In the last decade, magnetic resonance imaging (MRI) with the use of intravenous
extracellular contrast agents (for example, Gd-DTPA and Gd-DOTA) has been recognized as
the noninvasive diagnostic tool of choice in the evaluation of focal liver
lesions(11 Siegelman ES, Chauhan A. MR characterization of focal liver lesions:
pearls and pitfalls. Magn Reson Imaging Clin N Am. 2014;22:295-313.
2 Heiken JP. Distinguishing benign from malignant liver tumours. Cancer
Imaging. 2007;7 Spec No A:S1-14.
3 Bartolozzi C. MR of the liver: from breakthrough to clinical
application. Abdom Imaging. 2012;37:154.
4 Galvão BVT, Torres LR, Cardia PP, et al. Prevalence of simple liver
cysts and hemangiomas in cirrhotic and non-cirrhotic patients submitted to magnetic
resonance imaging. Radiol Bras. 2013;46:203-8.-55 Torres LR, Timbó LS, Ribeiro CMF, et al. Multifocal and metastatic
hepatic hemangioendothelioma: case report and literature review. Radiol Bras.
2014;47:194-6.) thanks to the fact that it does not
require ionizing radiation in association with its high spatial resolution and excellent
tissue contrast; its capability to study the vascular behavior of the lesion and to
detect the presence of fat component in the lesion, besides allowing the differentiation
of intrinsic tissue characteristics such as relaxation time and distribution of water in
the liver lesion as well as in the surrounding parenchyma. Such aspects, among others,
have led MRI to be rated as a molecular imaging method(33 Bartolozzi C. MR of the liver: from breakthrough to clinical
application. Abdom Imaging. 2012;37:154.).
However, despite those unquestionable advantages, MRI presents some limitations related to the differentiation of certain focal liver lesions in cirrhotic patients, such as focal nodular hyperplasia (FNH) versus adenoma and dysplastic nodule versus hepatocellular carcinoma (HCC) whose imaging findings are similar to each other but require distinctive approaches(66 Grazioli L, Bondioni MP, Haradome H, et al. Hepatocellular adenoma and focal nodular hyperplasia: value of gadoxetic acid-enhanced MR imaging in differential diagnosis. Radiology. 2012;262:520-9.,77 Bartolozzi C, Battaglia V, Bargellini I, et al. Contrast-enhanced magnetic resonance imaging of 102 nodules in cirrhosis: correlation with histological findings on explanted livers. Abdom Imaging. 2013;38:290-6.). Liver-specific contrast agents have been introduced to overcome such limitations and, among others, gadoxetic acid (Gd-EOB-DTPA)(88 Van Beers BE, Pastor CM, Hussain HK. Primovist, Eovist: what to expect? J Hepatol. 2012;57:421-9.,99 Seale MK, Catalano OA, Saini S, et al. Hepatobiliary-specific MR contrast agents: role in imaging the liver and biliary tree. Radiographics. 2009;29:1725-48.) that was recently made commercially available in Brazil, can be mentioned.
Gadoxetic acid (or gadoxetate disodium) is a paramagnetic contrast agent whose
enhancement effect is mediated by a linear ion complex formed by gadolinium and ethoxy
benzyl-diethylene-triaminepentaacetatic acid (EOB-DTPA). Because of the lipophilic
property of the EOB component (ethoxy benzyl) combined with the DTPA hydrophilic
property, the gadoxetic acid shows a two-phase or two-compartmental distribution
pattern, i.e., after injection, the agent distributes into the vessels and extracellular
spaces during the dynamic phases of hepatic enhancement (arterial, portal and
equilibrium phases) and later on shows progressive hepatocytes uptake and subsequent
complete renal and hepatobiliary excretion in equivalent amount in cases where the liver
and kidneys function is preserved(88 Van Beers BE, Pastor CM, Hussain HK. Primovist, Eovist: what to expect?
J Hepatol. 2012;57:421-9.
9 Seale MK, Catalano OA, Saini S, et al. Hepatobiliary-specific MR
contrast agents: role in imaging the liver and biliary tree. Radiographics.
2009;29:1725-48.-1010 Tanimoto A, Kadoya M, Kawamura Y, et al. Safety and efficacy of a novel
hepatobiliary MR contrast agent, Gd-DTPA-DeA: results of phase I and phase II
clinical trials. J Magn Reson Imaging. 2006;23:499-508.). Because
of such a characteristic, gadoxetic acid is considered to be a "mixed action"
(extracellular and hepatobiliary) contrast agent(99 Seale MK, Catalano OA, Saini S, et al. Hepatobiliary-specific MR
contrast agents: role in imaging the liver and biliary tree. Radiographics.
2009;29:1725-48.).
Thus, it provides not only information related to the extracellular enhancement during the dynamic phases of hepatic perfusion, but also data related to the enhancement resulting from its liver-specific properties during the hepatobiliary phase, which occurs between ten and twenty minutes after intravenous contrast injection(1111 Ringe KI, Husarik DB, Sirlin CB, et al. Gadoxetate disodium-enhanced MRI of the liver: part 1, protocol optimization and lesion appearance in the noncirrhotic liver. AJR Am J Roentgenol. 2010;195:13-28.). Therefore, the typical focal liver lesions enhancement pattern observed during the dynamic perfusion phase is reproduced with the utilization of gadoxetic acid(1111 Ringe KI, Husarik DB, Sirlin CB, et al. Gadoxetate disodium-enhanced MRI of the liver: part 1, protocol optimization and lesion appearance in the noncirrhotic liver. AJR Am J Roentgenol. 2010;195:13-28.). Additionally, as a function of the presence of its lipophilic component, there is a progressive contrast medium uptake by hepatocytes, and increase in the signal intensity of the parenchyma on T1-weighted images because of the shortening of T1 relaxation time, differently from the behavior in the cells of most liver nodules where hepatocytes are absent (for example, metastases and poorly differentiated HCCs), allowing their differentiation from hepatocytic nodules (for example, FNH, regenerative and dysplastic nodules)(1111 Ringe KI, Husarik DB, Sirlin CB, et al. Gadoxetate disodium-enhanced MRI of the liver: part 1, protocol optimization and lesion appearance in the noncirrhotic liver. AJR Am J Roentgenol. 2010;195:13-28.,1212 Cruite I, Schroeder M, Merkle EM, et al. Gadoxetate disodium-enhanced MRI of the liver: part 2, protocol optimization and lesion appearance in the cirrhotic liver. AJR Am J Roentgenol. 2010;195:29-41.).
In the last years, several studies have demonstrated that the use of gadoxetic acid is
safe(1313 Bluemke DA, Sahani D, Amendola M, et al. Efficacy and safety of MR
imaging with liver-specific contrast agent: U.S. multicenter phase III study.
Radiology. 2005;237:89-98.
14 Döhr O, Hofmeister R, Treher M, et al. Preclinical safety evaluation of
Gd-EOBDTPA (Primovist). Invest Radiol. 2007;42:830-41.-1515 Gschwend S, Ebert W, Schultze-Mosgau M, et al. Pharmacokinetics and
imaging properties of Gd-EOB-DTPA in patients with hepatic and renal impairment.
Invest Radiol. 2011;46:556-66.) and increases the MRI effectiveness
in the detection or diagnostic differentiation of several liver nodules such as
metastasis, HCC, adenomas and FNH(1616 Bieze M, van den Esschert JW, Nio CY, et al. Diagnostic accuracy of MRI
in differentiating hepatocellular adenoma from focal nodular hyperplasia: prospective
study of the additional value of gadoxetate disodium. AJR Am J Roentgenol.
2012;199:26-34.
17 Mohajer K, Frydrychowicz A, Robbins JB, et al. Characterization of
hepatic adenoma and focal nodular hyperplasia with gadoxetic acid. J Magn Reson
Imaging. 2012;36:686-96.
18 Chen L, Zhang J, Zhang L, et al. Meta-analysis of gadoxetic acid
disodium (Gd- EOB-DTPA)-enhanced magnetic resonance imaging for the detection of
liver metastases. PLoS One. 2012;7:e48681.-1919 Liu X, Zou L, Liu F, et al. Gadoxetic acid disodium-enhanced magnetic
resonance imaging for the detection of hepatocellular carcinoma: a meta-analysis.
PLoS One. 2013;8:e70896.), with a
performance superior or even complementary to extracellular contrast-enhanced computed
tomography and MRI(2020 Kim SH, Kim SH, Lee J, et al. Gadoxetic acid-enhanced MRI versus
triple-phase MDCT for the preoperative detection of hepatocellular carcinoma. AJR Am
J Roentgenol. 2009;192:1675-81.
21 Sofue K, Tsurusaki M, Murakami T, et al. Does gadoxetic acid-enhanced
3.0T MRI in addition to 64-detector-row contrast-enhanced CT provide better
diagnostic performance and change the therapeutic strategy for the preoperative
evaluation of colorectal liver metastases? Eur Radiol. 2014;28. [Epub ahead of
print].-2222 Haimerl M, Wächtler M, Platzek I, et al. Added value of
Gd-EOB-DTPA-enhanced Hepatobiliary phase MR imaging in evaluation of focal solid
hepatic lesions. BMC Med Imaging. 2013;13:41.).
In this sense, the study developed by Francisco et al.(2323 Francisco FAF, Araujo ALE, Oliveira Neto JA, et al. Hepatobiliary contrast agents: differential diagnosis of focal hepatic lesions, pitfalls and other indications. Radiol Bras. 2014;47:301-9.) and published in the present issue of Radiologia Brasileira, comprehensively approaching the role played by gadoxetic acid in the evaluation of focal liver lesions, is welcome. In such study, the authors clearly present the subject matter, describing the main features, indications, ways of administration and an optimized protocol for cases where the liver-specific (or hepatobiliary) contrast agent is adopted, besides describing its influence on the diagnosis of the different types of focal liver lesions.
Despite the higher cost as compared with other widely available extracellular contrast
agents, besides the necessity of a more elaborate injection technique to get
satisfactory results, and based on the findings of many published studies, it is our
opinion that the use of gadoxetic acid is safe and justified to differentiate between
adenoma and FNH, between HCC and dysplastic nodule, or to identify small primary or
secondary, malignant lesions (< 2 cm). We hope that, in the near future, the
scientific societies' guidelines contemplate liver-specific contrast-enhanced MRI as a
valid alternative included in the diagnostic algorithm of several focal liver
lesions(2424 Ichikawa T, Sano K, Morisaka H. Diagnosis of pathologically early HCC
with EOBMRI: experiences and current consensus. Liver Cancer.
2014;3:97-107.
25 Kudo M, Matsui O, Sakamoto M, et al. Role of
gadolinium-ethoxybenzyl-diethylene-triaminepentaacetic acid-enhanced magnetic
resonance imaging in the management of hepatocellular carcinoma: consensus at the
Symposium of the 48th Annual Meeting of the Liver Cancer Study Group of Japan.
Oncology. 2013;84 Suppl 1:21-7.-2626 Lee JM, Zech CJ, Bolondi L, et al. Consensus report of the 4th
International Forum for Gadolinium-Ethoxybenzyl-Diethylenetriamine Pentaacetic Acid
Magnetic Resonance Imaging. Korean J Radiol. 2011;12:403-15.).
REFERÊNCIAS
-
1Siegelman ES, Chauhan A. MR characterization of focal liver lesions: pearls and pitfalls. Magn Reson Imaging Clin N Am. 2014;22:295-313.
-
2Heiken JP. Distinguishing benign from malignant liver tumours. Cancer Imaging. 2007;7 Spec No A:S1-14.
-
3Bartolozzi C. MR of the liver: from breakthrough to clinical application. Abdom Imaging. 2012;37:154.
-
4Galvão BVT, Torres LR, Cardia PP, et al. Prevalence of simple liver cysts and hemangiomas in cirrhotic and non-cirrhotic patients submitted to magnetic resonance imaging. Radiol Bras. 2013;46:203-8.
-
5Torres LR, Timbó LS, Ribeiro CMF, et al. Multifocal and metastatic hepatic hemangioendothelioma: case report and literature review. Radiol Bras. 2014;47:194-6.
-
6Grazioli L, Bondioni MP, Haradome H, et al. Hepatocellular adenoma and focal nodular hyperplasia: value of gadoxetic acid-enhanced MR imaging in differential diagnosis. Radiology. 2012;262:520-9.
-
7Bartolozzi C, Battaglia V, Bargellini I, et al. Contrast-enhanced magnetic resonance imaging of 102 nodules in cirrhosis: correlation with histological findings on explanted livers. Abdom Imaging. 2013;38:290-6.
-
8Van Beers BE, Pastor CM, Hussain HK. Primovist, Eovist: what to expect? J Hepatol. 2012;57:421-9.
-
9Seale MK, Catalano OA, Saini S, et al. Hepatobiliary-specific MR contrast agents: role in imaging the liver and biliary tree. Radiographics. 2009;29:1725-48.
-
10Tanimoto A, Kadoya M, Kawamura Y, et al. Safety and efficacy of a novel hepatobiliary MR contrast agent, Gd-DTPA-DeA: results of phase I and phase II clinical trials. J Magn Reson Imaging. 2006;23:499-508.
-
11Ringe KI, Husarik DB, Sirlin CB, et al. Gadoxetate disodium-enhanced MRI of the liver: part 1, protocol optimization and lesion appearance in the noncirrhotic liver. AJR Am J Roentgenol. 2010;195:13-28.
-
12Cruite I, Schroeder M, Merkle EM, et al. Gadoxetate disodium-enhanced MRI of the liver: part 2, protocol optimization and lesion appearance in the cirrhotic liver. AJR Am J Roentgenol. 2010;195:29-41.
-
13Bluemke DA, Sahani D, Amendola M, et al. Efficacy and safety of MR imaging with liver-specific contrast agent: U.S. multicenter phase III study. Radiology. 2005;237:89-98.
-
14Döhr O, Hofmeister R, Treher M, et al. Preclinical safety evaluation of Gd-EOBDTPA (Primovist). Invest Radiol. 2007;42:830-41.
-
15Gschwend S, Ebert W, Schultze-Mosgau M, et al. Pharmacokinetics and imaging properties of Gd-EOB-DTPA in patients with hepatic and renal impairment. Invest Radiol. 2011;46:556-66.
-
16Bieze M, van den Esschert JW, Nio CY, et al. Diagnostic accuracy of MRI in differentiating hepatocellular adenoma from focal nodular hyperplasia: prospective study of the additional value of gadoxetate disodium. AJR Am J Roentgenol. 2012;199:26-34.
-
17Mohajer K, Frydrychowicz A, Robbins JB, et al. Characterization of hepatic adenoma and focal nodular hyperplasia with gadoxetic acid. J Magn Reson Imaging. 2012;36:686-96.
-
18Chen L, Zhang J, Zhang L, et al. Meta-analysis of gadoxetic acid disodium (Gd- EOB-DTPA)-enhanced magnetic resonance imaging for the detection of liver metastases. PLoS One. 2012;7:e48681.
-
19Liu X, Zou L, Liu F, et al. Gadoxetic acid disodium-enhanced magnetic resonance imaging for the detection of hepatocellular carcinoma: a meta-analysis. PLoS One. 2013;8:e70896.
-
20Kim SH, Kim SH, Lee J, et al. Gadoxetic acid-enhanced MRI versus triple-phase MDCT for the preoperative detection of hepatocellular carcinoma. AJR Am J Roentgenol. 2009;192:1675-81.
-
21Sofue K, Tsurusaki M, Murakami T, et al. Does gadoxetic acid-enhanced 3.0T MRI in addition to 64-detector-row contrast-enhanced CT provide better diagnostic performance and change the therapeutic strategy for the preoperative evaluation of colorectal liver metastases? Eur Radiol. 2014;28. [Epub ahead of print].
-
22Haimerl M, Wächtler M, Platzek I, et al. Added value of Gd-EOB-DTPA-enhanced Hepatobiliary phase MR imaging in evaluation of focal solid hepatic lesions. BMC Med Imaging. 2013;13:41.
-
23Francisco FAF, Araujo ALE, Oliveira Neto JA, et al. Hepatobiliary contrast agents: differential diagnosis of focal hepatic lesions, pitfalls and other indications. Radiol Bras. 2014;47:301-9.
-
24Ichikawa T, Sano K, Morisaka H. Diagnosis of pathologically early HCC with EOBMRI: experiences and current consensus. Liver Cancer. 2014;3:97-107.
-
25Kudo M, Matsui O, Sakamoto M, et al. Role of gadolinium-ethoxybenzyl-diethylene-triaminepentaacetic acid-enhanced magnetic resonance imaging in the management of hepatocellular carcinoma: consensus at the Symposium of the 48th Annual Meeting of the Liver Cancer Study Group of Japan. Oncology. 2013;84 Suppl 1:21-7.
-
26Lee JM, Zech CJ, Bolondi L, et al. Consensus report of the 4th International Forum for Gadolinium-Ethoxybenzyl-Diethylenetriamine Pentaacetic Acid Magnetic Resonance Imaging. Korean J Radiol. 2011;12:403-15.
Publication Dates
-
Publication in this collection
Sep-Oct 2014