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Usefulness of Sonazoid contrast-enhanced ultrasonography for hepatocellular carcinoma: comparison with pathological diagnosis and superparamagnetic iron oxide magnetic resonance images

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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Abstract

Objective

We investigated the usefulness of Sonazoid contrast-enhanced ultrasonography (Sonazoid-CEUS) in the diagnosis of hepatocellular carcinoma (HCC). The examination was performed by comparing the images during the Kupffer phase of Sonazoid-CEUS with superparamagnetic iron oxide magnetic resonance (SPIO-MRI).

Methods

The subjects were 48 HCC nodules which were histologically diagnosed (well-differentiated HCC, n = 13; moderately differentiated HCC, n = 30; poorly differentiated HCC, n = 5). We performed Sonazoid-CEUS and SPIO-MRI on all subjects. In the Kupffer phase of Sonazoid-CEUS, the differences in the contrast agent uptake between the tumorous and non-tumorous areas were quantified as the Kupffer phase ratio and compared. In the SPIO-MRI, it was quantified as the SPIO-intensity index. We then compared these results with the histological differentiation of HCCs.

Results

The Kupffer phase ratio decreased as the HCCs became less differentiated (P < 0.0001; Kruskal–Wallis test). The SPIO-intensity index also decreased as HCCs became less differentiated (P < 0.0001). A positive correlation was found between the Kupffer phase ratio and the SPIO-MRI index (r = 0.839). In the Kupffer phase of Sonazoid-CEUS, all of the moderately and poorly differentiated HCCs appeared hypoechoic and were detected as a perfusion defect, whereas the majority (9 of 13 cases, 69.2%) of the well-differentiated HCCs had an isoechoic pattern. The Kupffer phase images of Sonazoid-CEUS and SPIO-MRI matched perfectly (100%) in all of the moderately and poorly differentiated HCCs.

Conclusion

Sonazoid-CEUS is useful for estimating histological grading of HCCs. It is a modality that could potentially replace SPIO-MRI.

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References

  1. Kudo M. Contrast harmonic imaging in the diagnosis and treatment of hepatic tumors. Tokyo: Springer; 2003.

    Google Scholar 

  2. Wen YL, Kudo M, Zheng RQ, Ding H, Zhou P, Minami Y, et al. Characterization of hepatic tumors: value of contrast-enhanced coded phase-inversion harmonic angio. AJR Am J Roentgenol. 2004;182:1019–26.

    PubMed  Google Scholar 

  3. von Herbay A, Vogt C, Häussinger D. Late-phase pulse-inversion sonography using the contrast agent Levovist: differentiation between benign and malignant focal lesions of the liver. AJR Am J Roentgenol. 2002;179:1273–9.

    Google Scholar 

  4. Inoue T, Kudo M, Watai R, Pei Z, Kawasaki T, Minami Y, et al. Differential diagnosis of nodular lesions in cirrhotic liver by post-vascular phase contrast-enhanced US with Levovist: comparison with superparamagnetic iron oxide magnetic resonance images. J Gastroenterol. 2005;40:1139–47.

    Article  PubMed  Google Scholar 

  5. Minami Y, Kudo M, Kawasaki T, Kitano M, Chung H, Maekawa K, et al. Transcatheter arterial chemoembolization of hepatocellular carcinoma: usefulness of coded phase-inversion harmonic sonography. AJR Am J Roentgenol. 2003;180:703–8.

    PubMed  Google Scholar 

  6. Numata K, Isozaki T, Ozawa Y, Sakaguchi T, Kiba T, Kubota T, et al. Percutaneous ablation therapy guided by contrast-enhanced sonography for patients with hepatocellular carcinoma. AJR Am J Roentgenol. 2003;180:143–9.

    PubMed  Google Scholar 

  7. Minami Y, Kudo M, Chung H, Kawasaki T, Yagyu Y, Shimono T, et al. Contrast harmonic sonography-guided radiofrequency ablation therapy versus B-mode sonography in hepatocellular carcinoma: prospective randomized controlled trial. AJR Am J Roentgenol. 2007;188:489–94.

    Article  PubMed  Google Scholar 

  8. Watanabe R, Matsumura M, Chen CJ, Kaneda Y, Ishihara M, Fujimaki M. Gray-scale liver enhancement with Sonazoid (NC100100), a novel ultrasound contrast agent; detection of hepatic tumors in a rabbit model. Biol Pharm Bull. 2003;26:1272–7.

    Article  PubMed  CAS  Google Scholar 

  9. Hagen EK, Forsberg F, Aksnes AK, Merton DA, Liu JB, Tornes A, et al. Enhanced detection of blood flow in the normal canine prostate using an ultrasound contrast agent. Invest Radiol. 2000;35:118–24.

    Article  PubMed  CAS  Google Scholar 

  10. Yao J, Teupe C, Takeuchi M, Avelar E, Sheahan M, Connolly R, et al. Quantitative 3-dimensional contrast echocardiographic determination of myocardial mass at risk and residual infarct mass after reperfusion: experimental canine studies with intravenous contrast NC100100. J Am Soc Echocardiogr. 2000;13:570–81.

    Article  PubMed  CAS  Google Scholar 

  11. 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.

    Article  PubMed  Google Scholar 

  12. Watanabe R, Matsumura M, Chen CJ, Kaneda Y, Fujimaki M. Characterization of tumor imaging with microbubble-based ultrasound contrast agent, Sonazoid, in rabbit liver. Biol Pharm Bull. 2005;28:972–7.

    Article  PubMed  CAS  Google Scholar 

  13. Kindberg GM, Tolleshaug H, Roos N, Skotland T. Hepatic clearance of Sonazoid perfluorobutane microbubbles by Kupffer cells does not reduce the ability of liver to phagocytose or degrade albumin microspheres. Cell Tissue Res. 2003;312:49–54.

    PubMed  Google Scholar 

  14. Watanabe R, Matsumura M, Munemasa T, Fujimaki M, Suematsu M. Mechanism of hepatic parenchyma-specific contrast of microbubble-based contrast agent for ultrasonography: microscopic studies in rat liver. Invest Radiol. 2007;42:643–51.

    Article  PubMed  CAS  Google Scholar 

  15. 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.

    Article  PubMed  CAS  Google Scholar 

  16. Forsberg F, Piccoli CW, Liu JB, Rawool NM, Merton DA, Mitchell DG, et al. Hepatic tumor detection: MR imaging and conventional US versus pulse-inversion harmonic US of NC100100 during its reticuloendothelial system-specific phase. Radiology. 2002;222:824–9.

    Article  PubMed  Google Scholar 

  17. Nakano H, Ishida Y, Hatakeyama T, Sakuraba K, Hayashi M, Sakurai O, et al. Contrast-enhanced intraoperative ultrasonography equipped with late Kupffer-phase image obtained by sonazoid in patients with colorectal liver metastases. World J Gastroenterol. 2008;14:3207–11.

    Article  PubMed  Google Scholar 

  18. Hatanaka K, Kudo M, Minami Y, Ueda T, Tatsumi C, Kitai S, et al. Differential diagnosis of hepatic tumors: value of contrast-enhanced harmonic sonography using the newly developed contrast agent, Sonazoid. Intervirology. 2008;51(Suppl 1):61–9.

    Article  PubMed  Google Scholar 

  19. Numata K, Morimoto M, Ogura T, Sugimori K, Takebayashi S, Okada M, et al. Ablation therapy guided by contrast-enhanced sonography with Sonazoid for hepatocellular carcinoma lesions not detected by conventional sonography. J Ultrasound Med. 2008;27:395–406.

    PubMed  Google Scholar 

  20. 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.

    Article  PubMed  CAS  Google Scholar 

  21. International Working Party. Terminology of nodular hepatocellular lesions. Hepatology. 1995;22:983–93.

    Google Scholar 

  22. Kudo M, Hatanaka K, Chung H, Minami Y, Maekawa K. A proposal of novel treatment-assist technique for hepatocellular carcinoma in the Sonazoid-enhanced ultrasonography: value of defect re-perfusion imaging. Acta Hepatol Jpn. 2007;48:299–301.

    Google Scholar 

  23. Moriyasu F. Phase III multicenter clinical trial of Sonazoid in Japan for the characterization and the detection of focal liver lesions. Hepatology. 2004;40(Suppl 1):707A.

    Google Scholar 

  24. Asahina Y, Izumi N, Uchihara M, Noguchi O, Ueda K, Inoue K, et al. Assessment of Kupffer cells by ferumoxides-enhanced MR imaging is beneficial for diagnosis of hepatocellular carcinoma: comparison of pathological diagnosis and perfusion patterns assessed by CT hepatic arteriography and CT angioportography. Hepatol Res. 2003;27:196–204.

    Article  PubMed  Google Scholar 

  25. Imai Y, Murakami T, Hori M, Fukuda K, Kim T, Marukawa T, et al. Hypervascular hepatocellular carcinoma: combined dynamic MDCT and SPIO-enhanced MRI versus combined CTHA and CTAP. Hepatol Res. 2008;38:147–58.

    PubMed  Google Scholar 

  26. Kono Y, Steinbach GC, Peterson T, Schmid-Schönbein GW, Mattrey RF. Mechanism of parenchymal enhancement of the liver with a microbubble-based US contrast medium: an intravital microscopy study in rats. Radiology. 2002;224:253–7.

    Article  PubMed  Google Scholar 

  27. Huppertz A, Balzer T, Blakeborough A, Breuer J, Giovagnoni A, Heinz-Peer G, et al. Improved detection of focal liver lesions at MR imaging: multicenter comparison of gadoxetic acid-enhanced MR images with intraoperative findings. Radiology. 2004;230:266–75.

    Article  PubMed  Google Scholar 

  28. Kim SK, Kim SH, Lee WJ, Kim H, Seo JW, Choi D, et al. Preoperative detection of hepatocellular carcinoma: ferumoxides-enhanced versus mangafodipir trisodium-enhanced MR imaging. AJR Am J Roentgenol. 2002;179:741–50.

    PubMed  Google Scholar 

  29. Giorgio A, Ferraioli G, Tarantino L, de Stefano G, Scala V, Scarano F, et al. Contrast-enhanced sonographic appearance of hepatocellular carcinoma in patients with cirrhosis: comparison with contrast-enhanced helical CT appearance. AJR Am J Roentgnol. 2004;183:1319–26.

    Google Scholar 

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Acknowledgments

We thank Masahiro Saitoh and Ritsuko Fukushima, from Mochida Siemence systems Co., Ltd., for their helpful advice and expert technical assistance.

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Author notes

  1. Keiko Korenaga

    Present address: Division of Hepatology and Pancreatology, Department of Internal Medicine, Kawasaki Medical College, 577 Matsushima, Kurashiki, Okayama, 702-0192, Japan

Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan

    Keiko Korenaga, Masaaki Korenaga, Takahiro Yamasaki & Isao Sakaida

  2. Department of Radiology, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, Japan

    Matakazu Furukawa

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  1. Keiko Korenaga
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  2. Masaaki Korenaga
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Correspondence to Keiko Korenaga.

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Korenaga, K., Korenaga, M., Furukawa, M. et al. Usefulness of Sonazoid contrast-enhanced ultrasonography for hepatocellular carcinoma: comparison with pathological diagnosis and superparamagnetic iron oxide magnetic resonance images. J Gastroenterol 44, 733–741 (2009). https://doi.org/10.1007/s00535-009-0053-7

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  • DOI: https://doi.org/10.1007/s00535-009-0053-7

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