Development of a New Sonothrombolytic Treatment for Acute Ischemic Stroke with a Complete Occlusion of Cerebral Artery

• Project/Area Number: 17K01372
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Wang Zuojun 東京慈恵会医科大学, 医学部, 助教 (10758080)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 急性期脳梗塞 / 血栓溶解治療 / 超音波治療 / 超音波 / マイクロバブル / 超音波血栓溶解治療 / マイクロバブル(MB) / 脳神経疾患

Outline of Final Research Achievements

The applicant simulated the movement of MB in the ultrasonic sound field and devised a new ultrasonic thrombolytic treatment that may be used to re-open the brain arteries even completely obstructed by a thrombotic clot.
We have developed a new in vitro middle cerebral artery occlusion (MCAO) model that combines ultrasonic permeability and optical transparency to precisely control the intensity of ultrasonic irradiation to the target and the flow of pseudo-blood in the simulated blood vessels. In addition, a new optical precision measurement method was devised and completed based on the Mie's scattering theory for measuring the size of microbubbles.
We will publish papers on related research results and complete the basic theory of the new treatments for patients with acute cerebral infarction.

Academic Significance and Societal Importance of the Research Achievements

急性期脳梗塞患者の死亡率及び障害率が非常に高いが、その根本的治療は血管を閉塞した血栓の除去である。しかし、患者は血栓溶解治療薬rt-PAの投与を受けても、さらに経頭蓋超音波照射ないし超音波増強剤マイクロバブル（MB）の投与を加えても、半分近くは閉塞血管が再開通しない。
本研究は完全閉塞した脳動脈に対しても早く再開通させられることの実現へ一歩前進した。

Research Products

• [Journal Article] An In Vitro Assay for Sonothrombolysis Based on the Spectrophotometric Measurement of Clot Thickness (2017)
  • Author(s): Wang Zuojun、Sawaguchi Yoshikazu、Hirose Hideo、Ohara Kazumasa、Sakamoto Shinichiro、Mitsumura Hidetaka、Ogawa Takeki、Iguchi Yasuyuki、Yokoyama Masayuki
  • Journal Title: Journal of Ultrasound in Medicine Volume: 36 Issue: 4 Pages: 681-698
  • DOI: 10.7863/ultra.15.11018
  • Peer Reviewed / Open Access
• [Journal Article] An Uncovered Risk Factor of Sonothrombolysis: Substantial Fluctuation of Ultrasound Transmittance through the Human Skull. (2017)
  • Author(s): Zuojun Wang, Teppei Komatsu, Hidetaka Mitsumura, Norio Nakata, Takeki Ogawa, Yasuyuki Iguchi, Masayuki Yokoyama
  • Journal Title: Ultrasonics Volume: 77 Pages: 168-175
  • DOI: 10.1016/j.ultras.2017.02.012
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A polymeric micelle magnetic resonance imaging (MRI) contrast agent reveals blood-brain barrier (BBB) permeability for macromolecules in cerebral ischemia-reperfusion injury. (2017)
  • Author(s): Kouichi Shiraishi, ZuojunWanga, Daisuke Kokuryob, Ichio Aoki, Masayuki Yokoyama
  • Journal Title: J. Controlled Release Volume: 253 Pages: 165-171
  • DOI: 10.1016/j.jconrel.2017.03.020
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Ultrasound Acceleration of rt-PA Thrombolysis Depends on Acoustic Intensity (2017)
  • Author(s): Yoshikazu SAWAGUCHI, Zuojun WANG
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 40 Issue: 1 Pages: 97-103
  • DOI: 10.1248/bpb.b16-00702
  • NAID: 130005188773
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 超音波およびマイクロバブル併用のin vitroにおける血栓溶解増強効果の定量的評価 (2017)
  • Author(s): 王 作軍、横山昌幸、中田典生、澤口能一
  • Journal Title: 超音波TECHNO Volume: 29 Pages: 72-77
• [Presentation] Robotic Process Automation: Go Beyond Artificial Intelligence in the Radiology Department (2018)
  • Author(s): N. Nakata, Z. Wang, T. Watanabe T. Ohta, M. Nishioka, H. Ojiri
  • Organizer: RSNA 2018
  • Int'l Joint Research
• [Presentation] DEVELOPMENT OF SECONDARY PREVENTION OF REOCCLUSION BY ULTRASOUND (2018)
  • Author(s): Y. Sawaguchi, Z. Wang, H. Yamamoto, K. Tachibana, T. Nakajima, N. Nakata
  • Organizer: ESNCH 2018
  • Int'l Joint Research
• [Presentation] DEVELOPMENT OF SECONDARY PREVENTION OF REOCCLUSION BY ULTRASOUND (2018)
  • Author(s): Yoshikazu Sawaguchi、Zuojun Wang、Hiroyuki Yamamoto、Ken Tachibana、Takanori Nakajima、Norio Nakata
  • Organizer: the 23rd Meeting of the European Society of Neurosonology and Cerebral Hemodynamics
  • Int'l Joint Research
• [Presentation] Blood-brain barrier (BBB)の透過性亢進評価と脳神経疾患との関連 (2017)
  • Author(s): 白石 貢一、王 作軍、青木 伊知男、横山 昌幸
  • Organizer: 第33回日本DDS学会学術集会