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Kudo Nobuki

Faculty of Information Science and Technology　Bioengineering and Bioinformatics　BioengineeringResearch Fellow

Researcher basic information

■ Degree
  • MS and PhD degree in Biomedical Engineering in 1984 and 1987, Hokkaido University
  • 工学修士, 北海道大学
■ URL
researchmap URLホームページURL■ Various IDs
J-Global ID■ Research Keywords and Fields
Research Keyword
  • 超音波
  • 微小気泡
  • 光イメージング
  • 空間分解能
  • 微弱光検出
  • 光変調
  • 透過光
  • 減衰
  • 屈折
  • パルス超音波
  • 光パルス
  • ソノポレーション
  • ドプラ効果
  • タイムラプス観察
  • 血管内皮細胞
  • 遺伝子導入
  • シェル
  • 干渉計
  • 後方散乱光
  • 光ピンセット
  • スペックル
  • 血流計測
  • 超音波造影剤
  • RF信号
  • 粥腫
  • 超音波診断
  • 心筋細胞
  • 心室筋細胞
  • 音圧依存性減衰
  • ターゲティング気泡
  • 医用超音波
  • 医用光学
  • Biomedical UltrasoundBiomedical Optics
Research Field
  • Humanities & Social Sciences, Educational technology
  • Life Science, Medical systems
  • Life Science, Biomaterials
  • Life Science, Biomedical engineering

Career

■ Career
Career
  • 2009 - 2013
    Hokkaido University, 大学院・情報科学研究科, 准教授
  • 2009
    - 北海道大学（大学院情報科学研究科) 准教授
  • 2004 - 2007
    北海道大学助手（大学院情報科学研究科) 助手
  • 2004 - 2007
    Research Associate
  • 1997 - 2004
    北海道大学助手（大学院工学研究科) 助手
  • 1997 - 2004
    Research Associate,Graduate School of Engineering, Hokkaido University
  • 1995 - 1997
    Hokkaido University
  • 1995 - 1997
    Research Associate,Faculty of Engineering, Hokkaido University
  • 1987 - 1995
    Toshiba Corporation
Educational Background
  • 1987, Hokkaido University
  • 1984, Hokkaido University, 生体工学専攻, Japan
  • 1984, Hokkaido University
  • 1982, Hokkaido University, School of Engineering, Department of Electronics Engineering, Japan
  • 1982, Hokkaido University, Faculty of Engineering
Committee Memberships
  • Apr. 2017 - Present
    日本生体医工学会, 北海道支部長, Society
  • Sep. 2013 - Present
    IEEE, Area Editor, Society
  • 2012 - Present
    日本超音波医学会, 理事, Society
  • 2012 - Present
    日本超音波医学会機器及び安全に関する委員会, 副委員長, Society
  • 2010 - Present
    日本超音波医学会, 北海道地方会運営委員長, Society
  • 2008 - Present
    日本超音波医学会, Journal of Medical Ultrasonics, Area Editor, Society
  • 2004 - Present
    日本生体医工学会, 代議委員, Society

Research activity information

■ Awards
  • 2013, 日本超音波医学会, 第２回新人賞
    内田和輝
  • 2012, 日本超音波医学会, 第１回新人賞
    吉松幸里
  • 2010, 日本超音波医学会 第26回菊池賞（論文賞）
    Japan
  • 2009, 日本超音波医学会 第25回菊池賞（論文賞）
    Japan
  • 2007, 平成19年日本ソノケミストリー学会論文賞
    Japan
  • 2005, 日本超音波医学会 第21回菊池賞（論文賞）
    Japan
  • 2005, 日本超音波医学会 第７回奨励賞
    Japan
  • 2005, Best Presentation Award
  • 2004, 7th International Symposium on Ultrasound Contrast Imaging, Superb poster award
  • 2002, 6th International Symposium on Ultrasound Contrast Imaging, Poster session Silver Prize
  • 2002, Asian Symposium on Biomedical Optics and Photomedicine Best Poster Award
  • 2002, 日本超音波医学会 第３回奨励賞（優秀発表賞）
    Japan
  • 2002, 7th Ultrasound Contrast Research Symposium in Radiology Best Presentation Award
  • 1999, 日本超音波医学会第13回菊池賞（論文賞）
    Japan
  • 1992, 日本エム・イー学会科学新聞賞新技術開発賞
    Japan
■ Papers
■ Other Activities and Achievements
■ Books and other publications
  • 放射線医科学
    学会出版センター, 2007
  • 別冊・医学の歩み 超音波医学最前線ー新技術と臨床応用
    医歯薬出版, 2004
  • 超音波造影剤ガイドブック <森安史典，別府慎太郎，久 直史>
    金原出版, 2003
  • 『新超音波医学』<日本超音波医学会>
    医学書院, 2000
■ Lectures, oral presentations, etc.
■ Affiliated academic society
  • 日本音響学会
  • 電子情報通信学会
  • IEEE
  • 日本生体医工学会
  • 日本超音波医学会
  • IEEE
■ Research Themes
  • 薬剤搭載気泡アンチバブルによる膀胱癌治療法の開発
    科学研究費助成事業
    01 Apr. 2023 - 31 Mar. 2026
    佐々木 東; 工藤 信樹
    日本学術振興会, 基盤研究(C), 北海道大学, 23K11888
  • Near-infrared light delivery in deep tissue using vivo helical optical waveguide formed by a topological ultrasound beam
    Grants-in-Aid for Scientific Research
    30 Jun. 2022 - 31 Mar. 2025
    橋本 守; 工藤 信樹; 加藤 祐次
    Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Research (Pioneering), Hokkaido University, 22K18436
  • Elucidation of mechanical and biological effects of oscillating microbubbles on capillary endothelial cells and extravasation
    Grants-in-Aid for Scientific Research
    01 Apr. 2020 - 31 Mar. 2023
    工藤 信樹; 鈴木 亮; 佐々木 東; 松崎 典弥
    血管内に投与した薬剤を超音波の照射により血管外の組織に漏出させる超音波薬物送達法では，薬剤とともに投与される微小気泡が超音波の照射下で血管に与える作用を明らかにする必要がある．本年度は主に２つの方法により解明に向けた準備作業を行った．
    ①血管の物理特性を模擬するゲルファントムの開発
    微細径のタングステンワイヤを張った型にアクリルアミドゲルを流し込み，ゲル硬化後にワイヤを引き抜くことにより最小直径約10ミクロンの内腔を有する毛細血管ファントムを作成する技術を開発した．微細管腔への微小気泡導入は，初期的にはゲルからワイヤを引き抜く作業を微小気泡の懸濁液内で行うことにより実現できる．また，ゲルの浸透圧を気泡懸濁液の浸透圧よりも低く設定することにより持続的に管腔内に気泡を引き込む流れが形成できることを発見した．これにより，超音波照射により気泡が壊れても新たな気泡が自動的に導入され，繰り返し実験できるようになった．
    ②生体の組織構造を模擬する3次元培養細胞血管ファントムの開発
    コラーゲンゲルに懸濁した血管内皮細胞（HUVEC）を血管内皮増殖因子（VEGF）を加えた培地内で3次元培養することにより毛細血管ファントムを作成する手法を開発し，安定な作成プロセスを検討した．血管内腔に取り込んだ気泡が超音波照射下で生じるダイナミクスを高速度観察する手法，薬剤の漏出や内皮細胞に生じる損傷を可視化する蛍光観察手法を開発した．さらに，血管内に模擬薬剤を導入し，超音波を照射していない状態での漏出が薬剤の分子量によってどのように変化するかを調べた．
    さらに，次年度以降に向けた準備作業として，生体内の毛細血管を用いて超音波照射下での気泡のダイナミクスを観察する手法について文献調査を行い，ラットなどの腸間膜を使う手法について検討した．
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 20H04542
  • Development of novel cancer therapy based on promotion of tumor infiltrating lymphocyte by the immunomodulation with ultrasound technology
    Grants-in-Aid for Scientific Research
    01 Apr. 2020 - 31 Mar. 2023
    鈴木 亮; 工藤 信樹; 岡田 欣晃; 小山 正平
    現在、T 細胞療法に代表される養子免疫療法によるがん治療が行われており、血液系がんに対して良好な臨床成績をあげている。しかし、固形がんにおいては期待するほどの結果が得られていない。この要因として、移入した T 細胞の腫瘍組織への低浸潤性や腫瘍組織内の免疫抑制的環境による T 細胞の不活性化などが挙げられる。そこで本研究では、超音波照射によるマイクロバブルの収縮・膨張や圧壊といった機械的作用に着目し、固形がん組織内の血管透過性の促進や腫瘍組織の傷害に伴う腫瘍内環境の変化の誘導による、養子免疫療法の治療効果の増強を検討した。乳がん細胞株移植マウスにマイクロバブルを静脈内投与し、腫瘍組織へ超音波を照射した。その 1 日後に CD8 陽性 T 細胞を静脈内から移入する養子免疫療法を行った。その結果、未治療群と比較して、マイクロバブルと超音波照射群において、抗腫瘍効果は認められなかった。一方、CD8 陽性 T 細胞移入群において、わずかな抗腫瘍効果が認められた。さらに、マイクロバブルと超音波照射後に CD8 陽性 T 細胞を移入した群では、顕著な抗腫瘍効果が認められた。このことから、マイクロバブルと超音波照射が、腫瘍内環境の変化を誘導し、養子免疫療法の効果を増強したものと考えられた。今後は、マイクロバブルと超音波照射による腫瘍内環境の変化を免疫学的に解析し、抗腫瘍効果の増強メカニズムに関して検討を進める予定である。また、本治療効果の最適化を図るため、マイクロバブルの投与量や超音波照射条件の最適化を進める。
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Teikyo University, 20H04519
  • 細胞・微小気泡間相互作用のその場観察によるソノポレーションの機序解明と応用拡大
    科学研究費補助金（基盤研究（A））
    2017 - 2021
    工藤 信樹
    文部科学省, Principal investigator, Competitive research funding
  • Encapsulated Sensor-Telemeter Transmitter for Real-Time Continuous Monitoring of Intra-Corporeal Pressure
    Grants-in-Aid for Scientific Research
    01 Apr. 2016 - 31 Mar. 2019
    Matsumoto Seiji
    The study aims to devise the entitled device, with our own, at-hand, laboratory manageable method. We adopt diafragm on closed chamber to make pressure sensitive variable inductance variable frequency RF oscillator to be coupled to receiver via leakage flux coupling. Our 6mm dia 0.2mm wall thickness capsule has battery and oscillator circuit board behind the oscillator coil having one end of bobbin sealed by diafragm made of 12.5μm polyesther membrane having 3mm dia x 3mm length soft ferrite core at its center. A matched dia. protection dome having tiny escape hole is placed eternal to the diafragm. Oscillator coil inductance is about 140μH, oscillating frequency about 2.06MHz, battery life about 10days, 500Hz frequency shift per 10mmHg pressure increment, reasonable linearity and reproducibility up to about 100mmHg is obtained. This measurement dynamic range is quite sufficient for monitoring intra-bladder pressure during storing and voiding process.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Asahikawa Medical College, 16K11038
  • Development of new technique for spectral measurement in scattering medium using time-reverse principle with phase-conjugate wave
    Grants-in-Aid for Scientific Research
    01 Apr. 2016 - 31 Mar. 2018
    Shimizu Koichi
    We conducted this research to open a new possibility for the localized spectral measurement in a turbid medium by introducing the new time-reversal principle using a phase-conjugate wave. The following accomplishments were achieved.
    1. In theoretical analysis, we made the fundamental measurement technique to realize the proposed method clear. 2. Through repeated simulation, we optimized the function of the proposed technique. 3. We developed the measurement system to realize the time-reversal principle using the phase-conjugate light. 4. We confirmed the ability of the developed system using a model phantom of animal tissue. 5. We verified the applicability of the system to an animal body in the experiment with chicken breast meat. 6. The result of this study is published in a prestigious journal, Biomedical Optics Express of the Optical Society of America.
    Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Waseda University, 16K14239
  • Novel cancer therapy for spontaneous animal tumor using ultrasound irradiation with microbubble
    Grants-in-Aid for Scientific Research
    01 Apr. 2014 - 31 Mar. 2017
    TAKIGUCHI MITSUYOSHI; KUDO Nobuki
    This study revealed that sonoporation, the combination of ultrasound and microbubbles, enhances the antitumor effect of a chemotherapeutic agent with minimum invasiveness in preclinical canine thyroid and bladder cancer models. Moreover, the results of this study clarified the mechanism of sonoporation. This preclinical study may contribute to establish sonoporation as a theranostic tool in cancer therapy.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 26292155
  • Development of ALA-PET guided sonodynamic therapy for malignant gliomas
    Grants-in-Aid for Scientific Research
    01 Apr. 2014 - 31 Mar. 2016
    KOBAYASHI HIROYUKI; TERASAKA SHUNSUKE; KUDO NOBUKI; SHIGA TORU
    Malignant glioma is a poor prognosis cancer despite of multidisciplinary treatment such as aggressive surgery and chemoradiotherapy. Thus there has been a need for new therapeutic approaches to control deeply migrated tumor cells. For this aim, we investigated the efficacy of sonodynamic therapy (SDT) using sonosensitizers including 5-aminolevulinic acid, protoporphyrinⅨ, and talaporfin sodium on glioma cells. These substances have been known to be accumulated in glioma cell and are expected to have cytotoxic effect by sonication. Our in vitro study demonstrated that the cytotoxicity of sonication on glioma cells was enhanced by each sonosensitizers. And induction of apoptosis was suggested to be a major mechanism of cell death. While the efficacy of SDT may be depend on the degree of intracellular accumulation of sonosensitizer. Though further investigations will be necessary, our preliminary result showed a potential of STD with sonosensitizers for glioma treatment.
    Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Hokkaido University, 26670632
  • Realization of optical transillumination imaging of 3D internal body structure by integrating new principles
    Grants-in-Aid for Scientific Research
    01 Apr. 2013 - 31 Mar. 2016
    Shimizu Koichi; KUDO Nobuki; KATO Yuji; KITAMA Masataka
    To realize 3D transillumination imaging of macroscopic internal body structure, we integrated our principles to develop a new technique. Through optimization using Monte Carlo simulation, a measurement system was constructed. We analyzed the characteristics of the developed system, and necessary improvements were made. In the animal experiments, the feasibility of imaging the internal body structure with the safe near-infrared light without radio-active exposure was verified. The feasibility of functional imaging such as tissue oxygenation state was also verified.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 25282123
  • Improvement of optical tweezers and development of micro cell culture wells for realization of sono-injection technique
    Grants-in-Aid for Scientific Research
    2013 - 2014
    KUDO Nobuki; SHIGETOMI Kaori
    The studies investigated the two elemental technologies that are essential for experimental studies on gene and drug transduction by exposure of cells with attached microbubbles to ultrasound. Since the transduction occurs at the position of the attached bubbles, its efficiency can be controlled by the size and position of the attached bubbles. Therefore, in this study, conventional optical tweezers were improved to increase bubble trapping force to move a bubble on a cell nucleus. Small cell culture wells of around 100 microns were also fabricated to maintain cultured cells under in vivo-like conditions that have high cell membrane repairability. Transduction experiments were carried out using the fabricated wells, indicating that the wells are useful for basic studies on gene and drug delivery by ultrasound exposure.
    Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Hokkaido University, Principal investigator, Competitive research funding, 25560233
  • Realization of transcutaneous spectral measurement at local area in biological body by new principle
    Grants-in-Aid for Scientific Research
    2011 - 2012
    SHIMIZU Koichi; KUDO Nobuki; KATO Yuji; NAMITA Takeshi
    We conducted a study to realize the selective spectral analysis at a local area in strong scattering medium, such as biological tissues. In two years study, we have developed a technique to quantitatively measure the optical absorption at a local area in the body. This result opened the new possibility; for the non-invasive transcutaneous measurement of accurate optical absorption; and for the tissue spectral measurement while eliminating the effect of the interstitial tissue. We have reported these results in academic journals and international/domestic conferences, and applied patents.
    Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Hokkaido University, 23650297
  • Development of ultrasound field viewer using novel technique without Schlieren opticls
    Grants-in-Aid for Scientific Research
    2011 - 2012
    KUDO Nobuki; SHIMIZU Koichi; NISHIDA Mutsumi; MIZOJIRI Jun; OBARA Koki; SEKINE Daiki; SUMIYOSHI Koki
    Ultrasound techniques have been playing important roles both in diagnosis and therapy. As a basic technology to support development of these applications, improvements are also required for evaluation techniques of ultrasound fields. In this study, an ultrasound field visualization system using image subtraction Schlieren technique was designed and fabricated with corroboration of an experienced manufacture. The developed system was used for visualization of ultrasound fields generated by clinically used diagnostic and therapeutic ultrasound equipment. Short-pulsed ultrasound fields for diagnostic applications and continuous-wave high-intensity focused ultrasound fields for therapeutic applications were successfully visualized, indicating practical usefulness of our technique as basic technology to support further progress of ultrasound applications in medicine.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, Principal investigator, Competitive research funding, 23300182
  • Development of local cell stimulation method using ultrasound exposure in presence of microbubbles
    Grants-in-Aid for Scientific Research
    2011 - 2012
    KUDO Nobuki; OKUYAMA Manabu; KINOSHITA Yuto; MATSUI Tomoko; MIZUUCHI Misato; YOSHIMATSU Yuri
    A novel technique for local mechanical stimulation of cells was proposed to studymechanotransduction of living cells. A cell with an attached micron-sized bubble is stimulated by this techniqueby using the effect of larger acoustic radiation force being applied to the bubble than to the cell. Optical tweezerswere used to control the position of a bubble. Cardiac myocytes isolated from neonatal rats were used formechanical stimulation, and a cell culture chamber for microscopic observation under exposure of ultrasoundexposure was developed. Cardiac myocytes with attached microbubbles were irradiated with ultrasound, and thegeneration of premature ventricular contraction by the mechanical stimulation was confirmed. Experiments toevaluate the refractory period of the myocytes were carried out using this technique, and changes in the perioddepending on the beating frequency were found, suggesting the usefulness of the proposed technique for studying cell reactions to mechanical stimulation.
    Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Hokkaido University, Principal investigator, Competitive research funding, 23650247
  • Development of optical transillumination system to realize imaging of 3D structure using new principles
    Grants-in-Aid for Scientific Research
    2009 - 2012
    SHIMIZU Koichi; KUDO Nobuki; KATO Yuji; KITAMA Masataka; CHIBA Hitoshi
    To realize 3D transillumination imaging of internal structure and function of biological body, we developed new techniques based on original principles and created the systems to verify them. In this study, the feasibility of imaging the internal structure of experimental animals and human limbs using safe near-infrared light without radio-active exposure was verified. The feasibility of functional imaging such as tissue oxygenation state was also verified.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Hokkaido University, Coinvestigator not use grants, Competitive research funding, 21240045
  • Development of in vivo sonoporation method using short-pulsed ultrasound with microbubbles adjacent to cells.
    Grants-in-Aid for Scientific Research(基盤研究(A))
    2008 - 2010
    Nobuki KUDO; 山本 克之; Ryo SUZUKI; Katsuyuki YAMAMOTO; Kengo OKADA; Katsuji SKAGUCHI; Tomofumi YAGI; Noriko WATANABE; Yuuki CHIDA; Manabu OKUYAMA; Tomoko MATSUI; Yuri YOSHIMATU
    The final goal of this study was to develop a safe and efficient method for in vivo sonoporation that uses short-pulsed ultrasound in the presence of microbubbles adjacent to cells. A light microscopy system was developed for time-lapse observation of changes in cells generated during sonoporation and used to study methods to improve efficiency of the sonoporation. Optical tweezers were included in the system to control the position and extent of membrane damage by changing bubble size and position. Cell membrane damage and repair, which occur in a period shorter than 20 minutes, were obser...
    Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(A), 北海道大学, Principal investigator, Competitive research funding, 20240053
  • Temporal and spatial analysis on muscle oxiganation dynamics using near-infrared spectroscopy
    Grants-in-Aid for Scientific Research(基盤研究(C))
    2007 - 2008
    Yamamoto KATSUYUKI; Nobuki KUDO; Kiyonori KAWAHATSU; Khaijun KEK; Shun MITSUEDA; Ryuta KIBE
    本研究では,近赤外分光法(NIRS)を用いた絶対値計測可能な筋組織酸素濃度のイメージング装置を開発し,運動時における同一筋内や異なる筋について筋組織酸素濃度分布の計測を行い,運動強度や運動様式の違いによる酸素濃度分布の変化を把握できることを明らかにした.また,一般成人と運動選手を対象に足踏み込み運動時に協調して動作する3種類の筋の酸素濃度を計測し,装置が運動時における複数の筋の同時比較や練習効果の定量的評価に有用であることも明らかにした.さらに,実測とシミュレーションによる解析との比較により,NIRS計測波形を解釈する上で筋代謝モデルを用いた解析の有用性を明らかにした.
    Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(C), 北海道大学, Coinvestigator not use grants, Competitive research funding, 19500376
  • 微小気泡を用いた超音波遺伝子導入の発現効率向上法に関する検討
    科学研究費補助金(萌芽研究)
    2006 - 2007
    工藤 信樹; 山本 克之
    ○パルス超音波による遺伝子導入の実証従来,連続波もしくは波数の多いバースト波を用いて行われてきたソノポレーションが,波数3波程度の短い超音波パルスを1回照射するだけでも実現できることを,GFP遺伝子の導入と発現のタイムラプス観察を通じて実証した.しかしその導入効率は低く,パルス超音波が撹拌効果を持たないことが原因の一つと考えられた○遺伝子付着気泡の作成撹拌効果を持たないペルス超音波でも効率が高いソノポレーションを実現するための方法として,細胞に穿孔をもたらす微小気泡自体に遺伝子を付着させる方法について検討した.その結果,アルブミンとGFP遺伝子を混入した生理食塩水を撹拌することで,遺伝子が付着した直径数ミクロンの微小気泡を再現性良く作成できることを確認した.○導入効率の向上上記で作成した気泡を用いて,遺伝子導入効率の向上効果を調べた.GFT遺伝子を培養液中に懸濁させた条件と気泡に付着させた条件で発現効率を調べた結果,気泡に付着させることによって導入効率が,培養駅に懸濁させた場合の約4倍に向上することを確認した.○気泡の種類による膜損傷の違い種々の気泡を用いてパルス超音波を用いたソノポレーションを行い,細胞の損傷率と修復率が気泡の種類によってどのように変化をするかを調べた.その結果,気泡の種類に依存して修復率が60%から100%近くまで変化することが確認され,ソノポレーションに...
    文部科学省, 萌芽研究, 北海道大学, Principal investigator, Competitive research funding, 18650139
  • Evaluation of mechanical properties of the shell materials of ultrasound contrast agent microbubbles by high-speed observation of their radial oscillation.
    Grants-in-Aid for Scientific Research(基盤研究(B))
    2004 - 2006
    Nobuki KUDO; 山本 克之
    Improvement of a high-speed observation systemTo improve spatial and temporal resolutions of high-speed observation, the use of an image intensifier with a high-speed camera and the use of an improved optical condenser for a short-arc flash lamp were examined. The use of these devices resulted in a reduction in minimum exposure time from 200 ns to 20 ns at a 40x objective and an increase in maximum framing rate from 4-million to 16-million fps.Development of a system for measurement of pressure-dependent attenuationA system for measurement of attenuation of microbubble suspensions was devel...
    Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(B), 北海道大学, Principal investigator, Competitive research funding, 16300168
  • Development of an instrument for temporal and spatial analyses of distribution of muscle oxygenation using near-infrared spectroscopy and its applications
    Grants-in-Aid for Scientific Research(基盤研究(B))
    2004 - 2006
    Katsuyuki YAMAMOTO; 工藤 信樹; 川初 清典; 河原 剛一; 高橋 英嗣
    In this study, a small and lightweight instrument based on spatially resolved near-infrared spectroscopy (SR-NIRS) was developed for real-time imaging of muscle oxygenation. From the results of temporal and spatial analyses of muscle oxygenation during exercise tests, we elucidated the relationship between changes in muscle oxygenation and metabolism and established the basics of NIRS as a standard technique for functional imaging of muscle. The following results were obtained.1. Development of an imaging instrument for muscle oxygenation based on spatially resolved NIRSCompact multi-channe...
    Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(B), 北海道大学, Coinvestigator not use grants, Competitive research funding, 16300142
  • 微小気泡存在下での超音波照射による期外収縮発生の機序:培養心室筋細胞を用いた検討
    科学研究費補助金(萌芽研究)
    2004 - 2005
    工藤 信樹; 山本 克之; 河原 剛一
    ○超音波パルス照射による期外収縮の発生自律拍動する培養心筋細胞に,直径数ミクロンの微小気泡を接触させた状態とさせない状態で超音波パルスを照射し,心筋細胞に生じる拍動リズムの変化を観察した.その結果,超音波診断装置に準じたパルス超音波の照射でも,以下に述べる特定の音圧と照射タイミングにおいて,超音波照射と同期して期外収縮が発生することを確認した.また,蛍光試薬を用いて細胞損傷を調べた結果,細胞膜に損傷が無くても期外収縮が起き得ることが示された.○音圧閾値超音波パルスの音圧と期外収縮の発生頻度の関連を,培養心筋細胞を用いて調べた.この検討では,昨年開発した心筋拍動非接触計測装置を用いて,心筋の収縮開始から超音波照射までのディレイを一定(350-400ms)に制御した.実験の結果,期外収縮の発生には音圧閾値があること,その値は気泡が細胞に接触した条件では明らかに低下することを確認した.これは,気泡が細胞近傍に存在する場合,より強い放射圧を受けた気泡が2次的に細胞に機械的作用をおよぼすためと考えられた.○照射時相の影響音圧を一定として,超音波を照射するタイミングを変えながら期外収縮発生の頻度を調べた.その結果,超音波パルスを心筋の収縮開始直後から約200msまでの間に照射した場合には期外収縮がまったく発生せず,これを超えると発生したことから,期外収縮の発生には時間的な閾値も存在するこ...
    文部科学省, 萌芽研究, 北海道大学, Principal investigator, Competitive research funding, 16650118
  • Experimental verification of causal relationships between measurements of near-infrared spectroscopy and mechanisms of oxygen transport to skeletal muscles
    Grants-in-Aid for Scientific Research(基盤研究(B))
    2001 - 2003
    Katsuyuki YAMAMOTO; 河原 剛一; 浜岡 隆文; 工藤 信樹
    The purpose of this research project was to experimentally verify the causal relationships between measurements of near-infrared spectroscopy and the mechanisms of oxygen transport to the skeletal muscles. These relationships are essential for understanding temporal responses of NIRS measurements. The following results were obtained from measurements in volunteers, computer simulation of tissue metabolism and microspectroscopic studies in animals.(1) Spatio-temporal analyses of muscle metabolism based on muscle oxygenation imaging : An imaging system of muscle oxygen saturation using spatia...
    Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(B), 北海道大学, Coinvestigator not use grants, Competitive research funding, 13480286
  • Optical imaging of biological tissue using speckle patterns of ultrasound-modulated light
    Grants-in-Aid for Scientific Research(基盤研究(C))
    2001 - 2002
    Nobuki KUDO; 山本 克之
    To improve spatial resolution of optical imaging of biological tissue, a new method using speckle patterns of ultrasound-modulated light was proposed. Results of experimental evaluations of the proposed method are summarized as follows.1. A proposed method and an experimental system : To detect temporal variations of optical speckle patterns in ultrasound frequency, we used a conventional CCD still camera and introduced a principle of a strobe scope, that is, the shutter of the CCD still camera is open and the object observed is illuminated by pulsed light synchronized with exposed ultrasou...
    Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(C), 北海道大学, Principal investigator, Competitive research funding, 13680921
  • DDSを目的とした超音波照射によるマイクロカプセルの破壊制御
    科学研究費補助金(萌芽的研究, 萌芽研究)
    2001 - 2002
    山本 克之; 工藤 信樹
    マイクロカプセルを用いたDDSにおいて,カプセルに付加した薬剤が効率よく細胞内に取り込まれるよう超音波の照射条件を最適化し,カプセルの破壊を制御するには,マイクロカプセルなどの微小気泡の存在が細胞への薬剤取り込みを促進するメカニズムを明らかにする必要がある.そこで本年度は,下記の2点に関する検討を行った.1.細胞と気泡の相互作用の高速度観察前年度に行った高速度観察から,気泡が急速に収縮する際に微小な流れが発生し,これが気泡の崩壊の原因になっていることが示された.そこで本年度は,このような気泡のふるまいが細胞に作用を与える可能性に関する検討を行うために,培養した血管内皮細胞を用いて,細胞と微小気泡の相互作用の高速度撮影を行った.その結果,細胞の近傍に気泡が存在する場合に,明らかに気泡のふるまいに同期した細胞の変形が観察された.これは,気泡が存在しない場合には,超音波のエネルギは細胞にほとんど作用を及ぼさずに透過してしまうが,気泡が存在する場合には,超音波のエネルギが一旦気泡の運動エネルギに変換され.気泡のふるまいにより2次的に細胞が作用を受けているものと考えられた.2.Sonoporation(細胞穿孔)のメカニズムの解明高速度観察では,細胞の変形は観察できるものの画質が低く,細胞が受ける作用を詳細に観察することができなかった.そこで,パルス超音波照射下において気泡のふるまいが...
    文部科学省, 萌芽的研究, 萌芽研究, 北海道大学, Coinvestigator not use grants, Competitive research funding, 13878178
  • Development of a tissue oxygen monitor using near-infrared light with correction for influence of tissue inhomogeneity and quantitaive evaluation of muscle metabolism
    Grants-in-Aid for Scientific Research(基盤研究(B))
    1999 - 2001
    Katsuyuki YAMAMOTO; 清水 孝一; 川初 清典; 工藤 信樹; 浜岡 隆文
    The objectives of this study were to develop a tissue oxygen monitor that can eliminate the influence of a fat layer on muscle oxygenation measurement using near-infrared spectroscopy (NIRS) and to establish quantitative NIRS by verifying the validity of this technique in the field of sports medicine.1. Mean optical properties (absorption and scattering coefficients) of muscle and adipose tissues were determined by comparing results of in vivo measurements using time-resolved NIRS with those of Monte Carlo simulation using a multi-layered model.2. A nonlinear algorithm for tissue oxygenatio...
    Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(B), 北海道大学, Coinvestigator not use grants, Competitive research funding, 11558100
  • High-resolution imaging and tissue characterization using a miniaturized ultrasound probe mounted on a puncturing needle
    Grants-in-Aid for Scientific Research(基盤研究(B))
    1998 - 2000
    Nobuki KUDO; 清水 匡; 三神 大世; 山本 克之
    In this study, a high-frequency miniaturized ultrasound probe mounted on a puncturing needle and an imaging system for this probe have been developed. The usefulness of this imaging system has been evaluated in in vitro and in vivo experiments. We have also studied the feasibility of tissue characterization using ultrasound attenuation in a high-frequency region. The following results were obtained.Development of the miniaturized ultrasound probe and imaging system A miniaturized probe mounted on a 16-20 gage puncturing needle that can be stuck into a tissue has been developed. A 2-D ultras...
    Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(B), 北海道大学, Principal investigator, Competitive research funding, 10480239
  • Basic studies on optical imaging of biological tissue using ultrasound-modulated near-infrared light
    Grants-in-Aid for Scientific Research(基盤研究(B))
    1998 - 2000
    Katsuyuki YAMAMOTO; 工藤 信樹; 清水 孝一
    In this study, a new technique to improve a spatial resolution of optical imaging of biological tissues using ultrasound-modulated light was developed, and the following results were obtained.Study on mechanisms of light modulation by ultrasoundTwo high-sensitivity detection systems of ultrasound-modulated light using a photomultiplier or an interferometer were developed. Relationships between a signal intensity of ultrasound-modulated light and a scattering coefficient of a turbid medium were obtained from experiments on a tissue phantom. Based on these relationships, the mechanisms of lig...
    Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(B), 北海道大学, Coinvestigator not use grants, Competitive research funding, 10480238
  • Research on construction of inner-space of learning disabilities by audio-visual stimulation
    Grants-in-Aid for Scientific Research(基盤研究(B))
    1998 - 2000
    Makoto TAKAHASHI; 村田 和香; 工藤 信樹; 山本 克之; 水戸部 一孝
    A number of children with learning disabilities (LD) are not good at visuomotor control. In this study, we analyzed hand trajectories of reaching movements under rotated visual feedback in subjects with and without LD.Each reaching movement has two components : an "initial impulse" (ballistic movement) and a series of "secondary adjustments" (corrective movement) made subsequently to attain the final target position. In the present study, the error in ballistic movement was determined by measuring the angle between the direction in which the subject started to reach out and the direction of...
    Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(B), 北海道大学, Coinvestigator not use grants, Competitive research funding, 10558015
  • 超音波による光変調を用いた生体の構造と機能の近赤外光イメージング
    科学研究費補助金(萌芽的研究)
    1998 - 1999
    工藤 信樹; 山本 克之
    超音波で変調した光を用いて,強散乱体である生体の断層像を比較的高い空間分解能で画像化する手法に関し,平成11年度において以下に述べる検討を行った.・微弱光検出システムの改良 昨年度作成した微弱変調光検出システムの改良を行った.ロックインアンプの参照周波数の取得法を変更することなどにより,計測系のノイズレベルを50dB程度低減することができた.・透過光に含まれる変調成分の検出 超音波と光の進行方向を直交させた配置では,超音波による強度変調,位相変調ともに検出が可能であったが,散乱体の濃度が大きくなるとともにレーザ光のコヒーレンシィが低下し,強度変調のみが検出された.散乱体厚が35mmの場合,散乱係数が0.1mm^<-1>増加すると変調強度は約100dB低下した.これをもとに推測すると,超音波とレーザ光の強度の向上を合計80dB見込んだ上で,生体での観察可能な厚さは約10mmと考えられた.・後方散乱した変調光の検出 後方散乱光に含まれる変調光成分は,超音波と光を直交させた配置では検出できなかったが,光と超音波を対向させ,超音波による散乱体振動にもとづく光の位相変調を干渉光学系で検出する方式では検出できた.観察可能な深さは約5mmであり,後方散乱した超音波変調光を用いる手法の有用性が確認された.
    文部科学省, 萌芽的研究, 北海道大学, Principal investigator, Competitive research funding, 10878158
  • Development of portable near-infrared muscle oximeter using multi-sensor method.
    Grants-in-Aid for Scientific Research(基盤研究(A))
    1996 - 1998
    Katsuyuki YAMAMOTO; 志賀 利一; 工藤 信樹; 高橋 誠; 清水 孝一
    A portable tissue oximeter based on two-wavelength near-infrared spectroscopy with multiple photo sensors was developed for a real-time, ambulatory measurement of muscle oxygenation. This oximeter can eliminate the influences of inhomogeneous structure of tissues on the measurement and is useful for quantitative evaluation of muscle oxygenation in the fields of sports and rehabilitation medicine as well as in muscle tissue physiology. Important results of this study are summarized as follows.Development of the portable tissue oximeter : The oximeter was made compact for the ambulatory measu...
    Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(A), 北海道大学, Coinvestigator not use grants, Competitive research funding, 08558090
  • Research on relation between the inner space and posture of learning disabilities when audio-visual stimulating
    Grants-in-Aid for Scientific Research(基盤研究(C))
    1996 - 1998
    Makoto TAKAHASHI; 村田 和香; 工藤 信樹; 山本 克之
    The research objective is the construction process of the human inner space when several kinds of audio-visual stimulation are applied. When stimulating time is varied, accuracy of location of stimulation and posture movement were measured. Two types of experimentes have been performed. One is sitting experiment and the other is standing one. Sitting at the center of the semicircle (1.5 m radius) with arrangement of red LEDs and speakers of which interval is 10 degrees., subject indicates the direction of stimulus in a dark and silent room. Motion of the head and the indicating direction ar...
    Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(C), 北海道大学, Coinvestigator not use grants, Competitive research funding, 08680221
  • Blood Flow Imaging Technique for Intravascular Ultrasound
    Grants-in-Aid for Scientific Research(基盤研究(C))
    1996 - 1997
    Nobuki KUDO; 高橋 誠; 山本 克之
    1.RF echo processingWe developed a new time domain correlation technique for detecting displacement and velocity vectors. The technique is based on calculation of the correlation between RF echo detected by a single transducer at a fixed repetition rate. Relation between the velocity vector and correlation was derived theoretically. Advanced RF signal processing techniques for evaluation of structure and charactor of biological tissue were also discussed.2.Measurement system>>Transducers for IVUSSmall transducers (1.2mm * 0.8mm) which can be used in the IVUS catheter were developed. Improve...
    Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(C), 北海道大学, Principal investigator, Competitive research funding, 08680920
  • Development of CT Imaging Technique Using Multi-wavelengh and Ultra-short Light Pulse
    Grants-in-Aid for Scientific Research(基盤研究(B))
    1996 - 1997
    Koichi SHIMIZU; 福島 菊郎; 工藤 信樹; 加藤 祐次; 山本 克之
    A fundamental study was conduced to realize the transilumination and the CT imaging of biological functions using multi-wavelength and ultra-short light pulse. Through this research the following progresses were made.(1) Through theoretical and experimental study, it was shown that we can get the image of functional change occurred inside an animal body using the light of multiple wavelengths in near-infrared region. The imaging can be perfomed noninvasively with a relatively simple apparatus.(2) A transilumination imaging system was developed based on the proposed principle. Using this sys...
    Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(B), 北海道大学, Coinvestigator not use grants, Competitive research funding, 08458281
  • Study on biomechanics of bone remodeling at microscopic level during orthodontic treatment
    Grants-in-Aid for Scientific Research(基盤研究(C))
    1996 - 1997
    Katsuyuki YAMAMOTO; 森川 一; 工藤 信樹; 佐藤 嘉晃
    The purpose of this study is to clarify the causal relationship between mechanical stress and alveolar bone remodeling during orthodontic treatment. Material constants of the periodontal ligament (PDL) are indispensable parameters for stress analysis of a tooth and the surrounding tissues. However, few experimentally determined values have been reported. In this study, we developed a small compressive and tensile test machine in order to determine the material constants of the PDL.In tension tests, stress-strain curves did not significantly depend on strain rates. In contrast, compressive t...
    Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(C), 北海道大学, Coinvestigator not use grants, Competitive research funding, 08680919
  • 光および超音波による生体計測
    1995
    Competitive research funding
  • Measurements of biomedical parameters using optical and ultrasonic techniques
    1995
    Competitive research funding
■ Industrial Property Rights
  • 超音波プローブ及び超音波診断装置
    Patent right
    特許公開平９−５２２
  • 衝撃波治療装置
    Patent right
    特許公開平８−３０８８４９
  • 衝撃波治療装置
    Patent right
    特許公開平８−２９９３５０
  • 超音波診断装置
    Patent right
    特許公開平８−２９４４９０
  • 衝撃波治療装置
    Patent right
    特許公開平８−２５２２５９
  • 超音波探触子
    Patent right
    特許公開平８−１９１８３５
  • Heat measurement apparatus for inspecting therapeutic energy waves
    Patent right
    US-A1-005465625
  • 結石破砕装置
    Patent right
    特許公開平６−３２７６９１
  • 超音波測定用ハイドロホン
    Patent right
    特許公開平６−２４１８８５
  • Shockwave treatment apparatus
    Patent right
    US-A1-005174294
  • 音圧測定装置
    Patent right
    特許公開平５−３０６９６１
  • Pressure measurement apparatus for inspecting therapeutic energy waves
    Patent right
    US-A1-005357805
  • A pressure measurement apparatus for inspecting therapeutic energy waves (DE,FR)
    Patent right
    EP-A2-000509800
  • 圧力測定装置
    Patent right
    特許公開平５−７２０７１
  • Shock wave generating apparatus capable of setting moving direction of shock wave generating source to ultrasonic tomographic image plane
    Patent right
    US-A1-00521310
  • 超音波治療装置
    Patent right
    特許公開平５−１９２３４３
  • 超音波結石破砕装置
    Patent right
    特許公開平５−３１１１９
  • Acoustic wave therapy apparatus (DE,NL)
    Patent right
    EP-A1-000404121
  • Acoustic wave therapy apparatus
    Patent right
    US-A1-005095907
  • 衝撃波治療装置及び温熱治療装置
    Patent right
    第２９６８５６１号
  • Shock wave generating apparatus capable of setting moving direction of shock wave generating source to ultrasonic tomographic image plane (DE,FR)
    Patent right
    EP-A1-000397056
  • Shock wave treatment apparatus (DE,FR)
    Patent right
    EP-A1-000548048
  • Shock wave treatment apparatus (FR, DE)
    Patent right
    EP-A1-000367116
  • 超音波治療装置
    Patent right
    第２９３７３４４号
  • 衝撃波治療装置
    Patent right
    1867287
  • 衝撃波治療装置
    Patent right
    第２６４５０３８号

Research Profiles

■ Research Profiles