Radiologia Brasileira - Publicação Científica Oficial do Colégio Brasileiro de Radiologia

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^(1-5) 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⁽³⁾.

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^(6,7). Liver-specific contrast agents have been introduced to overcome such limitations and, among others, gadoxetic acid (Gd-EOB-DTPA)^(8,9) 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^(8-10). Because of such a characteristic, gadoxetic acid is considered to be a "mixed action" (extracellular and hepatobiliary) contrast agent⁽⁹⁾.

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⁽¹¹⁾. Therefore, the typical focal liver lesions enhancement pattern observed during the dynamic perfusion phase is reproduced with the utilization of gadoxetic acid⁽¹¹⁾. 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)^(11,12).

In the last years, several studies have demonstrated that the use of gadoxetic acid is safe^(13-15) and increases the MRI effectiveness in the detection or diagnostic differentiation of several liver nodules such as metastasis, HCC, adenomas and FNH^(16-19), with a performance superior or even complementary to extracellular contrast-enhanced computed tomography and MRI^(20-22).

In this sense, the study developed by Francisco et al.⁽²³⁾ 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^(24-26).


REFERENCES

1. 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.

5. Torres LR, Timbó LS, Ribeiro CMF, et al. Multifocal and metastatic hepatic hemangioendothelioma: case report and literature review. Radiol Bras. 2014;47:194-6.

6. 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.

7. 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.

8. 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.

10. 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.

11. 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.

12. 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.

13. 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.

15. 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.

16. 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.

19. 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.

20. 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].

22. 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.

23. 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.

24. 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.

26. 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.










Associate Professor, Department of Imaging Diagnosis - Escola Paulista de Medicina da Universidade Federal de São Paulo (EPM-Unifesp), MD, Radiologist, Laboratório Fleury - Hospital São Luiz, São Paulo, SP, Brazil. E-mail: giuseppe_dr@uol.com.br