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Magnetic resonance imaging of pulmonary embolism
Magnetic Resonance Imaging of Pulmonary Embolism William A. Erdman and Geoffrey D. Clarke Magnetic resonance imaging (MRI) has the unique ability to demonstrate pulmonary emboli, venous thrombosis, and normal pulmonary arteries in a single noninvasive study. Spin echo and gradient echo pulse sequences take advantage of the natural high contrast between flowing blood and intraluminal thrombus or embolus. Magnetic resonance angiographic (MRA) techniques offer three-dimensional display of the pulmonary vasculature. Each of these techniques may be viewed in cinematic fashion to depict hemodynamic changes associated with the cardiac cycle. Clinical studies have demonstrated sensitivity in the 75% to 100% range and specificities between 42% and 90% depending on technique. MRI technology is still rapidly advancing and clinical accuracy will no doubt improve as experience with new techniques develops. At present, MRI should play a complimentary role to conventional methods of diagnosing thromboembolic disease. Copyright © 1997 by W.B. Saunders Company
PIRAL CT and MRI have been shown to be valuable in establishing a diagnosis of pulmonary embolism. 14 Advances in technology and clinical experience with these new modalities have rekindled hopes that conventional angiographic and radionuclide examinations will ultimately be replaced by more accurate noninvasive and costeffective techniques. 1,6 This article will discuss, primarily from a clinical perspective, the potential role of MRI in the evaluation of pulmonary thromboembolic disease.
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TECHNICAL CONSIDERATIONS
In contrast to radiographic techniques such as spiral CT, conventional angiography or the radionuclide ventilation-perfusion scan, MRI offers a variety of unique approaches to visualization of venous thrombi or pulmonary emboli that do not require the administration of intravenous iodinated contrast or radioactive materials. The MR signal from thrombotic or embolic material is quite different from that of flowing blood around these intraluminal depositions. 7,s Indeed, MRI is the only modality with which pulmonary emboli can be visualized directly as opposed to indirect evidence such as displacement of contrast material or alteration in capillary perfusion. There are three basic approaches to MRI visualization of intraluminal thrombi or emboli: (1) spin echo imaging, which depicts flowing blood as black and emboli as white or light gray; (2) flow-compensated gradient recalled echo (GRE) From the Department of Radiology, University of Texas Southwestern Medical Center at Dallas, Dallas, 732. Address reprint requests to William A. Erdman, MD, Department of Radiology, University of Texas Southwestern Medical School, 5323 Harry Hines Blvd, Dallas, TX 75235-8896. Copyright © 1997 by W.B. Saunders Company 0887-2171/97/1805-000855. 00/0 338
sequences, which depict flowing blood as bright or white and emboli as dark; and (3) phase contrast images, which use the change in phase of the MRI signal that occurs with motion to differentiate the flowing blood from intraluminal stationary material (Fig 1). These techniques may be used, individually or in combination, to produce simple transaxial images similar to contrast enhanced CT or more complicated three-dimensional rendered cine anglograms, which show not only the anatomy, but also velocity changes associated with the cardiac cycle (Figs 2, 3). Ironically, the variety of theoretical advantages that MRI offers for the diagnosis of thromboembolic disease has retarded its more widespread implementation. Compared with more conventional noninvasive techniques, MR imaging is inherently more complicated and therefore more demanding both from the physician's and the patient's perspective. Furthermore, MRI is still undergoing rapid substantial technological advances. 913 As a result, even the more established MRI methods are unfamiliar to many radiologists in the setting of pulmonary embolism. Finally, subtle variations in the hardware and software currently available from different manufacturers has limited the clinical experience with any single MRI approach. Thus, it is difficult for the radiologist to progress along a relatively steep learning curve in the use of MRI in this arena. SPIN ECHO TECHNIQUE
The most simple MRI approach for demonstrafing intraluminal thrombi or emboli is the Tl-weighted spin echo sequence. Intraluminal thrombotic or embolic material appears as gray to medium bright signal within the vessel and is surrounded by the black signal void of dephased turbulent blood flow (Figs 1, 2). 7 This basic se-
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from entry slice or eddy pools of in-phase blood, either of which can exactly mimic the signal intensity of intraluminal thrombosis2 ,~4 The situation becomes vastly more complicated
Fig 1. (A) GRE transaxial MR images through upper thorax show bright signal from flowing blood and dark signal from left subclavian vein thrombosis (arrow). Note faint signal from peripheral vessels (arrowheads). (B) Spin echo sequence at same level shows flowing blood as black and subclavian vein thrombosis as gray (arrow). Note peripheral vessels are not visible at all. (C) Phase contrast image created from spin echo acquisition data in B shows thrombotic material (arrow) as the same level of grey as the surrounding stationary tissue. This shows that the grey intraluminal signal in B is true thrombus and not slow flow or turbulent artifact. (Reprinted with permission from Talbot S, Oliver MA: Techniques of Venous Imaging. Pasadena, CA, Davies Publishing, Inc, 1992.37)
quence is easily performed in a few minutes on virtually any currently implemented MRI hardware. If the study is performed outside the thorax (ie, in search of pelvic vein or extremity vein thrombosis), no cardiac or respiratory gating or compensatory mechanisms need be involved (Fig 4). There are, however, a number of limitations. Even if one is looking for lower extremity venous thrombosis, the search for gray intraluminal thrombi can be confounded by artifactually bright signal
Fig 2. (A) Gated spin echo MRI sequence shows grey embolic material in r!ght posterior descending pulmonary artery (straight arrows) surrounded by the black signal void of flowing blood. Note left descending pulmonary artery (curved arrow) is normal. (B) Breathhold contrast enhanced spiral CT in Same patient shows pulmonary embolus as dark surrounded bY bright iodine contrast (straight arrows), Note normal left descending pulmonary artery (curved arrow). (C) GRE MRI sequence in same patient shows flowing blood as white and pulmonary embolus as dark (straight arrows). Lower signal to noise ratio and spatial resolution make this GRE MR sequence more difficult to interpret. Note normal left descending pulmonary artery (curved arrow).
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Fig 3. Normal volunteer. Cardiac gated breathhold magneti c resonance angiogram (MRA] maximum intensity pixel projection of multiple transaxial GRE slices. Images progress from diastole (far left) through systole (far right). Note prominence of vein in diastolic image (arrows) which diminishes in systolic image as posterior descending pulmonary artery, (open arrow] becomes larger and more intense. Even though presaturation pulses were employed, venous structures may be difficult to separate from arterial branching without cinematic review of images.
when pulmonary arterial emboli are considered. Extremity veins have relatively stable slow flow. and the veins themselves are generally immobile. Pulmonary arteries, on the other hand, have a hyperdynamic pulsatile flow as well as a complex spatial translation from both cardiac and respiratory motion. In addition, the pulmonary vascular anatomy is extremely convoluted with extensive tortu0sity, branching, and inter-twisting of arteries and veins, which often defy capture and delineation in the usual orthogonal planes (Fig 3). Some of these difficulties in visualizing intrathoracic emboli can be overcome by the addition of cardiac gating. The gated spin echo sequence is timed to the cardiac cycle and has been fairly reliable in showing large central pulmonary emboli (Figs 2, 4). 15-19 However. more sophisticated techniques must be used for the visualization of smaller and more peripheral vessels and pulmonary emboll 2~-26(see alsG the article by Hatabu in this issue). In the spin echo sequence, artifactually bright signal of slowly flowing blood (or entry slice blood) can be diminished by applying dephasing pulses either within or beyond the imaging volume. These pulses are designed to decrease the signal of moving blood and thus make vessel lumens appear blacker, whereas the intraluminal thicombi retain their light gray signal intensity. In addition, respiratory gating or other forms of compensating for respiratory motion may be used to help in visualization of the smaller more mobile vasculature at the lung periphery. 17.25 GRADIENT RECALLED ECHO IMAGING
The gradient recalled echo sequence (GRE) uses rephasing pulses and short echo times in an attempt to enhance the signal from flowing blood. This
method produces the opposite tissue contrast from the spin echo sequence and provides a "bright blood" appearance to the vessels. 8 In GRE imaging, the flowing blood is bright or white as in conventional angiography or contrast-enhanced spiral CT, and the thrombus or embolism is relatively dark (Figs 1.2.4, and 5). Intravenous contrast such as gadolinium may be used to further enhance the brightness of flowing blood in the GRE image. 5-a2 Bright blood venography of the extremities can be accomplished more easily than bright blood pulmonary arteriography because of the relatively stable flow rates of the extremity veins compared with the hyperdynamic velocities of the pulmonary arteries. Timing and synchronizing the MR pulse sequence acquisitions with the cardiac cycle (ie, cardiac gating) enhances the ability to maximize the bright blood signal and also allows better visualization of perihilar structures Which are subject to cardiac-induced motion. Furthermore, cardiac gating allows creation of images which depict various phases of the cardiac cycle and can be viewed in a continuous cine loop. Thus. one can examine a naultiphasic cine sequence which shows each phase of the cardiac cycle from systole to diastole at a single or multiple slice levelsY In addition to reducing the spatial blurring and ghosting due to motion, this approach allows the evaluation of signal intensity changes of flowing blood throughout the cardiac cycle. Therefore, cine imaging enhances the ability to differentiate flow artifacts from true emboli. A pulmonary embolus would appear as dark signal throughout the cardiac cycle as compared with turbulent or oscillating blood flow. which would alternate from bright to dark during different phases of cardiac contraction (Fig 5).
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Gradient echo sequences can be acquired in significantly shorter time frames than spin echo sequences. This allows for the possibility of acquiring one or more slices within a 15- to 25-second breath-hold (Fig 2). 23,26Respiratory gating can also be used with the gradient echo sequences; however this generally prolongs the total acquisition time and does not completely eliminate motion. 17 MR acquisitions during suspended respiration require somewhat more sophisticated equipment as well as considerable patient cooperation. The latter may be a significant factor in a patient population known a priori to have respiratory symptoms. These techniques are, therefore, less well-established for imaging pulmonary arteries or pulmonary emboli. PHASE RECONSTRUCTED IMAGES
Data about motion during the acquisition is inherent in the MRI signal. This information may be used to create images, which reflect the phase shift that flowing blood or any other motion induces in the MRI signal (Fig 1). Such phase contrast or phase reconstructed images have been useful in differentiating blood flow artifact from thrombosis in extremity veins. 7,14 However, in the pulmonary arterial branches, there is considerable turbulence due to fast, pulsatile flow at bifurcations which make phase images more difficult to interpret. 28 Intraluminal turbulence, or even spatial translation motion of the vessel wall, may either obscure or mimic the diagnosis of pulmonary embolism. A further complication is that intravascular blood velocities and, therefore, turbulent artifacts are variable with the cardiac cycle, as well as with the size of the vessel and the distance from the heart. Thus, it is difficult to design a single pulse sequence which will be reliably artifact free and sensitive to flow in both large central and small peripheral vessels.
MR Angiography
Fig 4. (A) Right main pulmonary artery embolus (arrows) seen on gated/spin-echo transaxial MRI. Note smaller embolus partially filling left posterior descending artery (open arrow). (B) Gated GRE sequence at same slice level as (A) shows both right and left emboli as focal decreased signal surrounded by bright flowing blood. Note small left pleural effusion (e) not visible on spin echo sequence in (A) because of dephasing from respiratory motion. (C) Spin echo MRI evaluation of the lower extremities in this patient revealed an inferior vena caval thrombosis (arrow) which was the source of the emboli. Abbreviation: a, aorta.
MR angiography (MRA) refers to MR pulse sequences that enhance the bright signal of flowing blood while suppressing signals from static tissues. MRA sequences incorporate aspects such as phase shift, entry slice, magnetization transfer, and timeof-flight phenomena. 2°-26,29This bright blood signal is then reformatted and combined to form an image which resembles a conventional angiogram. Although there is little diagnostic information in visualization of pulmonary veins, the entire vascu-
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lature (veins and arteries) may be seen. This process, called the maximum intensity projection (MIP), searches for the voxels in a three-dimensional volume which produce the highest signal. These voxels are then mapped onto a twodimensional image matrix. 3° Intravenous gadolinium may be used for additional enhancement of blood signal. 5,12Furthermore, two-dimensional and three-dimensional reconstructions of data with cine of pulsatile changes throughout the cardiac cycle have been accomplished (Fig 3). Presaturation pulse sequences may be used to minimize signal from venous structures. 13
Clinical Applications As a result of the multiple hardware devices and pulse sequences currently available or in developmerit, the clinical evaluation of the efficacy of MRI for the diagnosis of pulmonary embolism can only be described as "evolving." Early investigators showed the ability to diagnose pulmonary embolism using spin echo sequences in animal models and anecdotally in a limited number of preselected patients. 15,16A8,19,31-33Later studies were successful in showing large central emboli and used more sophisticated multiphasic gated spin echo or gradient echo techniques. 2,33,34 Scheibler reported a blinded prospective MR evaluation of 14 patients suspected of either acute or chronic pulmonary embolism. 35 Most of these patients had disease documented by either angiography or surgery. Notably, the pulse sequences included a breath-hold two-dimensional time-offlight MR angiogram in addition to the more conventional transaxial gated spin echo as well as cine gradient echo sequences. Spatial modulation of magnetization (SPAMM) is a method by which a grid of unexcited spins is produced so that the subsequent motion of the tissue can be monitored. 36 SPAMM was used to help identify pulmonary embolism that was stationary from slowly flowing (
Fig 5. (A) Multiphasic transaxial GRE MR images: diastolic (top), mid systolic (middle), and late systolic (bottom) show large right main pulmonary artery embolus (arrow) as persistent dark signal. Note turbulence artifacts (open arrows) observed in systolic phases can mimic the appearance of an embolus. (B) Gated spin echo image shows large intraluminal embolus (arrow) which matches persistent defect seen on GRE image in (A). (Reprinted with permission from Erdman WA, Peshock RM, Redman HC, et al: Pulmonary embolism: Comparison of MR images with radionuclide and anglographic studies. Radiology 190:499-508, 1994. 2)
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Fig 6. (A) Multiphasic spin echo transaxial MRI shows right middle lobe pulmonary artery embolism (arrow) seen through all phases of cardiac cycle as persistent grey signal on multiphasic spin echo transaxial MRI. Diastolic phase (top) shows grey signal from slowly flowing blood proximal to embolus and also in right descending pulmonary artery (open arrow). This signal could mimic or obscure an embolus were it not for the clearing changes in mid systole (middle) and late systole (bottom) which differentiate true embolism from artifactual slow flow signal. (B) Conventional pulmonary arteriogram shows above described embolism. Note horizontal orientation and peripheral location of this solitary embolism might have hampered its detection with other MRI techniques or spiral CT. (C) Radionuclide perfusion lung scan, anterior projection shows a single segmental ventilation perfusion mismatch (arrows), ventilation scan was normal (not shown). The single defect was interpreted as intermediate probability for embolus and prompted the angiogram. (Reprinted with permission from Erdman WA, Peshock RM, Redman HC, et ah Pulmonary embolism of MR images with radionuclide and angiographic studies. Radiology 190:499508, 1994.2)
or turbulent blood flow. Emboli greater than 1 cm were identified with greater than 75% confidence in all pulse sequences. Small emboli were much more difficult to detect and overall sensitivity was only 42%. Interestingly, the MRA interpretations were no better or worse than the more conventional pulse
sequences. The investigators identified spatial resolution, slow blood flow artifacts, small lesion size, tachypnea, and inability to cooperate as the limiting factors in the MRA performance. A later study by Grist prospectively evaluated 20 patients suspected of pulmonary embolism using
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Fig 7. (A) Gated transaxial SE MRI shows infiltrate (inf) in left lung base which enhances rather than impedes visualization of left posterior descending pulmonary artery (arrow) as compared with the right posterior descending artery (curved arrow) on transaxial GE MRI. (B) Gated SE MRI at lower slice level, diastolic image (middle), shows pulmonary emboli in right lateral basilar and posterior basilar branches (arrows). Left posterior basilar branch pulmonary artery is still patent (black arrow). Mid systolic image at the same phase (bottom) and late systolic level (top right) demonstrate emboli persist throughout cardiac cycle (arrows). Note change in appearance of left ventricle [LV] as heart contracts. (C, D) Conventional pulmonary arteriogram of R lung (C) shows lateral basiiar and posterior basilar artery branches with intraluminal emboli (arrows) which were demonstrated on MRI in (B). Conventional pulmonary angiogram of left lung (D) shows all basilar branches and descending pulmonary artery to be patent as seen on MRI (B). (Reprinted with permission from Erdman WA, Peshock RM, Redman HC, et ah Pulmonary embolism of MR images with radionuclide and angiographic studies. Radiology 190:499-508, 1994.2)
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(Cont'd.)
GRE sagittal sequences. 34 The data were interpreted both in the sagittal slice format as well as an MIP image, which created a more complete angiographic appearance. Sensitivity was 92% to 100% and specificity was 63%. False-positive results occurred in regions of atelectasis, slow flow from previous pulmonary emboli, and misinterpretation of normal anatomic structures. The MIP images tended to obscure the pulmonary emboli in some cases. Our own group prospectively studied 86 patients suspected of pulmonary embolism in which 64 patients were ultimately diagnosed by either angiography (N = 34) or ventilation perfusion scans (N = 30). 2 Our technique used transaxial multiphasic gated spin echo and (in a subset of 25 patients) gated GRE cine (Figs 4, 5, and 6). We did not attempt MR angiographic reprojection or reconstruction of the data. We relied primarily on multiphasic images to differentiate embolus from flow artifact (Fig 6). When compared to conventional angiography, the sensitivity was measured at 90% and specificity was 77%. If we included
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diagnostic quality ventilation perfusion scans as a diagnostic endpoint, then the sensitivity was 88% and the specificity increased to 90%. There are two principle differences between our work and work of the earlier investigators: (1) rather than MRA, we relied more heavily on spin echo transaxial techniques that showed flowing blood as black and embolism as bright, and (2) we had more extensive experience with a single technique over a broad range of patients. This latter point may be the more significant because there seems to be a steep learning curve with MRI interpretation of pulmonary emboli. The use of spin echo technique actually allows visualization from the embolus itself and does not depend on visualization of small branch vessels, which are subject to slow flow and turbulence which present difficulties for the MRA technique. On the other hand, entry slice blood, particularly in pulmonary veins, can exactly mimic a thrombus with the spin echo technique. To overcome this, we relied on bright signal intensity changes that persisted throughout all phases of the cardiac cycle as a criterion for the diagnosis of pulmonary embolus. Because both arterial and venous blood generally change velocity during the cardiac cycle, this additional diagnostic criterion probably reduced the number of false-positive results in our study (Figs 6, 7). Our sensitivity for PE and those of other investigators were both reasonably high despite differences in technique. This is probably because small peripheral emboli were rare in our experience, and MRI techniques in general are fairly reliable in detecting larger more central emboli. Recent hardware and software developments such as shorter echo and repetition times, volumetric acquisition, respiratory triggering, and intravascular contrast have overcome many of the previously mentioned problems and are discussed elsewhere in this issue (see article by Hatabu). These promising new techniques await further clinical evaluation. POTENTIAL CLINICAL ROLE OF MRI
MRI of Venous Thrombosis Because pulmonary embolism is a complication of deep vein thrombosis and the treatment of the two is often the same, establishing the diagnosis of pulmonary embolism in the face of a known venous thrombosis may, in many instances, be a moot point. MRI has been shown to be exceptionally
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reliable in terms of sensitivity and specificity for venous thrombosis, regardless of location, using spin echo or the gradient recalled echo approach. 14,37,38 Thus, evaluation of a patient for venous thrombosis and/or PE may be accomplished in one MRI examination (Fig 4). Griest reported a subset of 13 such patients using GRE sequences. 34 We accomplished the same type of dual evaluation using spin echo in 10 patients (unpublished data). Neither Griest's work nor our own studies involved enough patients to draw any conclusions regarding the clinical efficacy of this combined approach. However, even in this limited population, we both experienced several patients suspected of pulmonary embolism in whom the diagnosis of a deep vein thrombosis was established by MRI and would have influenced the clinical outcome. Although not yet extensively evaluated, the clinical import of this approach should not be overlooked in future studies. MRI Versus Spiral CT
Spiral CT has been shown to reliably show central pulmonary embolism but, like MRI techniques, has not been proven effective in the smaller peripheral vasculature. 3,34,39Woodard has found CT to have better conspicuity than MRI in a series of experimental emboli created in laboratory animals. 4° Similarly, Holland showed a higher accuracy (94% vs 84%) to electron beam CT over MRI in a group of 16 patients. 41 CT has the advantage of higher spatial resolution, rapid acquisition time, broad availability, and relatively more straightforward technology as compared with MRI (Fig 2). Although both spiral CT and MRI require patient cooperation, prolonged suspension of respiration is not necessarily a prerequisite for a number of MR approaches. Furthermore, the need for iodine contrast and the delivery of that contrast in a relevant time frame still presents technical challenges for CT acquisition, which are obviated with MR. Lymph nodes, partial vascular opacification, congestive heart failure changes, and nonorthogonal vessels have presented potential difficulties in spiral CT image interpretation.42 These may also be factors in MR evaluations, although the use of multiple slice planes and gated cine review offer potential advantages to the MR interpreter. MRI Versus Radionuclide Technique
The radionuclide ventilation/perfusion scan still remains the procedure of choice for the work-up of
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pulmonary embolism. 43,44 High or low probability scans with concordant clinical impression have been shown to have a 96% predictive value. 45 The difficulty arises in the large number of patients with intermediate probability scans (Fig 6). Managing these patients without more definite tests may do a disservice to the patient's health and may ultimately be more expensive. The Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) trials, which were completed more than a decade ago, have only recently begun to improve the radionuclide diagnosis of pulmonary embolism. 46 The results of this exhaustive evaluation have substantially benefited the ventilation/perfusion scan by (1) replacing the myriad of diagnostic interpretative schemes with a more standardized set of criteria; (2) attaching meaningful numbers to particular scan patterns and thus enhancing the confidence of both clinicians and interpreters; and (3) significantly revising the criteria in a fashion that decreases the number of indeterminate scans and increases the accuracy of the high and low probability categories.4741These improvements notwithstanding, the ventilation/perfusion scan still represents an older technology that can never approach the accuracy of angiography because of its inability to show emboli directly. The role of MRI (or CT) in the diagnosis of pulmonary embolism should, presently, be complementary to the ventilation/perfusion scan. Suggestions that these newer modalities should replace ventilation/perfusion scanning are probably premature. 6,52 The strength of the ventilation/perfusion scan is in its high sensitivity, ease of performance, and almost universal implementation. Where the ventilation/perfusion scan fails is in those situations in which pulmonary pathology, such as extensive pneumonia, mimics or masks the radionuclide diagnosis of pulmonary embolism. 53 Effusions, infiltrates, and/or atelectasis are not necessarily problematic in evaluating spin echo MRI images (Fig 7). In our clinical series, we found MRI sensitivity to be 100% in a subset of 21 patients with indeterminate ventilation/perfusion scans. Specificity in this group was 77%. 2 Other pathological conditions, such as congestive heart failure, are a potential problem for MRI due to artifacts from slow blood velocity or from patients' inability to cooperate. Similarly, slow flow may limit the quality of spiral CT exams. Recent work has shown that the ventilation/perfusion scan retains diagnostic quality in congestive heart fail-
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ure. 53 These data further support the complementary nature of these newer techniques.
MRI Versus X-ray Angiography At present, conventional x-ray angiography should retain its role as the final arbiter of the diagnosis of pulmonary embolism because the accuracy and experience with the newer technologies are still evolving. Patients with intermediate probability V/Q scans would likely benefit from a confirmatory diagnosis with demonstration of intraluminal emboli by MRI or CT. However, patients with negative results on MRI or CT scans still have
as much as a 30% chance of having nonvisualized small peripheral emboli. 54 Although there is evidence that such small emboli have few clinical sequelae, this failure to establish the correct diagnosis may trigger a search for other causes of the patient's symptoms and may also delay appropriate therapy. 6 MR! alone has the potential to reliably and noninvasively show venous thrombosis, pulmonary embolism, and normal pulmonary vasculature. However, its premature clinical implementation should be avoided lest we unduly prejudice clinicians against what, ultimately, may be the best technology for diagnosing thromboembolic disease.
REFERENCES Gefter WB, Hatabu H, Holland GA, et ah Pulmonary thromboembolism: Recent developments in diagnosis with CT and MR imaging. Radiology 197:561-574, 1995 2. Erdman WA, Peshock RM, Redman HC, et al: Pulmonary embolism: Comparison of MR images with radionuclide and angiographic studies. Radiology 190:499-508, 1994 3. 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 /64: i369-1374, 1995 4. 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 5. Loubeyre P, Revel D, Douek R et ah Dynamic contrastenhanced MR angiography of pulmonary embolism: comparison with pulmonary angiography. AJR 162:1035-1039, 1994 6. Goodman LR, Lipchik RJ: Diagnosis of acute pulmonary embolism: Time for a new approach. Radiology 199:25-27, 1996 7. Erdman WA, Weinreb JC, Cohen JM, et aI: Venous thrombosis: clinical and experimental MR imaging. Radioiogy 151:233-238, 1986 8. Wu JJ, MacFall JR, Sostman HD, et al: Clot-blood contrast in fast gradient-echo magnetic resonance imaging. Invest Radiol 28:586-593, 1993 9. Hatabu H, Gaa J, Kim D, et al: Pulmonary perfusion and angiography--Evaluation with breath-hold enhanced threedimensional fast imaging steady-state precession MR imaging with short TR and TE. AJR 167:653-655, 1996 10. Laissy JR Assayag R Henry-Feugeas MC, et al: Pulmonary time-of-flight MR angiography at 1.0 T: Comparison between 2D and 3D tone acquisitions. Magn Reson Imag 13:949-957, 1995 i 1. Hatabu H, Gaa J, Kim D, et al: Puhnonary perfusion and angiograpby: Evaluation with breath-hold enhanced threedimensional fast imaging steady-state precession MR imaging with short TR and TE. AJR 167:653-655, 1996 12. Frank H, Weissleder R, Bogdanov AAJr, et ah Detection of pulmonary emboli by using MR angiography with MPEG-PLGdDTPA: An experimental study in rabbits. AJR 162:10411046, 1994 13. Erdman WA, Clarke GD, Lipscomb M, et al: High-
resolution, electrocardiogram-gated breath-hold pulmonary MR angiography with rotating 3D multiphasic cine display. Radiology 185:217, I992 (suppl) (abstr) i4. Erdman WA, Jayson HT, Redman HC, et al: Deep venous thrombosis of extremities: Role of MR imaging in the diagnosis. Radiology 174:425-431, 1990 15. Stein MG, Crues JV 3d, Bradley WG Jr, et al: MR imaging of pulmonary emboli: An experimental study in dogs. AJR 147:1133- l 137, 1986 I6. Ovenfors CO, Batra P: Diagnosis of peripheral pulmonary emboli by MR imaging: An experimental study in dogs. Magn Reson Imag 6:487-491, 1988 I7. Pope CF, Sostman D, Carbo R et al: The detection of pulmonary emboli by magnetic resonance imaging. Evaluation of imaging parameters. Invest Radiol 22:937-946, 1987 18. Fisher MR, Higgins CB: Central thrombi in pulmonary arterial hypertension detected by MR imaging. Radiology 158:223-226, 1986 19. White RD, Winkler ML, Higgins CB: MR imaging of pulmonary arterial hypertension and pulmonary emboli. AJR 149:15-21, 1987 20. Gefter WB, Hatabu H: Evaluation of pulmonary vascular anatomy and blood flow by magnetic resonance. J Thorac Imag 8:122-136, 1993 21. Hatabu H, Gefter WB, Listerud J, et al: Pulmonary MR angiography utilizing phased-array surface coils. J Comput Assist Tomogr 16:410-417, 1992 22. Hatabu H, Gefter WB, Konishi J, et ah Magnetic resonance approaches to the evaluation of pulmonary vascular anatomy and physiology. Magn Reson Q 7:208-225, 1991 23. MacFall JR, Sostman HD, Foo TK: Thick-section, single breath-hold magnetic resonance pulmonary angiography. Invest Radiol 27:318-322, 1992 24. Wielopolski PA, Haacke EM, Adler LP: Three-dimensional MR imaging of the pulmonary vasculature: Preliminary experience. Radiology 183:465-472, 1992 25. Hatabu H, Gefter WB, Kressel HY, et al: Pulmonary vasculature: High-resolution MR imaging. Radiology 171:391395, 1989 26. Foo TK, MacFall JR, Sostman HD, et al: Single-breathhold venous or arterial flow-suppressed pulmonary vascular MR imaging with phased-array coils. J Magn Reson Imag 3:611616, I993
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27. Posteraro RH, Sostman HD, Spritzer CE, et al: Cinegradient-refocused MR imaging of central pulmonary emboli. AJR 152:465-468, 1989 28. Krovetz LJ: The effect of vessel branching on haemodynamic stability. Phys Med Biol 10:417-427, 1965 29. Pike GB, Hu BS, Glover GH, Enzmann DR: Magnetization transfer time-of-flight magnetic resonance angiography. Magn Reson Med 25:372-379, 1992 30. Atkinson D, Teresi L: Magnetic resonance angiography. Magn Reson Q 10:149-172, 1994 31. Thickman D, Kressel HY, Axel L: Demonstration of pulmonary embolism by magnetic resonance imaging. AJR 142:921-922, 1984 32. Moore EH, Gamsu G, Webb WR, et al: Pulmonary embolus: detection and follow-up using magnetic resonance. Radiology 153:471-472, 1984 33. Gamsu G, Hirji M, Moore EH, et al: Experimental pulmonary emboli detected using magnetic resonance. Radiology 153:467-470, 1984 34. Grist TM, Sostman HD, MacFall JR, et al: Pulmonary angiography with MR imaging: Preliminary clinical experience. Radiology 189:523-530, 1993 35. Schiebler ML, Holland GA, Hatabu H, et al: Suspected pulmonary embolism: Prospective evaluation with pulmonary MR angiography. Radiology 189:125-131, 1993 36. Axel L, Dougherty L: MR imaging of motion with spatial modulation of magnetization. Radiology 171:841-845, 1989 37. Erdman WA: Magnetic resonance imaging, in Talbot S, Oliver MA (eds): Techniques of Venous Imaging. Pasadena, CA, Appleton-Davies, 1992, pp 175-185 38. Spritzer CE, Sostman HD, Wilkes D, et al: Deep venous thrombosis: Experience with gradient echo MR imaging in 66 patients. Radiology 177:235-241, 1990 39. van Rossum AB, Pattynama PM, Ton ER, et al: Pulmonary embolism: Validation of spiral CT angiography in 149 patients. Radiology 201:467-470, 1996 40. Woodard PK, Sostman HD, MacFall JR, et al: Detection of pulmonary embolism: Comparison of contrast-enhanced spiral CT and time-of-flight MR techniques. J Thorac Imag 10:59-72, 1995 41. Holland GA, Gefter WB, Baum RA, et al: Prospective comparison of pulmonary MR angiography and ultrafast CT for diagnosis of pulmonary thromboembolic disease. Radiology 189:234, 1993 (abstr)
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42. Drucker EA, Rivita SM, Shepard JP, et al: Assessment of helical CT in the diagnosis of acute pulmonary emboli. Radiology 20:303, 1996 (abstr) 43. Matsomoto AH, Tegtmeyer CJ: Contemporary diagnostic approaches to acute pulmonary emboli. Radiol Clin North Am 33:167-183, 1995 44. Robinson PJA: Ventilation-perfusion lung scanning and spiral computed tomography of the lungs--Competing or complementary modalities. Eur J Nucl Med 23:1547-1553, 1996 45. 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 46. Worsley DF, Alavi A: Comprehensive analysis of the results of the PIOPED study. J Nucl Med 36:2380-2387, 1995 47. Webber MM, Gomes AS, Roe D, et al: Comparison of Biello, McNeil, and PIOPED criteria for the diagnosis of pulmonary emboli on lung scans. AJR 154:975-981, 1990 48. Sostman HD, Coleman RE, DeLong DM, et al: Evaluation of revised criteria for ventilation-perfusion scintigraphy in patients with suspected pulmonary embolism. Radiology 193: 103-107, 1994 49. Freitas JE, Sarosi MG, Nagle CC, et al: Modified PIOPED criteria used in clinical practice. J Nucl Med 36:15731578, 1995 50. Stein PD, Relyea B, Gottschalk A: Evaluation of individual criteria for low probability interpretation of ventilationperfusion lung scans. J Nucl Med 37:577-581, 1996 51. Gottschalk A, Sostman HD, Coleman RE, et al: Ventilation-peffusion scintigraphy in the PIOPED study. Part II. Evaluation of the scintigraphic criteria and interpretations. J Nucl Med 34:1119-1126, 1993 52. Gumey JW: No fooling around: Direct visualization of pulmonary embolism. Radiology 188:618-619, 1993 (editorial) 53. Goldberg SN, Palmer EL, Scott JA, et al: Pulmonary embolism: Prediction of the usefulness of initial ventilationperfusion scanning with chest radiographic findings. Radiology 193:801-805, 1994 54. Oser RF, Zuckerman DA, Gutierrez ER, et al: Anatomic distribution of pulmonary emboli at pulmonary angiography: Implications for cross-sectional imaging. Radiology 199:31-35, 1996
PIRAL CT and MRI have been shown to be valuable in establishing a diagnosis of pulmonary embolism. 14 Advances in technology and clinical experience with these new modalities have rekindled hopes that conventional angiographic and radionuclide examinations will ultimately be replaced by more accurate noninvasive and costeffective techniques. 1,6 This article will discuss, primarily from a clinical perspective, the potential role of MRI in the evaluation of pulmonary thromboembolic disease.
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TECHNICAL CONSIDERATIONS
In contrast to radiographic techniques such as spiral CT, conventional angiography or the radionuclide ventilation-perfusion scan, MRI offers a variety of unique approaches to visualization of venous thrombi or pulmonary emboli that do not require the administration of intravenous iodinated contrast or radioactive materials. The MR signal from thrombotic or embolic material is quite different from that of flowing blood around these intraluminal depositions. 7,s Indeed, MRI is the only modality with which pulmonary emboli can be visualized directly as opposed to indirect evidence such as displacement of contrast material or alteration in capillary perfusion. There are three basic approaches to MRI visualization of intraluminal thrombi or emboli: (1) spin echo imaging, which depicts flowing blood as black and emboli as white or light gray; (2) flow-compensated gradient recalled echo (GRE) From the Department of Radiology, University of Texas Southwestern Medical Center at Dallas, Dallas, 732. Address reprint requests to William A. Erdman, MD, Department of Radiology, University of Texas Southwestern Medical School, 5323 Harry Hines Blvd, Dallas, TX 75235-8896. Copyright © 1997 by W.B. Saunders Company 0887-2171/97/1805-000855. 00/0 338
sequences, which depict flowing blood as bright or white and emboli as dark; and (3) phase contrast images, which use the change in phase of the MRI signal that occurs with motion to differentiate the flowing blood from intraluminal stationary material (Fig 1). These techniques may be used, individually or in combination, to produce simple transaxial images similar to contrast enhanced CT or more complicated three-dimensional rendered cine anglograms, which show not only the anatomy, but also velocity changes associated with the cardiac cycle (Figs 2, 3). Ironically, the variety of theoretical advantages that MRI offers for the diagnosis of thromboembolic disease has retarded its more widespread implementation. Compared with more conventional noninvasive techniques, MR imaging is inherently more complicated and therefore more demanding both from the physician's and the patient's perspective. Furthermore, MRI is still undergoing rapid substantial technological advances. 913 As a result, even the more established MRI methods are unfamiliar to many radiologists in the setting of pulmonary embolism. Finally, subtle variations in the hardware and software currently available from different manufacturers has limited the clinical experience with any single MRI approach. Thus, it is difficult for the radiologist to progress along a relatively steep learning curve in the use of MRI in this arena. SPIN ECHO TECHNIQUE
The most simple MRI approach for demonstrafing intraluminal thrombi or emboli is the Tl-weighted spin echo sequence. Intraluminal thrombotic or embolic material appears as gray to medium bright signal within the vessel and is surrounded by the black signal void of dephased turbulent blood flow (Figs 1, 2). 7 This basic se-
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from entry slice or eddy pools of in-phase blood, either of which can exactly mimic the signal intensity of intraluminal thrombosis2 ,~4 The situation becomes vastly more complicated
Fig 1. (A) GRE transaxial MR images through upper thorax show bright signal from flowing blood and dark signal from left subclavian vein thrombosis (arrow). Note faint signal from peripheral vessels (arrowheads). (B) Spin echo sequence at same level shows flowing blood as black and subclavian vein thrombosis as gray (arrow). Note peripheral vessels are not visible at all. (C) Phase contrast image created from spin echo acquisition data in B shows thrombotic material (arrow) as the same level of grey as the surrounding stationary tissue. This shows that the grey intraluminal signal in B is true thrombus and not slow flow or turbulent artifact. (Reprinted with permission from Talbot S, Oliver MA: Techniques of Venous Imaging. Pasadena, CA, Davies Publishing, Inc, 1992.37)
quence is easily performed in a few minutes on virtually any currently implemented MRI hardware. If the study is performed outside the thorax (ie, in search of pelvic vein or extremity vein thrombosis), no cardiac or respiratory gating or compensatory mechanisms need be involved (Fig 4). There are, however, a number of limitations. Even if one is looking for lower extremity venous thrombosis, the search for gray intraluminal thrombi can be confounded by artifactually bright signal
Fig 2. (A) Gated spin echo MRI sequence shows grey embolic material in r!ght posterior descending pulmonary artery (straight arrows) surrounded by the black signal void of flowing blood. Note left descending pulmonary artery (curved arrow) is normal. (B) Breathhold contrast enhanced spiral CT in Same patient shows pulmonary embolus as dark surrounded bY bright iodine contrast (straight arrows), Note normal left descending pulmonary artery (curved arrow). (C) GRE MRI sequence in same patient shows flowing blood as white and pulmonary embolus as dark (straight arrows). Lower signal to noise ratio and spatial resolution make this GRE MR sequence more difficult to interpret. Note normal left descending pulmonary artery (curved arrow).
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Fig 3. Normal volunteer. Cardiac gated breathhold magneti c resonance angiogram (MRA] maximum intensity pixel projection of multiple transaxial GRE slices. Images progress from diastole (far left) through systole (far right). Note prominence of vein in diastolic image (arrows) which diminishes in systolic image as posterior descending pulmonary artery, (open arrow] becomes larger and more intense. Even though presaturation pulses were employed, venous structures may be difficult to separate from arterial branching without cinematic review of images.
when pulmonary arterial emboli are considered. Extremity veins have relatively stable slow flow. and the veins themselves are generally immobile. Pulmonary arteries, on the other hand, have a hyperdynamic pulsatile flow as well as a complex spatial translation from both cardiac and respiratory motion. In addition, the pulmonary vascular anatomy is extremely convoluted with extensive tortu0sity, branching, and inter-twisting of arteries and veins, which often defy capture and delineation in the usual orthogonal planes (Fig 3). Some of these difficulties in visualizing intrathoracic emboli can be overcome by the addition of cardiac gating. The gated spin echo sequence is timed to the cardiac cycle and has been fairly reliable in showing large central pulmonary emboli (Figs 2, 4). 15-19 However. more sophisticated techniques must be used for the visualization of smaller and more peripheral vessels and pulmonary emboll 2~-26(see alsG the article by Hatabu in this issue). In the spin echo sequence, artifactually bright signal of slowly flowing blood (or entry slice blood) can be diminished by applying dephasing pulses either within or beyond the imaging volume. These pulses are designed to decrease the signal of moving blood and thus make vessel lumens appear blacker, whereas the intraluminal thicombi retain their light gray signal intensity. In addition, respiratory gating or other forms of compensating for respiratory motion may be used to help in visualization of the smaller more mobile vasculature at the lung periphery. 17.25 GRADIENT RECALLED ECHO IMAGING
The gradient recalled echo sequence (GRE) uses rephasing pulses and short echo times in an attempt to enhance the signal from flowing blood. This
method produces the opposite tissue contrast from the spin echo sequence and provides a "bright blood" appearance to the vessels. 8 In GRE imaging, the flowing blood is bright or white as in conventional angiography or contrast-enhanced spiral CT, and the thrombus or embolism is relatively dark (Figs 1.2.4, and 5). Intravenous contrast such as gadolinium may be used to further enhance the brightness of flowing blood in the GRE image. 5-a2 Bright blood venography of the extremities can be accomplished more easily than bright blood pulmonary arteriography because of the relatively stable flow rates of the extremity veins compared with the hyperdynamic velocities of the pulmonary arteries. Timing and synchronizing the MR pulse sequence acquisitions with the cardiac cycle (ie, cardiac gating) enhances the ability to maximize the bright blood signal and also allows better visualization of perihilar structures Which are subject to cardiac-induced motion. Furthermore, cardiac gating allows creation of images which depict various phases of the cardiac cycle and can be viewed in a continuous cine loop. Thus. one can examine a naultiphasic cine sequence which shows each phase of the cardiac cycle from systole to diastole at a single or multiple slice levelsY In addition to reducing the spatial blurring and ghosting due to motion, this approach allows the evaluation of signal intensity changes of flowing blood throughout the cardiac cycle. Therefore, cine imaging enhances the ability to differentiate flow artifacts from true emboli. A pulmonary embolus would appear as dark signal throughout the cardiac cycle as compared with turbulent or oscillating blood flow. which would alternate from bright to dark during different phases of cardiac contraction (Fig 5).
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Gradient echo sequences can be acquired in significantly shorter time frames than spin echo sequences. This allows for the possibility of acquiring one or more slices within a 15- to 25-second breath-hold (Fig 2). 23,26Respiratory gating can also be used with the gradient echo sequences; however this generally prolongs the total acquisition time and does not completely eliminate motion. 17 MR acquisitions during suspended respiration require somewhat more sophisticated equipment as well as considerable patient cooperation. The latter may be a significant factor in a patient population known a priori to have respiratory symptoms. These techniques are, therefore, less well-established for imaging pulmonary arteries or pulmonary emboli. PHASE RECONSTRUCTED IMAGES
Data about motion during the acquisition is inherent in the MRI signal. This information may be used to create images, which reflect the phase shift that flowing blood or any other motion induces in the MRI signal (Fig 1). Such phase contrast or phase reconstructed images have been useful in differentiating blood flow artifact from thrombosis in extremity veins. 7,14 However, in the pulmonary arterial branches, there is considerable turbulence due to fast, pulsatile flow at bifurcations which make phase images more difficult to interpret. 28 Intraluminal turbulence, or even spatial translation motion of the vessel wall, may either obscure or mimic the diagnosis of pulmonary embolism. A further complication is that intravascular blood velocities and, therefore, turbulent artifacts are variable with the cardiac cycle, as well as with the size of the vessel and the distance from the heart. Thus, it is difficult to design a single pulse sequence which will be reliably artifact free and sensitive to flow in both large central and small peripheral vessels.
MR Angiography
Fig 4. (A) Right main pulmonary artery embolus (arrows) seen on gated/spin-echo transaxial MRI. Note smaller embolus partially filling left posterior descending artery (open arrow). (B) Gated GRE sequence at same slice level as (A) shows both right and left emboli as focal decreased signal surrounded by bright flowing blood. Note small left pleural effusion (e) not visible on spin echo sequence in (A) because of dephasing from respiratory motion. (C) Spin echo MRI evaluation of the lower extremities in this patient revealed an inferior vena caval thrombosis (arrow) which was the source of the emboli. Abbreviation: a, aorta.
MR angiography (MRA) refers to MR pulse sequences that enhance the bright signal of flowing blood while suppressing signals from static tissues. MRA sequences incorporate aspects such as phase shift, entry slice, magnetization transfer, and timeof-flight phenomena. 2°-26,29This bright blood signal is then reformatted and combined to form an image which resembles a conventional angiogram. Although there is little diagnostic information in visualization of pulmonary veins, the entire vascu-
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lature (veins and arteries) may be seen. This process, called the maximum intensity projection (MIP), searches for the voxels in a three-dimensional volume which produce the highest signal. These voxels are then mapped onto a twodimensional image matrix. 3° Intravenous gadolinium may be used for additional enhancement of blood signal. 5,12Furthermore, two-dimensional and three-dimensional reconstructions of data with cine of pulsatile changes throughout the cardiac cycle have been accomplished (Fig 3). Presaturation pulse sequences may be used to minimize signal from venous structures. 13
Clinical Applications As a result of the multiple hardware devices and pulse sequences currently available or in developmerit, the clinical evaluation of the efficacy of MRI for the diagnosis of pulmonary embolism can only be described as "evolving." Early investigators showed the ability to diagnose pulmonary embolism using spin echo sequences in animal models and anecdotally in a limited number of preselected patients. 15,16A8,19,31-33Later studies were successful in showing large central emboli and used more sophisticated multiphasic gated spin echo or gradient echo techniques. 2,33,34 Scheibler reported a blinded prospective MR evaluation of 14 patients suspected of either acute or chronic pulmonary embolism. 35 Most of these patients had disease documented by either angiography or surgery. Notably, the pulse sequences included a breath-hold two-dimensional time-offlight MR angiogram in addition to the more conventional transaxial gated spin echo as well as cine gradient echo sequences. Spatial modulation of magnetization (SPAMM) is a method by which a grid of unexcited spins is produced so that the subsequent motion of the tissue can be monitored. 36 SPAMM was used to help identify pulmonary embolism that was stationary from slowly flowing (
Fig 5. (A) Multiphasic transaxial GRE MR images: diastolic (top), mid systolic (middle), and late systolic (bottom) show large right main pulmonary artery embolus (arrow) as persistent dark signal. Note turbulence artifacts (open arrows) observed in systolic phases can mimic the appearance of an embolus. (B) Gated spin echo image shows large intraluminal embolus (arrow) which matches persistent defect seen on GRE image in (A). (Reprinted with permission from Erdman WA, Peshock RM, Redman HC, et al: Pulmonary embolism: Comparison of MR images with radionuclide and anglographic studies. Radiology 190:499-508, 1994. 2)
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Fig 6. (A) Multiphasic spin echo transaxial MRI shows right middle lobe pulmonary artery embolism (arrow) seen through all phases of cardiac cycle as persistent grey signal on multiphasic spin echo transaxial MRI. Diastolic phase (top) shows grey signal from slowly flowing blood proximal to embolus and also in right descending pulmonary artery (open arrow). This signal could mimic or obscure an embolus were it not for the clearing changes in mid systole (middle) and late systole (bottom) which differentiate true embolism from artifactual slow flow signal. (B) Conventional pulmonary arteriogram shows above described embolism. Note horizontal orientation and peripheral location of this solitary embolism might have hampered its detection with other MRI techniques or spiral CT. (C) Radionuclide perfusion lung scan, anterior projection shows a single segmental ventilation perfusion mismatch (arrows), ventilation scan was normal (not shown). The single defect was interpreted as intermediate probability for embolus and prompted the angiogram. (Reprinted with permission from Erdman WA, Peshock RM, Redman HC, et ah Pulmonary embolism of MR images with radionuclide and angiographic studies. Radiology 190:499508, 1994.2)
or turbulent blood flow. Emboli greater than 1 cm were identified with greater than 75% confidence in all pulse sequences. Small emboli were much more difficult to detect and overall sensitivity was only 42%. Interestingly, the MRA interpretations were no better or worse than the more conventional pulse
sequences. The investigators identified spatial resolution, slow blood flow artifacts, small lesion size, tachypnea, and inability to cooperate as the limiting factors in the MRA performance. A later study by Grist prospectively evaluated 20 patients suspected of pulmonary embolism using
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Fig 7. (A) Gated transaxial SE MRI shows infiltrate (inf) in left lung base which enhances rather than impedes visualization of left posterior descending pulmonary artery (arrow) as compared with the right posterior descending artery (curved arrow) on transaxial GE MRI. (B) Gated SE MRI at lower slice level, diastolic image (middle), shows pulmonary emboli in right lateral basilar and posterior basilar branches (arrows). Left posterior basilar branch pulmonary artery is still patent (black arrow). Mid systolic image at the same phase (bottom) and late systolic level (top right) demonstrate emboli persist throughout cardiac cycle (arrows). Note change in appearance of left ventricle [LV] as heart contracts. (C, D) Conventional pulmonary arteriogram of R lung (C) shows lateral basiiar and posterior basilar artery branches with intraluminal emboli (arrows) which were demonstrated on MRI in (B). Conventional pulmonary angiogram of left lung (D) shows all basilar branches and descending pulmonary artery to be patent as seen on MRI (B). (Reprinted with permission from Erdman WA, Peshock RM, Redman HC, et ah Pulmonary embolism of MR images with radionuclide and angiographic studies. Radiology 190:499-508, 1994.2)
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Fig 7.
(Cont'd.)
GRE sagittal sequences. 34 The data were interpreted both in the sagittal slice format as well as an MIP image, which created a more complete angiographic appearance. Sensitivity was 92% to 100% and specificity was 63%. False-positive results occurred in regions of atelectasis, slow flow from previous pulmonary emboli, and misinterpretation of normal anatomic structures. The MIP images tended to obscure the pulmonary emboli in some cases. Our own group prospectively studied 86 patients suspected of pulmonary embolism in which 64 patients were ultimately diagnosed by either angiography (N = 34) or ventilation perfusion scans (N = 30). 2 Our technique used transaxial multiphasic gated spin echo and (in a subset of 25 patients) gated GRE cine (Figs 4, 5, and 6). We did not attempt MR angiographic reprojection or reconstruction of the data. We relied primarily on multiphasic images to differentiate embolus from flow artifact (Fig 6). When compared to conventional angiography, the sensitivity was measured at 90% and specificity was 77%. If we included
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diagnostic quality ventilation perfusion scans as a diagnostic endpoint, then the sensitivity was 88% and the specificity increased to 90%. There are two principle differences between our work and work of the earlier investigators: (1) rather than MRA, we relied more heavily on spin echo transaxial techniques that showed flowing blood as black and embolism as bright, and (2) we had more extensive experience with a single technique over a broad range of patients. This latter point may be the more significant because there seems to be a steep learning curve with MRI interpretation of pulmonary emboli. The use of spin echo technique actually allows visualization from the embolus itself and does not depend on visualization of small branch vessels, which are subject to slow flow and turbulence which present difficulties for the MRA technique. On the other hand, entry slice blood, particularly in pulmonary veins, can exactly mimic a thrombus with the spin echo technique. To overcome this, we relied on bright signal intensity changes that persisted throughout all phases of the cardiac cycle as a criterion for the diagnosis of pulmonary embolus. Because both arterial and venous blood generally change velocity during the cardiac cycle, this additional diagnostic criterion probably reduced the number of false-positive results in our study (Figs 6, 7). Our sensitivity for PE and those of other investigators were both reasonably high despite differences in technique. This is probably because small peripheral emboli were rare in our experience, and MRI techniques in general are fairly reliable in detecting larger more central emboli. Recent hardware and software developments such as shorter echo and repetition times, volumetric acquisition, respiratory triggering, and intravascular contrast have overcome many of the previously mentioned problems and are discussed elsewhere in this issue (see article by Hatabu). These promising new techniques await further clinical evaluation. POTENTIAL CLINICAL ROLE OF MRI
MRI of Venous Thrombosis Because pulmonary embolism is a complication of deep vein thrombosis and the treatment of the two is often the same, establishing the diagnosis of pulmonary embolism in the face of a known venous thrombosis may, in many instances, be a moot point. MRI has been shown to be exceptionally
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reliable in terms of sensitivity and specificity for venous thrombosis, regardless of location, using spin echo or the gradient recalled echo approach. 14,37,38 Thus, evaluation of a patient for venous thrombosis and/or PE may be accomplished in one MRI examination (Fig 4). Griest reported a subset of 13 such patients using GRE sequences. 34 We accomplished the same type of dual evaluation using spin echo in 10 patients (unpublished data). Neither Griest's work nor our own studies involved enough patients to draw any conclusions regarding the clinical efficacy of this combined approach. However, even in this limited population, we both experienced several patients suspected of pulmonary embolism in whom the diagnosis of a deep vein thrombosis was established by MRI and would have influenced the clinical outcome. Although not yet extensively evaluated, the clinical import of this approach should not be overlooked in future studies. MRI Versus Spiral CT
Spiral CT has been shown to reliably show central pulmonary embolism but, like MRI techniques, has not been proven effective in the smaller peripheral vasculature. 3,34,39Woodard has found CT to have better conspicuity than MRI in a series of experimental emboli created in laboratory animals. 4° Similarly, Holland showed a higher accuracy (94% vs 84%) to electron beam CT over MRI in a group of 16 patients. 41 CT has the advantage of higher spatial resolution, rapid acquisition time, broad availability, and relatively more straightforward technology as compared with MRI (Fig 2). Although both spiral CT and MRI require patient cooperation, prolonged suspension of respiration is not necessarily a prerequisite for a number of MR approaches. Furthermore, the need for iodine contrast and the delivery of that contrast in a relevant time frame still presents technical challenges for CT acquisition, which are obviated with MR. Lymph nodes, partial vascular opacification, congestive heart failure changes, and nonorthogonal vessels have presented potential difficulties in spiral CT image interpretation.42 These may also be factors in MR evaluations, although the use of multiple slice planes and gated cine review offer potential advantages to the MR interpreter. MRI Versus Radionuclide Technique
The radionuclide ventilation/perfusion scan still remains the procedure of choice for the work-up of
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pulmonary embolism. 43,44 High or low probability scans with concordant clinical impression have been shown to have a 96% predictive value. 45 The difficulty arises in the large number of patients with intermediate probability scans (Fig 6). Managing these patients without more definite tests may do a disservice to the patient's health and may ultimately be more expensive. The Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) trials, which were completed more than a decade ago, have only recently begun to improve the radionuclide diagnosis of pulmonary embolism. 46 The results of this exhaustive evaluation have substantially benefited the ventilation/perfusion scan by (1) replacing the myriad of diagnostic interpretative schemes with a more standardized set of criteria; (2) attaching meaningful numbers to particular scan patterns and thus enhancing the confidence of both clinicians and interpreters; and (3) significantly revising the criteria in a fashion that decreases the number of indeterminate scans and increases the accuracy of the high and low probability categories.4741These improvements notwithstanding, the ventilation/perfusion scan still represents an older technology that can never approach the accuracy of angiography because of its inability to show emboli directly. The role of MRI (or CT) in the diagnosis of pulmonary embolism should, presently, be complementary to the ventilation/perfusion scan. Suggestions that these newer modalities should replace ventilation/perfusion scanning are probably premature. 6,52 The strength of the ventilation/perfusion scan is in its high sensitivity, ease of performance, and almost universal implementation. Where the ventilation/perfusion scan fails is in those situations in which pulmonary pathology, such as extensive pneumonia, mimics or masks the radionuclide diagnosis of pulmonary embolism. 53 Effusions, infiltrates, and/or atelectasis are not necessarily problematic in evaluating spin echo MRI images (Fig 7). In our clinical series, we found MRI sensitivity to be 100% in a subset of 21 patients with indeterminate ventilation/perfusion scans. Specificity in this group was 77%. 2 Other pathological conditions, such as congestive heart failure, are a potential problem for MRI due to artifacts from slow blood velocity or from patients' inability to cooperate. Similarly, slow flow may limit the quality of spiral CT exams. Recent work has shown that the ventilation/perfusion scan retains diagnostic quality in congestive heart fail-
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ure. 53 These data further support the complementary nature of these newer techniques.
MRI Versus X-ray Angiography At present, conventional x-ray angiography should retain its role as the final arbiter of the diagnosis of pulmonary embolism because the accuracy and experience with the newer technologies are still evolving. Patients with intermediate probability V/Q scans would likely benefit from a confirmatory diagnosis with demonstration of intraluminal emboli by MRI or CT. However, patients with negative results on MRI or CT scans still have
as much as a 30% chance of having nonvisualized small peripheral emboli. 54 Although there is evidence that such small emboli have few clinical sequelae, this failure to establish the correct diagnosis may trigger a search for other causes of the patient's symptoms and may also delay appropriate therapy. 6 MR! alone has the potential to reliably and noninvasively show venous thrombosis, pulmonary embolism, and normal pulmonary vasculature. However, its premature clinical implementation should be avoided lest we unduly prejudice clinicians against what, ultimately, may be the best technology for diagnosing thromboembolic disease.
REFERENCES Gefter WB, Hatabu H, Holland GA, et ah Pulmonary thromboembolism: Recent developments in diagnosis with CT and MR imaging. Radiology 197:561-574, 1995 2. Erdman WA, Peshock RM, Redman HC, et al: Pulmonary embolism: Comparison of MR images with radionuclide and angiographic studies. Radiology 190:499-508, 1994 3. 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 /64: i369-1374, 1995 4. 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 5. Loubeyre P, Revel D, Douek R et ah Dynamic contrastenhanced MR angiography of pulmonary embolism: comparison with pulmonary angiography. AJR 162:1035-1039, 1994 6. Goodman LR, Lipchik RJ: Diagnosis of acute pulmonary embolism: Time for a new approach. Radiology 199:25-27, 1996 7. Erdman WA, Weinreb JC, Cohen JM, et aI: Venous thrombosis: clinical and experimental MR imaging. Radioiogy 151:233-238, 1986 8. Wu JJ, MacFall JR, Sostman HD, et al: Clot-blood contrast in fast gradient-echo magnetic resonance imaging. Invest Radiol 28:586-593, 1993 9. Hatabu H, Gaa J, Kim D, et al: Pulmonary perfusion and angiography--Evaluation with breath-hold enhanced threedimensional fast imaging steady-state precession MR imaging with short TR and TE. AJR 167:653-655, 1996 10. Laissy JR Assayag R Henry-Feugeas MC, et al: Pulmonary time-of-flight MR angiography at 1.0 T: Comparison between 2D and 3D tone acquisitions. Magn Reson Imag 13:949-957, 1995 i 1. Hatabu H, Gaa J, Kim D, et al: Puhnonary perfusion and angiograpby: Evaluation with breath-hold enhanced threedimensional fast imaging steady-state precession MR imaging with short TR and TE. AJR 167:653-655, 1996 12. Frank H, Weissleder R, Bogdanov AAJr, et ah Detection of pulmonary emboli by using MR angiography with MPEG-PLGdDTPA: An experimental study in rabbits. AJR 162:10411046, 1994 13. Erdman WA, Clarke GD, Lipscomb M, et al: High-
resolution, electrocardiogram-gated breath-hold pulmonary MR angiography with rotating 3D multiphasic cine display. Radiology 185:217, I992 (suppl) (abstr) i4. Erdman WA, Jayson HT, Redman HC, et al: Deep venous thrombosis of extremities: Role of MR imaging in the diagnosis. Radiology 174:425-431, 1990 15. Stein MG, Crues JV 3d, Bradley WG Jr, et al: MR imaging of pulmonary emboli: An experimental study in dogs. AJR 147:1133- l 137, 1986 I6. Ovenfors CO, Batra P: Diagnosis of peripheral pulmonary emboli by MR imaging: An experimental study in dogs. Magn Reson Imag 6:487-491, 1988 I7. Pope CF, Sostman D, Carbo R et al: The detection of pulmonary emboli by magnetic resonance imaging. Evaluation of imaging parameters. Invest Radiol 22:937-946, 1987 18. Fisher MR, Higgins CB: Central thrombi in pulmonary arterial hypertension detected by MR imaging. Radiology 158:223-226, 1986 19. White RD, Winkler ML, Higgins CB: MR imaging of pulmonary arterial hypertension and pulmonary emboli. AJR 149:15-21, 1987 20. Gefter WB, Hatabu H: Evaluation of pulmonary vascular anatomy and blood flow by magnetic resonance. J Thorac Imag 8:122-136, 1993 21. Hatabu H, Gefter WB, Listerud J, et al: Pulmonary MR angiography utilizing phased-array surface coils. J Comput Assist Tomogr 16:410-417, 1992 22. Hatabu H, Gefter WB, Konishi J, et ah Magnetic resonance approaches to the evaluation of pulmonary vascular anatomy and physiology. Magn Reson Q 7:208-225, 1991 23. MacFall JR, Sostman HD, Foo TK: Thick-section, single breath-hold magnetic resonance pulmonary angiography. Invest Radiol 27:318-322, 1992 24. Wielopolski PA, Haacke EM, Adler LP: Three-dimensional MR imaging of the pulmonary vasculature: Preliminary experience. Radiology 183:465-472, 1992 25. Hatabu H, Gefter WB, Kressel HY, et al: Pulmonary vasculature: High-resolution MR imaging. Radiology 171:391395, 1989 26. Foo TK, MacFall JR, Sostman HD, et al: Single-breathhold venous or arterial flow-suppressed pulmonary vascular MR imaging with phased-array coils. J Magn Reson Imag 3:611616, I993
348
27. Posteraro RH, Sostman HD, Spritzer CE, et al: Cinegradient-refocused MR imaging of central pulmonary emboli. AJR 152:465-468, 1989 28. Krovetz LJ: The effect of vessel branching on haemodynamic stability. Phys Med Biol 10:417-427, 1965 29. Pike GB, Hu BS, Glover GH, Enzmann DR: Magnetization transfer time-of-flight magnetic resonance angiography. Magn Reson Med 25:372-379, 1992 30. Atkinson D, Teresi L: Magnetic resonance angiography. Magn Reson Q 10:149-172, 1994 31. Thickman D, Kressel HY, Axel L: Demonstration of pulmonary embolism by magnetic resonance imaging. AJR 142:921-922, 1984 32. Moore EH, Gamsu G, Webb WR, et al: Pulmonary embolus: detection and follow-up using magnetic resonance. Radiology 153:471-472, 1984 33. Gamsu G, Hirji M, Moore EH, et al: Experimental pulmonary emboli detected using magnetic resonance. Radiology 153:467-470, 1984 34. Grist TM, Sostman HD, MacFall JR, et al: Pulmonary angiography with MR imaging: Preliminary clinical experience. Radiology 189:523-530, 1993 35. Schiebler ML, Holland GA, Hatabu H, et al: Suspected pulmonary embolism: Prospective evaluation with pulmonary MR angiography. Radiology 189:125-131, 1993 36. Axel L, Dougherty L: MR imaging of motion with spatial modulation of magnetization. Radiology 171:841-845, 1989 37. Erdman WA: Magnetic resonance imaging, in Talbot S, Oliver MA (eds): Techniques of Venous Imaging. Pasadena, CA, Appleton-Davies, 1992, pp 175-185 38. Spritzer CE, Sostman HD, Wilkes D, et al: Deep venous thrombosis: Experience with gradient echo MR imaging in 66 patients. Radiology 177:235-241, 1990 39. van Rossum AB, Pattynama PM, Ton ER, et al: Pulmonary embolism: Validation of spiral CT angiography in 149 patients. Radiology 201:467-470, 1996 40. Woodard PK, Sostman HD, MacFall JR, et al: Detection of pulmonary embolism: Comparison of contrast-enhanced spiral CT and time-of-flight MR techniques. J Thorac Imag 10:59-72, 1995 41. Holland GA, Gefter WB, Baum RA, et al: Prospective comparison of pulmonary MR angiography and ultrafast CT for diagnosis of pulmonary thromboembolic disease. Radiology 189:234, 1993 (abstr)
ERDMAN AND CLARKE
42. Drucker EA, Rivita SM, Shepard JP, et al: Assessment of helical CT in the diagnosis of acute pulmonary emboli. Radiology 20:303, 1996 (abstr) 43. Matsomoto AH, Tegtmeyer CJ: Contemporary diagnostic approaches to acute pulmonary emboli. Radiol Clin North Am 33:167-183, 1995 44. Robinson PJA: Ventilation-perfusion lung scanning and spiral computed tomography of the lungs--Competing or complementary modalities. Eur J Nucl Med 23:1547-1553, 1996 45. 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 46. Worsley DF, Alavi A: Comprehensive analysis of the results of the PIOPED study. J Nucl Med 36:2380-2387, 1995 47. Webber MM, Gomes AS, Roe D, et al: Comparison of Biello, McNeil, and PIOPED criteria for the diagnosis of pulmonary emboli on lung scans. AJR 154:975-981, 1990 48. Sostman HD, Coleman RE, DeLong DM, et al: Evaluation of revised criteria for ventilation-perfusion scintigraphy in patients with suspected pulmonary embolism. Radiology 193: 103-107, 1994 49. Freitas JE, Sarosi MG, Nagle CC, et al: Modified PIOPED criteria used in clinical practice. J Nucl Med 36:15731578, 1995 50. Stein PD, Relyea B, Gottschalk A: Evaluation of individual criteria for low probability interpretation of ventilationperfusion lung scans. J Nucl Med 37:577-581, 1996 51. Gottschalk A, Sostman HD, Coleman RE, et al: Ventilation-peffusion scintigraphy in the PIOPED study. Part II. Evaluation of the scintigraphic criteria and interpretations. J Nucl Med 34:1119-1126, 1993 52. Gumey JW: No fooling around: Direct visualization of pulmonary embolism. Radiology 188:618-619, 1993 (editorial) 53. Goldberg SN, Palmer EL, Scott JA, et al: Pulmonary embolism: Prediction of the usefulness of initial ventilationperfusion scanning with chest radiographic findings. Radiology 193:801-805, 1994 54. Oser RF, Zuckerman DA, Gutierrez ER, et al: Anatomic distribution of pulmonary emboli at pulmonary angiography: Implications for cross-sectional imaging. Radiology 199:31-35, 1996