Skip to main content
SpringerLink
Log in

Bioeffects of Ultrasound and Its Therapeutic Application

  • Living reference work entry
  • First Online:
Handbook of Ultrasonics and Sonochemistry

  • 422 Accesses

Abstract

Ultrasound has been safely utilized in the medical field for a long time, and its application range is still growing widely nowadays.

Analyses of interactions between ultrasound and aqueous solution were studied for a long time. Free radical formation, an important chemical effect of ultrasound, which causes a major impact on bioeffects was discovered more than 30 years ago. However, the bioeffects caused by ultrasound cannot be attributed only to free radical formation. They are interactions between the living body and a wide variety of very complex effects caused by ultrasound. Thus, one would have to say that mechanism underlying the ultrasound bioeffects is a long way from full clarification. However, analyzing how the living body could respond to ultrasound at a biomolecular level has become possible. Obtained results out of such analyses have advanced therapeutic ultrasound through its development, improvement, and assurance of safety. Thus, ultrasound in the medical field will be more and more dispensable from this time forward.

In this chapter, first we take a look at physical and chemical effects of ultrasound, which may provide some influence to the ultrasound bioeffects. Then, we move to ultrasound bioeffects and responses of cells and living tissues to ultrasound, particularly we review them at a biomolecular level. Later on, we discuss the therapeutic applications of ultrasound, including HIFU and LIPUS, which have already been applied clinically for cancer therapy and bone fracture healing, respectively. In addition to those, we also describe the latest research findings such as ultrasound-mediated gene therapy and drug delivery systems.

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

Access this chapter

Log in via an institution

Institutional subscriptions

References

  1. Makino M, Mossoba MM, Riesz P (1983) Chemical effects of ultrasound on aqueous solutions. Formation of hydroxyl radicals and hydrogen atoms. J Phys Chem 87:1369–1377

    Article  CAS  Google Scholar 

  2. Kondo T, Riesz P (1996) Sonolysis of ubiquinone in aqueous solutions. An EPR spin-trapping study. Int J Radiat Biol 69:113–121

    Article  CAS  Google Scholar 

  3. Riesz P, Kondo T (1992) Free radical formation induced by ultrasound and its biological implications. Free Radic Biol Med 13:247–270

    Article  CAS  Google Scholar 

  4. Draeger A, Monastyrskaya K, Babiychuk EB (2011) Plasma membrane repair and cellular damage control: the annexin survival kit. Biochem Pharmacol 81:703–712

    Article  CAS  Google Scholar 

  5. Fechheimer M, Denny C, Murphy RF, Taylor DL (1986) Measurement of cytoplasmic pH in Dictyostelium discoideum by using a new method for introducing macromolecules into living cells. Eur J Cell Biol 40:242–247

    CAS  Google Scholar 

  6. Fechheimer M, Boylan JF, Paker S, Sisken JE, Patel GL, Zimmer SG (1987) Transfection of mammalian cells with plasmid DNA by scrape loading and sonication loading. Proc Natl Acad Sci U S A 84:8463–8467

    Article  CAS  Google Scholar 

  7. Furusawa Y, Fujiwara Y, Campbell P, Zhao QL, Ogawa R, Hassan MA, Tabuchi Y, Takasaki I, Takahashi A, Kondo T (2012) DNA double-strand breaks induced by cavitational mechanical effects of ultrasound in cancer cell lines. PLoS One 7:e29012

    Article  CAS  Google Scholar 

  8. Ashush H, Rozenszajn LA, Blass M, Barda-Saad M, Azimov D, Radnay J, Zipori D, Rosenschein U (2000) Apoptosis induction of human myeloid leukemic cells by ultrasound exposure. Cancer Res 60:1014–1020

    CAS  Google Scholar 

  9. Lagneaux L, de Meulenaer EC, Delforge A, Dejeneffe M, Massy M, Moerman C, Hannecart B, Canivet Y, Lepeltier MF, Bron D (2002) Ultrasonic low-energy treatment: a novel approach to induce apoptosis in human leukemic cells. Exp Hematol 30:1293–1301

    Article  Google Scholar 

  10. Honda H, Kondo T, Zhao QL, Feril LB Jr, Kitagawa H (2004) Role of intracellular calcium ions and reactive oxygen species in apoptosis induced by ultrasound. Ultrasound Med Biol 30:683–692

    Article  Google Scholar 

  11. Tabuchi Y, Kondo T, Ogawa R, Mori H (2002) DNA microarray analyses of genes elicited by ultrasound in human U937 cells. Biochem Biophys Res Commun 290:498–503

    Article  CAS  Google Scholar 

  12. Tabuchi Y, Ando H, Takasaki I, Feril LB Jr, Zhao QL, Ogawa R, Kudo N, Tachibana K, Kondo T (2007) Identification of genes responsive to low intensity pulsed ultrasound in a human leukemia cell line Molt- 4. Cancer Lett 246:149–156

    Article  CAS  Google Scholar 

  13. Furusawa Y, Zhao QL, Hassan MA, Tabuchi Y, Takasaki I, Wada S, Kondo T (2010) Ultrasound-induced apoptosis in the presence of sonazoid and associated alterations in gene expression levels: a possible therapeutic application. Cancer Lett 288:107–115

    Article  CAS  Google Scholar 

  14. Machado CB, de Albuquerque Pereira WC, Talmant M, Padilla F, Laugier P (2010) Computational evaluation of the compositional factors in fracture healing affecting ultrasound axial transmission measurements. Ultrasound Med Biol 36:1314–1326

    Article  Google Scholar 

  15. Kruse DE, Mackanos MA, O’Connell-Rodwell CE, Contag CH, Ferrara KW (2008) Short-duration-focused ultrasound stimulation of Hsp70 expression in vivo. Phys Med Biol 53:3641–3660

    Article  CAS  Google Scholar 

  16. Gerstenfeld LC, Cullinane DM, Barnes GL, Graves DT, Einhorn TA (2003) Fracture healing as a post-natal developmental process: molecular, spatial, and temporal aspects of its regulation. J Cell Biochem 88:873–884

    Article  CAS  Google Scholar 

  17. Kusano K, Miyaura C, Inada M, Tamura T, Ito A, Nagase H, Kamoi K, Suda T (1998) Regulation of matrix metalloproteinases (MMP-2, -3, -9, and -13) by interleukin-1 and interleukin-6 in mouse calvaria: association of MMP induction with bone resorption. Endocrinology 139:1338–1345

    CAS  Google Scholar 

  18. Whitney NP, Lamb AC, Louw TM, Subramanian A (2012) Integrin-mediated mechanotransduction pathway of low-intensity continuous ultrasound in human chondrocytes. Ultrasound Med Biol 38:1734–1743

    Article  Google Scholar 

  19. Takeuchi R, Ryo A, Komitsu N, Mikuni-Takagaki Y, Fukui A, Takagi Y, Shiraishi T, Morishita S, Yamazaki Y, Kumagai K, Aoki I, Saito T (2008) Low-intensity pulsed ultrasound activates the phosphatidylinositol 3 kinase/Akt pathway and stimulates the growth of chondrocytes in three-dimensional cultures: a basic science study. Arthritis Res Ther 10:R77

    Article  Google Scholar 

  20. Doan N, Reher P, Meghji S, Harris M (1999) In vitro effects of therapeutic ultrasound on cell proliferation, protein synthesis, and cytokine production by human fibroblasts, osteoblasts, and monocytes. J Oral Maxillofac Surg 57:409–419

    Article  CAS  Google Scholar 

  21. Kumagai K, Takeuchi R, Ishikawa H, Yamaguchi Y, Fujisawa T, Kuniya T, Takagawa S, Muschler GF, Saito T (2012) Low-intensity pulsed ultrasound accelerates fracture healing by stimulation of recruitment of both local and circulating osteogenic progenitors. J Orthop Res 30:1516–1521

    Article  Google Scholar 

  22. Wang FS, Kuo YR, Wang CJ, Yang KD, Chang PR, Huang YT, Huang HC, Sun YC, Yang YJ, Chen YJ (2004) Nitric oxide mediates ultrasound-induced hypoxia-inducible factor-1alpha activation and vascular endothelial growth factor-A expression in human osteoblasts. Bone 35:114–123

    Article  CAS  Google Scholar 

  23. Naruse K, Miyauchi A, Itoman M, Mikuni-Takagaki Y (2003) Distinct anabolic response of osteoblast to low-intensity pulsed ultrasound. J Bone Miner Res 18:360–369

    Article  CAS  Google Scholar 

  24. Suzuki A, Takayama T, Suzuki N, Sato M, Fukuda T, Ito K (2009) Daily low- intensity pulsed ultrasound-mediated osteogenic differentiation in rat osteoblasts. Acta Biochim Biophys Sin (Shanghai) 41:108–115

    Article  CAS  Google Scholar 

  25. Sena K, Leven RM, Mazhar K, Sumner DR, Virdi AS (2005) Early gene response to low-intensity pulsed ultrasound in rat osteoblastic cells. Ultrasound Med Biol 31:703–708

    Article  Google Scholar 

  26. Unsworth J, Kaneez S, Harris S, Ridgway J, Fenwick S, Chenery D, Harrison A (2007) Pulsed low intensity ultrasound enhances mineralisation in preosteoblast cells. Ultrasound Med Biol 33:1468–1474

    Article  Google Scholar 

  27. Lee HJ, Choi BH, Min BH, Son YS, Park SR (2006) Low-intensity ultrasound stimulation enhances chondrogenic differentiation in alginate culture of mesenchymal stem cells. Artif Organs 30:707–715

    Article  CAS  Google Scholar 

  28. Ren I, Yang Z, Song J, Wang Z, Deng F, Li W (2013) Involvement of p38 MAPK pathway in low intensity pulsed ultrasound induced osteogenic differentiation of human periodontal ligament cells. Ultrasonics 53:686–690

    Article  CAS  Google Scholar 

  29. Tabuchi Y, Sugahara Y, Ikegami M, Suzuki N, Kitamura K, Kondo T (2013) Genes responsive to low- intensity pulsed ultrasound in MC3T3-E1 preosteoblast cells. Int J Mol Sci 14:22721–22740

    Article  Google Scholar 

  30. Vardi Y, Appel B, Jacob G, Massarwi O, Gruenwald I (2010) Can low-intensity extracorporeal shockwave therapy improve erectile function? A 6-month follow-up pilot study in patients with organic erectile dysfunction. Eur Urol 58:243–248

    Article  Google Scholar 

  31. Gruenwald I, Appel B, Vardi Y (2012) Low-intensity extracorporeal shock wave therapy – a novel effective treatment for erectile dysfunction in severe ED patients who respond poorly to PDE5 inhibitor therapy. J Sex Med 9:259–264

    Article  Google Scholar 

  32. Vardi Y, Appel B, Kilchevsky A, Gruenwald I (2012) Does low intensity extracorporeal shock wave therapy have a physiological effect on erectile function? Short-term results of a randomized, double-blind, sham controlled study. J Urol 187:1769–1775

    Article  Google Scholar 

  33. Yee CH, Chan ES, Hou SS, Ng CF (2014) Extracorporeal shockwave therapy in the treatment of erectile dysfunction: a prospective, randomized, double-blinded, placebo controlled study. Int J Urol 21:1041–1045

    Article  Google Scholar 

  34. Nishida T, Shimokawa H, Oi K, Tatewaki H, Uwatoku T, Abe K, Matsumoto Y, Kajihara N, Eto M, Matsuda T, Yasui H, Takeshita A, Sunagawa K (2004) Extracorporeal cardiac shock wave therapy markedly ameliorates ischemia-induced myocardial dysfunction in pigs in vivo. Circulation 110:3055–3061

    Article  Google Scholar 

  35. Qiu X, Lin G, Xin Z, Ferretti L, Zhang H, Lue TF, Lin CS (2013) Effects of low-energy shockwave therapy on the erectile function and tissue of a diabetic rat model. J Sex Med 10:738–746

    Article  CAS  Google Scholar 

  36. Ogawa R, Watanabe A, Moriia A (2015) Ultrasound up-regulates expression of heme oxygenase-1 gene in endothelial cells. J Med Ultrason 42:467–475

    Google Scholar 

  37. Ogawa R, Kagiya G, Feril LB Jr, Nakaya N, Nozaki T, Fuse H, Kondo T (2004) Ultrasound mediated intravesical transfection enhanced by treatment with lidocaine or heat. J Urol 172:1469–1473

    Article  CAS  Google Scholar 

  38. Anwer K, Kao G, Proctor B, Anscombe I, Florack V, Earls R, Wilson E, McCreery T, Unger E, Rolland A, Sullivan SM (2000) Ultrasound enhancement of cationic lipid-mediated gene transfer to primary tumors following systemic administration. Gene Ther 7:1833–1839

    Article  CAS  Google Scholar 

  39. Wang DS, Panje C, Pysz MA, Paulmurugan R, Rosenberg J, Gambhir SS, Schneider M, Willmann JK (2012) Cationic versus neutral microbubbles for ultrasound-mediated gene delivery in cancer. Radiology 264:721–732

    Article  Google Scholar 

  40. Suzuki R, Takizawa T, Negishi Y, Utoguchi N, Maruyama K (2008) Effective gene delivery with novel liposomal bubbles and ultrasonic destruction technology. Int J Pharm 354:49–55

    Article  CAS  Google Scholar 

  41. Yuan QY, Huang J, Chu BC, Li XS, Si LY (2011) A visible, targeted high-efficiency gene delivery and transfection strategy. BMC Biotechnol 11:56

    Article  CAS  Google Scholar 

  42. Negishi Y, Hamano N, Tsunoda Y, Oda Y, Choijamts B, Endo-Takahashi Y, Omata D, Suzuki R, Maruyama K, Nomizu M, Emoto M, Aramaki Y (2013) AG73-modified bubble liposomes for targeted ultrasound imaging of tumor neovasculature. Biomaterials 34:501–507

    Article  CAS  Google Scholar 

  43. Negishi Y, Tsunoda Y, Hamano N, Omata D, Endo-Takahashi Y, Suzuki R, Maruyama K, Nomizu M, Aramaki Y (2013) Ultrasound-mediated gene delivery systems by AG73-modified bubble liposomes. Biopolymers 100:402–407

    Article  CAS  Google Scholar 

  44. Madio DP, van Gelderen P, DesPres D, Olson AW, de Zwart JA, Fawcett TW, Holbrook NJ, Mandel M, Moonen CT (1998) On the feasibility of MRI-guided focused ultrasound for local induction of gene expression. J Magn Reson Imaging 8:101–104

    Article  CAS  Google Scholar 

  45. Deckers R, Quesson B, Arsaut J, Eimer S, Couillaud F, Moonen CT (2009) Image-guided, noninvasive, spatiotemporal control of gene expression. Proc Natl Acad Sci U S A 106:1175–1180

    Article  CAS  Google Scholar 

  46. Braiden V, Ohtsuru A, Kawashita Y, Miki F, Sawada T, Ito M, Cao Y, Kaneda Y, Koji T, Yamashita S (2000) Eradication of breast cancer xenografts by hyperthermic suicide gene therapy under the control of the heat shock protein promoter. Hum Gene Ther 11:2453–2463

    Article  CAS  Google Scholar 

  47. Ogawa R, Lee SI, Izumi H, Kagiya G, Yohsida T, Watanabe A, Morii A, Kakutani S, Kondo T, Feril LB Jr, Ishimoto T (2009) Enhancement of artificial promoter activity by ultrasound-induced oxidative stress. Ultrason Sonochem 16:379–386

    Article  CAS  Google Scholar 

  48. Watanabe A, Kakutani S, Ogawa R, Lee SI, Yoshida T, Morii A, Kagiya G, Feril LB Jr, Fuse H, Kondo T (2009) Construction of artificial promoters sensitively responsive to sonication. J Med Ultrason 36:9–17

    Article  Google Scholar 

  49. Hassan MA, Campbell P, Kondo T (2010) The role of Ca2+ in ultrasound-elicited bioeffects: progress, perspectives and prospects. Drug Discov Today 15:892–906

    Article  CAS  Google Scholar 

  50. Rosenthal I, Sostaric JZ, Riesz P (2004) Sonodynamic therapy- a review of the synergistic effects of drugs and ultrasound. Ultrason Sonochem 11:349–363

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan

    Ryohei Ogawa & Takashi Kondo

  2. Departments of Urology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan

    Akihiro Morii & Akihiko Watanabe

  3. Departments of Public Health, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan

    Zheng-Guo Cui

  4. Urology Department, Kurobe City Hospital, Kurobe, Japan

    Akihiro Morii

Authors
  1. Ryohei Ogawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akihiro Morii
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Akihiko Watanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zheng-Guo Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takashi Kondo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ryohei Ogawa .

Editor information

Editors and Affiliations

  1. School of Chemistry, The University of Melbourne, Melbourne, Victoria, Australia

    Muthupandian Ashokkumar

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media Singapore

About this entry

Cite this entry

Ogawa, R., Morii, A., Watanabe, A., Cui, ZG., Kondo, T. (2015). Bioeffects of Ultrasound and Its Therapeutic Application. In: Ashokkumar, M. (eds) Handbook of Ultrasonics and Sonochemistry. Springer, Singapore. https://doi.org/10.1007/978-981-287-470-2_25-1

Download citation

  • DOI: https://doi.org/10.1007/978-981-287-470-2_25-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Singapore

  • Online ISBN: 978-981-287-470-2

  • eBook Packages: Springer Reference Chemistry and Mat. ScienceReference Module Physical and Materials ScienceReference Module Chemistry, Materials and Physics

Publish with us

Policies and ethics

Search

Navigation