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Development of Noninvasive Therapeutic Devices and Clinical Techniques for Treating Uterine Fibroid by Occluding Feeding Vessels Through Exposure to High Intensity Focused Ultrasound

Research Project

Project/Area Number 15200042
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Medical systems
Research InstitutionShowa Unviersity School of Medicine

Principal Investigator

OKAI Takashi  Showa Univ, School of Med, MD, Professor, 医学部, 教授 (40126016)

Co-Investigator(Kenkyū-buntansha) SAITO Hiroshi  Showa Univ, School of Med, MD, Associate, Professor, 医学部, 助教授 (30119193)
OTUKI Katufumi  Showa Univ, School of Med, MD, Associate, Professor, 医学部, 講師 (90276527)
ICHIZUKA Kiyotake  Showa Univ, School of Med, MD, Assistant Professor, 医学部, 助手 (00338451)
MATSUOKA Ryu  Showa Univ, School of Med, MD, Assistant Professor, 医学部, 助手 (20349111)
BABA Kazunori  Center for Maternal, Fetal, and Neonatal Medicine, Saitama Med, Sch, Professor, 総合医療センター, 教授 (30181035)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥41,860,000 (Direct Cost: ¥32,200,000、Indirect Cost: ¥9,660,000)
Fiscal Year 2005: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Fiscal Year 2004: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
Fiscal Year 2003: ¥21,840,000 (Direct Cost: ¥16,800,000、Indirect Cost: ¥5,040,000)
KeywordsHIFU / Rat femoral artery / ultrasound contrast media / feeding vessel occulusion / myoma uteri / non pregnant rabit / pregnant rabit / イヌ子宮動脈
Research Abstract

The ultimate purpose of this study is to develop a noninvasive therapy for gynecologic tumors, particularly uterine fibroid, using high intensity focused ultrasound (HIFU) to occlude the feeding vessels. The following basic studies comprise our first step toward that goal. First, we constructed a prototype HIFU transducer which has a resonant frequency of 3.2 MHz, in combination with an imaging probe that provides color Doppler imaging and Doppler velocimetry. HIFU was applied through the skin to deep femoral arteries in left thighs of Sprague-Dawley rats ; color images of the blood flow were used to aim the HIFU beam. Peak intensities used were 530, 1080, 2750 and 4300 W/cm2. The duration of each HIFU exposure was 5 seconds. Blood flow occlusion was accomplished by HIFU at an intensity of 4300 W/cm2, but the flow continued with the lower intensities. Peak systolic velocities (PSVs) of blood flow as measured by Doppler velocimetry increased in the arteries to which HIFU had been applie … More d at 1080 and 2750 W/cm2. The increase corresponded with HIFU intensity. Exposure to HIFU at 530 W/cm2 did not change the blood flow velocity. Histologic studies have demonstrated that exposure to HIFU at 2750 and 4300 W/cm2 leads to vacuolar degeneration and destruction of elastic fibers of the tunica media of the artery. Exposure at 1080 W/cm2 led to increased PSV, but did not induce histologic changes in the vessel wall. These results suggest that the response of the artery to HIFU varied with intensity. Vascular contraction without tissue degeneration occurred at low intensity; with increasing intensity, the tissue degeneration detectable in histology reduced the vascular diameter and, finally, at high intensity, the blood flow was occluded. In the second study, we hypothesized that the injection of ultrasound contrast agents into blood flow might decrease the minimal HIFU intensity for the occlusion. The study was conducted to investigate the effect of contrast agents on changes in blood flow and morphology of arteries by HIFU exposure. Five rats had injection of 60mg of Levovist, and other 5 had 0.5ml of saline as control. Blood flow occlusion was achieved in 0%(0/5), 60%(3/5), 100%(5/5) and 100%(5/5) of rats with administration of Levovist by HIFU exposure at the intensity of 530, 870, 1550 and 2750 W/cm2, respectively. In control rats, the rate of successful blood flow occlusion were 0%(0/5), 0%(0/5), 0%(0/5), and 80%(4/5), for each HIFU intensity. The H-E stain revealed a strong vacuolar degeneration in the tunica media and endothelium cells fall off the vessel wall in rats with Levovist. These results imply that the cavitation of contrast agents under HIFU exposure exerts significant effects on the endothelium of vessels, therefore, the, injection of contrast agents suggests the possibility for reduction of the intensity of HIFU to achieve the occlusion of targeting arteries. In conclusion, HIFU at clinically applicable intensity might prove useful in occluding feeding arteries for treating tumors non-invasively. Less

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (17 results)

All 2005 2004 2003 Other

All Journal Article (16 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] 強出力集束超音波(High intensity focused ultrasound;HIFU)を用いた栄養血管閉塞による子宮筋腫の無侵襲治療装置の開発と臨床手技の確立を目指した基礎的研究2005

    • Author(s)
      市塚清健, 岡井崇, 藤原礼, 石川哲也, 市原三義, 梅村晋一郎, 佐々木一昭, 川畑健一, 馬場一憲
    • Journal Title

      超音波医学 32(3)

      Pages: 339-346

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] HIFU照射による動脈閉塞に対する超音波造影剤の効果及びそれによる血管内皮の組織学的変化2005

    • Author(s)
      内山心美, 石川哲也, 安藤智, 市原三義, 松岡隆, 市塚清健, 岡井崇, 佐々木一昭, 梅村晋一郎, 九島巳樹
    • Journal Title

      昭和医学会雑誌 65巻2号

      Pages: 165-173

    • NAID

      130001818828

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] EFFECT OF CONTRAST AGENTS ON ARTERIES OCCLUDED BY EXPOSURE TO HIFU2005

    • Author(s)
      Uchiyama N, Ishikawa T, Ando S, Ichihara M, Matsuoka R, Ichizuka K, Okai T
    • Journal Title

      J Showa Med Assoc 65(2)

      Pages: 165-173

    • NAID

      130001818828

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 強出力集束超音波(High intensity focused ultrasound;HIFU)を用いた栄養血管閉塞による子宮筋腫の無侵襲治療装置の開発と臨床手技の確立を目指した基礎的研究2005

    • Author(s)
      市塚清健, 岡井 崇, 藤原 礼, 石川哲也, 市原三義, 梅村晋一郎, 佐々木一昭, 川畑健一, 馬場一憲
    • Journal Title

      超音波医学 37(3)

      Pages: 1412-1417

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 胎児病の低侵襲治療を目指した高出力集束超音波照射による動脈閉塞実験2005

    • Author(s)
      市塚清健, 石川哲也, 松岡隆, 長谷川潤一, 関沢明彦, 岡井崇
    • Journal Title

      日本周産期・新生児医学会雑誌 41(2)

      Pages: 530-530

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 強出力集束超音波(High intensity focused ultrasound ; HIFU)を用いた栄養血管閉塞による子宮筋腫の無侵襲治療装置の開発と臨床手技の確立を目指した基礎的研究2005

    • Author(s)
      市塚清健, 岡井崇他
    • Journal Title

      超音波医学 (発表予定)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] HIFU照射による動脈閉塞に対する超音波造影剤の効果及びそれによる血管内皮の組織学的変化2005

    • Author(s)
      内山心美, 岡井崇他
    • Journal Title

      昭和医学会雑誌 (In press)

    • NAID

      130001818828

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 微小気泡と超音波間歇送信法を用いた子宮筋腫の相対的組織血流量に関する研究2004

    • Author(s)
      市原三義, 石川哲也, 内山心美, 安藤智, 松岡隆, 市塚清健, 盛本太郎, 岡井崇
    • Journal Title

      昭和医学会雑誌 64巻3号

      Pages: 277-285

    • NAID

      130001819294

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] MEASUREMENT OF BLOOD FLOW TO UTERINE FIBROIDS USING MICROBUBBLES AND ULTRASOUND INTERMITTENT SONICATION METHOD2004

    • Author(s)
      Ichihara M, Ishikawa T, Uchiyama N, Ando S, Matsuoka R, Morimoto T, Ichizuka K, Okai T
    • Journal Title

      J Showa Med Assoc 64(3)

      Pages: 277-285

    • NAID

      130001819294

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 微小気泡と超音波間歇送信法を用いた子宮筋腫の相対的組織血流量に関する研究2004

    • Author(s)
      市原 三義, 岡井 崇 他
    • Journal Title

      昭和医学会雑誌 64・3

      Pages: 227-285

    • NAID

      130001819294

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Function and histological changes in rat femoral arteries by HIFU exposure, Ultrasound2003

    • Author(s)
      Ishikawa, T., Okai T, Sasaki K, Uemura S, Fujiwara R, Kushima M, Ichihara M, Ichizuka K.
    • Journal Title

      Med Biol. 29(10)

      Pages: 1471-7

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] HIFU照射の動脈血流に及ぼす影響に関する研究2003

    • Author(s)
      石川哲也, 藤原礼, 市原三義, 市塚清健, 岡井崇, 佐々木一昭, 梅村晋一郎, 九島巳樹
    • Journal Title

      昭和医学会雑誌 63巻3号

      Pages: 279-285

    • NAID

      130001822128

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Functional and histological changes in rat femoral arteries by HIFU exposure.2003

    • Author(s)
      Ishikawa T, Okai T, Sasaki K, Umemura S, Fujiwara R, Kushima M, Ichihara M, Ichizuka K.
    • Journal Title

      Ultrasound Med Biol. Oct;29(10)

      Pages: 1471-1477

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] ASTUDY ON INFLUENCE OF HIFU EXPOSURE TO ARTERIAL BLOOD FLOW IN THE RAT2003

    • Author(s)
      Ishikawa T, Fujiwara R, Ichihara M, Ichizuka K, Okai T
    • Journal Title

      J Showa Med Assoc 63(3)

      Pages: 279-285

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effect of simultaneous application of ultrasound contrast agents and HIFU on occlusion of arteries

    • Author(s)
      Uchiyama N, Okai T, Kasuaki S, Shinichiro U, Ishikawa T, Kushima M, Ando S, Ichihara M, Matsuoka R, Ichizuka K.
    • Journal Title

      J Urtrasonics. (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effect of simultaneous application of ultrasound contrast agents and HIFU on occlusion of arteries

    • Author(s)
      Uchiyama N, Okai T, Sasaki K, Umemura S, Ishikawa T, Kushima M, Ando S, Ichihara M, Matsuoka R, Ichizuka K
    • Journal Title

      J Urtrasonics (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 子宮筋腫の治療方法及び装置2003

    • Inventor(s)
      岡井 崇
    • Industrial Property Rights Holder
      岡井 崇
    • Filing Date
      2003-11-25
    • Related Report
      2004 Annual Research Report

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

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