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Using microbubbles to increase the destruction of liver tumors by high-intensity focused ultrasound

Research Project

Project/Area Number 15390228
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionThe University of Tokyo

Principal Investigator

MARUYAMA Toshiyuki  The University of Tokyo, Graduate School of Medicine, Lecturer, 大学院・医学系研究科, 講師 (30219571)

Co-Investigator(Kenkyū-buntansha) MATSUMOTO Yoichiro  The University of Tokyo, Graduate School of Engineering, Professor, 大学院・工学系研究科, 教授 (60111473)
TAKAGI Shu  The University of Tokyo, Graduate School of Engineering, Associate Professor, 大学院・工学系研究科, 助教授 (30272371)
KOIKE Kazuhiko  The University of Tokyo, Graduate School of Medicine, Lecturer Professor, 大学院・医学系研究科, 教授 (80240703)
NANGAKU Masaomi  The University of Tokyo, Graduate School of Medicine, Research Associate, 医学部附属病院, 助手 (90311620)
UMEMURA Shinichiro  Hitachi Kenkyuusho, Chief Researcher, 中央研究所, 主管研究員
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 2004: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2003: ¥8,400,000 (Direct Cost: ¥8,400,000)
KeywordsHIFU / microbubble / tumor necrosis / development of liver tumors / coagulated volume / 焼灼体積 / 経門脈的投与 / 肝臓癌モデルrat
Research Abstract

We studied the possibility of using high-intensity focused ultrasound (HIFU) together with a microbubble agent to treat hepatocellular carcinoma.
The transducer for HIFU was 40 mm in diameter ; it produced a continuous 2.18-MHz wave for 30 seconds.
The spatial peak temporal average intensity was 600 W/cm2.
Development of liver tumors in rats was induced by administration of Dimethylnitrosamin (100 ppm).
Rats with liver tumors were anesthetized, underwent laparotomy, and were given the microbubble agent Levovist or saline intravenously.
After 60 seconds of Levovist or saline injection, the liver was exposed to HIFU for 30 seconds. Immediately after HIFU exposure, ultrasound images of the HIFU area were evaluated. Then the liver was excised and the volume of coagulated tissue was measured.
The mean volume of hyperechoic areas after HIFU were as follows (mm3, Levovist vs. saline : 355.3 ± 180.7 vs. 47.4 ± 35.6, p < 0.001, n=13).
The volumes of liver tissue coagulated by HIFU were as follows (mm3, Levovist vs. saline : 275.3 ± 120.0 vs. 60.1 ± 23.6, p < 0.001, n=13).
On microscopic examination of areas exposed to HIFU, implosion cysts were seen, and many cancer cells were found to have been disrupted or destroyed completely.
Some tumor cells had been distorted by loss of cell membranes or nuclei.
In conclusion, the microbubble agent Levovist, by increasing the effect of HIFU, could also have a direct role in anti-cancer therapy.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (32 results)

All 2005 2004 2003 Other

All Journal Article (25 results) Book (1 results) Publications (6 results)

  • [Journal Article] Use of a microbubble agent to increase the effects of high intensity focused ultrasound on liver tissue.2005

    • Author(s)
      Kaneko Y, Maruyama T, et al.
    • Journal Title

      European Radiology 15

      Pages: 1415-1420

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Erythrocytes, as well as microbubble contrast agents, are important factors in improving thermal and therapeutic effects of high-intensity focused ultrasound.2005

    • Author(s)
      Takegami K, et al.
    • Journal Title

      Ultrasound in Medicine and Biology 31

      Pages: 385-390

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Comparison of Optison and MRX-133 microbubble contrast agent in improving heating and coagulation volume efficiency of high intensity focused ultrasound.2005

    • Author(s)
      Takegami K, et al.
    • Journal Title

      Radiology 237

      Pages: 132-136

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 18F-FDGPET for hepatocellular carcinoma presenting with portal vein thrombus.2005

    • Author(s)
      Hanajiri K, Mitsui H, Maruyama T, Kondo Y, Shiina S, Omata M, Nakagawa K
    • Journal Title

      Journal of Gastroenterology. 2005.40

      Pages: 1005-1006

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Use of a microbubble agent to increase the effects of high intensity focused ultrasound on liver tissue.2005

    • Author(s)
      Kaneko Y, Maruyama T, Takegami K, Watanabe T, Mitsui M, Hanajiri K, Nagawa H, Matsumoto Y.
    • Journal Title

      European Radiology 15

      Pages: 1415-1420

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Erythrocytes, as well as microbubble contrast agents, are important factors in improving thermal and therapeutic effects of high-intensity focused ultrasound.2005

    • Author(s)
      Takegami K, Kaneko K, Watanabe T, Maruyama T, Matsumoto Y, Nagawa H.
    • Journal Title

      Ultrasound in Medicine and Biology 31

      Pages: 385-390

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Comparison of Optison and MRX-133 microbubble contrast agent in improving heating and coagulation volume efficiency of high intensity focused ultrasound.2005

    • Author(s)
      Takegami K, Kaneko K, Watanabe T, Maruyama T, Matsumoto Y, Nagawa H.
    • Journal Title

      Radiology 237

      Pages: 132-136

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 18F-FDG PET for hepatocellular carcinoma presenting with portal vein thrombus.2005

    • Author(s)
      Hanajiri K, Mitsui H, Maruyama T, Kondo Y, Shiina S, Omata M, Nakagawa K.
    • Journal Title

      Journal of Gastroenterology. 40

      Pages: 1005-1006

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Use of a microbubble agent to increase the effect2005

    • Author(s)
      Kaneko Y
    • Journal Title

      European Radiology (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Comparison of Optison and MRX microbubble2005

    • Author(s)
      Takegami K
    • Journal Title

      Radiology (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Polyacrylamide gel containing egg white as new model for irradiation experiments using focused ultrasound.2004

    • Author(s)
      Takegami K, et al.
    • Journal Title

      Ultrasound in Medicine and Biology 30

      Pages: 1419-1422

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] hepatitis C virus infection and diabetes : direct involvement of the virus in the development of insulin resistance2004

    • Author(s)
      Shintani Y, Fujie H, Miyoshi H, Tsutsumi T, Tsukamoto K, Kimura S, Moriya K, Koike K
    • Journal Title

      Gastroenterology. 126

      Pages: 840-848

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Polyacrylamide gel containing egg white as new model for irradiation experiments using focused ultrasound.2004

    • Author(s)
      Takegami K, Kaneko K, Watanabe T, Maruyama T, Matsumoto Y, Nagawa H.
    • Journal Title

      Ultrasound in Medicine and Biology 30

      Pages: 1419-1422

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hepatitis C virus infection and diabetes : direct involvement of the virus in the development of insulin resistance.2004

    • Author(s)
      Shintani Y.Fujie H.Miyoshi H.Tsutsumi T.Tsukamoto K.Kimura S.Moriya K.Koike K.
    • Journal Title

      Gastroenterology 126

      Pages: 840-848

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Polyacrylamide gel containing egg white2004

    • Author(s)
      Takegami K
    • Journal Title

      Ultrasound in Med.and Biology 30

      Pages: 531-533

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Mechanism of tubulointerstitial injury2004

    • Author(s)
      Nangaku M
    • Journal Title

      Internal Medicine 43

      Pages: 9-17

    • Related Report
      2004 Annual Research Report
  • [Journal Article] HCV infection and diabetes2004

    • Author(s)
      Shintani Y
    • Journal Title

      Gastroenterology 126

      Pages: 840-848

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Anti-HBs antibodies produced after liver transplantation : from the donor or the recipient?2003

    • Author(s)
      Maruyama T, et al.
    • Journal Title

      Hepatology 38

      Pages: 271-72

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Clinical efficacy and toxicity of gefitinib in patients with lung cancer.2003

    • Author(s)
      Mitsui H, et al.
    • Journal Title

      Lancet 361

      Pages: 1993-1993

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] hepatitis C virus core protein activates ERK and p38 MAPK in cooperation with ethanolin transgenic mice.2003

    • Author(s)
      Tsutsumi T, Suzuki T, Moriya K, Shintani Y, Fujie H, Miyoshi H, Matsuura Y, Koike K, Miyamura T.
    • Journal Title

      Hepatology. 38

      Pages: 820-828

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Anti-HBs antibodies produced after liver transplantation : from the donor or the recipient?2003

    • Author(s)
      Maruyama T., Mitsui H., Hanajir Ki, Sugawara Y, Imamura H, Makuuchi M.
    • Journal Title

      Hepatology 38

      Pages: 271-272

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The effect of microbubbles as a heat transducer.2003

    • Author(s)
      Kaneko Y., Higaki T., Maruyama T., Matsumoto Y.
    • Journal Title

      In Proceedings of 3rd International Symposium on Therapeutic Ultrasound; Lyon, France

      Pages: 55-60

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Clinical efficacy and toxicity of gefitinib in patients with lung cancer.2003

    • Author(s)
      Mitsui H, Nakajima J, Maruyama T, Hanajiri K, Omata M.
    • Journal Title

      Lancet 361

      Pages: 1993-1993

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hepatitis C virus core protein activates ERK and p38 MAPK in cooperation with ethanol in transgenic mice.2003

    • Author(s)
      Tsutsumi T.Suzuki T.Moriya K.Shintani Y.Fujie H.Miyoshi H.Matsuura Y.Koike K.Miyamura T.
    • Journal Title

      Hepatology 38

      Pages: 820-828

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Complement regulatory proteins2003

    • Author(s)
      Nangaku M
    • Journal Title

      J.American Society of Nephrology 14

      Pages: 2411-2413

    • Related Report
      2004 Annual Research Report
  • [Book] In Proceedings of 3rd International Symposium on Therapeutic Ultrasound2005

    • Author(s)
      Kaneko Y, Maruyama T, et al.
    • Publisher
      The effect of microbubbles as a heat transducer.
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Maruyama T.: "Anti-HBs antibodies produced after liver transplantation"Hepatology. 38. 271-272 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Mitsui H, Mruyama T: "Clinical efficacy and toxicity of gefitinib in patients"Lancet. 361. 1993-1993 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nangaku M: "Complement regulatory proteins"J.American Society Nephrology. 14. 2411-2413 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nangaku M: "Anti-hypertensive agents inhibit in vivo the formation"J.American Society Nephrology. 14. 1212-1222 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tsutsumi T, Koike K: "Hepatitis C virus core protein activates ERK and p38 MARK"Hepatology. 38. 820-828 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Moriishi K, Koike K: "Protease activator PA28γ-dependent nuclear retention"J.Virology. 77. 10237-10249 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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