MRI proves clinical value in lung cancer

December 2, 2004

Non-small cell lung cancer is the leading cause of cancer-related deaths in women and men in the Western Hemisphere. Surgical resection remains the mainstay of therapy in disease at stages I and II, and this treatment has an acceptable morbidity and mortality rate. Imaging is needed for effective treatment planning and accurate diagnosis, including preoperative assessment of resectability.

Non-small cell lung cancer is the leading cause of cancer-related deaths in women and men in the Western Hemisphere. Surgical resection remains the mainstay of therapy in disease at stages I and II, and this treatment has an acceptable morbidity and mortality rate. Imaging is needed for effective treatment planning and accurate diagnosis, including preoperative assessment of resectability.

MR imaging has failed to assume the same importance as CT in the radiological evaluation of lung cancer. It is usually considered as an alternative modality when CT findings are inconclusive or as a primary modality in cases of contraindication to iodinated contrast media.1 Key reasons for the limited role of MRI relate to technical limitations, including longer scan times, inferior spatial resolution, and low signal of the lung parenchyma.2,3 Unfavorable signal characteristics are due to the lungs' low proton density and high magnetic susceptibility.4

MR offers several benefits over CT for assessing lung cancer, however. Its contrast media have lower toxicity than contrast used in CT scans, the examination involves no ionizing radiation, and resulting images provide much better soft-tissue contrast. MR also offers a variety of contrast options (T1 weighting, T2 weighting, fat saturation, etc.), which in practice facilitates differentiation of pathologic tissue growth.2 The modality allows imaging in any desired plane without further need for image processing.

Contrast-enhanced MR angiography has also proved valuable for evaluating the thoracic vascular system, allowing noninvasive assessments of tumor invasion.2,5

Continuous improvements in MR hardware, including high-performance gradient systems and new pulse sequences, are counteracting the modality's technical drawbacks. Improved triggering options and pulse sequence techniques, for example, reduce cardiac and/or respiratory motion artifacts.

Use of fast MR sequences now enables the entire thorax to be imaged during a single breath-hold.3,6,7 Application of long-term averaging to conventional turbo spin-echo MRI produces high image quality with reduced motion artifacts.8 Single-shot pulse sequences, such as half-Fourier single-shot turbo spin-echo (HASTE),6 further decrease susceptibility to cardiac or respiratory motion, reducing scan times to below one second per image. Problems arising from T2*-related signal loss can be reduced by using short echo times, which allow improved visualization of lung parenchyma.6 Results can be improved by applying parallel imaging techniques.9

MRI TUMOR STAGING

Pathologic changes to lung parenchyma, such as pulmonary nodules, show an increased T2* relaxation time of more than 140 msec.

4

This results in high contrast to the surrounding normal lung, which has a T2* relaxation time of approximately five msec. Detection rate of solitary pulmonary nodules on MRI varies according to nodule size. MRI has a sensitivity of over 80% (compared with gold standard CT or surgery) for detection of nodules with diameter greater than 10 mm.

7,10,11

Limited spatial resolution causes sensitivity to drop below 70% for nodules smaller than 10 mm in diameter.

3,10

Introduction of new 3D pulse sequences with a higher spatial resolution and implementation of parallel imaging techniques should boost the accuracy of MRI further for the detection of solitary pulmonary nodules.

9,12

MRI can also be used to characterize lung nodules. Several studies using dynamic contrast-enhanced MRI have shown malignant nodules to have faster and stronger enhancement than benign lesions.13,14 Inflammatory lesions also show rapid and strong enhancement, however, and this overlap should be kept in mind.14

Low soft-tissue contrast on CT images makes it difficult to differentiate secondary lung changes (i.e., atelectasis, postobstructive pneumonia) from the lung tumor. MRI offers much better soft-tissue contrast, which facilitates this identification. T2-weighted MRI characterizes postobstructive lung changes as having higher signal intensity than the tumor, owing to their retention of mucus and bronchial secretion (Figure 1).15 Differences in the magnitude and kinetics of contrast enhancement between the tumor and secondary lung changes can also be used for differentiation. Postobstructive lung changes typically show an increased and faster enhancement than tumors.16

Knowledge of mediastinal tumor invasion (T3 and T4) is important when assessing the resectability of central lung tumors. Tumors exhibiting minimal invasion into mediastinal fat tissue, the parietal pleura, or the pericardium (T3), are still considered technically resectable. Tumor invasion can be assessed by examining continuity of mediastinal fat planes on T1-weighted MRI (Figure 2). This method offers some advantages over CT, including much better soft-tissue contrast, and choice of imaging plane. MRI makes it possible to acquire axial, coronal, sagittal, oblique, or double oblique images adapted to the structure of interest, providing the best image quality to, for example, evaluate tumor infiltration. Documented studies record a sensitivity of 75% to 80% for MR assessments of mediastinal invasion.17,18

So-called black blood MR techniques have proved effective for assessment of vascular invasion.19 Contrast-enhanced 3D MR angiography could also be used in this role.2,5 MRA remains inferior to CT for assessments of segmental or subsegmental lung vessels, owing to its inferior spatial resolution. The accuracy of CT and MRI in assessments of mediastinal vessels, however, is similar. Application of parallel MR techniques promises improvement in the spatial and temporal resolution of MRA.20

Preoperative assessment of chest wall invasion by lung cancer remains a common clinical problem.21 The superior soft-tissue contrast of MR over CT again could be of benefit. Chest wall invasion should be suspected if T1-weighted MRI shows the usually continuous thin extrapleural fat layer invaded by tissue of medium signal intensity. These tumor infiltrations appear as high signal intensity on T2-weighted MRI.

Both fat-saturated T2-weighted MRI and fat-saturated contrast-enhanced T1-weighted MRI offer valuable alternatives for assessment of chest wall invasion. A number of studies have shown the advantages of MR in evaluations of Pancoast tumors.22 MRI provides an excellent delineation of important soft-tissue structures such as brachial plexus roots, neck blood vessels, and the arms, as well as important bone structures such as ribs and vertebral bodies. This is not the case on CT. The accuracy of MRI for detecting tumor infiltration in the brachial plexus, spine, or subclavian artery has been given as 94%, compared with 63% on CT.22

METASTATIC SPREAD

Assessment of nodal metastasis is an important prognostic factor for patients with lung cancer. Nodal staging can also affect treatment choice. Ipsilateral hilar nodal spread (N1) reduces the overall prognosis but poses no contraindication for surgical therapy. Tumors with ipsilateral mediastinal nodal involvement (N2) can also be treated with surgery. Contralateral mediastinal nodal spread (N3), however, excludes the possibility of curative surgical resection.

MR-based lymph node evaluation is based mainly on an assessment of nodal size and shape, as with CT. Both T1- and T2-weighted pulse sequences can be used in the detection and morphologic evaluation of lymph nodes. T2-weighted fat-saturated pulse sequences such as STIR show lymph nodes with very high contrast. ECG triggering or single-shot sequences should be considered to reduce pulsation artifacts.

MRI has recorded a similar accuracy to CT in the assessment of nodal involvement. In comparative studies, the sensitivity of MRI and CT was between 48% and 90% and 52% and 82%, respectively. The specificity ranged from 64% to 93% and 69% to 88%, respectively.17,18 Attempts to increase the accuracy of MRI further, using measurements of signal intensity or contrast enhancement to differentiate between nodal hyperplasia and nodal metastasis, have proved disappointing.23

Use of lymphotropic MR contrast media holds promise as a new approach to nodal staging.24,25 Dextran-coated ultrasmall superparamagnetic iron oxide particles (USPIO) developed for this purpose have already entered clinical trials. The mechanism of action is based on phagocytosis by nodal macrophages, causing signal loss on T2-weighted MRI. Cases of nodal metastasis, where nodal macrophages are replaced by tumor, reveal a similar signal on pre- and postcontrast images.

One study for the assessment of mediastinal nodes in patients with lung cancer concluded that USPIO-enhanced MRI was equal to PET and superior to CT. Accuracy levels for PET, MRI, and CT (against the gold standard of surgical biopsy) were 84%, 83%, and 76% respectively.24 Another multicenter trial found the sensitivity, specificity, and accuracy of USPIO-enhanced MRI in the detection of nodal metastasis to be 92%, 80%, and 85%, respectively.25 Most false-positive results found on USPIO-enhanced MRI are due to follicular hyperplasia, which also replaces nodal macrophages.

The most frequent hematogenous sites of metastasis in patients with lung cancer are the brain, axial skeleton, adrenals, and lungs. The accuracy of CT and MRI is equal for the assessment of adrenal metastasis, but MRI offers superior performance for detecting brain or bone metastasis.26-28

New developments in MR technology, such as whole-body scans with automatic table movement, will further improve systemic assessments. Application of multiple coil arrays, using multiple receiver channel technology and fast pulse sequences with parallel MRI, can reduce imaging time considerably. This time saving will make whole-body acquisitions feasible in a clinical context.28-30

Fat-saturated T2-weighted MRI or contrast-enhanced fat-saturated T1-weighted MRI are typically used to detect metastasis. Clinical studies show ventilation MRI agrees well with conventional bone scintigraphy, while additionally detecting metastases in soft tissue and organs (Figure 3).30,31

FUNCTIONAL STUDIES

MRI can provide functional evaluations of lung cancer patients as well. These include time-resolved dynamic measurements of the tumor and chest wall mobility during the breathing cycle.

31-33

Clinical studies have demonstrated the potential of this technique for assessing chest wall invasion (Figure 4).

32,33

Knowledge of tumor motion can also help when optimizing target volume in radiotherapy planning.

34

Functional MRI studies can also assess lung perfusion, either through unenhanced arterial spin labeling, or dynamic contrast-enhanced MRI.35-38 Several studies have shown a high correlation of pulmonary perfusion MRI with conventional radionuclide lung perfusion scintigraphy (Figure 5).35-38 Parallel imaging techniques are improving temporal and spatial resolution of pulmonary perfusion MRI, enabling 3D acquisitions of the whole lung.35 Pulmonary perfusion MRI has been proposed as a viable method of assessing functional operability in lung cancer patients.38

MR-based assessments of ventilation are also possible. Proposed techniques include inhalation of aerosolized gadolinium chelates,39 hyperpolarized noble gases (for example, He-3),40,41 or molecular oxygen.42 Clinical studies have shown that ventilation MRI correlates well with both conventional lung function tests and CT.41 Combined ventilation and pulmonary perfusion MRI studies will eventually permit comprehensive assessment of pulmonary gas exchange.

MRI is likely to play a greater role in assessment of lung cancer patients in the future. It is already the imaging modality of choice for certain clinical problems such as superior sulcus tumors. Combinations of sophisticated morphologic and functional imaging techniques-for example, whole-body MRI, perfusion MRI, and ventilation MRI-will provide a comprehensive evaluation of lung cancer within a single examination. This could make MRI even more cost-effective than a combination of conventional imaging modalities.

DR. FINK and DR. PLATHOW are residents, and PROF. DR. KAUCZOR is department head, all in the radiology department of Deutsches Krebsforschungszentrum (DKFZ) in Heidelberg, Germany. DR. MICHAEL KLOPP and DR. ASTRID SCHMAHL assisted in the preparation of this manuscript.

References

1. Thompson BH, Stanford W. MR imaging of pulmonary and mediastinal malignancies. Magn Reson Imaging Clin N Am 2000;8(4):729-739.

2. Kauczor HU, Kreitner KF. Contrast-enhanced MRI of the lung. Europ J Radiol 2000;34(3):196-207.

3. Biederer J, Both M, Graessner J, et al. Lung morphology: fast MR imaging assessment with a volumetric interpolated breath-hold technique: initial experience with patients. Radiology 2003;226(1):242-249.

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

5. Ohno Y, Adachi S, Motoyama A, et al. Multiphase ECG-triggered 3D contrast-enhanced MR angiography: utility for evaluation of hilar and mediastinal invasion of bronchogenic carcinoma. J Magn Reson Imag 2001;13(2):215-224.

6. Hatabu H, Gaa J, Tadamura E, et al. MR imaging of pulmonary parenchyma with a half-Fourier single-shot turbo spin-echo (HASTE) sequence. Europ J Radiol 1999;29(2):152-159.

7. Knopp MV, Hess T, Schad LR, et al. [MR tomography of lung metastases with rapid gradient-echo sequences. Initial results in diagnostic applications]. Radiologe 1994;34(10):581-587. German.

8. Seitz J, Strotzer M, Volk M, et al. Reduction of motion artifacts in magnetic resonance imaging of the neck and cervical spine by long-term averaging. Invest Radiol 2000;35(6):380-384.

9. Heidemann RM, Griswold MA, Kiefer B, et al. Resolution enhancement in lung 1H imaging using parallel imaging methods. Magn Reson Med 2003;49(2):391-394.

10. Kersjes W, Mayer E, Buchenroth M, et al. Diagnosis of pulmonary metastases with turbo-SE MR imaging. Europ Radiol 1997;7(8):1190-1194.

11. Feuerstein IM, Jicha DL, Pass HI, et al. Pulmonary metastases: MR imaging with surgical correlation-a prospective study. Radiology 1992;182(1):123-129.

12. Biederer J, Schoene A, Freitag S, et al. Simulated pulmonary nodules implanted in a dedicated porcine chest phantom: sensitivity of MR imaging for detection. Radiology 2003;227(2):475-483.

13. Guckel C, Schnabel K, Deimling M, Steinbrich W. Solitary pulmonary nodules: MR evaluation of enhancement patterns with contrast-enhanced dynamic snapshot gradient-echo imaging. Radiology 1996;200(3):681-686.

14. Ohno Y, Hatabu H, Takenaka D, et al. Solitary pulmonary nodules: potential role of dynamic MR imaging in management initial experience. Radiology 2002;224(2):503-511.

15. Bourgouin PM, McLoud TC, Fitzgibbon JF, et al. Differentiation of bronchogenic carcinoma from postobstructive pneumonitis by magnetic resonance imaging: histopathologic correlation. J Thorac Imaging 1991;6(2):22-27.

16. Kono M, Adachi S, Kusumoto M, Sakai E. Clinical utility of Gd-DTPA-enhanced magnetic resonance imaging in lung cancer. J Thorac Imaging 1993;8(1):18-26.

17. Webb WR, Gatsonis C, Zerhouni EA, et al. CT and MR imaging in staging non-small cell bronchogenic carcinoma: report of the Radiologic Diagnostic Oncology Group. Radiology 1991;178(3):705-713.

18. Manfredi R, Pirronti T, Bonomo L, Marano P. Accuracy of computed tomography and magnetic resonance imaging in staging bronchogenic carcinoma. MAGMA 1996;4(3-4):257-262.

19. Hanson JA, Armstrong P. Staging intrathoracic non-small-cell lung cancer. Europ Radiol. 1997;7(2):161-172.

20. Ohno Y, Kawamitsu H, Higashino T, et al. Time-resolved contrast-enhanced pulmonary MR angiography using sensitivity encoding (SENSE). J Magn Reson Imaging 2003;17(3):330-336.

21. Glazer HS, Duncan-Meyer J, Aronberg DJ, et al. Pleural and chest wall invasion in bronchogenic carcinoma: CT evaluation. Radiology 1985;157(1):191-194.

22. Heelan RT, Demas BE, Caravelli JF, et al. Superior sulcus tumors: CT and MR imaging. Radiology 1989;170(3 pt 1):637-641.

23. Schaefer-Prokop C, Prokop M. New imaging techniques in the treatment guidelines for lung cancer. Europ Respir J Suppl 2002;35:71s-83s.

24. Kernstine KH, Stanford W, Mullan BF, et al. PET, CT, and MRI with Combidex for mediastinal staging in non-small cell lung carcinoma. Ann Thorac Surg 1999;68(3):1022-1028.

25. Nguyen BC, Stanford W, Thompson BH, et al. Multicenter clinical trial of ultrasmall superparamagnetic iron oxide in the evaluation of mediastinal lymph nodes in patients with primary lung carcinoma. J Magn Reson Imaging 1999;10(3):468-473.

26. Mayo-Smith WW, Boland GW, Noto RB, Lee MJ. State-of-the-art adrenal imaging. Radiographics 2001;21(4):995-1012.

27. Davis PC, Hudgins PA, Peterman SB, Hoffman JC Jr. Diagnosis of cerebral metastases: double-dose delayed CT vs contrast-enhanced MR imaging. AJNR 1991;12(2):293-300.

28. Steinborn M, Tiling R, Heuck A, et al. [The diagnosis of metastases in the bone marrow by MRT]. Radiologe 2000;40(9):826-834. German.

29. Kavanagh E, Smith C, Eustace S. Whole-body turbo STIR MR imaging: controversies and avenues for development. Europ Radiol 2003;13(9):2196-2205.

30. Lauenstein TC, Freudenberg LS, Goehde SC, et al. Whole-body MRI using a rolling table platform for the detection of bone metastases. Europ Radiol 2002;12(8):2091-2099.

31. Gierada DS, Curtin JJ, Erickson SJ, et al. Diaphragmatic motion: fast gradient-recalled-echo MR imaging in healthy subjects. Radiology 1995;194(3):879-884.

32. Shiotani S, Sugimura K, Sugihara M, et al. Diagnosis of chest wall invasion by lung cancer: useful criteria for exclusion of the possibility of chest wall invasion with MR imaging. Radiat Med 2000;18(5):283-290.

33. Sakai S, Murayama S, Murakami J, et al. Bronchogenic carcinoma invasion of the chest wall: evaluation with dynamic cine MRI during breathing. JCAT 1997;21(4):595-600.

34. Plathow C, Ley S, Fink C, et al. Analysis of intrathoracic tumor mobility during the whole breathing cycle by dynamic MRI. Int J Radiat Oncol Biol Phys 2004;59(4):952-9.

35. Keilholz SD, Mai VM, Berr SS, et al. Comparison of first-pass Gd-DOTA and FAIRER MR perfusion imaging in a rabbit model of pulmonary embolism. J Magn Reson Imaging 2002;16(2):168-171.

36. Fink C, Bock M, Puderbach M, et al. Partially parallel three-dimensional magnetic resonance imaging for the assessment of lung perfusion-initial results. Invest Radiol 2003;38(8):482-488.

37. Lehnhardt S, Thorsten Winterer J, Strecker R, et al. Assessment of pulmonary perfusion with ultrafast projection magnetic resonance angiography in comparison with lung perfusion scintigraphy in patients with malignant stenosis. Invest Radiol 2002;37(11):594-599.

38. Iwasawa T, Saito K, Ogawa N, et al. Prediction of postoperative pulmonary function using perfusion magnetic resonance imaging of the lung. J Magn Reson Imaging 2002;15(6):685-692.

39. Misselwitz B, Muhler A, Heinzelmann I, et al. Magnetic resonance imaging of pulmonary ventilation. Initial experiences with a gadolinium-DTPA-based aerosol. Invest Radiol 1997;32(12):797-801

40. Kauczor HU, Hofmann D, Kreitner KF, et al. Normal and abnormal pulmonary ventilation: visualization at hyperpolarized He-3 MR imaging. Radiology 1996;201(12):564-568.

41. Zaporozhan J, Ley S, Gast KK, et al. Functional analysis in single-lung transplant recipients: a comparative study of high-resolution CT, 3He-MRI, and pulmonary function tests. Chest 2004;125(1):173-181.

42. Edelman RR, Hatabu H, Tadamura E, et al. Noninvasive assessment of regional ventilation in the human lung using oxygen-enhanced magnetic resonance imaging. Nat Med 1996;2(11):1236-1239.

43. Fink C, Plathow C, Klopp M, et al. [MRI of lung cancer]. Radiologe 2004;44(5):435-443. German.