Correlation of liver parenchymal gadolinium-ethoxybenzyl diethylenetriaminepentaacetic acid enhancement and liver function in humans with hepatocellular carcinoma

Kubota,Kei; Tamura,Taiji; Aoyama,Nobutaka; Nogami,Munenobu; Hamada,Norihiko; Nishioka,Akihito; Ogawa,Yasuhiro

doi:10.3892/ol.2012.629

Correlation of liver parenchymal gadolinium-ethoxybenzyl diethylenetriaminepentaacetic acid enhancement and liver function in humans with hepatocellular carcinoma

Authors:
- Kei Kubota
- Taiji Tamura
- Nobutaka Aoyama
- Munenobu Nogami
- Norihiko Hamada
- Akihito Nishioka
- Yasuhiro Ogawa
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Affiliations: Department of Radiology, Kochi Medical School, Kochi University, Kohasu, Oko-Cho, Nankoku, Kochi 783-8505, Japan
Published online on: March 1, 2012 https://doi.org/10.3892/ol.2012.629
Pages: 990-994

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Abstract

Animal studies have demonstrated that liver function parameters affect the degree of liver enhancement by gadolinium-ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA). The present study prospectively investigated whether liver function parameters and liver damage scores similarly correlate with the degree of liver enhancement by Gd-EOB-DTPA in humans with hepatocellular carcinoma (HCC). A total of 41 patients (32 males, 9 females; mean age, 71.9 years; range, 38-86 years) with suspected HCC provided written, informed consent to undergo a Gd-EOB-DTPA (30 µmol/kg of body weight)-enhanced T1-gradient-echo (GRE) magnetic resonance imaging (MRI) study. The signal intensity of the liver parenchyma was quantified at various time points following injection of Gd-EOB-DTPA. We investigated the correlations between maximal relative enhancement (RE) values and liver function parameters, and liver damage scores. Correlations between parameters and maximum RE values were determined using the Student's t-test and univariate regression analyses. The effect of potential confounding factors was controlled by multiple stepwise regression analysis. Two-tailed values of p<0.05 were considered to indicate a statistically significant difference. The RE values were maximal in 8 and 33 patients at 20 and 30 min, respectively, following Gd-EOB-DTPA injection and did not significantly differ between respective liver damage scores. Univariate analyses revealed that maximal RE values were associated with serum aspartate aminotransferase, total bilirubin, albumin and 15-min indocyanine green retention rates. Multiple stepwise regression analyses revealed that serum albumin and total bilirubin remained independently significant. The degree of liver parenchyma enhancement by Gd-EOB-DTPA depends on liver function parameters in humans, as in animals. The results from this study suggest that Gd-EOB-DTPA has potential for use as a liver function test, and for providing a short examination time for liver MRI results in patients with normal liver function.

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1	Hamm B, Staks T, Muhler A, et al: Phase I clinical evaluation of Gd-EOB-DTPA as a hepatobiliary MR contrast agent: safety, pharmacokinetics, and MR imaging. Radiology. 195:785–792. 1995. View Article : Google Scholar : PubMed/NCBI
2	Vogl TJ, Kummel S, Hammerstingl R, et al: Liver tumors: comparison of MR imaging with Gd-EOB-DTPA and Gd-DTPA. Radiology. 200:59–67. 1996. View Article : Google Scholar : PubMed/NCBI
3	Reimer P, Rummeny EJ, Shamsi K, et al: Phase II clinical evaluation of Gd-EOB-DTPA: dose, safety aspects, and pulse sequence. Radiology. 199:177–183. 1996. View Article : Google Scholar : PubMed/NCBI
4	Reimer P, Rummeny EJ, Daldrup HE, et al: Enhancement characteristics of liver metastases, hepatocellular carcinomas, and hemangiomas with Gd-EOB-DTPA: preliminary results with dynamic MR imaging. Eur Radiol. 7:275–280. 1997. View Article : Google Scholar : PubMed/NCBI
5	Stern W, Schick F, Kopp AF, et al: Dynamic MR imaging of liver metastases with Gd-EOB-DTPA. Acta Radiol. 41:255–262. 2000. View Article : Google Scholar : PubMed/NCBI
6	Huppertz A, Balzer T, Blakeborough A, et al: Improved detection of focal liver lesions at MR imaging: multicenter comparison of gadoxetic acid-enhanced MR images with intraoperative findings. Radiology. 230:266–275. 2004. View Article : Google Scholar : PubMed/NCBI
7	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. 237:89–98. 2005. View Article : Google Scholar : PubMed/NCBI
8	Huppertz A, Haraida S, Kraus A, et al: Enhancement of focal liver lesions at gadoxetic acid-enhanced MR imaging: correlation with histopathologic findings and spiral CT - initial observations. Radiology. 234:468–478. 2005. View Article : Google Scholar : PubMed/NCBI
9	Zech CJ, Grazioli L, Breuer J, Reiser MF and Schoenberg SO: Diagnostic performance and description of morphological features of focal nodular hyperplasia in Gd-EOB-DTPA-enhanced liver magnetic resonance imaging: results of a multicenter trial. Invest Radiol. 43:504–511. 2008. View Article : Google Scholar
10	Hammerstingl R, Huppertz A, Breuer J, et al: Diagnostic efficacy of gadoxetic acid (Primovist)-enhanced MRI and spiral CT for a therapeutic strategy: comparison with intraoperative and histopathologic findings in focal liver lesions. Eur Radiol. 18:457–467. 2008. View Article : Google Scholar
11	Bollow M, Taupitz M, Hamm B, Staks T, Wolf KJ and Weinmann HJ: Gadolinium-ethoxybenzyl-DTPA as a hepatobiliary contrast agent for use in MR cholangiography: results of an in vivo phase-I clinical evaluation. Eur Radiol. 7:126–132. 1997. View Article : Google Scholar : PubMed/NCBI
12	Asbach P, Warmuth C, Stemmer A, et al: High spatial resolution T1-weighted MR imaging of liver and biliary tract during uptake phase of a hepatocyte-specific contrast medium. Invest Radiol. 43:809–815. 2008. View Article : Google Scholar : PubMed/NCBI
13	Clement O, Muhler A, Vexlar V, Berthezene Y and Brasch RC: Gadolinium-ethoxybenzyl-DTPA, a new liver-specific magnetic resonance contrast agent. Kinetic and enhancement patterns in normal and cholestatic rats. Invest Radiol. 27:612–619. 1992. View Article : Google Scholar : PubMed/NCBI
14	Muhler A, Freise CE, Kuwatsuru R, et al: Acute liver rejection: evaluation with cell-directed MR contrast agents in a rat transplantation model. Radiology. 186:139–146. 1993. View Article : Google Scholar : PubMed/NCBI
15	Muhler A, Heinzelmann I and Weinmann HJ: Elimination of gadolinium-ethoxybenzyl-DTPA in a rat model of severely impaired liver and kidney excretory function. An experimental study in rats. Invest Radiol. 29:213–216. 1994. View Article : Google Scholar : PubMed/NCBI
16	Schmitz SA, Muhler A, Wagner S and Wolf KJ: Functional hepatobiliary imaging with gadolinium-EOB-DTPA. A comparison of magnetic resonance imaging and 153gadolinium-EOB-DTPA scintigraphy in rats. Invest Radiol. 31:154–160. 1996. View Article : Google Scholar : PubMed/NCBI
17	Kim T, Murakami T, Hasuike Y, et al: Experimental hepatic dysfunction: evaluation by MRI with Gd-EOB-DTPA. J Magn Reson Imaging. 7:683–688. 1997. View Article : Google Scholar : PubMed/NCBI
18	Ryeom HK, Kim SH, Kim JY, et al: Quantitative evaluation of liver function with MRI using Gd-EOB-DTPA. Korean J Radiol. 5:231–239. 2004. View Article : Google Scholar : PubMed/NCBI
19	Makuuchi M, Kokudo N, Arii S, et al: Development of evidence-based clinical guidelines for the diagnosis and treatment of hepatocellular carcinoma in Japan. Hepatol Res. 33:37–51. 2008. View Article : Google Scholar : PubMed/NCBI
20	Clement O, Muhler A, Vexler VS, et al: Evaluation of radiation-induced liver injury with MR imaging: comparison of hepatocellular and reticuloendothelial contrast agents. Radiology. 185:163–168. 1992. View Article : Google Scholar : PubMed/NCBI
21	Kaplowitz N: Physiological significance of glutathione S-transferases. Am J Physiol. 239:G439–G444. 1980.PubMed/NCBI
22	Schuhmann-Giampieri G, Schmitt-Willich H, Press WR, Negishi C, Weinmann HJ and Speck U: Preclinical evaluation of Gd-EOB-DTPA as a contrast agent in MR imaging of the hepatobiliary system. Radiology. 183:59–64. 1992. View Article : Google Scholar : PubMed/NCBI
23	Kwon AH, Ha-Kawa SK, Uetsuji S, Inoue T, Matsui Y and Kamiyama Y: Preoperative determination of the surgical procedure for hepatectomy using technetium-99m-galactosyl human serum albumin (99mTc-GSA) liver scintigraphy. Hepatology. 25:426–429. 1997. View Article : Google Scholar
24	Lau H, Man K, Fan ST, Yu WC, Lo CM and Wong J: Evaluation of preoperative hepatic function in patients with hepatocellular carcinoma undergoing hepatectomy. Br J Surg. 84:1255–1259. 1997. View Article : Google Scholar : PubMed/NCBI
25	Shimizu J, Dono K, Gotoh M, et al: Evaluation of regional liver function by gadolinium-EOB-DTPA-enhanced MR imaging. Dig Dis Sci. 44:1330–1337. 1999. View Article : Google Scholar : PubMed/NCBI
26	Tsuda N, Okada M and Murakami T: Potential of gadolinium- ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB- DTPA) for differential diagnosis of nonalcoholic steatohepatitis and fatty liver in rats using magnetic resonance imaging. Invest Radiol. 42:242–247. 2007. View Article : Google Scholar
27	Ono M and Saibara T: Clinical features of nonalcoholic steatohepatitis in Japan: Evidence from the literature. J Gastroenterol. 41:725–732. 2006. View Article : Google Scholar : PubMed/NCBI
28	Shimada M, Hashimoto E, Taniai M, et al: Hepatocellular carcinoma in patients with non-alcoholic steatohepatitis. J Hepatol. 37:154–160. 2002. View Article : Google Scholar : PubMed/NCBI
29	Asanuma T, Ono M, Kubota K, et al: Super paramagnetic iron oxide MRI shows defective Kupffer cell uptake function in non-alcoholic fatty liver disease. Gut. 59:258–266. 2010. View Article : Google Scholar : PubMed/NCBI
30	Saadeh S, Younossi ZM, Remer EM, et al: The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology. 123:745–750. 2002. View Article : Google Scholar : PubMed/NCBI
31	Murata Y, Ogawa Y, Saibara T, et al: Tamoxifen-induced non-alcoholic steatohepatitis in patients with breast cancer: Determination of a suitable biopsy site for diagnosis. Oncol Rep. 10:97–100. 2003.PubMed/NCBI
32	Kubota K, Hisa N, Fujiwara Y, Fukumoto M, Yoshida D and Yoshida S: Evaluation of the intratumoral vasculature of hepatocellular carcinoma by power Doppler sonography: advantages and disadvantages versus conventional color Doppler sonography. Abdom Imaging. 25:172–178. 2000. View Article : Google Scholar
33	Kubota K, Hisa N, Nishikawa T, Ohnishi T, Ogawa Y and Yoshida S: The utility of tissue harmonic imaging in the liver: A comparison with conventional gray-scale sonography. Oncol Rep. 7:767–771. 2000.PubMed/NCBI
34	Kubota K, Hisa N, Nishikawa T, et al: Evaluation of hepatocellular carcinoma after treatment with transcatheter arterial chemoembolization: comparison of Lipiodol-CT, power Doppler sonography, and dynamic MRI. Abdom Imaging. 26:184–190. 2001. View Article : Google Scholar
35	Kubota K, Yamanishi T, Itoh S, et al: Role of diffusion-weighted imaging in evaluating therapeutic efficacy after transcatheter arterial chemoembolization for hepatocellular carcinoma. Oncol Rep. 24:727–732. 2010. View Article : Google Scholar