Pulmonary embolism (PE) remains a common and important clinical condition that cannot be accurately diagnosed on the basis of signs, symptoms, and history alone. In the absence of high pretest probability and with a negative high-sensitivity D-dimer test, PE can be effectively excluded; in other situations, diagnostic imaging is necessary. The diagnosis of PE has been facilitated by technical advancements and multidetector computed tomography pulmonary angiography, which is the major diagnostic modality currently used. Ventilation and perfusion (V/Q) scans remain largely accurate and useful in certain settings. Lower-extremity ultrasound can substitute by demonstrating deep vein thrombosis; however, if negative, further studies to exclude PE are indicated. In all cases, correlation with the clinical status, particularly with risk factors, improves not only the accuracy of diagnostic imaging but also overall utilization. Other diagnostic tests have limited roles. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The development and review of the guidelines include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
*Department of Radiology, Wake Forest University School of Medicine, Winston-Salem, NC
†Department of Radiology, Ohio State University Medical Center, Columbus, OH
‡Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MS
§Department of Radiology, Massachusetts General Hospital, Boston, MA
∥Department of Diagnostic Imaging, The Warren Alpert School of Medicine at Brown University, Providence, RI
¶Department of Radiology, Brigham and Women’s Hospital, Society of Nuclear Medicine, Boston, MA
#Department of Radiology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY
**American College of Cardiology, Univeristy of Miami Miller School of Medicine, Outpatient Services Cardiovascular Division, Miami, FL
††American College of Cardiology, Oklahoma Heart Institute, Cardiovascular Magnetic Resonance Imaging, Tulsa, OK
‡‡American college of Cardiology, The Ohio State University Heart and Vascular Center, Columbus, OH
§§Department of Radiology, Temple University Health System, Philadelphia, PA
This article is a summary of the complete version of this topic, which is available on the ACR Website at www.acr.org/ac>www.acr.org/ac. Practitioners are encouraged to refer to the complete version.
The American College of Radiology (ACR) seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria® through society representation on expert panels. Participation by representatives from collaborating societies on the expert panel does not necessarily imply society endorsement of the final document.
Robert M. Steiner, is an consultant and course director Educational Symposium Inc. and also consultant to Johnson and Johnson Co. Sharmila Dorbala, has a research grant from Astellas Pharma US Inc. and funded by NIH, a K23 grant. The other authors declare no conflicts of interest.
Reprints: Michael A. Bettmann, MD, Department of Quality & Safety, American College of Radiology, 1891 Preston White Dr., Reston, VA 20191 (e-mail: email@example.com).
SUMMARY OF LITERATURE REVIEW
Pulmonary thromboembolism (PE) remains common—it is a significant cause of morbidity and mortality and is often not diagnosed until premortem. PE is usually secondary to deep vein thrombosis (DVT). As initial or recurrent PE can be fatal, and as there is significant risk associated with anticoagulant therapy, the aim of diagnosis is to accurately confirm or rule out the presence of either PE or DVT.1 This is most often done using a Bayesian approach in which the pretest likelihood of PE is modified by the results of appropriate radiologic and other tests to estimate a posttest probability of PE/DVT. The Wells criteria are the most validated support tool for this, beginning with clinical information that is then generally supplemented by high-sensitivity D-dimer testing. D-dimer levels will be elevated with any significant thrombotic process; hence, this test is of limited value in pregnant, postoperative, and trauma patients, as well as in patients at high risk for PE by validated clinical criteria. In all other settings a negative D-dimer test effectively excludes PE and DVT (Table 1).2–5
Several diagnostic tests form the basis for definitive confirmation of PE and are reviewed in the following sections of this document.
This is an effective first test for suspected PE; it may eliminate the need for additional procedures by revealing other causes for acute symptoms (eg, pneumonia, large effusion). Normal CXR does not exclude PE, nor are there specific findings that confirm PE. A recent CXR is required to allow accurate interpretation of an abnormal radionuclide ventilation/perfusion lung scan.
CT Pulmonary Angiography
Multidetector computed tomography pulmonary angiography (CTPA) is now the primary imaging modality for evaluating acute PE. Since the first major clinical study in 1992 by Remy-Jardin et al,6 it has become the dominant imaging study. Technological advancements have led to high accuracy for detecting large and small PE, as shown in studies that compare CTPA with ventilation/perfusion (V/Q) imaging and conventional angiography.7,8
Discrepancies with conventional angiography are mainly at the subsegmental level, at which pulmonary angiography has poor interobserver agreement. In contrast, CTPA has good agreement, even at the segmental level, and better than with V/Q imaging or catheter angiography.
A positive CTPA study for PE, combined with high or intermediate clinical suspicion, has a high positive predictive value; with low clinical suspicion and a negative CTPA, acute PE can be safely excluded. Adjunctive CT venography improves sensitivity by detecting DVT, with similar specificity, thereby increasing overall accuracy of the diagnosis of both PE and DVT.9
CTPA also has fewer “nondiagnostic” studies compared with V/Q scans and a low false-negative rate. Outcome studies have shown no adverse outcomes in patients with a negative CTPA who were not subsequently treated; further, it is cost-effective in conjunction with lower-extremity duplex examinations. In addition, CTPA may demonstrate pathology other than PE that could explain the patient’s signs/symptoms.
CTPA can also identify signs of right ventricular dysfunction that may have prognostic significance or implications for treatment (eg, need for the institution of thrombolytic therapy vs. conventional anticoagulation alone). Recent technological advancements such as electrocardiogram-gated CT and dual-source CT have allowed accurate evaluation of the pulmonary vasculature, thoracic aorta, and coronary arteries on a single CT, although this “triple rule out” approach has yet to be proven useful or cost-effective.10–13
In general, multidetector CTPA is more accurate than single-slice CT or V/Q scans. Conventional CT with contrast (not performed as dedicated CTPA) is generally not indicated in the routine workup of patients with acute chest pain with suspected PE.
Ventilation and Perfusion Imaging
Since its introduction in the mid-1960s, lung perfusion imaging has been indicated in the workup of suspected PE, although its role14 has diminished considerably with the increased use of CTPA. Nevertheless, a normal pattern of regional perfusion in multiple projections, accompanied by a normal ventilation scan, is widely accepted as indicating that pulmonary emboli are not present and that no further workup for PE is necessary. The choice between V/Q scans and CTPA remains somewhat controversial.15 Both have good diagnostic accuracy, and, in the presence of a normal radiograph in a cooperative patient, a strong argument can be made that they are equally effective in diagnosing clinically significant pulmonary emboli.
Several approaches have been validated for V/Q scan patterns to assign probabilities for the presence of PE.16,17 Most often, these are categorized as “high,” “intermediate” (not meeting the criterion of either “high” or “low”), “low,” or “very low” probability, or “normal.” All schemes incorporate the results of a recent CXR. At least one study suggests that using single photon emission CT improves the sensitivity and specificity of V/Q scans.18
Use of a low-dose Tc-99m macroaggregated albumin (MAA) perfusion scan before a Xe-133 ventilation scan allows the latter to be performed in the appropriate projection, rather than in the usual posterior projection. Further, a normal perfusion scan can eliminate the need for a ventilation scan, lowering radiation dose for the patient. Results obtained using Tc-99m-labeled microaerosol agents (DTPA, pertechnetate, etc.) are comparable to those using inert gases (xenon, krypton) and have the advantage of providing multiple views for regional V/Q comparisons.
A follow-up MAA perfusion scan may be recommended 6 to 8 weeks after the discovery of a “mismatched” V/Q pattern (presumption of PE). Failure of observed resolution, or of at least significant improvement in regional perfusion, may warn of developing pulmonary hypertension secondary to chronic pulmonary vascular obstruction. This complication occurs in <1% of patients. Caution should be exercised in interpreting perfusion imaging in the days after acute PE, because reestablishment of regional perfusion (resolution of defects) occurs at varying and unpredictable rates. In contrast, local ventilation may be compromised for minutes to hours after an acute PE.
Lung scans may be indicated in pregnant women with suspected PE. The administered dose of the radiopharmaceutical(s) should be reduced by a factor of 2 or more, with correspondingly longer acquisition times but reduced radiation dose. If the MAA perfusion scan is performed first and is normal, the ventilation scan can be avoided.
The modality of choice (CTPA vs. V/Q scan) in pregnant patients remains a matter of debate.19,20 The maternal breast dose is clearly higher with CTPA, but the fetal dose may not be. Studies suggest that if the chest radiograph is normal a perfusion scan alone may be satisfactory. In contrast, dose-lowering techniques may make the absorbed dose lower with CT.
MAA Perfusion Imaging Without Ventilation Imaging
This technique may be indicated when the condition of the patient deteriorates suddenly and acute PE is suspected as a significant contributing cause. The demonstration of regions of reduced perfusion, not explained by recent chest radiograph findings, warrants a consideration of PE and possibly the need for further workup such as pulmonary angiography. Perfusion scan alone may be considered in patients who are not candidates for multidetector CTA (those who are too large to fit into CT gantries, who are unable to remain still and hold their breath, and those with severe renal impairment).
Catheter-directed Selective Pulmonary Angiography (PAgram)
Catheter-directed, conventional PAgram, including right heart catheterization and measurement of pulmonary artery and right heart pressure levels, is an invasive but safe procedure when performed by an experienced operator with adequate monitoring of patients. Results may demonstrate PE when an acceptable level of certainty cannot be reached otherwise.16 Given the accuracy of CTPA, even compared with PAgrams, unacceptably low levels of certainty are increasingly rare.
In the past, indications for PAgram have included the following: (a) a low or intermediate probability V/Q scan, particularly when accompanied by high clinical suspicion for PE and high risk for or relative contraindication to anticoagulation; (b) circumstances in which a specific diagnosis of PE is considered necessary for the proper management of the patient; (c) clinical settings in which catheter-directed intervention may be neccessary (eg, chronic pulmonary hypertension secondary to major vessel thromboembolic occlusion or symptomatic massive or submassive PE); and (d) before placement of an inferior vena cava filter. Because of the high accuracy of CTPA, PAgrams are now largely confined to situations in which catheter-directed thrombectomy or thrombolysis is thought to be clinically indicated.
Transthoracic echo and transesophageal echo studies are generally not indicated in the diagnosis of acute PE in the setting of acute chest pain, although they are useful in evaluating right ventricular morphology and function that in turn have prognostic implications for morbidity, mortality, and development of future venous thromboembolism.21–23
Because of the high association of DVT with PE, US evaluation of the venous drainage of the lower-extremity deep veins is probably indicated. US studies include duplex Doppler with leg compression and continuous-wave Doppler; as noted, if DVT is demonstrated, further studies are usually not indicated. A negative extremity US, however, does not exclude PE, although it decreases its likelihood significantly.24,25 For a more detailed discussion on DVT, refer to the ACR Appropriateness Criteria® on “Suspected Lower Extremity Deep Vein Thrombosis.”
Magnetic Resonance Angiography (MRA), Magnetic Resonance Imaging (MRI), and Perfusion Imaging
MRA and MR perfusion imaging can provide a rapid, noninvasive evaluation of the central and segmental pulmonary arteries.26,27 MR perfusion imaging has high sensitivity for PE and is most useful in combination with MRI and MRA.26 Its use is mainly limited to institutions with particular interest and expertise in these methods, and in pregnant patients, although there is not yet proof that the use of gadolinium-containing contrast agents is safe in pregnancy.28
MRI without MRA is probably not indicated in the routine evaluation of patients with suspected PE. It may rarely be useful in patients who have large central emboli, particularly if used in conjunction with MRI for other indications, such as cardiac morphologic evaluation.
* PE remains a common and important condition.
* A chest radiograph cannot exclude or confirm PE, but it is important (as a complementary study) as it can guide further investigations and suggest alternative diagnoses.
* In general, any test that can confirm either DVT (ie, lower-extremity venous duplex) or PE is sufficient. Only certain studies, however, have sufficient accuracy to exclude PE.
* Multidetector CT pulmonary angiography is the current standard of care for diagnosis of PE.
* V/Q scanning also seems to have high overall accuracy.
* In pregnancy, because of increased concerns about radiation, the choice between V/Q or Q scanning and CTPA depends on local equipment and expertise, as well as on patient factors (normal chest radiograph, ability to hold one’s breath).
1. Stein PD, Hull RD, Saltzman HA, et al. Strategy for diagnosis of patients with suspected acute pulmonary embolism. Chest. 1993;103:1553–1559
2. Agnelli G, Becattini C. Acute pulmonary embolism. N Engl J Med. 2010;363:266–274
3. Gandara E, Wells PS. Diagnosis: use of clinical probability algorithms. Clin Chest Med. 2010;31:629–639
4. Gimber LH, Travis RI, Takahashi JM, et al. Computed tomography angiography in patients evaluated for acute pulmonary embolism with low serum D-dimer levels: a prospective study. Perm J. 2009;13:4–10
5. Gupta RT, Kakarla RK, Kirshenbaum KJ, et al. D-dimers and efficacy of clinical risk estimation algorithms: sensitivity in evaluation of acute pulmonary embolism. AJR. 2009;193:425–430
6. Remy-Jardin M, Remy J, Wattinne L, et al. Central pulmonary thromboembolism: diagnosis with spiral volumetric CT with the single-breath-hold technique—comparison with pulmonary angiography. Radiology. 1992;185:381–387
7. 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;208:201–208
8. Mayo JR, Remy-Jardin M, Muller NL, et al. Pulmonary embolism: prospective comparison of spiral CT with ventilation-perfusion scintigraphy. Radiology. 1997;205:447–452
9. Stein PD, Fowler SE, Goodman LR, et al. Multidetector computed tomography for acute pulmonary embolism. N Engl J Med. 2006;354:2317–2327
10. Haidary A, Bis K, Vrachliotis T, et al. Enhancement performance of a 64-slice triple rule-out protocol vs 16-slice and 10-slice multidetector CT-angiography protocols for evaluation of aortic and pulmonary vasculature. J Comput Assist Tomogr. 2007;31:917–923
11. Ghuysen A, Ghaye B, Willems V, et al. Computed tomographic pulmonary angiography and prognostic significance in patients with acute pulmonary embolism. Thorax. 2005;60:956–961
12. He H, Stein MW, Zalta B, et al. Computed tomography evaluation of right heart dysfunction in patients with acute pulmonary embolism. J Comput Assist Tomogr. 2006;30:262–266
13. van der Meer RW, Pattynama PM, van Strijen MJ, et al. Right ventricular dysfunction and pulmonary obstruction index at helical CT: prediction of clinical outcome during 3-month follow-up in patients with acute pulmonary embolism. Radiology. 2005;235:798–803
14. Wagner HN Jr, Sabiston DC Jr, Iio M, et al. Regional pulmonary blood flow in man by radioisotope scanning. JAMA. 1964;187:601–603
15. Anderson DR, Kahn SR, Rodger MA, et al. Computed tomographic pulmonary angiography vs ventilation-perfusion lung scanning in patients with suspected pulmonary embolism: a randomized controlled trial. JAMA. 2007;298:2743–2753
16. . Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA. 1990;263:2753–2759
17. 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. 1993;34:1119–1126
18. Reinartz P, Wildberger JE, Schaefer W, et al. Tomographic imaging in the diagnosis of pulmonary embolism: a comparison between V/Q lung scintigraphy in SPECT technique and multislice spiral CT. J Nucl Med. 2004;45:1501–1508
19. Revel MP, Cohen S, Sanchez O, et al. Pulmonary embolism during pregnancy: diagnosis with lung scintigraphy or CT angiography? Radiology. 2011;258:590–598
20. Shahir K, Goodman LR, Tali A, et al. Pulmonary embolism in pregnancy: CT pulmonary angiography versus perfusion scanning. AJR. 2010;195:W214–W220
21. Kjaergaard J, Schaadt BK, Lund JO, et al. Quantitative measures of right ventricular dysfunction by echocardiography in the diagnosis of acute nonmassive pulmonary embolism. J Am Soc Echocardiogr. 2006;19:1264–1271
22. Lechleitner P, Riedl B, Raneburger W, et al. Chest sonography in the diagnosis of pulmonary embolism: a comparison with MRI angiography and ventilation perfusion scintigraphy. Ultraschall Med. 2002;23:373–378
23. Mathis G, Bitschnau R, Gehmacher O, et al. Chest ultrasound in diagnosis of pulmonary embolism in comparison to helical CT. Ultraschall Med. 1999;20:54–59
24. Quinn RJ, Nour R, Butler SP, et al. Pulmonary embolism in patients with intermediate probability lung scans: diagnosis with Doppler venous US and D-dimer measurement. Radiology. 1994;190:509–511
25. Smith LL, Iber C, Sirr S. Pulmonary embolism: confirmation with venous duplex US as adjunct to lung scanning. Radiology. 1994;191:143–147
26. Kluge A, Luboldt W, Bachmann G. Acute pulmonary embolism to the subsegmental level: diagnostic accuracy of three MRI techniques compared with 16-MDCT. AJR. 2006;187:W7–W14
27. Kluge A, Mueller C, Strunk J, et al. Experience in 207 combined MRI examinations for acute pulmonary embolism and deep vein thrombosis. AJR. 2006;186:1686–1696
28. Chen MM, Coakley FV, Kaimal A, et al. Guidelines for computed tomography and magnetic resonance imaging use during pregnancy and lactation. Obstet Gynecol. 2008;112(2 Pt 1):333–340