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Editorial |
1 Department of Radiology, Boston Medical Center, 88 E Newton St, Boston, MA 02118.
Index terms: Embolism, pulmonary, 564.783, 944.77 • Magnetic resonance (MR), angiography, 564.12142, 944.12942 • Magnetic resonance (MR), comparative studies • Pulmonary angiography, 564.12142, 564.124, 944.1222, 944.12942 • Pulmonary arteries, stenosis or obstruction, 564.783, 944.77
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Introduction |
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Extracellular fluid contrast-enhanced three-dimensional MR angiography lowers the blood T1 well below that of background tissues, so the T1 rather than the flow provides the basic contrast on the MR angiogram. This eliminates many of the flow-related artifacts associated with time-of-flight imaging and has improved the ease and reproducibility of MR angiography in several problematic vascular territories, including the aorta and its major branches, since the initial descriptions of this technique (9–11). Contrast-enhanced three-dimensional MR angiography has received increasing acceptance for MR aortography in the clinical setting despite the fact that the use of contrast agents for this procedure generally is not reimbursed by third-party payers.
The extension of contrast-enhanced three-dimensional MR angiography to the pulmonary circulation is a natural one in that many of the limitations of unenhanced pulmonary MR angiography can be overcome by using contrast agents. As Gupta et al (1) demonstrate, contrast-enhanced three-dimensional MR angiography allows both lungs to be imaged in a single 20–23-second breath hold. The contrast agent provides homogeneous, high signal intensity in the blood and permits reliable, high contrast between patent arterial segments and those with emboli over the brief first-pass imaging window. The group of patients examined by Gupta et al was challenging in that patients with high-probability lung scans were not included. This ensured a relatively high proportion of smaller (ie, segmental and subsegmental) emboli. In addition, this makes their results all the more impressive, with a final consensus sensitivity of 85% and specificity of 96%.
Although the data are encouraging, further analysis revealed some potential concerns. In the first place, although the sensitivity on a per-patient basis was 85%, on a per-embolus basis, it was 68%. The authors were clearly operating well to the left on the receiver operating characteristic curve, because the per-lesion specificity was 99.7%, presumably because they correctly do not want to treat patients with anticoagulation therapy with its well-known risks unless the patients truly have PE. On the basis of this high specificity, the identification of an embolus by using contrast-enhanced three-dimensional MR angiography appears to be sufficient to justify treatment for PE, including the more aggressive treatments of thrombolysis or inferior vena cava filter placement, where clinically indicated. However, it is equally clear that the sensitivity of the examination, while high, would not be adequate to exclude PE on the basis of a negative examination. Not only were three of five subsegmental emboli missed, but two (20%) of 10 segmental emboli were missed in the final interpretation with contrast-enhanced three-dimensional MR angiography.
Of equal concern is the evident variability in MR angiogram interpretation between observers; the 
statistic between the two readers was 0.54, which indicates fair agreement. The variability is also evident in the sensitivities and specificities achieved by the individual readers. One reader achieved a sensitivity of 92% at the cost of a specificity of 83%, whereas the second reader, who achieved a specificity of 91%, reached a sensitivity of 77%. Data for individual readers were not provided on the basis of vessel size. For all the criticisms that can appropriately be leveled at the reproducibility and accuracy of x-ray pulmonary angiography, it is noteworthy that the statistic with x-ray angiography between the two readers in the study by Gupta et al was 0.75, which is much higher than that with MR angiography.
To our knowledge, Loubeyre et al (3) were the first to report on dynamic contrast-enhanced three-dimensional MR angiography for PE. They also noted a substantial difference in sensitivity in the detection of emboli between the proximal and distal vascular segments; 13 of 13 proximal thrombi and none of six distal thrombi were detected. Meaney et al (2) reported a higher sensitivity of 100% based on a consensus interpretation. However, as Gupta et al noted, this patient group was unusual in that they had no subsegmental emboli. Given the more realistic distribution of disease in the current study compared with that in the study by Meaney et al (2), as well as the closer agreement in findings between this study and the earlier study (3), the results reported here are more likely to reflect those that could be achieved in clinical practice by using the best current MR angiographic equipment. Meaney et al (2) also reported substantial interobserver variability, with the sensitivity ranging from 75% to 100% and the interobserver correlation (ie, statistic) for segmental vessels as low as 0.40.
Computed tomographic (CT) angiography is another imaging modality for PE diagnosis that competes with MR angiography as a minimally invasive alternative to conventional angiography (12–15). CT angiography and contrast-enhanced three-dimensional MR angiography appear to be comparable to conventional angiography in accuracy. Like contrast-enhanced three-dimensional MR angiography, CT angiography appears to be sensitive for the detection of larger emboli but has the potential to miss substantial numbers of smaller (ie, subsegmental) emboli (16,17). This similarity in results is not surprising in that the two examinations are conceptually similar in that a single breath hold is used to image a bolus of contrast agent as it passes through the lungs. Because of its wider availability, lower cost, easier access, greater comfort level for most radiologists, and status as the standard method for imaging the lung parenchyma, CT angiography can be expected to dominate the field of imaging examinations for minimally invasive diagnosis of PE unless MR angiography can enable one to achieve clinically superior results. At its current level of performance, MR angiography could have a niche role in the diagnosis in patients with contraindications to iodinated contrast agents such as a severe allergic history or renal insufficiency.
More fundamentally, the role of both CT angiography and MR angiography in the algorithm for assessing PE remains unclear. Thanks to the Prospective Investigation of Pulmonary Embolism Diagnosis trial (18), the role of ventilation-perfusion scanning in the evaluation of PE is well established despite its clear limitations, as is the role of pulmonary angiography as the second definitive examination for patients who have an indeterminate ventilation-perfusion scanning result or discordancy between the ventilation-perfusion scanning results and clinical findings. The power of this algorithm is based on its simplicity—that is, only two tests are involved—and the definitive nature of pulmonary angiography.
The risks of modern pulmonary angiography with nonionic contrast agents and digital angiography are low. Zuckerman et al (19) reported a major complication rate of 0.9% in 547 consecutive patients; there were no deaths. If properly used, digital angiography should not result in a diminution in the quality or definitive nature of pulmonary angiography. van Beek et al (20), in a study of conventional versus digital angiography, reported significantly improved interobserver reliability ( = 0.77) with digital angiography compared with that with conventional angiography. It is interesting that the interobserver correlation determined by these investigators is in close agreement with that obtained in the current study by Gupta et al.
Standard rates of injection (20 mL/sec for normal pulmonary arterial pressures) of nonionic contrast agent (300 mg of iodine per milliliter) with high-speed imaging, a 1,024 matrix, and use of magnification views and selective injection, when indicated, should be used when performing digital pulmonary angiography to ensure quality that is comparable to that of screen-film angiography but with a substantial savings in catheterization time. Digital subtraction is a useful adjunct to diagnosis, but adequate amounts of contrast agent should be administered to allow full depiction of the pulmonary arterial tree on nonsubtracted images. This permits diagnostic quality angiograms to be obtained, even in patients who are uncooperative or unable to hold their breath.
The role of the newer cross-sectional angiographic techniques of contrast-enhanced three-dimensional MR angiography and CT angiography in this algorithm remains unresolved. It is clear that at current levels of resolution, neither a negative MR angiogram nor a negative CT angiogram enables one to exclude the presence of small pulmonary emboli. Oser et al (16), in a retrospective review of pulmonary angiograms, determined that missing subsegmental emboli would cause a failure to diagnose PE in 30% of patients. In the spectrum of thromboembolic disease, PE is different from deep venous thrombosis in that embolism, unless massive, is a harbinger of clinically important, possibly fatal disease. Therefore, even small emboli could represent the forerunner of massive, lethal PE and are worthy of diagnosis. On the other hand, with deep venous thrombosis, the thrombus is the disease, and therefore it is now widely accepted that there is very little risk of missing a small amount of disease in a patient by using compression US.
The authors of the current study should be commended. MR angiography has clearly made great strides in a short time with the advent of fast imaging combined with dynamic administration of extracellular fluid contrast agents. However, further advances in MR angiography are required before it can achieve comparability with pulmonary angiography. The feasibility of imaging pulmonary perfusion with MR imaging has been demonstrated (21). This may provide a useful adjunct to contrast-enhanced three-dimensional MR angiography of the arteries (22). Achieving the resolution of conventional angiography with MR imaging will require the ability to perform imaging beyond the time of a breath hold. This will likely require the use of respiratory navigators that are comparable to those being developed for coronary MR angiography (23,24) in conjunction with contrast agents that provide prolonged blood pool enhancement, which also are under development (25,26).
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Footnotes |
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E.K.Y. is Chief Medical Officer and a stockholder of EPIX Medical.
See also the article by Gupta et al (pp 353–359) in this issue.
Received September 15, 1998;
accepted September 22, 1999.
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