MRI expands options in lung assessment

November 1, 2005

Pulmonary embolism is a common, potentially life-threatening condition.1 Diagnosing PE remains a major challenge because typical symptoms such as dyspnea, tachycardia, acute chest pain, and syncope are unspecific and may not be present in all patients. Imaging therefore plays a pivotal role in establishing a diagnosis.2

Pulmonary embolism is a common, potentially life-threatening condition.1 Diagnosing PE remains a major challenge because typical symptoms such as dyspnea, tachycardia, acute chest pain, and syncope are unspecific and may not be present in all patients. Imaging therefore plays a pivotal role in establishing a diagnosis.2

Chest x-ray is often the initial imaging study in patients with suspected PE, but it is highly unspecific and can neither rule out nor confirm the diagnosis. Lung perfusion scintigraphy, which is frequently performed as a combined ventilation-perfusion (V/Q) scan, has traditionally been the mainstay for imaging patients with suspected PE. Negative scintigraphy essentially rules it out. When studies indicate a high probability of PE, about 85% of diagnoses will be confirmed on pulmonary angiography.3 In 50% to 72% of scans, however, a low or intermediate likelihood of PE will be suggested, and readers will disagree in 25% to 35% of these cases. This uncertainty holds for expert readers as well as less experienced radiologists.3,4

Conventional catheter angiography of the pulmonary arteries is generally considered the reference standard for PE diagnosis. But it is rarely performed due to its high costs, requirement for expert operators, and invasive nature.3 Bedside echocardiography, used mainly in hemodynamically unstable patients, permits detection of impaired right heart function such as tricuspid regurgitation, dilatation of right ventricle and atrium, paradoxical septal motion, and widening of the pulmonary artery diameter. Its value for minor PE is limited, however, because peripheral pulmonary arteries cannot be visualized.

Spiral CT is emerging as a first-line imaging test for the assessment of suspected acute PE. The introduction of multislice CT has improved spatial resolution, allowing considerably shorter scan times. CT angiograms of the pulmonary arterial tree-the fifth to eighth-order branches-can be acquired in less than 15 seconds. CT can also visualize thoracic mediastinal and parenchymal structures, allowing diagnosis of other acute pathology with presentation similar to PE: aortic dissection, pneumonia, and pneumothorax.5

PROMISE OF MR

Although several studies have reported promising results for the assessment of PE on MR imaging, the overall clinical importance of MR for imaging of PE has been minor.6-9 Both the spatial and temporal resolution of MRI have been low compared with CT, resulting in poor visualization of peripheral pulmonary arteries and a high susceptibility to respiratory motion artifact.

Pulmonary MRI is also hampered by unfavorable signal characteristics caused by the lungs' low proton density and high magnetic susceptibility.10 Special conditions related to high magnetic fields, limited access to patients within the magnet bore, and the limited availability of scanners have also counted against MR as a first-line tool for imaging acute cardiovascular disease.

PE assessment with MRI does offer a number of potential advantages, however. Examinations require no ionizing radiation, unlike CT and scintigraphy. It may be argued that exposure to radiation is only a secondary issue when diagnosing potentially life-threatening conditions such as PE, but radiation dosage can be relevant in certain clinical circumstances. Radiation delivered to the female breast during a CT-based PE assessment has been reported to be the equivalent of 10 to 25 two-view x-ray mammograms or 100 to 400 chest radiographs.11 Approximately 90% of patients with low or moderate clinical probability of PE-about 90% of all patients with suspected PE-may be exposed to up to 10 mSv of radiation despite not having the condition.12

While CT is indisputably superior for the detection of subsegmental emboli, thanks to its higher spatial resolution, the clinical and therapeutic relevance of these emboli remains controversial.13

MR, unlike any other imaging modality, offers the advantage of combining morphologic and functional imaging; for instance, angiography and perfusion. This capability has led to its adoption as a first-line imaging tool in the assessment of cardiovascular and cerebrovascular disease, even in the acute stage.14,15 An MRI-based assessment of PE may include angiography of the pulmonary arteries and systemic veins (the latter to check for deep vein thrombosis), functional imaging of lung perfusion and ventilation, assessment of right heart function and pulmonary hemodynamics, and morphologic imaging of the lung.

Technical innovations continue to improve the suitability of MRI for PE diagnosis. Parallel imaging techniques, which use spatial information from the geometry of surface coil arrays to reduce the number of phase-encoding steps, allow significantly faster acquisitions. Both temporal and spatial resolution of MRI can be substantially improved with parallel imaging. Better spatial resolution enhances the detection of peripheral emboli. Superior temporal resolution reduces the susceptibility to breathing artifacts and further improves the capability of functional MRI techniques.

Developments in MR hardware include new magnet designs with reduced length (less than 1.3 meters) and wider bores to address the patient access issue. Dedicated whole-body MRI systems, such as the Magnetom Espree from Siemens, also permit comprehensive head-to-toe protocols for the assessment of PE and DVT.

PULMONARY MRA, MR VENOGRAPHY

In the mid-1990s, development of high-performance gradient systems and fast gradient-echo pulse sequences made breath-hold 3D contrast-enhanced MR angiography of the lung (pulmonary MRA) clinically feasible. One of the first studies to report on this technique achieved a sensitivity of 70% and specificity of 100%, compared with conventional angiography, in 23 patients with suspected PE.16 Another study performed on 30 patients with suspected PE yielded sensitivities and specificities of 75% to 100%, and 95% to 100%, respectively. Observer agreement achieved kappa values of 0.57 to 0.83.6

A study by Gupta et al evaluated the accuracy of pulmonary MRA in 36 patients with intermediate or low probability on lung scintigraphy. All patients also underwent pulmonary angiography, which demonstrated PE in 13 patients. Pulmonary MRA diagnosed 12 patients as having PE (specificity 96%) and missed two cases (sensitivity 85%). Both missed emboli were isolated and subsegmental in location.7 A larger study involving 141 patients with abnormal perfusion lung scintigraphy reported that MRA detected 27 of 35 cases with confirmed PE (overall sensitivity 77%). The sensitivity values for isolated subsegmental, segmental, and central/lobar PE were 40%, 84%, and 100%, respectively. Pulmonary MRA could be performed in two patients in whom conventional pulmonary angiography was contraindicated. It also demonstrated emboli in two patients with a normal angiogram (specificity 98%).8

Time-resolved MRA has also been evaluated for PE assessment. This approach offers the advantage of reduced scan time, which decreases susceptibility for motion artifacts and improves arteriovenous discrimination. A feasibility study of eight dyspneic patients with known or suspected PE allowed assessment of the pulmonary arterial tree up to a subsegmental level, identifying PE in all four subsequently confirmed cases. The chosen time-resolved 3D MRA protocol involved an acquisition time of less than four seconds. All patients could hold their breath for at least eight seconds, enough time to obtain data for an angiogram of the pulmonary arteries.9

A separate study compared the diagnostic accuracy of time-resolved 3D MRA with parallel imaging (SENSE) against MSCT and V/Q scanning in 48 patients with suspected PE. Conventional pulmonary angiography served as the gold standard. MRA had a higher sensitivity than either MSCT or V/Q scanning (92%, 83%, and 67%, respectively). Specificity for both MRA and MSCT was the same (94%) and higher than that for a V/Q scan (78%).17

MRI assessment of systemic veins as a potential source of embolic material (MR venography) has also been considered (Figure 1). Researchers have investigated unenhanced MR venography as well as direct and indirect contrast-enhanced scanning. One study of indirect contrast-enhanced MR venography for the assessment of DVT in iliac and femoral veins reported a sensitivity of 100% and a specificity of 97% to 100%.18 Another group achieved sensitivity and specificity of 93.3% and 96.5%, respectively, when comparing MR venography performed with an intravascular MR contrast agent against conventional x-ray venography.19 A separate study of 48 patients, using indirect MR venography, demonstrated a sensitivity of 100% and specificity of 92% for DVT detection.20

PERFUSION AND VENTILATION

Pulmonary perfusion MRI enables visualization of the pulmonary capillary bed. This approach generally involves peripheral injection of a contrast bolus, which is then tracked as it moves through the capillary bed of the lungs. Subtraction of precontrast imaging data from a data set acquired in phase with maximum enhancement of the lung parenchyma gives a perfusion-weighted data set.

Pulmonary perfusion MRI offers several advantages over conventional perfusion scintigraphy: A 3D MRI perfusion-weighted data set can be acquired in a single breath-hold, injected contrast is not radioactive, and the examination has superior interobserver agreement.21

Images have greater spatial resolution and provide additional temporal information that is not available in static pulmonary perfusion scintigraphy. From this temporal information, additional quantitative parameters, such as pulmonary blood flow (PBF) and blood volume (PBV), can be obtained. We evaluated the feasibility of 3D quantitative perfusion MRI in a pilot study involving eight patients with PE or pulmonary hypertension. Imaging of patients with acute PE or chronic thromboembolism showed characteristic wedge-shaped perfusion defects, with decreased PBF and PBV. Patients with primary pulmonary hypertension or Eisenmenger syndrome showed a more homogeneous perfusion pattern.22

MRI can visualize ventilated lung parenchyma as well. Strategies include imaging after patients have inhaled aerosolized MR contrast media or hyperpolarized noble gases such as helium. One of the most promising ventilation methods, which can be implemented with conventional equipment, is oxygen-enhanced MRI. This exploits the T1-shortening effect of molecular oxygen dissolved in the capillary blood of the lungs. The combination of contrast-enhanced pulmonary perfusion MRI and oxygen-enhanced MRI can visualize PE ventilation/perfusion mismatches, just as V/Q scanning can.23

Combining pulmonary perfusion MRI with conventional morphologic MRI and high-spatial-resolution MRA may provide the most sensitive and specific method of PE assessment (Figures 2 and 3).17

HEART FUNCTION, HEMODYNAMICS

MRI, like echocardiography, can be used to assess the hemodynamics of the pulmonary circulation and right ventricle in PE patients. MRI is less dependent on an individual examiner's expertise, however, and results are more reproducible.

Cine MRI may be used to quantify right ventricular ejection fraction, using a technique similar to that employed in evaluating left ventricular disease. The geometry of the right ventricle is somewhat different from the left ventricle's, however, and less well defined.24

Cine MRI can also demonstrate pathologic changes to the heart's physiologic motion. Systolic bulging of the interventricular septum toward the left ventricle (paradoxical movement), for example, correlates with mean pulmonary arterial pressure.25,26 Tricuspid regurgitation, another sign of right heart decompensation, can also be demonstrated by cine MRI and quantified using phase-contrast MRI.27

Advances in hardware design and the introduction of new pulse sequences have improved the potential of MRI for pulmonary circulation assessment. MRI may therefore be considered more often for PE assessment. Possible clinical applications include follow-up of PE resolution during thrombolytic therapy, exclusion of PE in low-risk patients, and PE assessment in patients for whom radiation-free imaging is preferred such as young women.

ACKNOWLEDGMENT

All images were acquired at the radiology department (chair, Prof. Dr. Kauczor) of the German Cancer Research Center in Heidelberg, Germany.

DR. FINK is a resident, DR. SCHOENBERG is associate chair for clinical operations and MR section chief, and PROF. DR. REISER is chair of clinical radiology at the University of Munich in Germany. Assisting in the preparation of this manuscript was Dr. Konstantin Nikolaou, department of clinical radiology, University of Munich.

REFERENCES

1. Silverstein MD, Heit JA, Mohr DN, et al. Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch Int Med 1998;158(6):585-593.

2. Goldhaber SZ. Pulmonary embolism. Lancet 2004; 363(9417):1295-1305.

3. Tan KT, van Beek EJ. Diagnosis and treatment of pulmonary embolism: An overview. Imaging Decisions 2002;6(3):3-10.

4. Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). The PIOPED Investigators. JAMA 1990;263(20):2753-2759.

5. Schoepf UJ, Costello P. CT angiography for diagnosis of pulmonary embolism: state of the art. Radiology 2004;230(2): 329-337.

6. Meaney JF, Weg JG, Chenevert TL, et al. Diagnosis of pulmonary embolism with magnetic resonance angiography. NEJM 1997;336(20):1422-1427.

7. Gupta A, Frazer CK, Ferguson JM, et al. Acute pulmonary embolism: diagnosis with MR angiography. Radiology 1999; 210(2):353-359.

8. Oudkerk M, van Beek EJ, Wielopolski 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(9318): 1643-1647.

9. Goyen M, Laub G, Ladd ME, et al. Dynamic 3D MR angiography of the pulmonary arteries in under four seconds. J Mag Res 2001;13(3):372-377.

10. Bergin CJ, Glover GH, Pauly JM. Lung parenchyma: magnetic susceptibility in MR imaging. Radiology 1991; 180(3):845-848.

11. Parker MS, Hui FK, Chung JK, et al. Pulmonary embolism in young women: Does the benefit outweigh the potential risk? Presented at annual meeting of American Roentgen Ray Society, Miami; May 2004:182.

12. Wells PS, Ginsberg JS, Anderson DR, et al. Use of a clinical model for safe management of patients with suspected pulmonary embolism. Ann Intern Med 1998;129(12):997-1005.

13. Eyer BA, Goodman LR, Washington L. Clinicians' response to radiologists' reports of isolated subsegmental pulmonary embolism or inconclusive interpretation of pulmonary embolism using MDCT. AJR 2005;184(2):623-628.

14. Kwong RY, Schussheim AE, Rekhraj S, et al. Detecting acute coronary syndrome in the emergency department with cardiac magnetic resonance imaging. Circulation 2003;107(4): 531-537.

15. Schellinger PD, Jansen O, Fiebach JB, et al. Feasibility and practicality of MR imaging of stroke in the management of hyperacute cerebral ischemia. AJNR 2000;21(7):1184-1189.

16. Loubeyre P, Revel D, Douek P, et al. Dynamic contrast-enhanced MR angiography of pulmonary embolism: comparison with pulmonary angiography. AJR 1994;162(5):1035-1039.

17. Ohno Y, Higashino T, Takenaka D, et al. MR angiography with sensitivity encoding (SENSE) for suspected pulmonary embolism: comparison with MDCT and ventilation-perfusion scin8igraphy. AJR 2004;183(1):91-98.

18. Fraser DG, Moody AR, Davidson IR, et al. Deep venous thrombosis: diagnosis by using venous enhanced subtracted peak arterial MR venography versus conventional venography. Radiology 2003;226(3):812-820.

19. Aschauer M, Deutschmann HA, Stollberger R, et al. Value of a blood pool contrast agent in MR venography of the lower extremities and pelvis: preliminary results in 12 patients. Magn Reson Med 2003;50(5):993-1002.

20. Kluge A, Rominger M, Schonburg M, Bachmann G. [Indirect MR venography: contrast medium protocols, postprocessing and combination in diagnosing pulmonary emboli with MR]. Rofo 2004;176:976-984. German.

21. 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 Mag Res 2002;15(4): 386-394.

22. Fink C, Risse F, Buhmann R, et al. Quantitative analysis of pulmonary perfusion using time-resolved parallel 3D MRI - initial results. Rofo 2004;176(2):170-174.

23. Nakagawa T, Sakuma H, Murashima S, et al. Pulmonary ventilation-perfusion MR imaging in clinical patients. J Mag Res 2001;14(4):419-424.

24. Rominger MB, Bachmann GF, Pabst W, Rau WS. Right ventricular volumes and ejection fraction with fast cine MR imaging in breath-hold technique: applicability, normal values from 52 volunteers, and evaluation of 325 adult cardiac patients. J Mag Res 1999;10(6):908-918.

25. Kreitner KF, Ley S, Kauczor HU, et al. Chronic thromboembolic pulmonary hypertension: pre- and postoperative assessment with breath-hold MR imaging techniques. Radiology 2004;232(2):535-543.

26. Roeleveld RJ, Marcus JT, Faes TJ, et al. Interventricular septal configuration at MR imaging and pulmonary arterial pressure in pulmonary hypertension. Radiology 2005;234(3): 710-717.

27. Ley S, Kreitner KF, Fink C, et al. Assessment of pulmonary hypertension by CT and MR imaging. Europ Radiol 2004;14(3):359-368.