Abstract
Background
Little is known about the difference in enhancement patterns of hepatocellular carcinoma (HCC) during multistep hepatocarcinogenesis between the post-vascular phase of Sonazoid-enhanced ultrasonography (SEUS) and hepatobiliary phase of gadolinium ethoxybenzyl diethylenetriamine (Gd-EOB-DTPA)-enhanced MRI, as well as uptakes of Sonazoid and Gd-EOB-DTPA by HCC.
Methods
Seventy patients with 73 histologically proven HCCs (33 hypovascular well-differentiated HCCs and 40 progressed HCCs) and 9 dysplastic nodules (DNs) were enrolled. Enhancement patterns of the lesions on the post-vascular phase of SEUS and hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI were evaluated. Uptakes of Sonazoid and Gd-EOB-DTPA were assessed by Sonazoid enhancement index and EOB enhancement ratio in relation to immunohistochemistry of CD68 and organic anion transporting polypeptide 8 (OATP8), respectively.
Results
On the post-vascular phase of SEUS, none of the 9 DNs and 3 of 33 hypovascular well-differentiated HCCs (9 %) were hypoechoic, whereas 3 of 9 DNs (33 %) and 31 of 33 hypovascular well-differentiated HCCs (94 %) showed hypointensity on the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI. Of 31 progressed HCCs, 95 and 93 % were hypoechoic and hypointense on the post-vascular phase of SEUS and hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI, respectively. Sonazoid enhancement indexes decreased in progressed HCCs, correlating with lower Kupffer cell numbers (P < 0.001). EOB enhancement ratios decreased in hypovascular well-differentiated and progressed HCCs, as OATP8 expression declined (P < 0.001).
Conclusions
In stepwise hepatocarcinogenesis, uptake of Sonazoid starts decreasing later than that of Gd-EOB-DTPA. Although signal reductions on the post-vascular phase of SEUS or hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI suggest HCC, hypoechoic appearance on the post-vascular phase of SEUS might be HCC-specific, particularly progressed HCC.
Similar content being viewed by others
Abbreviations
- DN:
-
Dysplastic nodule
- Gd-EOB-DTPA:
-
Gadolinium ethoxybenzyl diethylenetriamine
- GRE:
-
Gradient echo
- HCC:
-
Hepatocellular carcinoma
- LAVA:
-
Liver acquisition with volume acceleration
- OATP8:
-
Organic anion transporting polypeptide 8
- SEUS:
-
Sonazoid-enhanced ultrasonography
- SPIO:
-
Superparamagnetic iron oxide
References
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.
Sakamoto M, Hirohashi S, Shimosato Y. Early stages of multistep hepatocarcinogenesis: adenomatous hyperplasia and early hepatocellular carcinoma. Hum Pathol. 1991;22:172–8.
The International Consensus Group for Hepatocellular Neoplasia. Pathologic diagnosis of early hepatocellular carcinoma: a report of the International Consensus Group for Hepatocellular Neoplasia. Hepatology. 2009;49:658–64.
Nakashima O, Sugihara S, Kage M, Kojiro M. Pathomorphologic characteristics of small hepatocellular carcinoma: a special reference to small hepatocellular carcinoma with indistinct margins. Hepatology. 1995;22:101–5.
Okusaka T, Okada S, Ueno H, Ikeda M, Shimada K, Yamamoto J, et al. Satellite lesions in patients with small hepatocellular carcinoma with reference to clinicopathologic features. Cancer. 2002;95:1931–7.
Nakashima Y, Nakashima O, Tanaka M, Okuda K, Nakashima M, Kojiro M. Portal vein invasion and intrahepatic micrometastasis in small hepatocellular carcinoma by gross type. Hepatol Res. 2003;26:142–7.
Yanagisawa K, Moriyasu F, Miyahara T, Yuki M, Iijima H. Phagocytosis of ultrasound contrast agent microbubbles by Kupffer cells. Ultrasound Med Biol. 2007;33:318–25.
Moriyasu F, Itoh K. Efficacy of perflubutane microbubble-enhanced ultrasound in the characterization and detection of focal liver lesions: phase 3 multicenter clinical trial. AJR Am J Roentgenol. 2009;193:86–95.
Murakami T, Imai Y, Okada M, Hyodo T, Lee WJ, Kim MJ, et al. Ultrasonography, computed tomography and magnetic resonance imaging of hepatocellular carcinoma: toward improved treatment decisions. Oncology. 2011;81(Suppl 1):86–99.
Kudo M, Hatanaka K, Kumada T, Toyoda H, Tada T. Double-contrast ultrasound: a novel surveillance tool for hepatocellular carcinoma. Am J Gastroenterol. 2011;106:368–70.
Luo W, Numata K, Morimoto M, Oshima T, Ueda M, Okada M, et al. Role of Sonazoid-enhanced three-dimensional ultrasonography in the evaluation of percutaneous radiofrequency ablation of hepatocellular carcinoma. Eur J Radiol. 2010;75:91–7.
Korenaga K, Korenaga M, Furukawa M, Yamasaki T, Sakaida I. Usefulness of Sonazoid contrast-enhanced ultrasonography for hepatocellular carcinoma: comparison with pathological diagnosis and superparamagnetic iron oxide magnetic resonance images. J Gastroenterol. 2009;44:733–41.
Sugimoto K, Moriyasu F, Saito K, Taira J, Saguchi T, Yoshimura N, et al. Comparison of Kupffer-phase Sonazoid-enhanced sonography and hepatobiliary-phase gadoxetic acid-enhanced magnetic resonance imaging of hepatocellular carcinoma and correlation with histologic grading. J Ultrasound Med. 2012;31:529–38.
Ahn SS, Kim MJ, Lim JS, Hong HS, Chung YE, Choi JY. Added value of gadoxetic acid-enhanced hepatobiliary phase MR imaging in the diagnosis of hepatocellular carcinoma. Radiology. 2010;255:459–66.
Sano K, Ichikawa T, Motosugi U, Sou H, Muhi AM, Matsuda M, et al. Imaging study of early hepatocellular carcinoma: usefulness of gadoxetic acid-enhanced MR Imaging. Radiology. 2011;261:834–44.
Zech CJ, Grazioli L, Jonas E, Ekman M, Niebecker R, Gschwend S, et al. Health-economic evaluation of three imaging strategies in patients with suspected colorectal liver metastases: Gd-EOB-DTPA-enhanced MRI vs. extracellular contrast media-enhanced MRI and 3-phase MDCT in Germany, Italy and Sweden. Eur Radiol. 2009;19(Suppl 3):S753–63.
Kogita S, Imai Y, Okada M, Kim T, Onishi H, Takamura M, et al. Gd-EOB-DTPA-enhanced magnetic resonance images of hepatocellular carcinoma: correlation with histological grading and portal blood flow. Eur Radiol. 2010;20:2405–13.
Kitao A, Zen Y, Matsui O, Gabata T, Kobayashi S, Koda W, et al. Hepatocellular carcinoma: signal intensity at gadoxetic acid-enhanced MR imaging—correlation with molecular transporters and histopathologic features. Radiology. 2010;256:817–26.
Tsuboyama T, Onishi H, Kim T, Akita H, Hori M, Tatsumi M, et al. Hepatocellular carcinoma: hepatocyte-selective enhancement at gadoxetic acid-enhanced MR imaging—correlation with expression of sinusoidal and canalicular transporters and bile accumulation. Radiology. 2010;255:824–33.
Imai Y, Murakami T, Yoshida S, Nishikawa M, Ohsawa M, Tokunaga K, et al. Superparamagnetic iron oxide-enhanced magnetic resonance images of hepatocellular carcinoma: correlation with histological grading. Hepatology. 2000;32:205–12.
Kunishi Y, Numata K, Morimoto M, Okada M, Kaneko T, Maeda S, et al. Efficacy of fusion imaging combining sonography and hepatobiliary phase MRI with Gd-EOB-DTPA to detect small hepatocellular carcinoma. AJR Am J Roentgenol. 2012;198:106–14.
Makino Y, Imai Y, Fukuda K, Seki Y, Kogita S, Sawai Y, et al. Sonazoid-enhanced ultrasonography for the diagnosis of an intrapancreatic accessory spleen: a case report. J Clin Ultrasound. 2011;39:344–7.
Takayasu K, Muramatsu Y, Furukawa H, Wakao F, Moriyama N, Takayama T, et al. Early hepatocellular carcinoma: appearance at CT during arterial portography and CT arteriography with pathologic correlation. Radiology. 1995;194:101–5.
Tanaka M, Nakashima O, Wada Y, Kage M, Kojiro M. Pathomorphological study of Kupffer cells in hepatocellular carcinoma and hyperplastic nodular lesions in the liver. Hepatology. 1996;24:807–12.
Kitao A, Matsui O, Yoneda N, Kozaka K, Shinmura R, Koda W, et al. The uptake transporter OATP8 expression decreases during multistep hepatocarcinogenesis: correlation with gadoxetic acid enhanced MR imaging. Eur Radiol. 2011;21:2056–66.
Conflict of interest
The authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ohama, H., Imai, Y., Nakashima, O. et al. Images of Sonazoid-enhanced ultrasonography in multistep hepatocarcinogenesis: comparison with Gd-EOB-DTPA-enhanced MRI. J Gastroenterol 49, 1081–1093 (2014). https://doi.org/10.1007/s00535-013-0859-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00535-013-0859-1