Skip to main content
SpringerLink
Log in

Ablation of High-Intensity Focused Ultrasound Assisted with SonoVue on Rabbit VX2 Liver Tumors: Sequential Findings with Histopathology, Immunohistochemistry, and Enzyme Histochemistry

  • Laboratory and Translational Research
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

We investigated sequential effects of HIFU ablation combined with contrast agent SonoVue by using histopathology examination, immunohistochemistry, and enzyme histochemistry.

Materials and Methods

Forty rabbits with VX2 liver tumors were subjected to HIFU ablation. Before ablation, a bolus injection of 0.2 mL SonoVue was administrated in group II (n = 20), and normal saline solution was injected in group I (n = 20). On day 0, 3, 7, and 14 after ablation, 5 animals in each group were sacrificed. The tissue in ablated zone, transient zone (within 3 mm around ablated area), and surrounding zone (beyond 3 mm around ablated area) were collected. Coagulated volume measurement, hematoxylin-eosin staining, immunohistochemistry of Ki 67, Bcl-2, CD54, and MMP-2 to determine cell proliferation and tissue repair, and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) and succinic dehydrogenase (SDH) staining to evaluate tissue viability were performed.

Results

The coagulated volume in group II at each time point was larger than that in group I (P < .05). After day 3, hematoxylin-eosin staining demonstrated necrosis in ablated zones and increasing surrounding fibra bands in group I and group II, while increasing expression of Ki 67, Bcl-2, CD54, and MMP-2 in transient zones was detected using immunohistochemistry in both groups (P > .05). NADPH-d and SDH staining showed dramatic decrease of enzyme activities in ablated zones immediately after ablation, while residual viable tissues in ablated zones of group II were less than those of group I (P < .05).

Conclusion

Contrast agent SonoVue enables improvement of HIFU ablation on rabbit VX2 liver tumors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

FIG. 1
FIG. 2
FIG. 3
FIG. 4
FIG. 5
FIG. 6

Similar content being viewed by others

References

  1. Leslie TA, Kennedy JE. High intensity focused ultrasound in the treatment of abdominal and gynaecological diseases. Int J Hyperthermia. 2007;23:173–82.

    Article  PubMed  CAS  Google Scholar 

  2. Illing RO, Kennedy JE, Wu F, ter Haar GR, Protheroe AS, Friend PJ, et al. The safety and feasibility of extracorporeal high-intensity focused ultrasound (HIFU) for the treatment of liver and kidney tumours in a Western population. Br J Cancer. 2005;93:890–5.

    Article  PubMed  CAS  Google Scholar 

  3. Li CX, Xu GL, Jiang ZY, Li JJ, Luo GY, Shan HB, et al. Analysis of clinical effect of high-intensity focused ultrasound on liver cancer. World J Gastroenterol. 2004;10:2201–4.

    PubMed  Google Scholar 

  4. Kennedy JE, Ter Haar GR, Cranston D. High intensity focused ultrasound: surgery of the future? Br J Radiol. 2003;76:590–9.

    Article  PubMed  CAS  Google Scholar 

  5. Haar GT, Coussios C. High intensity focused ultrasound: physical principles and devices. Int J Hyperthermia. 2007;23:89–104.

    Article  PubMed  Google Scholar 

  6. Rabkin BA, Zderic V, Vaezy S. Hyperecho in ultrasound images of HIFU therapy: involvement of cavitation. Ultrasound Med Biol. 2005;31:947–56.

    Article  PubMed  Google Scholar 

  7. Feng F, Mal A, Kabo M, Wang JC, Bar-Cohen Y. The mechanical and thermal effects of focused ultrasound in a model biological material. J Acoust Soc Am. 2005;117:2347–55.

    Article  PubMed  Google Scholar 

  8. Murat FJ, Poissonnier L, Pasticier G, Gelet A. High-intensity focused ultrasound (HIFU) for prostate cancer. Cancer Control. 2007;14:244–9.

    PubMed  Google Scholar 

  9. Li YY, Sha WH, Zhou YJ, Nie YQ. Short and long term efficacy of high intensity focused ultrasound therapy for advanced hepatocellular carcinoma. J Gastroenterol Hepatol. 2007;22:2148–54.

    Article  PubMed  Google Scholar 

  10. Wu F, Wang ZB, Chen WZ, Zhu H, Bai J, Zou JZ, et al. Extracorporeal high intensity focused ultrasound ablation in the treatment of patients with large hepatocellular carcinoma. Ann Surg Oncol. 2004;11:1061–9.

    Article  PubMed  Google Scholar 

  11. Li JJ, Xu GL, Gu MF, Luo GY, Rong Z, Wu PH, et al. Complications of high intensity focused ultrasound in patients with recurrent and metastatic abdominal tumors. World J Gastroenterol. 2007;21:2747–51.

    Google Scholar 

  12. Ahmed M, Goldberg SN. Thermal ablation therapy for hepatocellular carcinoma. J Vasc Interv Radiol. 2002;13:S231–44.

    Article  PubMed  Google Scholar 

  13. Melodelima D, N’djin W, Parmentier H, Rivoire M, Chapelon J.-Y. Using a toroid transducer for thermal ablation by high-intensity-focused ultrasound increases the coagulated volume. J Acoust Soc Am. 2008;123:2995.

    Article  Google Scholar 

  14. Luo W, Zhou X, Tian X, Ren X, Zheng M, Gu K, et al. Enhancement of ultrasound contrast agent in high-intensity focused ultrasound ablation. Adv Ther. 2006;23:861–8.

    Article  PubMed  Google Scholar 

  15. Cheng SQ, Zhou XD, Tang ZY, Yu Y, Bao SS, Qian DC. Iodized oil enhances the thermal effect of high-intensity focused ultrasound on ablating experimental liver cancer. J Cancer Res. Clin Oncol. 1997;123:639–44.

    Article  PubMed  CAS  Google Scholar 

  16. Kessel D, Jeffers R, Fowlkes JB, et al. Porphyrin-induced enhancement of ultrasound cytotoxicity. Int J Radiat Biol. 1994;66: 221-8.

    Article  PubMed  CAS  Google Scholar 

  17. Luo W, Zhou X, Ren X, Zheng M, Zhang J, He G. Enhancing effects of SonoVue, a microbubble sonographic contrast agent, on high-intensity focused ultrasound ablation in rabbit livers in vivo. J Ultrasound Med. 2007;26:469–76.

    PubMed  Google Scholar 

  18. Yu T, Xiong S, Mason TJ, Wang Z. The use of a micro-bubble agent to enhance rabbit liver destruction using high intensity focused ultrasound. Ultrason Sonochem. 2006;13:143–9.

    Article  PubMed  CAS  Google Scholar 

  19. Kaneko Y, Maruyama T, Takegami K, Watanabe T, Mitsui H, Hanajiri K, et al. Use of a microbubble agent to increase the effects of high intensity focused ultrasound on liver tissue. Eur Radiol. 2005;15:1415–20.

    Article  PubMed  Google Scholar 

  20. Luo W, Zhou X, He G, Li Q, Zheng X, Fan Z, et al. Ablation of high intensity focused ultrasound combined with SonoVue on rabbit VX2 liver tumors: Assessment with conventional gray-scale US, conventional color/power Doppler US, contrast-enhanced color Doppler US, and contrast-enhanced pulse-inversion harmonic US. Ann Surg Oncol. 2008;15:2943–53.

    Article  PubMed  Google Scholar 

  21. Wang Z, Bai J, Li F, Du Y, Wen S, Hu K, et al. Study of a “biological focal region” of high-intensity focused ultrasound. Ultrasound Med Biol. 2003;29:749–54.

    Article  PubMed  Google Scholar 

  22. Wu F, Wang ZB, Cao YD, Xu ZL, Zhou Q, Zhu H, et al. Heat fixation of cancer cells ablated with high-intensity-focused ultrasound in patients with breast cancer. Am J Surg. 2006;192:179–84.

    Article  PubMed  Google Scholar 

  23. Nikfarjam M, Muralidharan V, Malcontenti-Wilson C, McLaren W, Christophi C. Impact of blood flow occlusion on liver necrosis following thermal ablation. ANZ J Surg. 2006;76:84–91.

    Article  PubMed  Google Scholar 

  24. Ozaki T, Tabuse K, Tsuji T, Nakamura Y, Kakudo K, Mori I. Microwave cell death: Enzyme histochemical evaluation for metastatic carcinoma of the liver. Pathol Int. 2003;53:837–45.

    Article  PubMed  Google Scholar 

  25. Yamashiki N, Kato T, Bejarano PA, Berho M, Montalvo B, Shebert RT, et al. Histopathological changes after microwave coagulation therapy for patients with hepatocellular carcinoma: review of 15 explanted livers. Am J Gastroenterol. 2003;98:2052–9.

    Article  PubMed  Google Scholar 

  26. Frich L, Bjørnland K, Pettersen S, Clausen OP, Gladhaug IP. Increased activity of matrix metalloproteinase 2 and 9 after hepatic radiofrequency ablation. J Surg Res. 2006;135:297–304.

    Article  PubMed  CAS  Google Scholar 

  27. Luo W, Zhou X, Zhang J, Qian Y, Zheng M, Yu M, et al. Analysis of apoptosis and cell proliferation after high intensity-focused ultrasound ablation combined with microbubbles in rabbit livers. Eur J Gastroenterol Hepatol. 2007;19:962–8.

    Article  PubMed  Google Scholar 

  28. Rai R, Richardson C, Flecknell P, Robertson H, Burt A, Manas DM. Study of apoptosis and heat shock protein (HSP) expression in hepatocytes following radiofrequency ablation (RFA). J Surg Res. 2005;129:147–51.

    Article  PubMed  CAS  Google Scholar 

  29. Nikfarjam M, Muralidharan V, Christophi C. Altered growth patterns of colorectal liver metastases after thermal ablation. Surgery. 2006;139:73–81.

    Article  PubMed  Google Scholar 

  30. Karavias DD, Tsamandas AC, Tepetes K, Kritikos N, Kourelis T, Ravazoula P, et al. BCL-2 and BAX expression and cell proliferation, after partial hepatectomy with and without ischemia, on cholestatic liver in rats: an experimental study. J Surg Res. 2003;110:399–408.

    Article  PubMed  CAS  Google Scholar 

  31. Scholzen T, Gerdes J. The Ki-67 protein: from the known and the unknown. J Cell Physiol. 2000;182:311–22.

    Article  PubMed  CAS  Google Scholar 

  32. Nelson AR, Fingleton B, Rothenberg ML, Matrisian LM. Matrix metalloproteinases: Biologic activity and clinical implications. J Clin Oncol. 2000;18:1135–49.

    PubMed  CAS  Google Scholar 

  33. Qin LX, Tang ZY. Recent progress in predictive biomarkers for metastatic recurrence of human hepatocellular carcinoma: a review of the literature. J Cancer Res Clin Oncol. 2004;130:497–513.

    Article  PubMed  CAS  Google Scholar 

  34. Zhou XD. Recurrence and metastasis of hepatocellular carcinoma: progress and prospects. Hepatobiliary Pancreat Dis Int. 2002;1:35–41.

    PubMed  Google Scholar 

  35. Tran BC, Seo J, Hall TL, Fowlkes JB, Cain CA. Effects of contrast agent infusion rates on thresholds for tissue damage produced by single exposures of high-intensity ultrasound. IEEE Trans Ultrason Ferroelectr Freq Control. 2005;52:1121–30.

    Article  PubMed  Google Scholar 

  36. Takegami K, Kaneko Y, Watanabe T, Maruyama T, Matsumoto Y, Nagawa H. Erythrocytes, as well as microbubble contrast agents, are important factors in improving thermal and therapeutic effects of high-intensity focused ultrasound. Ultrasound Med Biol. 2005;31:385–90.

    Article  PubMed  Google Scholar 

  37. Miller DL, Li P, Dou C, Gordon D, Edwards CA, Armstrong WF. Influence of contrast agent dose and ultrasound exposure on cardiomyocyte injury induced by myocardial contrast echocardiography in rats. Radiology. 2005;237:137–43.

    Article  PubMed  Google Scholar 

Download references

Acknowledgment

The authors sincerely thank Jianguo He, Haiying Qin, Li Wang (Department of Ultrasound in Xijing Hospital, China), and Dr. Zhiyong Fan (Department of Hepatobiliary Surgery in Xijing Hospital, China) for the excellent assistance in HIFU performance, surgical operation, and animal care.

Author information

Authors and Affiliations

  1. Department of Ultrasound, Xijing Hospital, Fourth Military Medical University, Shaanxi, China

    Wen Luo MD, Xiaodong Zhou MD, Ming Yu MD, Guangbin He MD, Xiaoying Zheng MD, Qiuyang Li MD, Qing Liu MD, Zenghui Han MD, Jun Zhang MD & Yunqiu Qian MD

Authors
  1. Wen Luo MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaodong Zhou MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ming Yu MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Guangbin He MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiaoying Zheng MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Qiuyang Li MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Qing Liu MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zenghui Han MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jun Zhang MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yunqiu Qian MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xiaodong Zhou MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Luo, W., Zhou, X., Yu, M. et al. Ablation of High-Intensity Focused Ultrasound Assisted with SonoVue on Rabbit VX2 Liver Tumors: Sequential Findings with Histopathology, Immunohistochemistry, and Enzyme Histochemistry. Ann Surg Oncol 16, 2359–2368 (2009). https://doi.org/10.1245/s10434-009-0419-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-009-0419-3

Keywords

Search

Navigation