Skip to main content
Log in

Liver haemostasis using microbubble-enhanced ultrasound at a low acoustic intensity

  • Ultrasound
  • Published:
European Radiology Aims and scope Submit manuscript

Abstract

Objectives

To explore the haemostatic effects of microbubble-enhanced ultrasound (MEUS) at a very low acoustic intensity on the bleeding liver of rabbits.

Methods

Liver incisions made on 20 rabbits were treated with a pulsed therapeutic ultrasound transducer. The transducer was operated at 831 KHz with an acoustic intensity of 0.4 W/cm2. The treatment was coordinated with intravenous injection of microbubbles. Ultrasound only and sham treatment served as the controls. Visual bleeding score and 10-min bleeding volume were evaluated for haemostatic efficacy. Contrast-enhanced ultrasound (CEUS) was performed to assess the liver perfusion. Nine treated livers were harvested for acute histological examination.

Results

Regarding the bleeding incisions made on rabbit livers, the haemorrhage stopped immediately after 2 min of MEUS treatment but bleeding continued in the controls treated by ultrasound or microbubble injection alone. The bleeding scores and the 10-min haemorrhagic volumes dropped significantly in the MEUS group compared with those of the controls (p < 0.01). The mechanism of MEUS haemostasis appears to involve the extensive swelling of hepatocytes and the haemorrhage of the portal area, which formed a joint compression on the regional liver circulation.

Conclusions

Low acoustic intensity MEUS might provide a novel method for liver haemostasis.

Key Points

This animal experiment demonstrates a novel method of controlling hepatic haemorrhage

The treatment uses therapeutic ultrasound during enhancement with intravenous microbubbles

This combined therapy was more effective than ultrasound or intravenous microbubbles alone

More work is required with larger animals before potential human trials.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Lim RC (1982) Injuries to the liver and extra ducts. In: Blaisedell FW, Trunkey DD (eds) Trauma Management. Thieme-Stratton Inc, New York, YW, pp 123–147

    Google Scholar 

  2. Moore EE (1984) Critical decisions in the management of hepatic trauma. Am J Surgery 148:712–716

    Article  CAS  Google Scholar 

  3. Beal SL (1996) Liver. In: Ivatury RR, Cayten CG (eds) The textbook of penetrating trauma. William & Wilkins, Baltimore. MD, pp 571–585

    Google Scholar 

  4. Beal SL (1990) Fatal Hepatic Hemorrhage: An Unresolved Problem in the Management of Complex Liver Injuries. J Trauma 30:163–169

    Article  PubMed  CAS  Google Scholar 

  5. Wadia Y, Xie H, Kajitani M, Gregory K, Prahl S (2000) Liver repair and hemorrhage control using laser soldering of liquid albumin in a porcine model. Lasers Surg Med 27:319–328

    Article  PubMed  CAS  Google Scholar 

  6. Cue JI, Cryer HG, Miller FB (1990) Packing and planned reexploration for hepatic and retroperitoneal hemorrhage: Critical refinements of a useful technique. J Trauma 30:1007–1013

    Article  PubMed  CAS  Google Scholar 

  7. Vaezy S, Martin R, Schmiedl U et al (1997) Liver hemostasis using high-intensity focused ultrasound. Ultrasound Med Biol 23:3413–1420

    Article  Google Scholar 

  8. Vaezy S, Martin R, Mourad P, Crum LA (1999) Hemostasis using high intensity focused ultrasound. Eur J Ultrasound 9:79–87

    Article  PubMed  CAS  Google Scholar 

  9. Zderic V, Brayman AA, Sharar SR, Crum LA, Vaezy S (2006) Microbubble-enhanced hemorrhage control using high intensity focused ultrasound. Ultrasonics 45:113–120

    Article  PubMed  CAS  Google Scholar 

  10. Burgess S, Zderic V, Vaezy S (2007) Image-guided acoustic hemostasis for hemorrhage in the posterior liver. Ultrasound Med Biol 33:113–119

    Article  PubMed  Google Scholar 

  11. Prentice P, Cuschieri A, Dholakia K, Prausnitz M, Campbell P (2005) Membrane disruption by optically controlled microbubble cavitation. Nat Phys 1:107–110

    Article  CAS  Google Scholar 

  12. Miller DL, Gies RA (2000) The influence of ultrasound frequency and gas body composition on the contrast agent-mediated enhancement of vascular bioeffects in mouse intestine. Ultrasound Med Biol 26:307–313

    Article  PubMed  CAS  Google Scholar 

  13. Li P, Cao LQ, Dou CY et al (2003) Impact of Myocardial contrast echocardiography on vascular permeability: An in vivo dose response study of delivery mode, pressure amplitude and contrast dose. Ultrasound Med Biol 29:1341–1349

    Article  PubMed  Google Scholar 

  14. Li P, Armstrong WF, Miller DL (2004) Impact of myocardial contrast echocardiography on vascular permeability: comparison of three different contrast agents. Ultrasound Med Biol 30:83–91

    Article  PubMed  CAS  Google Scholar 

  15. Miller DL, Quddus J (2000) Diagnostic ultrasound activation of contrast agent gas bodies induces capillary rupture in mice. Proc Natl Acad Sci 97:10179–10184

    Article  PubMed  CAS  Google Scholar 

  16. Hwang JH, Brayman AA, Reidy MA et al (2005) Vascular effects induced by combined 1-MHz ultrasound and microbubble contrast agent treatments in vivo. Ultrasound Med Biol 31:553–564

    Article  PubMed  Google Scholar 

  17. Hwang JH, Tu J, Brayman AA et al (2006) Correlation between inertial cavitation dose and endothelial cell damage in vivo. Ultrasound Med Biol 32:1611–1619

    Article  PubMed  Google Scholar 

  18. Gao YJ, Liu Z, Zhao BZ, Gao SJ, Zhao Y, Liu J, Tan KB (2010) Obstruction of normal hepatic blood perfusion by microbubble-enhanced ultrasound cavitation. Chinese J Ultrasound Med 26:104–107

    Google Scholar 

  19. Liu P, Wang X, Zhou S, Hua X, Liu Z, Gao Y (2011) Effects of a novel ultrasound contrast agent with long persistence on right ventricular pressure: Comparison with SonoVue. Ultrasonics 51:210–214

    Article  PubMed  CAS  Google Scholar 

  20. Dubinsky TJ, Cuevas C, Dighe MK, Kolokythas O, Hwang JH (2008) High-Intensity Focused Ultrasound: Current Potential and Oncologic Applications. Am J Roentgenol 190:191–199

    Article  Google Scholar 

  21. Cosgrove D (2006) Ultrasound contrast agents: An overview. Eur J Radiol 60:324–330

    Article  PubMed  Google Scholar 

  22. Liu JB, Merton DA, Goldberg BB et al (2002) Contrast-enhanced two- and three- dimensional sonography for evaluation of intra-abdominal hemorrhage. J Ultrasound Med 21:161–169

    PubMed  Google Scholar 

  23. Ohl CD, Arora M, Ikink R, de Jong N, Versluis M, Delius M, Lohse D (2006) Sonoporation from jetting cavitation bubbles. Biophys J 91:4285–4295

    Article  PubMed  CAS  Google Scholar 

  24. Karshafian R, Bevan PD, Williams R, Samac S, Burns PN (2009) Sonoporation by ultrasound-activated microbubble contrast agents: effect of acoustic exposure parameters on cell membrane permeability and cell viability. Ultrasound Med Biol 35:847–860

    Article  PubMed  Google Scholar 

  25. Fan Z, Kumon RE, Park J, Deng CX (2010) Intracellular delivery and calcium transients generated in sonoporation facilitated by microbubbles. J Control Release 142:31–39

    Article  PubMed  CAS  Google Scholar 

  26. Kudo N, Okada K, Yamamoto K (2009) Sonoporation by single-shot pulsed ultrasound with microbubbles adjacent to cells. Biophys J 96:4866–4876

    Article  PubMed  CAS  Google Scholar 

  27. Park J, Fan Z, Deng CX (2011) Effects of shear stress cultivation on cell membrane disruption and intracellular calcium concentration in sonoporation of endothelial cells. J Biomech 44:164–169

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by Chongqing Science and Technology Project (No. 2011GGB044) and Natural Science Foundation of China (No. 30672014). We would like to thank Dr. Chunji Huang and Dr. Rong Zhang for their help on management. We also thank Dr. Zaigen Zhang for pathological examinations.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Zheng Liu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhao, X., Li, L., Zhao, H. et al. Liver haemostasis using microbubble-enhanced ultrasound at a low acoustic intensity. Eur Radiol 22, 379–386 (2012). https://doi.org/10.1007/s00330-011-2273-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00330-011-2273-5

Keywords

Navigation