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(Chest. 2003;124:2324-2328.)
© 2003 American College of Chest Physicians

Gadolinium-Enhanced Magnetic Resonance Angiography for Detection of Acute Pulmonary Embolism*

An In-depth Review

Paul D. Stein, MD, FCCP; Pamela K. Woodard, MD, FCCP; Russell D. Hull, MBBS, MSc, FCCP; Fadi Kayali, MD; John G. Weg, MD, FCCP; Ronald E. Olson, PhD and Sarah E. Fowler, PhD

* From the St. Joseph Mercy Oakland Hospital (Drs. Stein and Kayali), Pontiac, MI; Washington University (Dr. Woodard), St. Louis, MO; University of Calgary (Dr. Hull), Calgary, AB, Canada; University of Michigan (Dr. Weg), Ann Arbor, MI; Oakland University (Dr. Olson), Rochester, MI; and George Washington University (Dr. Fowler), Washington, DC.

Correspondence to: Paul D. Stein, MD, FCCP, Director of Research, St. Joseph Mercy Oakland, 44555 Woodward Ave, Suite 107, Pontiac, MI 48341-2985; e-mail: steinp{at}trinity-health.org


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Study objective: To review the published experience with gadolinium-enhanced magnetic resonance angiography (MRA) for the detection of acute pulmonary embolism (PE) in order to test the hypothesis that gadolinium-enhanced MRA may be potentially sensitive and specific enough to include it among diagnostic alternatives in the evaluation of patients with suspected PE.

Methods: Studies were identified by searching MEDLINE for trials that used gadolinium-enhanced MRA to diagnose acute PE based on the visualization of an intraluminal filling defect or a cutoff vessel, using pulmonary angiography as a reference standard.

Results: Twenty-eight investigations were identified in which MRA was used to diagnose PE. Only three studies, however, met the criteria for inclusion in the analysis. In these three case series, the sensitivity of gadolinium-enhanced MRA ranged from 77 to 100%, and the specificity ranged from 95 to 98%.

Conclusion: Gadolinium-enhanced MRA may be a useful diagnostic alternative in some patients with suspected acute PE, particularly if they have an elevated creatinine level, have an allergy to radiographic contrast material, or should, if possible, avoid exposure to ionizing radiation.

Key Words: gadolinium • magnetic resonance angiography • pulmonary embolism • pulmonary thromboembolism


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Diagnostic strategies for acute pulmonary embolism (PE) have evolved over the last several decades with the development of new diagnostic methods. These started with pulmonary angiography about 4 decades ago, and were followed by ventilation-perfusion lung scintigraphy, objective leg tests for a surrogate diagnosis of PE, d-dimer assay for the exclusion of PE, digital subtraction pulmonary angiography, contrast-enhanced spiral CT scanning, and, most recently, magnetic resonance angiography (MRA).1 Many of these diagnostic tests continue to be evaluated and refined, and their roles, alone or in combination, continue to evolve. Contrast-enhanced spiral CT scanning has a particularly wide appeal and has been adopted at many centers, although the procedure is still undergoing extensive evaluation in a national collaborative investigation, the Prospective Investigation of Pulmonary Embolism Diagnosis II.2

The purpose of this review, therefore, was to evaluate the published experience with gadolinium-enhanced MRA for the detection of acute PE to test the hypothesis that it may be potentially sensitive and specific enough to include it among diagnostic alternatives in the evaluation of patients with suspected PE. Patients who are allergic to contrast material, who have a high serum creatinine level, or who should avoid ionizing radiation, if possible, would be likely to benefit from MRA. However, pregnant patients can be evaluated for PE using standard techniques such as ventilation-perfusion lung scans and pulmonary angiography via the median basilic vein with abdominal shielding without known risk to the fetus from radiation.3


   Materials and Methods
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 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Study Identification
We attempted to identify all published trials that used gadolinium-enhanced MRA to diagnose acute PE. Two independent MEDLINE searches were obtained from 1987 to 2002 using the key words pulmonary embolism and magnetic resonance imaging. We augmented our searches by manually reviewing the reference lists of all original articles and all review articles. This was done by two of the authors working together (PDS and FK).

Study Eligibility
Each study was evaluated for inclusion by two investigators. Any disagreements were resolved by discussion. Investigators were not blinded to journal, author, or institution. Studies were included if they met all of the following criteria: (1) the diagnosis of PE had been made on the basis of objective tests; (2) patients had been studied consecutively; (3) the study had been performed prospectively; (4) all MRA images were obtained with gadolinium as a contrast agent; (5) the criteria for the diagnosis of PE by MRA was visualization of an intraluminal filling defect or a cutoff vessel; (6) the data acquisition was three-dimensional; (7) gadolinium-enhanced MRA and the diagnostic tests for PE were interpreted independently; (8) all patients studied were suspected of having PE; (9) the study included patients with and without PE; (10) the decision to perform the reference diagnostic test was made independently of the MRA result; (11) descriptions of the MRA methods were sufficiently detailed to permit replication; and (12) sensitivity and specificity, or the raw data for these calculations, were presented.

Data Synthesis and Statistical Analysis
Sensitivity was calculated as the percentage of patients with PE in whom MRA showed the presence of a PE. Specificity was calculated as the percentage of patients who did not have a PE and in whom MRA did not show a PE. The 95% confidence interval (CI) was determined from the normal approximation to the binomial distribution.


   Results
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 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
We identified 28 investigations in which MRA was used to diagnose PE. Many of these, however, did not meet the criteria for inclusion in our study. Some investigations failed to meet the criteria for inclusion for more than one reason. The reasons for exclusion were as follows: an objective diagnostic test had not been ordered independently of the results of the MRA,4 the MRA data had not been acquired three-dimensionally (and may not have used gadolinium),5 6 7 8 or some of the patients were not suspected of having PE or had had not undergone a definitive diagnostic test9 10 ; tests were observational and did not test sensitivity and specificity11 12 ; tests used gadolinium-enhanced MRA only for perfusion imaging13 14 15 16 17 18 ; studies had researched chronic thromboembolic hypertension rather than acute PE19 20 21 22 ; or studies had not used gadolinium-enhanced MRA.23 24 25 26 27 28

Three investigations met the criteria for inclusion in the analysis.29 30 31 The diagnostic reference standard for PE in each of these investigations was pulmonary angiography. Patients in the study were consecutive patients with suspected acute PE who had been referred for pulmonary angiography.29 30 31 Patients were excluded if there was a contraindication to MRA. In one investigation,29 patients were excluded if they were receiving mechanical ventilation. Imaging techniques used in these investigations are shown in Table 1 . The results of the individual investigations are shown in Table 2 . In these three case series for the diagnosis or exclusion of PE, the sensitivity of gadolinium-enhanced MRA ranged from 77 to 100%, and the specificity ranged from 95 to 98% (Table 2) .


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  		Table 1.. Imaging Techniques Used for Gadolinium-Enhanced MRA for Diagnosing Acute PE*

 

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  		Table 2.. Gadolinium-Enhanced Pulmonary MRA for Acute Pulmonary Embolism

 

   Discussion
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 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
The strength of the data on the use of gadolinium-enhanced MRA for the diagnosis of acute PE is limited because the data are sparse. There were more data on the specificity of gadolinium-enhanced MRA than on its sensitivity.29 30 31 The evaluation of the sensitivities of individual investigations requires caution because of the small sample sizes. Pooling may give an impression based on more patients, but patient demographics were not stated and there were differences in MRA technique. The overall estimate of the sensitivity and specificity derived from pooling, therefore, may serve as a preliminary guide, but further studies are needed.

While overall the imaging techniques used in the three included investigations of gadolinium-enhanced MRA were similar, there are a few notable differences. First, Meaney et al29 used a triple dose of contrast agent, compared with the dose of IV gadolinium used by Oudkerk et al30 and Gupta et al.31 Of note, in the article by Meaney and colleagues,29 while the consensus sensitivity was 100%, the average sensitivity of the three blinded readers prior to the consensus reading was 87%, which is more in keeping with the results of the other studies.29

A second difference is that while Oudkerk and colleagues30 used a technique with a relatively high spatial resolution, they imaged each lung sagittally and then constructed coronal and axial images from this data set, using all three planes for interpretation. Constructed images in the axial and coronal planes have poorer resolution than the original images obtained in the sagittal plane. In the other studies,29 31 images were acquired and read in the coronal plane, although Meaney and colleagues29 permitted the creation of additional images in operator-defined planes. These differences in data acquisition and image interpretation may or may not have contributed to the lower sensitivity reported by Oudkerk and colleagues.30

The preliminary experience using MRA for acute PE without a contrast agent, in small case series, showed either a high sensitivity, but suboptimal specificity,7 23 24 or vice versa.8 A variety of imaging techniques were used. Grist and colleagues,24 among 12 patients with PE, showed a sensitivity of 92 to 100%, but among 8 patients in whom PE was excluded, specificity was only 62%. Erdman and colleagues,25 among 21 patients with PE, showed a sensitivity of 90%, but among 13 patients in whom PE was excluded, specificity was 77%. Moody and colleagues,7 in four patients showed a sensitivity of 100%, but the specificity in nine patients was 67%. On the other hand, among 53 patients, expert readers of MRA showed a sensitivity of 71% and a specificity of 97%.8

The use of MRA of the pulmonary vasculature has been hampered by artifacts due to respiratory and cardiac motion, poor signal-to-noise ratio, long image acquisition times, and limited spatial resolution.32 These drawbacks have been overcome by improvements in hardware and software and by the use of magnetic resonance contrast agents.32 Contrast-enhanced MRA is more robust than MRA techniques that do not use a contrast agent. The added signal provided from the contrast agent permits increased spatial resolution and reduces artifacts within the blood pool, thereby increasing vascular signal homogeneity. Current techniques permit high-resolution (512 matrix) imaging during a single breath-hold of 20 to 25 s or thinner slices (1.0 to 1.25 mm). Patients with a decreased capacity to hold their breath can undergo moderate-resolution imaging (256 matrix) during a shorter breath-hold.

Some investigators have used gadolinium-enhanced MRA to show pulmonary perfusion based on the filling of small vessels.13 This is analogous to the perfusion phase of a pulmonary angiogram, which has been shown to be useful but nonspecific.33 It is also analogous to a perfusion lung scan. The most appealing approach to the application of gadolinium-enhanced MRA is its potential use for showing intraluminal filling defects. The intraluminal filling defect was shown to be a diagnostic feature on pulmonary angiograms,33 and it continues to be considered the characteristic that is diagnostic of PE.2 34

Gadolinium-enhanced MRA potentially can be used to image the veins of the pelvis and lower extremities as well as the pulmonary arteries during the same examination. Experience with MRA, even without the use of a magnetic resonance contrast agent, for the detection of proximal deep venous thrombosis and extension into the pelvic veins has shown a sensitivity of 94 to 100% and a specificity of 90 to 100%.35 36 37 Contrast-enhanced MRA following injection of the contrast medium into a pedal vein, showed postthrombotic changes with a sensitivity of 100% (13 of 13 patients) and a specificity of 98% (88 of 90 patients).38

Our article reviewed clinical trials that implemented the latest MRA technology (breath-hold contrast-enhanced, volumetric [three-dimensional]), gradient-recalled echo techniques). Yet, since these articles were written, MRA technology has continued to improve. Intravascular contrast agents, which remain in the blood pool longer than conventional gadolinium-based contrast agents, are currently in phase III US Food and Drug Administration trials and may soon be on the market. Because of their long intravascular half-life, these agents maintain a higher concentration within the blood pool than conventional agents, and have the potential of providing both a better signal and improved blood pool contrast against the low-signal-intensity pulmonary embolus. In addition, the deep venous system of the lower extremity potentially can be evaluated in the same examination without the administration of an additional contrast agent.39 40 41

Based on a sample of 7,889 patients with suspected PE who were evaluated for recruitment into the Prospective Investigation of Pulmonary Embolism Diagnosis II, 3% were pregnant, 4% were allergic to iodinated contrast material, and 19% had an elevated serum creatinine level. One or more were present in 24%. The data are insufficient to recommend where gadolinium-enhanced MRA might fit in a diagnostic pathway for PE. With the present state of the art and its limited availability, it is likely that gadolinium-enhanced MRA would be most useful in patients with a strong suspicion of PE, in whom the results of other tests are equivocal and radiographic contrast material or ionizing radiation are relatively contraindicated.


   Footnotes
 
Abbreviations: CI = confidence interval; MRA = magnetic resonance angiography; PE = pulmonary embolism

Received for publication October 14, 2002. Accepted for publication March 25, 2003.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Tapson, VF, Carroll, BA, Davidson, BL, et al (1999) The diagnostic approach to acute venous thromboembolism: clinical practice guideline. Am J Respir Crit Care Med 160,1043-1066[Free Full Text]
  2. Gottschalk, A, Stein, PD, Goodman, LR, et al Overview of prospective investigation of pulmonary embolism diagnosis II. Semin Nucl Med 2002;32,173-182[CrossRef][ISI][Medline]
  3. Weg, JG Venous thromboembolism in pregnancy. Semin Respir Crit Care Med 1998;19,231-241
  4. Kruger, S, Haage, P, Hoffmann, R, et al Diagnosis of pulmonary arterial hypertension and pulmonary embolism with magnetic resonance angiography. Chest 2001;120,1556-1561[Abstract/Free Full Text]
  5. Loubeyre, P, Revel, D, Douek, P, et al Dynamic contrast-enhanced MR angiography of pulmonary embolism: comparison with pulmonary embolism. AJR Am J Roentgenol 1994;162,1035-1039[Abstract/Free Full Text]
  6. Laissy, J-P, Bancal, C, Sekkal, S, et al Pulmonary MR angiography at 1.0 T: early results with k-space segmented and post-contrast TurboFLASH two-dimensional time-of-flight sequences. Eur J Radiol 1995;20,9-15[CrossRef][ISI][Medline]
  7. Moody, AR, Liddicoat, A, Krarup, K Magnetic resonance pulmonary angiography and direct imaging of embolus for the detection of pulmonary emboli. Invest Radiol 1997;32,431-440[CrossRef][ISI][Medline]
  8. Sostman, HD, Layish, DT, Tapson, VF, et al Prospective comparison of helical CT and MR imaging in clinically suspected acute pulmonary embolism. J Magn Reson Imaging 1996;6,275-281[ISI][Medline]
  9. Goyen, M, Laub, G, Ladd, ME, et al Dynamic 3D MR angiography of the pulmonary arteries in under four seconds. J Magn Reson Imaging 2001;13,372-377[CrossRef][ISI][Medline]
  10. Haage, P, Bucker, A, Kruger, S, et al Radial k-scanning for real-time MR imaging of central and peripheral pulmonary vasculature. Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 2000;172,203-206[ISI][Medline]
  11. Drevet, D, Revel, D, Marx, P, et al Obstruction des arteres pulmonaires apport du scanner et de l’IRM: a propos de dix cas. Ann Radiol (Paris) 1991;34,349-354[Medline]
  12. Posteraro, RH, Sostman, HD, Spritzer, CE, et al Cine-gradient-refocused MR imaging of central pulmonary emboli. AJR Am J Roentgenol 1989;152,465-468[Abstract/Free Full Text]
  13. Berthezene, Y, Croisille, P, Wiart, M, et al Prospective comparison of MR lung perfusion and lung scintigraphy. J Magn Reson Imaging 1999;9,61-68[CrossRef][ISI][Medline]
  14. Amundsen, T, Kvaerness, J, Jones, RA, et al Pulmonary embolism: detection with MR perfusion imaging of lung: a feasibility study. Radiology 1997;203,181-185[Abstract/Free Full Text]
  15. Amundsen, T, Torheim, G, Kvistad, KA, et al Perfusion abnormalities in pulmonary embolism studied with perfusion MRI and ventilation-perfusion scintigraphy: an intra-modality and inter-modality agreement study. J Magn Reson Imaging 2002;15,386-394[CrossRef][ISI][Medline]
  16. Nakagawa, T, Sakuma, H, Murashima, S, et al Pulmonary ventilation-perfusion MR imaging in clinical patients. J Magn Reson Imaging 2001;14,419-424[CrossRef][ISI][Medline]
  17. Hatabu, H, Gaa, J, Kim, D, et al Pulmonary perfusion and angiography: evaluation with breath-hold enhanced three-dimensional fast imaging steady-state precession MR imaging with short TR and TE. AJR Am J Roentgenol 1996;167,653-655[Free Full Text]
  18. Hatabu, H, Tadamura, E, Levin, DL, et al Quantitative assessment of pulmonary perfusion with dynamic contrast-enhanced MRI. Magn Reson Med 1999;42,1033-1038[CrossRef][ISI][Medline]
  19. Bergin, CJ, Sirlin, CB, Hauschildt, JP, et al Chronic thromboembolism: diagnosis with helical CT and MR imaging with angiographic and surgical correlation. Radiology 1997;204,695-702[Abstract/Free Full Text]
  20. Bergin, CJ, Hauschildt, J, Rios, G, et al Accuracy of MR angiography compared with radionuclide scanning in identifying the cause of pulmonary arterial hypertension. AJR Am J Roentgenol 1997;168,1549-1555[Abstract/Free Full Text]
  21. Kreitner, K-F, Ley, S, Kauczor, HU, et al Assessment of chronic thromboembolic pulmonary hypertension by three-dimensional contrast-enhanced MR angiography-comparison with selective intraarterial DSA. Fortschr Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 2000;172,122-128[CrossRef]
  22. Wolff, K, Bergin, CJ, King, MA, et al Accuracy of contrast-enhanced magnetic resonance angiography in chronic thromboembolic disease. Acad Radiol 1996;3,10-17[CrossRef][ISI][Medline]
  23. Schiebler, ML, Holland, GA, Hatabu, H, et al Suspected pulmonary embolism: prospective evaluation with pulmonary MR angiography. Radiology 1993;189,125-131[Abstract/Free Full Text]
  24. Grist, TM, Sostman, HD, MacFall, JR, et al Pulmonary angiography with MR imaging: preliminary clinical experience. Radiology 1993;189,523-530[Abstract/Free Full Text]
  25. Erdman, WA, Peshock, RM, Redman, HC, et al Pulmonary embolism: comparison of MR images with radionuclide and angiographic studies. Radiology 1994;190,499-508[Abstract/Free Full Text]
  26. Hatabu, H, Gefter, WB, Axel, L, et al MR imaging with spatial modulation of magnetization in the evaluation of chronic central pulmonary thromboemboli. Radiology 1994;190,791-796[Abstract/Free Full Text]
  27. Gefter, WB, Hatabu, H, Dinsmore, BJ, et al Pulmonary vascular cine MR imaging: a noninvasive approach to dynamic imaging of the pulmonary circulation. Radiology 1990;176,761-770[Abstract/Free Full Text]
  28. White, RD, Winkler, ML, Higgins, CB MR imaging of pulmonary arterial hypertension and pulmonary emboli. AJR Am J Roentgenol 1987;149,15-21[Abstract/Free Full Text]
  29. Meaney, JFM, Weg, JG, Chenevert, TL, et al Diagnosis of pulmonary embolism with magnetic resonance angiography. N Engl J Med 1997;336,1422-1427[Abstract/Free Full Text]
  30. Oudkerk, M, Van Beek, EJR, Weilopolski, P, et al Comparison of contrast-enhanced magnetic resonance angiography and conventional pulmonary angiography for the diagnosis of pulmonary embolism: a prospective study. Lancet 2002;359,1643-1647[CrossRef][ISI][Medline]
  31. Gupta, A, Frazer, CK, Ferguson, JM, et al Acute pulmonary embolism: diagnosis with MR angiography. Radiology 1999;210,353-359[Abstract/Free Full Text]
  32. Kauczor, H-U Contrast-enhanced magnetic resonance angiography of the pulmonary vasculature: a review. Invest Radiol 1998;33,606-617[CrossRef][ISI][Medline]
  33. Stein, PD, O’Connor, JF, Dalen, JE, et al The angiographic diagnosis of acute pulmonary embolism: evaluation of criteria. Am Heart J 1967;73,730-741[CrossRef][ISI][Medline]
  34. The PIOPED Investigators. 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[Abstract]
  35. Evans, AJ, Sostman, HD, Witty, LA, et al Detection of deep venous thrombosis: prospective comparison of MR imaging and sonography. J Magn Reson Imaging 1996;6,44-51[ISI][Medline]
  36. Laissy, J-P, Cinqualbre, A, Loshkajian, A, et al Assessment of deep venous thrombosis in the lower limbs and pelvis: MR venography versus duplex Doppler sonography. AJR Am J Roentgenol 1996;167,971-975[Abstract/Free Full Text]
  37. Fraser, DGW, Moody, AR, Morgan, PS, et al Diagnosis of lower-limb deep venous thrombosis: a prospective blinded study of magnetic resonance direct thrombus imaging. Ann Intern Med 2002;136,89-98[Abstract/Free Full Text]
  38. Ruehm, SG, Weisner, W, Debatin, JF Pelvic and lower extremity veins: contrast-enhanced three-dimensional MR venography with a dedicated vascular coil-initial experience. Radiology 2000;215,421-427[Abstract/Free Full Text]
  39. Woodard, PK, Yusen, RD Diagnosis of pulmonary embolism with spiral computed tomography and magnetic resonance angiography. Curr Opin Cardiol 1999;14,442-447[CrossRef][ISI][Medline]
  40. Hoffman, U, Loewe, C, Bernhard, C, et al MRA of the lower extremities in patients with pulmonary embolism using a blood pool contrast agent: initial experience. J Magn Reson Imaging 2002;15,429-437[CrossRef][ISI][Medline]
  41. Sostman, HD MRA for diagnosis of venous thromboembolism. Q J Nucl Med 2001;45,311-323[ISI][Medline]



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