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Ultrasound pharmacology using low intensity ultrasound generated by microtransducer arrays: Evaluation of therapeutic effectiveness in animal models of diseases

Research Project

Project/Area Number 21K19755
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 60:Information science, computer engineering, and related fields
Research InstitutionHokkaido University

Principal Investigator

Tateno Takashi  北海道大学, 情報科学研究院, 教授 (00314401)

Co-Investigator(Kenkyū-buntansha) 村上 修一  地方独立行政法人大阪産業技術研究所, 和泉センター, 主幹研究員 (70359420)
Project Period (FY) 2021-07-09 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2023: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2022: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2021: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords超音波トランスデューサ / 神経刺激法 / 微細加工技術
Outline of Research at the Start

本研究課題では,機械的振動で効率的に中枢神経系を低侵襲的に刺激し,体内臓器や末梢系効果器に神経信号を送信する新技術の開発を目指している.また,局所領域にある細胞に機械的振動を印加した際に,その振動が脳活動を誘起する細胞レベルでの作用機序の解明を試みる.上記の目標の実現に向けて,脳の局所領域に対して弱強度の超音波を放射し,低侵襲的に神経活動を誘起するサブミリサイズのデバイスを製作する.また,その実験系,および,効率的な神経活動誘起の実験プロトコルを開発する.上記の課題を通じて,ヒトに医療応用するために,空間高分解能の特性をもつ中枢神経系の低侵襲性刺激システムを構築する基盤技術を確立する.

Outline of Final Research Achievements

This study aimed to develop a technology utilizing ultrasonic vibrations to modulate the central nervous system activity in a minimally invasive manner. To this aim, we fabricated micro-sized diaphragm devices capable of modulating neural activity through localized emission of ultrasound waves in the brain. The microfabricated transducer substrate generated ultrasonic stimulation, and the resulting neural activity induction was confirmed through calcium imaging with brain slices. These findings were reported in a paper submitted to an international journal. Additionally, an experimental system was devised for application in animal models, along with the exploration of experimental protocols. Consequently, optimal conditions were identified for effectively stimulating solely the central nervous system. Further, using a drug-induced hearing-loss animals, we experimentally verified the direct induction of neural activity in the auditory central system through ultrasound stimulation.

Academic Significance and Societal Importance of the Research Achievements

学術的意義として,本研究課題で開発したマイクロスケールの振動板をもつトランスデューサは,局所的な超音波振動によって,神経系の試料や脳内の神経細胞膜を刺激でき,細胞膜の神経興奮の機序を知る有用な方法となり得る.
社会的意義として,本研究課題の微細加工技術で製作された超音波トランスデューサは,脳刺激用の小型機器として医療応用が可能である.また,神経系に作用する薬剤の効果を本手法で代替することによって脳神経疾患の治療に応用できるため,将来的に医療費の削減に一部貢献できる可能性がある.

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (30 results)

All 2024 2023 2022 2021

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 1 results) Presentation (25 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] A piezoelectric micromachined ultrasound transducer combined with recording electrodes for acute brain preparations in vitro2024

    • Author(s)
      Furukawa Ryo、Yoshikawa Takahiro、Murakami Shuichi、Tateno Takashi
    • Journal Title

      Journal of Neuroscience Methods

      Volume: 403 Pages: 110048-110048

    • DOI

      10.1016/j.jneumeth.2023.110048

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Low-Cost Electroencephalographic Recording System Combined with a Millimeter-Sized Coil to Transcranially Stimulate the Mouse Brain in vivo2023

    • Author(s)
      Yoshikawa Takahiro、Sato Hiromu、Kawakatsu Koki、Tateno Takashi
    • Journal Title

      Journal of Visualized Experiments

      Volume: - Issue: 195

    • DOI

      10.3791/65302

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Temporal and spatial profiles of evoked activity induced by magnetic stimulation using millimeter-sized coils in the mouse auditory cortex in vivo2022

    • Author(s)
      Yoshikawa Takahiro、Higuchi Hisaya、Furukawa Ryo、Tateno Takashi
    • Journal Title

      Brain Research

      Volume: 1796 Pages: 148092-148092

    • DOI

      10.1016/j.brainres.2022.148092

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] A Multielectrode Array-Based Recording System for Analyzing Ultrasound-Driven Neural Responses in Brain Slices in vitro2022

    • Author(s)
      Furukawa Ryo、Kaneta Hiroki、Tateno Takashi
    • Journal Title

      Frontiers in Neuroscience

      Volume: 16

    • DOI

      10.3389/fnins.2022.824142

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of a Piezoelectric Micromachined Ultrasound Transducer using Microfabrication Technology for in Vitro Neuromodulation2022

    • Author(s)
      Furukawa Ryo、Tateno Takashi
    • Journal Title

      Proceedings of the 15th International Joint Conference on Biomedical Engineering Systems and Technologies - BIODEVICES

      Volume: 1 Pages: 196-203

    • DOI

      10.5220/0010938500003123

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] An Event-driven Closed-loop Ultrasound Stimulator Composed of a Micro-transducer and Multi-site Electrodes In Vitro2024

    • Author(s)
      Ryo Furukawa, Shuichi Murakami, and Takashi Tateno
    • Organizer
      International Joint Conference on Biomedical Engineering Systems and Technologies (BIOSTEC 2024)
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 音響圧空間分布推定に基づく超音波駆動の神経可塑性誘発法の開発 ー神経細胞間結合の低侵襲的な制御方法の開発に向けて一2024

    • Author(s)
      柴公晟,舘野高
    • Organizer
      令和5年度 電子情報通信学会 北海道支部 インターネットシンポジウム
    • Related Report
      2023 Annual Research Report
  • [Presentation] Bidirectional modulation effects on neural activity induced by near-infrared light stimulation to the mouse inferior colliculus in vivo2023

    • Author(s)
      T. TATENO, F. SUGIMOTO, and H. SATO
    • Organizer
      Neuroscience 2023 (Society for Neuroscience)
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 耳毒性難聴マウスを用いた超音波脳刺激における聴覚の末梢系と中枢系の神経応答解析2023

    • Author(s)
      舘野 高,石川 瑛大,坂上 雅明
    • Organizer
      第46回日本神経科学学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 近赤外光温熱刺激がin vivoマウス下丘の音誘発と自発の神経活動に及ぼす変調効果2023

    • Author(s)
      佐藤 広務,杉本 太,舘野 高
    • Organizer
      第46回日本神経科学大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 簡易的可塑性モデルがin vitroマウス聴覚皮質の受容体拮抗薬下の長期抑圧の時間的動態を明らかにする2023

    • Author(s)
      古川凌,舘野高
    • Organizer
      第46回日本神経科学大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 数値解析および動物実験に基づく電気刺激極性が特徴づけるマウス脳波誘発応答の解析2023

    • Author(s)
      川勝 孝基,舘野 高
    • Organizer
      第46回日本神経科学学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 小動物の機能的神経結合の推定を目指したin vivo 局所電磁気刺激と脳波多点計測2023

    • Author(s)
      川勝 孝基,舘野 高
    • Organizer
      2023年電気学会 電子・情報・システム部門大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 近赤外光刺激がマウス下丘に及ぼすin vivo神経活動の変調効果2023

    • Author(s)
      佐藤 広務, 舘野 高
    • Organizer
      令和4年 電子情報通信学会ニューロコンピューティング(NC)研究会
    • Related Report
      2022 Research-status Report
  • [Presentation] A spatiotemporal analysis of ultrasound-driven responses reflecting acoustic pressure distributions and cortical circuits in mouse brain slices in vitro2022

    • Author(s)
      Ryo Furukawa, Hiroki Kaneta, and Takashi Tateno
    • Organizer
      第45回日本神経科学大会(NEURO2022)
    • Related Report
      2022 Research-status Report
  • [Presentation] In vivo近赤外光神経刺激によって誘発されるマウス下丘での双方向性の神経活動変調効果2022

    • Author(s)
      佐藤 広務、舘野高
    • Organizer
      第45回日本神経科学大会(NEURO2022)
    • Related Report
      2022 Research-status Report
  • [Presentation] A piezoelectric micromachined ultrasound transducer with the interface of simultaneous measurement of neural activity in vitro2022

    • Author(s)
      Ryo Furukawa and Takashi Tateno
    • Organizer
      電気学会 電子・情報・システム部門大会
    • Related Report
      2022 Research-status Report
  • [Presentation] Magnetic Stimulation Conditions Needed for Localized Electrophysiological Responses in Mouse Auditory Cortex in vivo2022

    • Author(s)
      Takahiro Yoshikawa and Takashi Tateno
    • Organizer
      電気学会 電子・情報・システム部門大会
    • Related Report
      2022 Research-status Report
  • [Presentation] 経頭蓋超音波刺激における齧歯類の頭蓋振動と聴性脳幹誘発応答の相関解析2022

    • Author(s)
      坂上雅明,舘野 高
    • Organizer
      電気学会 電子・情報・システム部門大会
    • Related Report
      2022 Research-status Report
  • [Presentation] 局所的反復磁気刺激による脳内電場分布と電気生理学的応答の特徴: 聴覚皮質の可塑性誘導条件の探索2022

    • Author(s)
      吉川 隆洋, 舘野 高
    • Organizer
      令和4年 電気・情報関係学会北海道支部大会
    • Related Report
      2022 Research-status Report
  • [Presentation] 聴覚末梢・中枢系の同時計測法による超音波刺激の誘発応答解析: 骨伝導の影響評価2022

    • Author(s)
      坂上 雅明, 舘野 高
    • Organizer
      令和4年 電気・情報関係学会北海道支部大会
    • Related Report
      2022 Research-status Report
  • [Presentation] 光誘発温熱刺激による脳活動変調: 物理モデルとマウス脳での実験的評価2022

    • Author(s)
      佐藤 広務, 舘野 高
    • Organizer
      令和4年 電気・情報関係学会北海道支部大会
    • Related Report
      2022 Research-status Report
  • [Presentation] Development of a Piezoelectric Micromachined Ultrasound Transducer using Microfabrication Technology for in Vitro Neuromodulation2022

    • Author(s)
      Ryo Furukawa, and Takashi Tateno
    • Organizer
      15th International Joint Conference on Biomedical Engineering Systems and Technologies (BIOSTEC 2022)
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 脳内電場分布計算に基づく局所パルス磁気刺激のマウス大脳皮質誘発応答特性 -効果的な経頭蓋可塑性誘導法の開発に向けて-2022

    • Author(s)
      吉川隆洋,舘野高
    • Organizer
      令和3年度電子情報通信学会北海道支部学生会インターネットシンポジウム
    • Related Report
      2021 Research-status Report
  • [Presentation] Evaluation of hearing loss and temporal processing deficits in senescence-accelerated mice: a study using auditory brainstem response and gap pre-pulse inhibition of acoustic startle reflex2021

    • Author(s)
      Hayato Ishizaka, Takashi Tateno and Jun Nishikawa
    • Organizer
      Neuroscience 2021 (日本神経科学学会,the 44th Annual Meeting of the Japan Neuroscience Society)
    • Related Report
      2021 Research-status Report
  • [Presentation] Spatio-temporal analysis of cortical response properties induced by the magnetic stimulation of millimeter-sized coils to mouse brain in vivo2021

    • Author(s)
      Takashi Tateno
    • Organizer
      Neuroscience 2021 (日本神経科学学会,the 44th Annual Meeting of the Japan Neuroscience Society)
    • Related Report
      2021 Research-status Report
  • [Presentation] Development of a piezoelectric micromachined ultrasound transducer using microfabrication technology -Aiming to realize the efficient induction of responses in local neural networks2021

    • Author(s)
      Ryo Furukawa, Takashi Tateno
    • Organizer
      電気学会 電子・情報・システム部門大会,オンライン開催
    • Related Report
      2021 Research-status Report
  • [Presentation] MEMS圧電性トランスデューサの開発:超音波ニューロモジュレーションへの応用2021

    • Author(s)
      古川凌,舘野高
    • Organizer
      北海道大学部局横断シンポジウム,オンライン開催
    • Related Report
      2021 Research-status Report
  • [Presentation] 微細加工技術による圧電型マイクロ超音波トランスデューサの開発-In vitro超音波神経刺激実験への応用-2021

    • Author(s)
      古川凌,舘野高
    • Organizer
      令和3年度電気・情報関係学会北海道支部連合大会,オンライン開催
    • Related Report
      2021 Research-status Report
  • [Presentation] 老化促進モデルマウスにおける難聴および時間処理障害の評価:聴性脳幹反応および音響驚愕反射ギャッププレパルス抑制を用いた研究2021

    • Author(s)
      石坂 駿人,舘野 高,西川 淳
    • Organizer
      第36回老化促進モデルマウス(SAM)学会学術大会
    • Related Report
      2021 Research-status Report

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Published: 2021-07-13   Modified: 2025-01-30  

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