MRI of the adrenal glands

MRI of the Adrenal Glands By Thomas K. Egglin, Peter F. Hahn, and David D. Stark

IN CE THE ADVENT OF MRI, the adrenal glands have been the object of repeated study. I The challenges of adrenal MRI are due in part to their biochemical complexity, which has been examined by MR spectroscopists in vitro for more than two decades. The more recent development of medical MRI of the adrenals has been fostered by their frequent involvement by disease and the lack of diagnostic specificity offered by other imaging modalities.P MRI offers exceptional tissue contrast, allowing easy identification of normal and abnormal adrenal glands, as well as the perinephric fat and adjacent organs. However, the ability of MRI to characterize detected adrenal abnormalities remains controversial.

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GENERAL REMARKS

Image contrast in MR is determined by differences in tissue relaxation parameters (Tl, T2) and proton density rather than by the variations in electron density measured by CT. 3 Although proton density, TI , and T2 of a tissue influence the detected signal, the TR and TE may be adjusted to emphasize one parameter or another. Generally, increasing TR and TE produces T2weighted images; conversely, the shorter the TR and TE, the more influence Tl differences among tissues contribute to differences in signal intensity. Hydrogen density may vary little between adjacent structures, or between normal and pathologic tissue, whereas the relaxation parameters, representing inherent characteristics of the tissue, often do.' Rapidly metabolizing neoplastic tissue, for example, tends to have increased water content, with longer Tl and T2 than adjacent normal tissue; fatty infiltration produces TI shortening. In adrenal abnormali-

From the Department of Radiology, Massachusetts General Hospital, Harvard Medical School. Thomas K. Egglin: Clinical Fellow in Radiology; Peter F. Kahn: Instructor in Radiology; David D. Stark: Associate Professor ofRadiology. Address reprint requests to David D. Stark. MD, Department of Radiology, Massachusetts General Hospital, Boston, MA 02JI4. © 1988 by Grune & Stratton, Inc. 0037-198X/88/2304-0008$5.00/0 280

ties, Tl and T2, and therefore the signal intensity, are also influenced by such extracellular material as hemorrhage, necrosis, or calcifica-

tion." Technique Most reported clinical experience in adrenal MRI has been at intermediate field strength (0.3 to 0.6 Tesla) and has used transverse non-ECG gated, SE examinations with a 256 x 128 pixel matrix. Multislice transverse whole body images are generally acquired with a 1 em slice thickness, either contiguously or with a small gap. Both Tl-weighted (eg, SE 300-500/50-100/2: spin echo TR ma/TB ms/signal averages) and T2-weighted (SE 2000-2500/50-100/2) pulse sequences are usually obtained."? Imaging time is generally 15 to 20 minutes. The role of intravenous paramagnetic contrast agents (eg, GdDTPA) in evaluation of adrenal abnormalities has yet to be studied systematically. Transverse images correlate with those from CT. MRI is also able to image in orthogonal planes, which allows the examination to be tailored to the clinical situation. Multiplanar imaging is useful in the assessment of origin and extension of a large lesion." Coronal imaging extends the field of view to the entire abdomen. Since up to 10% of pheochromocytomas are extra-adrenal and may lie anywhere along the sympathetic chain, this conveniently extends coverage without unduly prolonging the examination. While body coil images usually delineate both the normal adrenal glands, image quality within a limited field of view can be improved with the use of a surface coil against the flank. This technique allows increased spatial resolution and reduces the noise contributed by moving structures outside the sensitive volume of the coil." This can produce threefold improvement in SNR, with better visualization of a small adrenal lesion and clearer definition of the relationships of a large mass to nearby organs. On the other hand, the use of surface coils complicates the setup of a study and restricts the field of view, which can obscure internal reference standards such as the liver, and may, prevent adequate

Seminars in Roentgenology, Vol XXIII. No 4 (October). 1988: pp 280-287

MRI OF THE ADRENAL GLANDS

visualization of even one gland in large individuals." ANATOMY

Histologically, the adrenal gland represents two separate endocrine organs, cortex and medulla. While both have a high lipid content, in vitro only weak resonances are observed from the lipid proteins in a medulla while the signal from the adrenal cortex is high. Therefore, it was expected that MRI would readily delineate the two structures I and preliminary reports suggested this to be true in vivo. More recent work indicates that this separation cannot be reliably accomplished in a clinical situation as the adrenal glands usually have a uniform MRI appearance. Occasionally , the central portion of the gland will exhibit a lower signal intensity than the peripheral rim on Tl-weighted images. This presumed corticomedullary differentiation, which does not appear to have clinical significance, is present in about 15% of cases.P'" In some circumstances , chemical shift artifact may be mistaken for such a corticomedulary signal difference. Normal adrenal tissue has an intermediate signa l intensity slightly less than liver and renal cortex on Tl-weighted images and much lower than the surrounding fat on all but the most heavily T2-weighted pulse sequences. On all pulse sequences, the borders of the glands are defined by the adjacent retroperitoneal fat; they can be difficult to identify by CT in lean patients, but because of the greater soft tissue contrast, the adrenals can generally be distinguished with MRI even in these patients. I I Periadrenal blood vessels can easily be distinguished from adrenal nodules because of the flow void in vessels on routine spin echo images. This is important in patients with portal hypertension because by CT a dilated left inferior phrenic vein (a so-called adrenal pseudotumor) may simulate a nodule at the anterior margin of the left adrenal gland.'? Detection of adrenal gland pathology by MRI requires that the contours of the gland be deformed, since biochemical overproduction or depletion alone cannot be detected with currently available MR techniques. Experience with CT has shown that such enlargement may be nodular or diffuse, unilateral or bilateral." It has been shown that MRI can demonstrate normal adre-

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nals as reliably as CT lO,I l and that adrenal nodules larger than I to 2 em in diameter are detectable as accurately with MRI as with CT.7, lO,11 Unfortunately, MRI does not reliably detect adrenal pathology as part of an abdominal staging examination; in a recent blinded comparison of the two modalities for staging upper abdominal malignant tumors, adrenal masses were missed with three times the frequency by MRI as by CT. 14This discrepancy may in part be explained by methodologic differences, including the low proportion of adrenal lesions in that study and the greater slice thickness needed to cover the entire upper abdomen with MRI as compared to CT. Despite these limitations, the adrenals should be evaluated in any MRI examination that includes them, such as high-resolution surface coil images of the lumbar spine. ADRENAL ABNORMALITIES

Adenoma Adrenal adenoma is usually identified during the evaluation of adrenal hyperfunction (socalled hyperfunctioning adenoma) or as a silent mass discovered during a staging scan of the abdomen. The cross-sectional appearance of the lesion ofTl-weighted sequences is similar to that observed with CT, since most adenomas are generally larger than 2 em when discovered.' The mass is generally homogeneous and can range in diameter from a barely detectable thickening to a large tumor 8 em or greater in size. The Tl and T2 relaxation parameters of the nonhyperfunctioning adenoma are typically similar to those of the normal gland; most appear on Tl-weighted images either slightly hypointense or isointense compared to the liver and on T2-weighted sequences either slightly hyperintense or isointense relative to the hepatic parenchyma (Fig 1) .4,5,15,16

On T2-weighted images many hyperfunctioningadenomas exhibit an increase in signal intensity relative to the liver.! At the same time, several hyper functioning adenomas that were isointense with the hepatic parenchyma on T2weighted images have been reported." Although no controlled studies have been conducted using a well-defined patient population, it .is evident that present MRI techniques cannot reliably distinguish hyperfunctioning from nonhyperfunctioning adenomas, and there is no.consistent

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correlation between signal intensity and adrenal cortical function. 17

Cortical Carcinoma When discovered with either CT or MRI, a cortical carcinoma tends to be large and grossly distorts the normal adrenal morphology. The MRI appearance of only a few of these lesions has been described. While most were homogeneous and behaved like adrenal adenoma on Tl-weighted images, carcinoma generally increases in signal intensity on T2-weighted SE sequences.I'" Inhomogeneity, with foci of high signal intensity, corresponding to cysticappearing areas of necrosis on CT scans, has been observed.':" Liver metastases from adrenal carcinoma behave similar to the primary tumor, with increased intensity on T2-weighted images; they are also generally less intense than the liver on relatively Tl-weighted SE 500/56 (0.5 T) sequences. 15 The largest single series reported to date describes the five cases of adrenal carcinoma, all of which were hyperintense relative to the liver on 2,500/80 images (Fig 2). Metastases to Adrenal The MRI appearance of metastatic disease is generally similar to that of cortical carcinoma, although the metastases tend to be smaller when discovered. The metastases are less intense than the liver on Tl-weighted images and, like carcinoma, generally increase in signal intensity on T2-weighted SE sequences.l" Of special note are a recent report of a colon metastasis with a T2 signal intensity almost equal to liver" and three examples of proven metastases of low signal intensity simulating the appearance of the typical nonhyperfunctioning adenoma on T2weighted sequences.'

Fig 1. Nonhyperfunctioning right adrenal adenoma. biopsy proven. (A) The lesion is isotense with hepatic parenchyma at SE 300/14 (0.6 T). (S,C) At SE 2,350/60 and 2,350/120, the lesion remains essentially isotense with liver.

Myelolipoma Both the CT and MRI appearance of myelolipoma are predictable on the basis of histology. CT scans typically show masses of fat density. These lesions may be heterogeneous on either CT or MRI images. 11,13 In isolated case reports, MRI has shown lesions with signal intensity equal to subcutaneous and retroperitoneal fat (and greater than the liver) on all spin echo pulse sequences (Fig 3).7,16

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Fig 2.

Adrenal cortical carcinoma metastatlc to liver. biopsy proven. (A) At SE 375/20 (00'6 T], the lesion is and hypointense relative to the liver. (8) At SE 2.350/60. and 2.350/120. The heterogenicity of the right adrenal mass IS accentuated and numerous metastatic lesions become evident in the liver. mhomogeneo~s

Pheochromocytoma Pheochromocytomas, tumors of the adrenal medulla, are typically larger than 2 em in diameter when identified and, within the adrenal gland, are equally well-detected using either CT or MRe All reported pheochromocytomas have been hyperintense relative to the liver on T2weighted images and have been described as being either heterogeneous" or homogeneous.' There appears to be little overlap in MRI behavior in pheochromocytoma with adenoma, cortical carcinomas, or metastases, although some exceptions have been reported.v? In children, neuroblastoma of the adrenal medulla, may have a similar appearance. Other adrenal lesions such as cyst or myelolipoma may have a long T2, but usually present under different clinical circumstances. A cyst or hemangioma of the liver or spleen may present in the suprarenal space adjacent to the adrenal gland and also have high signal intensity on T2-weighted sequences. For these reasons, signal intensity alone is insufficient to make the diagnosis of pheochromocytoma, and careful attention to anatomic detail and clinical presentation is necessary (Fig 4). During the workup of a hypertensive patient with an adrenal mass, CT cannot reliably differentiate between an adenoma and a pheochromocytoma." In a recent prospective comparison of 131I-metaiodobenzylguanidine (MIBG) scintigraphy, CT, and MRI, the three modalities

were roughly equivalent in the demonstration of primary adrenal pheochromocytoma. Scintigraphy and MRI were superior in demonstrating primary extraadrenal and metastatic pheochromocytomas." The same series suggested that MRI might be superior for the detection of recurrent disease, since follow-up CT is often limited by the surgical obliteration of fascial planes or artifact due to metal clips." While approximately 90% of pheochromocytomas are confined to the adrenal gland, muItiplanar MRI allows large anatomic regions (especially along the sympathetic chain) to be imaged in a short period of time, improving the detection of extraadrenal or extraabdominal lesions.' This capability is especially important in the evaluation of patients with a predisposition to multiple pheochromocytomas, including those with Hippel-Lindau syndrome, multiple endocrine neoplasia syndromes, or familial pheochromocytoma. A case of a child with known bilateral pheochromocytomas found to have three additional adrenal lesions with coronal MRI has been described." Instances of recurrent, metastatic, and ectopic pheochromocytoma imaged with MR, including two intrapericardial tumors, have been reported. 6,20,21

Other Lesions The heavy calcifications that help to identify chronic adrenal hemorrhage with CT 13 are

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Fig 3. Right adrenal myelolipoma, biopsy proven. The patient was obllqued in an attempt to project the aortic pulsation artifact off ofthe liver . (AI At SE 300/14 (0.6 T), the mass is complex with certain elements isolntense with fat . (B.C) SE 2,350/60 and 2.350/120.

poorly seen with MRI. 1 Acute and subacute hemorrhage within the adrenal glands probably has the same MR characteristics as elsewhere in the body." Adrenal hemorrhage is most easily recognized when streaks or foci of short T'l material in an enlarged adrenal gland indicate the presence of paramagnetic oxidation products of hemoglobin. Cystic or necrotic areas within an adrenal tumor tend to have low signal intensity on T'l-weighted sequences and become hyperintense on T2-weighted images.v' TISSUE CHARACTERIZATION

The primary clinical role for MRI has been the characterization of abnormalities detected by other modalities, most commonly the evaluation

of a small adrenal mass discovered during staging of a patient with lung carcinoma or other malignancy. Even in these patients, an isolated adrenal mass is often an adenoma rather than metastatic disease .4.7.22.23 While certain CT signs (size >4 em, heterogeneous appearance, irregular margination) favor the diagnosis of malignancy rather than cortical adenoma," these findings are nonspecific and percutaneous biopsy is usually needed for a confident diagnosis. v' :" It has been suggested that the MRI signal characteristics of adrenal masses could distinguish three histologically separate populations: adenoma, primary, and secondary malignancy, and pheochromocytoma.I'P'' v" These reports noted that when tumors were plotted according

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Fig 4. Leh adrenal pheochromocytoma in a patient with adrenal medullary hyperfunction. {AI At SE 275/14 {O.6 n, the les ion is homogeneous and isotense with liver. {Bl At SE 2.350/120, the mass becomes progressively hyperintense relative to both liver and fat. a characterlstlc appearance of pheochromocytoma.

to the ratio of their signa l intensity to that of the liver on both Tl- and T 2-weighted images , three distin ct groups could be identified. The first consisted of lesions that were isointense or hypointense compared to hepatic parenchyma , and included both hyperfunctioning and nonhyperfunctioning adenomas. The next group consisted of metastasis a nd adrenal cortical car cinoma, which were somewhat more intense than the liver on T 2-weighted images. Early work suggested that the T2 -wcighted pulse sequences provided the most spec ific information and best separation of these populations.l":" To characterize adrenal lesions with signa l intensity information obtained during MRI, several different methods of quantitative analysis have been described : visual inspection of

images ,5,6,23 ratios of adrenal signal intensity to the liver ,s·6,19 paraspinous muscle or fa t," as well as ratios of signal intensity of the abnor mality on both TI- and T2-weighted images. " No rationale or quantitative theory has been proposed to justify the use of any particular set of timing parameters (TR, TE) for spin echo imaging. Calculation of the T2 of an adrenal abnormality from signal intensity data has been advocated for increased diagnostic specificity." None of these qu antitative methods has provided any compensation for the various forms of noise inherent to MRI or for variations in signal characteristics due to partial volume averaging. II In addition, the variable signal intensity of the liver in the presence of hepatic abnormalities, such as fatty infiltration, hemachromatosis, or diffuse metas-

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tases complicates the use of adrenal mass/liver ratios." Two recent studies-both performed at 0.5 T-found that a ratio of adrenal-to-fat signal intensity offered the best pathologic differentiation .4•s In one of these, the accuracy of Tlweighted imaging (SE 250-310/20-21) alone was reported to be similar to that obtained using T2-weighted sequences." Although most other authors have used T2-weighted images for this purpose, this approach, if substantiated, offers the advantage of shortened imaging time, as well as the ability to characterize smaller lesions as a result of improved image quality, because the increased signal averaging and signal -to-noise ratio results in less motion artifact. The large number of analytic methods still in use suggests that none of them has proven completely satisfactory. Indeed, recent publications confirm that MRI fails to characterize up to a third of adrenal lesions." :" While some intraobserver variation in results should be expected, reflecting differences in imaging systems, pulse sequences, and patient populations," several series have stressed the considerable heterogeneity within populations of adenoma and metastasis, as well as the substantial overlap in intensity of those benign and malignant disease processes on T2-weighted images. Using analytic techniques, two recent studies were able to establish a certain range of signal intensity that included only adenoma, another that contained metastases alone, and an inconclusive zone in which signal intensity data were not specific and a lesion may have represented either an adenoma or a metastasis. In these series, 21 %16 and 31%5 of adrenal masses, respectively, fell into this indeterminate region where benign and malignant processes cannot be distinguished.v" In one of these series, for example, all adrenal lesions with an intensity ratio of lesion to liver of less than or equal to 1.2 at SE2500/80 (0.5 T) were found to be adenomas, while all lesions with a ratio greater than or equal to 1.4 were rnalig-

nant. Ratios between 1.2 and 1.4 were said to be indeterminate.v" Other centers have reported similar findings, although the precise MRI intensity ratio seems to depend on pulse sequences and field strength.v -" Most studies have been performed at intermediate field strength and it is unclear if the data are applic able to high field strength imaging systems.' Recently, the efficacy of MRI in the differentiation of benign from malignant lesions, even within the limited signal intensity boundaries noted above, has been questioned. Benign lesions, especially of hyperfunctioning adenomas,· with prolonged T2 and increased adrenal/liver ratios have been reported.v-" While such benign conditions might be mistaken for malignant neoplasm and unnecessarily excised, the observation that metastases may not appear hyperintense, and thus be dismissed as benign, is more disturbing.' Since all of the reported series have been relatively small, the true incidence of highintensity adenoma and low-intensity metastases remains uncertain. While offering some additional diagnostic information, measurements derived from MR signal intens ity are not an adequate tool for characterizing an adrenal mass as benign or malignant. Finding the most efficacious and reproducible means of analyzing the signal characteristics of identified lesions remains an immediate concern. Two recent studies-both performed at 0.5 Tfound a ratio of adrenal-to-fat signal intensity that offered the best pathologic differentiation. In one of these, the accuracy of Tl-weighted imaging (SE 250-310/20-21) alone was reported to be similar to that obtained using T2-weighted sequences.' Although most other authors have used T2-weighted images for this purpose, this approach if substantiated, offers the advantages of shortened imaging time, as well as the ability to characterize smaller lesions as a result of improved image quality, since the increased signal averaging and the ratio of signal to noise results in less motion artifact.

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