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Advanced imaging techniques to evaluate mediastinal pathologies.

There has been rapid and vigorous growth of medical technologies over the past decades with radiological imaging being one of the most visible of the technology-intensive fields in medicine. (1-4) These advances have improved medical diagnosis and contributed substantially to the precision of medical and surgical treatments. An analysis of Medicare data shows that by 1992, two-thirds of all radiologic imaging involved modalities that did not exist 20 years earlier or that existed only in embryonic form. (4)

As a result of this rapid technological development, several multidetector computed tomography (MDCT), positron emission tomography and computed tomography (PET-CT), and magnetic resonance imaging (MRI) techniques became available to address particular clinical questions. (5-10) Part of the task of the radiologist is to be adept at selecting the study with the greatest likelihood of providing the correct diagnostic answer safely and at an acceptable cost.

The evaluation of both extensions of primary mediastinal tumors into adjacent structures and mediastinal invasion from surrounding malignancies has been a challenge for radiologists. Chest radiography is widely used as the initial examination in patients with suspected thoracic disease. However, the question of whether a radiographically detected mediastinal abnormality has clinical significance is frequently encountered. CT, PET and MRI are able to provide additional information to improve disease staging and patient care. (6,7,11,12)

In the past, the main limitation of CT was attributable to reduced resolution of images acquired on the coronal and sagittal planes, compared with MRI. This has been overcome by the capability of new, faster multidetector scanners that acquire isotropic data. These reformatted images play an important role in reducing the workload by providing pertinent information in a single image. (13-16) This article demonstrates current imaging techniques in diagnosing mediastinal lesions using MDCT, PET-CT and MRI.

Imaging techniques Multidetector computed tomography

Recently developed MDCT scanners with increasing numbers of detectors and improved techniques allow acquisition of isotropic volume data that can be displayed in any selected 2-dimensional plane with the use of 2-dimensional multiplanar reformations (2-dimensional MPR). Coronal and sagittal reformations are the planes routinely performed but reformations in oblique and curved directions can also be made and allow a structure to be traced and displayed as if it was laid along a single axis. (13-16)

Three-dimensional rendering techniques like maximum intensity projection (MIP) and minimum intensity projection (MinIP) are created in a similar fashion, however, they have the tendency to misrepresent spatial relationships and are limited by overlapping structures. These limitations can be partially overcome with the use of sliding-slab MIP reconstruction. (16)

Three-dimensional volume rendering (3DVR) has the inherent advantage of displaying the entire voxel attenuation values. (17) Data can be segmented by attenuation value to display the desired structure. Volume rendered (VR) images can be performed from external and internal perspectives allowing the user to "fly around" and "fly through" the structures. (18) The main disadvantages of CT remain the use of ionizing radiation and need for IV contrast administration.

Magnetic resonance imaging

MRI has not been emphasized in thoracic imaging due to some shortcomings such as the low signal-to-noise ratio (SNR) related to low proton density in inflated lungs; susceptibility artifacts caused by many air-tissue interfaces; and, motion-artifact vulnerability related to intrinsic cardiac pulsation and respiration in the setting of a relatively long acquisition time. However, some studies have described the potential role of MRI in accurately detecting mediastinal invasion by lung cancer, in predicting hilar and mediastinal nodal metastasis, and in evaluating morphologic differences between malignant and benign solitary pulmonary nodules through dynamic studies. (19-23)

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There are specific techniques that reduce the negative factors associated with MRI acquisition when evaluating lung parenchyma. (19,24,25) For example, the turbo spin-echo (TSE) sequence reduces susceptibility artifacts and increases SNR by applying rapid, repetitive rephrasing pulses, and, therefore, reducing the echo spacing. The improved soft-tissue contrast, intrinsic flow sensitivity and absence of ionizing radiation are additional advantages of MRI instead of CT when evaluating the mediastinum and vascular structures. When evaluating the mediastinum, the protocol may include T1- and T2-weighted images (T1W and T2W) using fast spin echo (FSE) techniques, chemical shift imaging, pre- and post-contrast 2-dimensional and 3-dimensional gradient echo techniques, parallel imaging with true fast spin imaging with balance steady state free precession (FISP), and dynamic multiphase 3-dimensional spoiled gradient echo imaging (LAVA, FAME or VIBE) (22-23,26,27)

Chemical shift imaging is of special value and encompasses different techniques such as moderate T2W FSE with fat suppression (STIR), in-phase and opposed-phase gradient echo images, and fast multiplanar T1W spoiled gradient echo fat suppressed sequences. The chemical shift ratio (CSR) may be used to compare relative changes in the signal intensity of thymic tissue, relative to the paraspinal muscles, in opposed-phase and in-phase images: This method is useful in differentiating thymic hyperplasia from a neoplasm when encountering a mass in the anterior mediastinum. (28,29) Three-dimensional gradient echo sequences (3DGRE) allow rapid acquisition of volumetric data with a single breath hold, contiguous thin-slice images without interslice gap and dynamic imaging after gadolinium injection. It increases the lesion identification rate, reduces sensitivity to phase artifacts, and markedly improves homogeneous fat suppression. (30-34) A double inversion recovery (DIR) sequence may be used in assessing vascular invasion within the mediastinum by nulling the signal from the adjacent blood pool and better depicting the vessel walls. (35-37)

PET-CT

PET is an innovative imaging modality that uses 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) to demonstrate increased glucose metabolism in malignant cells. This technique provides information that is different from that obtainable with other imaging modalities because it reflects the metabolic, rather than the anatomic, characteristics of a lesion. (38) Given the lack of anatomic resolution of PET, the addition of a cross-sectional study is necessary to reach adequate accuracy. The most commonly used cross-sectional modality is CT and images can be acquired at the same time on combined PET-CT scanners. (39) Integrated PET-CT adds important clinical information in comparison with PET alone, CT alone or separate comparison of PET and CT images that were acquired at different times--owing to better lesion identification and localization. (40-42)

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In lung cancer, whole-body FDG PET plays an important role in the evaluation of solitary lung nodules, preoperative staging, diagnosis of recurrent disease and planning of radiation treatment. (39) The presence of ipsilateral (N2) or contralateral (N3) metastatic mediastinal lymph nodes indicates advanced lung cancer and, usually, those patients are not considered for primary surgical treatment. PET has proven to be effective in mediastinal nodal staging. (39) The main disadvantage of PET-CT is the lack of IV contrast, limiting differentiation contiguity of tumor and mediastinum from direct invasion.

Practical applications

CT in general is probably the imaging modality of choice for most mediastinal lesions. (8,43-49) It has been thought previously that MRI was the study of choice in evaluating neurogenic and vascular lesions but recent studies have shown that MDCT with MPR and VR reconstruction are of similar value and we will demonstrate similarity between the two. (14,50,51) The choice of modality should primarily rely on availability. In this article, we will compare the use of different modalities by illustrating specific lesions using information needed as a guide (Table 1).

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Local extent of disease

sCross sectional imaging is very helpful in delineating the extent of disease, borders and relationships with adjacent structures. Additional reformatted images improve accuracy of measurements and better depict extension of disease. CT attenuation measurements provide tissue characterization with greater spatial resolution. CT also easily identifies calcifications and more accurately diagnoses bone destruction.

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MRI has lower spatial resolution but great soft-tissue contrast resolution, allowing more precise characterization of the tissues. It is less accurate in identifying bone destruction but has greater sensitivity when demonstrating bone marrow infiltration. MRI can be directly acquired in coronal and sagittal planes, while MDCT images can be rapidly reformatted on these planes at the scanner console. CT additionally allows acquired images to be reformatted in curved or oblique planes, demonstrating an entire structure that does not lie on one of these planes in a single image (Figure 1).

Airway assessment

When assessing the airways, intraluminal masses are easier detected by CT and the extension of the disease is better assessed when using reformatted images, allowing ideal guiding before stent placement (Figure 2). Two-dimensional MPR images of the airways allow the lumen to be traced as displayed as if it lies in a single plane, facilitating detection of tracheobronchial pathologies. MinIP images can also depict the lumina of the airways. (16)

The 3-dimensional fly-through application is particularly useful in evaluating the airways because it allows the performance of a virtual bronchoscopy (VB). This computer-generated 3D CT post-processing technique produces high resolution images of the tracheobronchial tree and endobronchial views with sensitivity and specificity similar to optic bronchoscopy. (52-56) The main limitation of VB is the inability to perform tissue sampling at the same time as diagnosis.

For example, spindle cell sarcoma mediastinal invasion with near complete occlusion of the left main stem bronchus is better depicted by curved reformatted, oblique, coronal, MinIP and 3-dimensional VR images, compared with the acquired axial images (Figure 3).

Mediastinal invasion

In patients with locally advanced tumors, it is important to distinguish between potentially resectable (T3) and technically unresectable (T4) disease. Direct extension into the chest wall, diaphragm, mediastinal pleura or pericardium stages the tumor as T3, while invasion of the mediastinum, great vessels, trachea, esophagus or vertebral body upgrades the stage to T4. The correct staging is mandatory for choosing treatment and surgical planning for optimal outcomes. (7) Anatomic and morphologic features used to establish tumor extension and adjacent structure invasion are similar for CT and MR and include loss of fat planes, extension into mediastinal fat and tumoral encasement of >50% of structure circumference. (7)

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CT and MRI are not precise in differentiating contiguity of tumor from subtle invasion, making it difficult to assess chest wall and mediastinal invasion. (57) Overall, both CT and MRI are reasonably accurate in assessing resectability, but not in assessing non-resectability. (5) They can both identify gross invasion of the mediastinum with vascular invasion but are poor at identifying subtle changes.

CT is usually the primary imaging modality used for disease staging in patients who are being considered for resection. CT is widely available, less expensive and relatively fast. Mediastinal invasion manifests as obliteration of surrounding fat planes with irregularity of the interface between the tumor and the adjacent mediastinal organ (Figure 4). (7) Mediastinal invasion from nearby cancers, such as lung cancer and mesothelioma, is better evaluated on CT through reconstructed images where the loss of fat plane is seen between the lesion and the adjacent organ. Webb et al. (58) found CT sensitivity of 62% in differentiating between T3 and T4 tumors, while Glazer et al. (59) found sensitivity and specificity for chest wall invasion to be 87% and 59% respectively. (5) CT is faster and has better spatial resolution but needs improvement to better assess mediastinal invasion. Sensitivity for depicting mediastinal invasion by CT ranged from 40% to 84% while specificity ranged from 57% to 94%. (24,48,60-63)

MRI has better soft-tissue contrast resolution and better depicts chest wall invasion with reported sensitivity and specificity of 90% and 86% respectively. (64) MRI has excellent contrast resolution, allowing improved detection of tumor extension. With the use of newer MRI pulse sequences and gadolinium-based contrast material, differentiation between tumor and normal tissue provides additional staging information in patients with potentially resectable disease (Figures 5 and 6). (7)

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No difference was reported between CT and MRI in distinguishing T3 to T4 tumors from T0 to T2 tumors or in the ability to detect lymph node metastasis. However, MRI was significantly more accurate than CT in the diagnosis of mediastinal invasion. (58,65) MRI is good for diagnosing involvement of the inferior branches of the brachial plexus, vascular infiltration, and invasion of the spinal canal or vertebral body. (5) Although less sensitive for diagnosing spinal canal extension of tumor, CT can also be used (Figures 7 and 8). MRI is better than CT particularly for superior sulcus tumors, with an accuracy of 94% compared with 63% for CT. (66) When the borders of the lesion are irregular and not well-defined and/or the lesion demonstrates heterogeneous contrast enhancement on CT, MRI may be helpful in the preoperative tumor evaluation to achieve complete resection and plan adjunctive radiation or chemotherapy. (10) The most valuable use of MRI is in evaluating patients with questionable areas of local tumor extension on CT or in whom IV administration of iodinated contrast is contraindicated. (7)

Vascular invasion

MR angiography (MRA) has been proposed as an adequate technique for assessing tumor invasion of adjacent great vessels and pulmonary veins. A cardiac triggering technique improves the quality of pulmonary MRA without decreasing temporal resolution, increasing diagnostic accuracy for detecting tumor invasion. Ohno et al. found that overall image quality and diagnostic confidence were higher with ECG-gated MRA compared with conventional MRA. (23) Diagnosis of vascular involvement can be made when the lesion contacts the vessel more than 90[degrees]; or when there is distortion, remarkable stenosis, obstruction of the vessel, evidence of intraluminal tumor or when irregularity of the vessel wall is seen (Figure 9).

Pericardial invasion

Pericardial invasion is seen on cross-sectional imaging as nodular pericardial thickening or pericardial effusion. (7,9) MDCT enables motion-free imaging of the pericardium when performed with ECG gating or triggering, as well as reformation of images for better visualization of pericardial diseases. MRI can also be performed using ECG gating. The main limitation for using cardiac gated imaging is on patients with arrhythmia. (9,44)

MRI provides comprehensive depiction of the pericardium without use of either iodinated contrast material or ionizing radiation and is superior in characterizing pericardial fluid and masses. When an effusion is secondary to malignancy, an irregular thickened pericardium or pericardial nodularity may be depicted on MRI. CT is more limited than MRI in differentiating pericardial fluid from thickened pericardial tissue. (9,44,67) Tumors that invade the pericardium may be recognized by focal obliteration of the pericardial line and presence of pericardial effusion and usually demonstrate avid enhancement following IV administration of gadolinium. (9,44,68) Hemorrhagic pericardial effusions secondary to invasion or metastasis can be accurately characterized by MRI because they usually have high signal intensity on spin-echo images.

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Lymphadenopathy

Presence of hilar adenopathy in patients with lung cancer changes the tumor's stage and surgical approach but does not render the tumor nonresectable. (12,21,22,43) MRI provides comparable information regarding the presence and size of mediastinal lymph nodes when compared with CT. Normal and abnormal lymph nodes demonstrate the same signal characteristics on MRI. (21)

Enhancement pattern

Contrast-enhanced CT is crucial in differentiating mediastinal masses from abnormal vessels or hypervascular lesions, thus preventing life-threatening interventions (Figure 10). When a mediastinal tumor appears well circumscribed, homogeneously enhancing and without cystic areas or necrosis on MDCT, MRI usually does not provide any additional information. (43,65) Mediastinal tumors can be mainly differentiated by location and enhancement pattern. For example, the distinguishing feature of schwannoma is the enhancement pattern, characterized by enhancement of the peripheral zone or the lack of enhancement of high T2 signal intensity lesions (Figure 11).

Neurofibromas, on the other hand, demonstrate a high signal intensity peripheral zone (target appearance) on T2W imaging. This high signal intensity zone correlates histologically to gelatinous material, while the more central intermediate signal intensity area corresponds to solid tissues. Ganglioneuromas have homogeneous intermediate signal intensity and a whorled appearance on both T1W and T2W imaging. (69) Thymomas demonstrating a high degree of homogeneous enhancement may indicate World Health Organization (WHO) types A and B while heterogeneous enhancement is more often seen in WHO types B3 and C (Figure 12). Castleman's disease in the middle mediastinum demonstrates intense contrast enhancement with internal flow voids on MRI (Figure 13).

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Tissue content

The density of the lesion on CT reflects its tissue contents. CT is more accurate in demonstrating calcium within a lesion compared with MRI. Fat, soft tissue and fluid can be accurately characterized by CT in most of the cases. (47)

MRI has greater soft-tissue contrast resolution and is useful in characterizing the fluid content and age of hemorrhage. (70-72) Fat-suppression techniques such as STIR and chemical shift imaging allow diagnosis of microscopic fat tissue. (28,29) MRI may also be used when a density is too small to be accurately measured by CT. It has been suggested that certain fat-suppression MRI techniques, namely chemical shift imaging, are useful in differentiating thymic hyperplasia from other solid thymic lesions. Chemical shift imaging is acquired using a fast multiplanar T1W spoiled gradient echo fat-suppressed sequence with in- and out-of-phase images (Figure 14). This drop in signal is calculated using the relative change in the ratio of signal intensity of thymic tissue relative to muscle:

Chemical shift ratio (CSR) [(SI t/SI m) opposed phase / (SI t /SI m) in phase].

Since thymic hyperplasia contains fat, the CSR is higher. (28) Inaoka et al. found a CSR of 0.614 [+ or -] 0.130 in hyperplasia and 1.026 [+ or -] 0.039 in tumor. Mean CSR in thymic hyperplasia with Graves' disease, rebound thymic hyperplasia, thymoma, invasive thymoma, thymic carcinoma and lymphoma were: 0.594 [+ or -] 0.120, 0.688 [+ or -] 0.154, 1.033 [+ or -] 0.043, 1.036 [+ or -] 0.040, 1.020 [+ or -] 0.044 and 0.997 [+ or -] 0.010, respectively. (29)

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MRI characterization of tissue, including the presence or absence of a capsule in evaluating thymomas, is especially useful and helps to grade and assess a patient's prognosis. In a study by Sadohara et al. the presence of a complete or almost complete capsule indicated low-risk thymoma in 27%, high-risk thymoma in 17% and thymic carcinoma in 0% of patients. (10) On the other hand, a partial capsule may be seen in 42% of patients with thymic carcinoma. In this same study, presence of necrotic or cystic components were seen in 67% of patients with thymic carcinomas, 20% with low-risk thymoma and 28% with high-risk thymoma. They found heterogeneous signal intensity in 100% of patients with thymic carcinoma, 33% with low-risk thymoma and 56% with high-risk thymoma. They also demonstrated that presence of sharply defined fibrous septa dividing the tumor is more commonly seen in patients with thymoma. (10) The use of Indium-111-DTPA-D-Phe-octreotide scintigraphy apparently did not improve the rate of tumor detection compared with CT or MRI if the tumor was <1.5 cm. (73)

Vascular lesions and collateral vessels

Evaluation of patency of mediastinal vessels and diagnosis of vascular invasion by adjacent tumors are essential in staging and surgical planning. Obliteration of the surrounding fat planes and presence of soft-tissue mass surrounding >50% of the vessel circumference on cross-sectional imaging are strong evidence of invasion. (7)

Vascular lesions, such as pseudoaneurysms or congenital malformations, can be evaluated by CT or MRA. (20,23,37) MRI is acquired in different planes while acquired axial CT can be reformatted in several planes at the scanner or workstations.

In patients with suspected sequestration, the axial CT images show the systemic blood supply and the reformatted images easily depict the proximal connection of the feeding artery with the descending thoracic aorta and the distal course into the mass (Figure 15). The draining vein connection with the IVC can also be identified on the same settings of images, pathognomonic of pulmonary sequestration. Collateral vessels within the mediastinum appear as tubular soft-tissue structures on the unenhanced CT and their identification is important as they may develop secondarily to an obstruction of the central vessels. Those vessels may also indicate a mediastinal tumor with hypervascularity. The collateral vessels are well depicted in the multiplanar reformations and volume-rendered images (Figure 16).

On contrasted-enhanced CT, vascular structures may be as well-delineated as in angiographic studies. In the setting of a mediastinal or paramediastinal abnormality, the assessment of the surrounding vasculature is crucial for diagnosis and surgical planning. For example, scimitar syndrome can be well-demonstrated in a single 3-dimensional volume-rendering reconstructed image--diminishing radiologist fatigue by reducing the time for image evaluation (Figure 17). Invasion of mediastinal vascular structures may also be assessed by a double inversion recovery MRI technique, because it nulls the adjacent blood pool signal. (35-37)

Biologic, metabolic and functional activity

The use of PET-CT assesses the biologic, metabolic and functional activity of the tumors and allows diagnosis of lymph node and distant metastasis, increasing the sensitivity, specificity, and accuracy when compared with CT alone. (74) But FDG-PET imaging has its own limitations since some benign or non-aggressive lesions may demonstrate FDG avidity and inflammatory lesions usually are intensely FDG-avid. For example, thymic extension into the superior mediastinum in patients with thymic hyperplasia and neurofibromas can both show FDG-avidity on the PET scan (Figure 18). On the other hand, slow growing malignancies may not be FDG-avid due to the low metabolism, such as carcinoid and bronchoalveolar carcinomas, which may not demonstrate FDG uptake on PET.

A study from Yi et al. demonstrates that PET has sensitivity, specificity and accuracy of 65%, 89% and 83%, respectively, for prediction of mediastinal nodal metastasis in patients with stage I non-small-cell lung cancer (NSCLC) and mediastinal adenopathy. (75) When PET and CT are used together, the sensitivity, specificity and accuracy change to 56%, 100% and 90%, respectively. Kim et al. found sensitivity, specificity and accuracy of 42%, 100% and 94%, respectively, for evaluation of stage T1 NSCLC mediastinal nodes. (76) The possibility of avoiding mediastinoscopy was demonstrated when the primary lesion measures <2.5 standard uptake value and mediastinal PET is negative. (77)

Conclusion

The decision regarding which imaging modality should be used when evaluating the mediastinum depends on what information is needed based on the clinical and laboratory findings. PET-CT is useful for biological, metabolic and functional information rather than depicting morphologic features; hence, it is better in staging malignances. Always be aware of the false-positive and false-negative results due to coexisting clinical conditions such as rheumatoid arthritis, diabetes, tuberculosis and other infectious and inflammatory processes. MRI may be advantageous in assessing the tissue content particularly in thymic lesions and in excluding vascular invasion.

Special attention should be given when evaluating anterior mediastinal masses, especially thymomas. For example, a well-defined, homogeneously enhancing, soft-tissue mass seen within the anterior mediastinum appears completely surgically resectable; therefore no MRI is needed. On the other hand, if a distinct capsule is not identified, the mass has irregular or lobulated borders, or if it demonstrates heterogeneous enhancement after IV contrast administration, preoperative evaluation by MRI may be helpful in assuring complete resection or in improving the capabilities of plain radiotherapy and/or postoperative adjuvant chemotherapy.

Overall, MDCT appears to be the best study as it provides information regarding airway invasion and patency, extension of the tumor, presence of collateral vessels, and lesion enhancement pattern. Post-processing techniques further improve the diagnosis and surgical planning by better depicting the anatomy and reducing radiologist fatigue. In combination, these modalities are crucial in determining the most appropriate treatment option.

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Isabel B. Oliva, MD, and Andetta Hunsaker, MD

Dr. Oliva is a Cardiothoracic Radiology Fellow, and Dr. Hunsaker is Assistant Professor of Radiology, Harvard Medical School, Boston, MA, and Section Head, Division of Thoracic Radiology, Brigham and Women's Hospital, Boston, MA.
Table 1. Comparison of Imaging Modalities

Clinical Application of Imaging Modalities

MDCT                    MRI                     PET/CT

Extent of disease       Invasion                Biologic, metabolic
Assessment of airways   Tissue                    and functional
Mediastinal invasion      characterization        activity
Enhancement pattern     Enhancement pattern     Distant metastases
Tissue content          Vascular lesions
Vascular lesions
Collateral vessels
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Author:Oliva, Isabel B.; Hunsaker, Andetta
Publication:Applied Radiology
Article Type:Report
Geographic Code:1USA
Date:Jun 1, 2010
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