties in patient monitoring. Spiral CT for Imaging Acute PE In many institutions, spiral CT is becoming the first-line imaging test for the assessment of patients with suspected acute PE in daily clinical practice. Both mediastinal and parenchymal structures are evaluated, and thrombus is directly visualized (Figure 1). Many patients with an initial suspicion of PE receive other diagnoses, 37 sometimes such potentially life-threatening diseases as aortic dissection, pneumonia, lung cancer (Figure 2), and pneumothorax. 38 With spiral CT, a specific cause for the patients symptoms and important additional diagnoses can be established in many cases. 33 In addition, not only intravascular thromboembolic filling defects but also other manifestations of precedent pulmonary thromboembolic, including parenchymal infarction (Figure 3), pleural effusion, vascular remodeling (dilation, pouches, thrombotic wall thickening), and oligemia (Figure 4), can readily be visualized with spiral CT. The interobserver agreement for spiral CT is better than for nuclear scintigraphy. 29,39 Spiral CT also appears to be the most cost-effective modality in the diagnostic algorithm of PE compared with algorithms that do not include spiral CT. 40 Spiral CT Limitations for Imaging Peripheral Pulmonary Emboli The main impediment for spiral CT has been limitations of this modality for the accurate detection of small peripheral emboli Early studies comparing conventional singleslice spiral CT with selective pulmonary angiography demonstrated the high accuracy of spiral CT for detecting PE from the main pulmonary artery to the segmental arterial level 41,44,45 but suggested that subsegmental pulmonary emboli may be overlooked by spiral CT scanning. With older generations of conventional single-slice spiral CT scanners, false-negative rates of up to 30% were reported. Detection and Treatment of Isolated Peripheral Pulmonary Emboli: Clinical Significance Limitations for the accurate diagnosis of isolated peripheral emboli with single-slice spiral CT so far have prevented the unanimous embrace of spiral CT as the new standard of reference for imaging PE. The clinical significance of such isolated peripheral emboli, however, in subsegmental or smaller pulmonary arteries in the absence of central emboli is uncertain. It has been shown that 6% 28 to 30% 46 of patients with documented PE present with clots only in subsegmental and smaller arteries. It is speculated that one important function of the lung is to prevent small emboli from entering the arterial circulation. Such emboli may form even in healthy individuals, although this notion has never been substantiated. 47 Controversy also exists about the treatment of small emboli and whether this will result in improved clinical outcome. 48,49 It is assumed that the presence of such emboli may indicate current DVT that potentially heralds more severe embolic events. 37,46,50 A burden of small peripheral emboli is also thought to have prognostic relevance in individuals with cardiopulmonary disease 46 and for the de-

5 2164 Circulation May 11, 2004 Figure 5. Normal pulmonary vessels in 56-year-old man presenting with mild chest pain after long-distance flight. Contrastenhanced 16-slice CT examination covers entire chest within 10-second examination time, allowing analysis of even the most peripheral pulmonary vessels with exquisite detail. Coronal reconstruction is shown by maximum-intensity projection (A) and 3D volume-rendering techniques (B). velopment of chronic pulmonary hypertension in patients with thromboembolic disease. 46 Although the accuracy of conventional single-slice spiral CT for the detection of isolated peripheral emboli may be limited, encouraging data are accumulating on the high negative predictive value of a normal spiral CT study 29,51 60 (Table 2). According to these retrospective 29,51 58 and prospective 59,60 studies, patient outcome is not adversely affected if anticoagulation is withheld on the basis of a negative spiral CT study. The negative predictive value of a normal spiral CT study is high, compares very favorably with catheter pulmonary angiography, 61 and approaches 98%, regardless of Figure 6. Contrast-enhanced 16-slice CT examination with 0.75-mm slice thickness in 45-year-old man with DVT in left calf after longdistance flight. Isolated peripheral pulmonary embolus in subsegmental pulmonary artery in lower lobe of left lung is visualized on 3 consecutive transaxial sections (arrows in A) and on oblique-sagittal multiplanar reformat (arrow in B). The 3D volume-rendered display seen from posterior shows isolated peripheral filling defect (arrow in C) within otherwise normal pulmonary vascular tree. whether underlying lung disease is present. 55,56 The frequency of a subsequent clinical diagnosis of PE or DVT after a negative spiral CT pulmonary angiogram is low, lower than that after a negative or low-probability V-Q scan. 29,53 Thus,

6 Schoepf et al Spiral CT for Acute Pulmonary Embolism 2165 even single-slice spiral CT appears to be a reliable imaging tool for excluding clinically relevant PE, so it appears that anticoagulation can be safely withheld when the spiral CT scan is normal and of good diagnostic quality. 53,57,59,60 Advantages of Multidetector-Row Spiral CT for PE Imaging Remaining concerns about the accuracy of spiral CT for PE detection may be overcome by the introduction of multidetector-row spiral CT. Multidetector-row spiral CT, with simultaneous acquisition of 4 sections per scanner rotation instead of a single section, first became available in ,63 The advantages of fast, high-resolution image acquisition with multidetector-row spiral CT led to the widespread embrace of this modality, with close to 3000 installed units in the United States. The current generation of 4-, 6-, 8-, 10-, and 16-slice multidetector-row spiral CT scanners now allows acquisition of the entire chest with 1-mm or submillimeter resolution within a short single breath-hold ( 10 seconds in the case of the 16-slice CT) (Figure 5). Covering substantial parts of the human anatomy with ever-finer spatial resolution has obvious advantages for imaging PE. Shorter breath-hold times benefit patients with underlying lung disease and reduce the percentage of nondiagnostic CT scans. 64 High-resolution multidetector-row spiral CT data can be transformed easily for 2D and 3D visualization. This may, in some instances, improve PE diagnosis but is generally of greater importance for conveying information on localization and extent of embolic disease in a more intuitive display format (Figure 1). Probably the most important advantage of multidetectorrow spiral CT is improved diagnosis of small peripheral emboli (Figure 6). The degree of accuracy that could be achieved for the visualization of subsegmental pulmonary arteries and for the detection of emboli in these vessels with previously available modalities (single-slice, dual-slice, and electron-beam CT) was found to range between 61% and 79%. 41,65 67 The high spatial resolution (ie, mm in the x, y, and z extensions) of multidetector-row spiral CT data sets now allows evaluation of pulmonary vessels down to 6th-order branches and significantly increases the detection rate of segmental and subsegmental pulmonary emboli This improved detection rate is likely due to the accurate analysis of progressively smaller vessels by use of thinner sections. Animal experiments that use artificial emboli as an independent gold standard indicate that high-resolution 4-slice multidetector-row spiral CT is at least as accurate as invasive pulmonary angiography for the detection of small peripheral emboli. The interobserver correlation for confident diagnosis of subsegmental emboli with high-resolution multidetector-row spiral CT exceeds the reproducibility of selective pulmonary angiography. 69,71,72 The true accuracy of multidetector-row spiral CT for the detection of small peripheral emboli in patients with suspected PE will be difficult to determine. As a direct result of high-resolution imaging capabilities, small peripheral clots that may have gone unnoticed in the past are now frequently seen, often in patients with minor symptoms (Figure 6). It appears highly unlikely that pulmonary angiography will be performed on a patient merely to prove the presence of a small (2 to 3 mm) isolated embolus. The efficacy of multidetector-row spiral CT in patients suspected of having acute PE is currently being assessed by the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) II 73 study. This prospective multicenter study began recruiting patients in 2001 and is expected to complete recruitment in In contrast to the original PIOPED 28 study, which used contrast pulmonary angiography as the primary reference test for PE, PIOPED II uses a composite reference test for venous thromboembolism that is based on the ventilation/perfusion lung scan, venous compression ultrasound of the lower extremities, digital subtraction pulmonary angiography, and contrast venography in various combinations to establish the PE status of the patient. 73 Conclusions CT has become an attractive means for a safe, highly accurate, cost-effective diagnosis of acute PE and may provide alternative diagnoses and explanations for symptoms in the absence of PE. Multidetector-row spiral CT technology has overcome past limitations of CT and is emerging as a preferred modality for imaging patients with suspected acute PE. New-generation multidetector-row spiral CT scanners now challenge catheter pulmonary angiography, once the standard of reference, for the accurate detection of PE. References 1. Wells PS, Anderson DR, Rodger M, et al. Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer. Thromb Haemost. 2000;83: Stein PD, Goldhaber SZ, Henry JW, et al. Arterial blood gas analysis in the assessment of suspected acute pulmonary embolism. Chest. 1996;109: Stein PD, Goldhaber SZ, Henry JW. Alveolar-arterial oxygen gradient in the assessment of acute pulmonary embolism. Chest. 1995;107: Dunn KL, Wolf JP, Dorfman DM, et al. Normal D-dimer levels in emergency department patients suspected of acute pulmonary embolism. J Am Coll Cardiol. 2002;40: Kline JA, Nelson RD, Jackson RE, et al. Criteria for the safe use of D-dimer testing in emergency department patients with suspected pulmonary embolism: a multicenter US study. Ann Emerg Med. 2002;39: Wells PS, Anderson DR, Rodger M, et al. Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and D-dimer. Ann Intern Med. 2001;135: Kruip MJ, Slob MJ, Schijen JH, et al. Use of a clinical decision rule in combination with D-dimer concentration in diagnostic workup of patients with suspected pulmonary embolism: a prospective management study. Arch Intern Med. 2002;162: Kruip MJ, Leclercq MG, van der Heul C, et al. Diagnostic strategies for excluding pulmonary embolism in clinical outcome studies: a systematic review. Ann Intern Med. 2003;138: Ferrari E, Imbert A, Chevalier T, et al. The ECG in pulmonary embolism: predictive value of negative T waves in precordial leads: 80 case reports. Chest. 1997;111: Daniel KR, Courtney DM, Kline JA. Assessment of cardiac stress from massive pulmonary embolism with 12-lead ECG. Chest. 2001;120: Kucher N, Walpoth N, Wustmann K, et al. QR in V1: an ECG sign associated with right ventricular strain and adverse clinical outcome in pulmonary embolism. Eur Heart J. 2003;24:

7 2166 Circulation May 11, Elliott CG, Goldhaber SZ, Visani L, et al. Chest radiographs in acute pulmonary embolism: results from the International Cooperative Pulmonary Embolism Registry. Chest. 2000;118: Jongbloets LM, Lensing AW, Koopman MM, et al. Limitations of compression ultrasound for the detection of symptomless postoperative deep vein thrombosis. Lancet. 1994;343: Wells PS, Lensing AW, Davidson BL, et al. Accuracy of ultrasound for the diagnosis of deep venous thrombosis in asymptomatic patients after orthopedic surgery: a meta-analysis. Ann Intern Med. 1995;122: Turkstra F, Kuijer PM, van Beek EJ, et al. Diagnostic utility of ultrasonography of leg veins in patients suspected of having pulmonary embolism. Ann Intern Med. 1997;126: Mac Gillavry MR, Sanson BJ, Buller HR, et al. Compression ultrasonography of the leg veins in patients with clinically suspected pulmonary embolism: is a more extensive assessment of compressibility useful? Thromb Haemost. 2000;84: Loud P, Grossman CD, Klippenstein DL, et al. Combined CT venography and pulmonary angiography: a new diagnostic technique for suspected thromboembolic disease. AJR Am J Roentgenol. 1998;170: Cham MD, Yankelevitz DF, Shaham D, et al. Deep venous thrombosis: detection by using indirect CT venography: the Pulmonary Angiography- Indirect CT Venography Cooperative Group. Radiology. 2000;216: Ribeiro A, Lindmarker P, Johnsson H, et al. Pulmonary embolism: one-year follow-up with echocardiography Doppler and five-year survival analysis. Circulation. 1999;99: Goldhaber SZ. Echocardiography in the management of pulmonary embolism. Ann Intern Med. 2002;136: Crawford T, Yoon C, Wolfson K, et al. The effect of imaging modality on patient management in the evaluation of pulmonary thromboembolism. J Thorac Imaging. 2001;16: Prologo JD, Glauser J. Variable diagnostic approach to suspected pulmonary embolism in the ED of a major academic tertiary care center. Am J Emerg Med. 2002;20: Mills SR, Jackson DC, Older RA, et al. The incidence, etiologies, and avoidance of complications of pulmonary angiography in a large series. Radiology. 1980;136: Stein P, Athanasoulis C, Alavi A, et al. Complications and validity of pulmonary angiography in acute pulmonary embolus. Circulation. 1992; 85: Hudson ER, Smith TP, McDermott VG, et al. Pulmonary angiography performed with iopamidol: complications in 1,434 patients. Radiology. 1996;198: Schibany N, Fleischmann D, Thallinger C, et al. Equipment availability and diagnostic strategies for suspected pulmonary embolism in Austria. Eur Radiol. 2001;11: Leveau P. Diagnostic strategy in pulmonary embolism: National French survey. Presse Med. 2002;31: PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism. JAMA. 1990;95: Blachere H, Latrabe V, Montaudon M, et al. Pulmonary embolism revealed on helical CT angiography: comparison with ventilationperfusion radionuclide lung scanning. AJR Am J Roentgenol. 2000;174: Stein PD, Relyea B, Gottschalk A. Evaluation of individual criteria for low probability interpretation of ventilation-perfusion lung scans. J Nucl Med. 1996;37: Stein PD, Gottschalk A. Review of criteria appropriate for a very low probability of pulmonary embolism on ventilation-perfusion lung scans: a position paper. Radiographics. 2000;20: Bajc M, Bitzen U, Olsson B, et al. Lung ventilation/perfusion SPECT in the artificially embolized pig. J Nucl Med. 2002;43: Garg K, Welsh CH, Feyerabend AJ, et al. Pulmonary embolism: diagnosis with spiral CT and ventilation-perfusion scanning: correlation with pulmonary angiographic results or clinical outcome. Radiology. 1998;208: Meaney J, Weg JG, Chenevert TL, et al. Diagnosis of pulmonary embolism with magnetic resonance angiography. N Engl J Med. 1997; 336: Oudkerk M, van Beek EJ, Wielopolski P, et al. Comparison of contrastenhanced magnetic resonance angiography and conventional pulmonary angiography for the diagnosis of pulmonary embolism: a prospective study. Lancet. 2002;359: Gupta A, Frazer CK, Ferguson JM, et al. Acute pulmonary embolism: diagnosis with MR angiography. Radiology. 1999;210: Hull R, Raskob GE, Ginsberg JS, et al. A noninvasive strategy for the treatment of patients with suspected pulmonary embolism. Arch Intern Med. 1994;154: van Rossum AB, Pattynama PM, Mallens WM, et al. Can helical CT replace scintigraphy in the diagnostic process in suspected pulmonary embolism? A retrolective-prolective cohort study focusing on total diagnostic yield. Eur Radiol. 1998;8: van Rossum AB, van Erkel AR, van Persijn van Meerten EL, et al. Accuracy of helical CT for acute pulmonary embolism: ROC analysis of observer performance related to clinical experience. Eur Radiol. 1998;8: van Erkel AR, van Rossum AB, Bloem JL, et al. Spiral CT angiography for suspected pulmonary embolism: a cost-effectiveness analysis. Radiology. 1996;201: 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 Am J Roentgenol. 1995;164: Drucker EA, Rivitz SM, Shepard JA, et al. Acute pulmonary embolism: assessment of helical CT for diagnosis. Radiology. 1998;209: Perrier A, Howarth N, Didier D, et al. Performance of helical computed tomography in unselected outpatients with suspected pulmonary embolism. Ann Intern Med. 2001;135: Remy-Jardin M, Remy J, Deschildre F, et al. Diagnosis of pulmonary embolism with spiral CT: comparison with pulmonary angiography and scintigraphy. Radiology. 1996;200: Teigen CL, Maus TP, Sheedy PF II, et al. Pulmonary embolism: diagnosis with contrast-enhanced electron beam CT and comparison with pulmonary angiography. Radiology. 1995;194: Oser RF, Zuckerman DA, Gutierrez FR, et al. Anatomic distribution of pulmonary emboli at pulmonary angiography: implications for cross sectional imaging. Radiology. 1996;199: Tetalman MR, Hoffer PB, Heck LL, et al. Perfusion lung scan in normal volunteers. Radiology. 1973;106: Novelline R, Baltarowich O, Athanasoulis C, et al. The clinical course of patients with suspected pulmonary embolism and a negative pulmonary angiogram. Radiology. 1978;126: Cauvain O, Remy-Jardin M, Remy J, et al. Spiral CT angiography in the diagnosis of central pulmonary embolism: comparison with pulmonary angiography and scintigraphy. Rev Mal Respir. 1996;13: Patriquin L, Khorasani R, Polak JF. Correlation of diagnostic imaging and subsequent autopsy findings in patients with pulmonary embolism. AJR Am J Roentgenol. 1998;171: Garg K, Sieler H, Welsh CH, et al. Clinical validity of helical CT being interpreted as negative for pulmonary embolism: implications for patient treatment. AJR Am J Roentgenol. 1999;172: Lomis NN, Yoon HC, Moran AG, et al. Clinical outcomes of patients after a negative spiral CT pulmonary arteriogram in the evaluation of acute pulmonary embolism. J Vasc Interv Radiol. 1999;10: Goodman LR, Lipchik RJ, Kuzo RS, et al. Subsequent pulmonary embolism: risk after a negative helical CT pulmonary angiogram: prospective comparison with scintigraphy. Radiology. 2000;215: Gottsater A, Berg A, Centergard J, et al. Clinically suspected pulmonary embolism: is it safe to withhold anticoagulation after a negative spiral CT? Eur Radiol. 2001;11: Ost D, Rozenshtein A, Saffran L, et al. The negative predictive value of spiral computed tomography for the diagnosis of pulmonary embolism in patients with nondiagnostic ventilation-perfusion scans. Am J Med. 2001; 110: Tillie-Leblond I, Mastora I, Radenne F, et al. Risk of pulmonary embolism after a negative spiral CT angiogram in patients with pulmonary disease: 1-year clinical follow-up study. Radiology. 2002;223: Swensen SJ, Sheedy PF 2nd, Ryu JH, et al. Outcomes after withholding anticoagulation from patients with suspected acute pulmonary embolism and negative computed tomographic findings: a cohort study. Mayo Clin Proc. 2002;77: Nilsson T, Olausson A, Johnsson H, et al. Negative spiral CT in acute pulmonary embolism. Acta Radiol. 2002;43: Musset D, Parent F, Meyer G, et al. Diagnostic strategy for patients with suspected pulmonary embolism: a prospective multicentre outcome study. Lancet. 2002;360: van Strijen MJ, de Monye W, Schiereck J, et al. Single-detector helical computed tomography as the primary diagnostic test in suspected pulmo-

8 Schoepf et al Spiral CT for Acute Pulmonary Embolism 2167 nary embolism: a multicenter clinical management study of 510 patients. Ann Intern Med. 2003;138: Henry JW, Relyea B, Stein PD. Continuing risk of thromboemboli among patients with normal pulmonary angiograms. Chest. 1995;107: Klingenbeck-Regn K, Schaller S, Flohr T, et al. Subsecond multi-slice computed tomography: basics and applications. Eur J Radiol. 1999;31: Hu H, He HD, Foley WD, et al. Four multidetector-row helical CT: image quality and volume coverage speed. Radiology. 2000;215: Remy-Jardin M, Tillie-Leblond I, Szapiro D, et al. CT angiography of pulmonary embolism in patients with underlying respiratory disease: impact of multislice CT on image quality and negative predictive value. Eur Radiol. 2002;12: Remy-Jardin M, Remy J, Artaud D, et al. Peripheral pulmonary arteries: optimization of the spiral CT acquisition protocol. Radiology. 1997;204: Qanadli SD, Hajjam ME, Mesurolle B, et al. Pulmonary embolism detection: prospective evaluation of dual-section helical CT versus selective pulmonary arteriography in 157 patients. Radiology. 2000;217: Schoepf UJ, Helmberger T, Holzknecht N, et al. Segmental and subsegmental pulmonary arteries: evaluation with electron- beam versus spiral CT. Radiology. 2000;214: Ghaye B, Szapiro D, Mastora I, et al. Peripheral pulmonary arteries: how far in the lung does multi-detector row spiral CT allow analysis? Radiology. 2001;219: Schoepf U, Holzknecht N, Helmberger TK, et al. Subsegmental pulmonary emboli: improved detection with thin-collimation multidetector-row spiral CT. Radiology. 2002;222: Patel S, Kazerooni EA, Cascade PN. Pulmonary embolism: optimization of small pulmonary artery visualization at multi-detector row CT. Radiology. 2003;227: Diffin D, Leyendecker JR, Johnson SP, et al. Effect of anatomic distribution of pulmonary emboli on interobserver agreement in the interpretation of pulmonary angiography. AJR Am J Roentgenol. 1998;171: Stein PD, Henry JW, Gottschalk A. Reassessment of pulmonary angiography for the diagnosis of pulmonary embolism: relation of interpreter agreement to the order of the involved pulmonary arterial branch. Radiology. 1999;210: Gottschalk A, Stein PD, Goodman LR, et al. Overview of prospective investigation of pulmonary embolism diagnosis II. Semin Nucl Med. 2002;32: