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Last Updated :2024/06/07

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Master

Affiliation (Master)

  • Faculty of Information Science and Technology　Bioengineering and Bioinformatics　Bioengineering

Affiliation (Master)

  • Faculty of Information Science and Technology　Bioengineering and Bioinformatics　Bioengineering

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Profile and Settings

Affiliation

  • Hokkaido University, Graduate School of Information Science and Technology, Division of Bioengineering and Bioinformatics, Biomedical Systems Engineering, Associate Professor

Degree

  • MS and PhD degree in Biomedical Engineering in 1984 and 1987（Hokkaido University）

Profile and Settings

  • Name (Japanese)

    Kudo

  • Name (Kana)

    Nobuki

  • Name

    200901019019923127

Alternate Names

Affiliation

  • Hokkaido University, Graduate School of Information Science and Technology, Division of Bioengineering and Bioinformatics, Biomedical Systems Engineering, Associate Professor

Achievement

Research Interests

  • 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 Areas

  • Humanities & social sciences / Educational technology
  • Life sciences / Medical systems
  • Life sciences / Biomaterials
  • Life sciences / Biomedical engineering

Research Experience

  • 2009 - 2013 Hokkaido University
  • 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

Education

  •        - 1987  Hokkaido University
  •        - 1984  Hokkaido University
  •        - 1984  Hokkaido University
  •        - 1982  Hokkaido University  School of Engineering  Department of Electronics Engineering
  •        - 1982  Hokkaido University  Faculty of Engineering

Awards

  • 2013 日本超音波医学会 第２回新人賞
     
    受賞者: 内田和輝
  • 2012 日本超音波医学会 第１回新人賞
     
    受賞者: 吉松幸里
  • 2010 日本超音波医学会 第26回菊池賞（論文賞）
  • 2009 日本超音波医学会 第25回菊池賞（論文賞）
  • 2007 平成19年日本ソノケミストリー学会論文賞
  • 2005 日本超音波医学会 第21回菊池賞（論文賞）
  • 2005 日本超音波医学会 第７回奨励賞
  • 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）
  • 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）
  • 1992 日本エム・イー学会科学新聞賞新技術開発賞

Published Papers

  • 超音波医学をどう広めるか?～医学教育と一般広報について～ 超音波医学をどう広めるか?
    小川 眞広, 秋山 いわき, 工藤 信樹, 紺野 啓, 長沼 裕子, 新田 尚隆, 水野 隆, 畠 二郎
    超音波医学 (公社)日本超音波医学会 50 (Suppl.) S547 - S547 1346-1176 2023/04
  • マイクロバブルと超音波照射による固形がん組織の腫瘍微小環境変化を介した養子免疫療法の抗腫瘍効果増強に関する検討
    鈴木 亮, 丸山 保, 宗像 理紗, 鈴木 悠乃, 小俣 大樹, 工藤 信樹, 小山 正平, 岡田 欣晃
    Thermal Medicine (一社)日本ハイパーサーミア学会 38 (Suppl.) 085 - 085 1882-2576 2022/08
  • マイクロバブルと超音波照射による固形がん組織の腫瘍微小環境変化を介した養子免疫療法の抗腫瘍効果増強に関する検討
    鈴木 亮, 丸山 保, 宗像 理紗, 鈴木 悠乃, 小俣 大樹, 工藤 信樹, 小山 正平, 岡田 欣晃
    Thermal Medicine (一社)日本ハイパーサーミア学会 38 (Suppl.) 085 - 085 1882-2576 2022/08
  • 毛細血管ゲルファントムを用いた微小気泡ダイナミクスの高速度観察による弾性率の推定
    Hu Xinyue, 小俣 大樹, 鈴木 亮, 佐々木 東, 工藤 信樹
    超音波医学 (公社)日本超音波医学会 49 (Suppl.) S802 - S802 1346-1176 2022/04
  • 抗がん剤付着型アルブミンナノ粒子と微小気泡を用いた超音波薬物送達の機序検討
    新里 美瑠, 胡 新げつ, 小俣 大樹, 鈴木 亮, 佐々木 東, 工藤 信樹
    超音波医学 (公社)日本超音波医学会 49 (Suppl.) S803 - S803 1346-1176 2022/04
  • 気泡を貪食した樹状細胞への超音波照射による継続的なCa2+濃度変化誘導
    大竹 直幸, 鈴木 亮, 小俣 大樹, 工藤 信樹
    超音波医学 (公社)日本超音波医学会 49 (Suppl.) S825 - S825 1346-1176 2022/04
  • 微小気泡を貪食した樹状細胞の超音波照射によるCa2+濃度変化誘導現象の高速度観察
    大竹 直幸, 鈴木 亮, 小俣 大樹, 工藤 信樹
    超音波医学 (公社)日本超音波医学会 49 (Suppl.) S827 - S827 1346-1176 2022/04
  • 毛細血管ゲルファントムを用いた微小気泡ダイナミクスの高速度観察による弾性率の推定
    Hu Xinyue, 小俣 大樹, 鈴木 亮, 佐々木 東, 工藤 信樹
    超音波医学 (公社)日本超音波医学会 49 (Suppl.) S802 - S802 1346-1176 2022/04
  • 抗がん剤付着型アルブミンナノ粒子と微小気泡を用いた超音波薬物送達の機序検討
    新里 美瑠, 胡 新げつ, 小俣 大樹, 鈴木 亮, 佐々木 東, 工藤 信樹
    超音波医学 (公社)日本超音波医学会 49 (Suppl.) S803 - S803 1346-1176 2022/04
  • マイクロバブルと超音波併用による免疫微小環境の変化と養子免疫療法の抗腫瘍効果増強に関する基礎的検討
    丸山 保, 宗像 理紗, 小俣 大樹, 萩原 芙美子, 鈴木 悠乃, 小山 正平, 岡田 欣晃, 工藤 信樹, 鈴木 亮
    日本薬学会年会要旨集 (公社)日本薬学会 142年会 28H - pm05S 0918-9823 2022/03
  • マイクロバブルと超音波併用による免疫微小環境の変化と養子免疫療法の抗腫瘍効果増強に関する基礎的検討
    丸山 保, 宗像 理紗, 小俣 大樹, 萩原 芙美子, 鈴木 悠乃, 小山 正平, 岡田 欣晃, 工藤 信樹, 鈴木 亮
    日本薬学会年会要旨集 (公社)日本薬学会 142年会 28H - pm05S 0918-9823 2022/03
  • Naoyuki Otake, Ryo Suzuki, Daiki Omata, Nobuki Kudo
    IEEE International Ultrasonics Symposium, IUS 2022-October 1948-5719 2022 
    The possibility of intracellular Ca2+ elevation being induced by short-pulsed ultrasound was investigated using cultured cells of the murine dendritic cell line DC2.4. Dendric cells (DCs) with phagocytosed microbubbles were irradiated by 3-cycle ultrasound of 0.2-0.6 MPa in peak-negative pressure to achieve safe and efficient mechanical stimulation. Two types of microbubbles, lipid-shell bubbles of about 1 μmn diameter and plastic-shell bubbles of 3-5 μm in diameter, were used to examine the effect of bubble dynamics on triggering Ca2+ elevation and cell damage generation. Experimental results showed that, in the presence of microbubbles, even pulsed ultrasound at diagnostic levels could induce Ca2+ elevation. It was also shown that the plastic-shell bubbles, which show contraction-only oscillation, can induce repetitive Ca2+ elevations under multiple exposures of pulsed ultrasound. The results indicate that ultrasonic irradiation can induce sustained mechanical sensation of DCs, enhancing their antigen-presenting ability through cell maturation.
  • Noboru Sasaki, Yoshinori Ikenaka, Keisuke Aoshima, Teiichiro Aoyagi, Nobuki Kudo, Kensuke Nakamura, Mitsuyoshi Takiguchi
    Frontiers in pharmacology 13 837754 - 837754 2022 
    Intravesical chemotherapy after transurethral resection is a treatment option in patients with non-muscle invasive bladder cancer. The efficacy of intravesical chemotherapy is determined by the cellular uptake of intravesical drugs. Therefore, drug delivery technologies in the urinary bladder are promising tools for enhancing the efficacy of intravesical chemotherapy. Ultrasound-triggered microbubble cavitation may enhance the permeability of the urothelium, and thus may have potential as a drug delivery technology in the urinary bladder. Meanwhile, the enhanced permeability may increase systemic absorption of intravesical drugs, which may increase the adverse effects of the drug. The aim of this preliminary safety study was to assess the systemic absorption of an intravesical drug that was delivered by ultrasound-triggered microbubble cavitation in the urinary bladder of normal dogs. Pirarubicin, a derivative of doxorubicin, and an ultrasound contrast agent (Sonazoid) microbubbles were administered in the urinary bladder. Ultrasound (transmitting frequency 5 MHz; pulse duration 0.44 μsec; pulse repetition frequency 7.7 kHz; peak negative pressure -1.2 MPa) was exposed to the bladder using a diagnostic ultrasound probe (PLT-704SBT). The combination of ultrasound and microbubbles did not increase the plasma concentration of intravesical pirarubicin. In addition, hematoxylin and eosin staining showed that the combination of ultrasound and microbubble did not cause observable damages to the urothelium. Tissue pirarubicin concentration in the sonicated region was higher than that of the non-sonicated region in two of three dogs. The results of this pilot study demonstrate the safety of the combination of intravesical pirarubicin and ultrasound-triggered microbubble cavitation, that is, ultrasound-assisted intravesical chemotherapy.
  • Kazuhiro Nishida, Yuji Kato, Nobuki Kudo, Koichi Shimizu
    Japanese Journal of Applied Physics 60 (7) 0021-4922 2021/07 
    For a practical technique of cross-sectional imaging of animal bodies, we developed a new method using spatially resolved backscattered light. This method is based on the solution of the one-dimensional nonlinear inverse problem, and on the lateral scan of the source-detector pair along the object surface. Using this method, unknown variables in inverse problems can be reduced more greatly than when using conventional methods. A stable solution for the inverse problem becomes possible. The possibility of using the proposed method was assessed using simulation analysis. The results verified that cross-sectional imaging from several to 10 millimeter depths is possible for animal tissue. This analysis clarified the specific spatial resolution and accuracy in the estimated absorption coefficient. Distortionless imaging was confirmed. Results suggest that the proposed method represents new options as a stable and practical method for biological cross-sectional imaging.
  • マイクロバブルの繰り返し投与における血流造影への影響に関する基礎的検討
    鈴木 亮, 島 忠光, 丸山 保, 小俣 大樹, 宗像 理紗, 工藤 信樹, 丸山 一雄
    超音波医学 (公社)日本超音波医学会 48 (Suppl.) S648 - S648 1346-1176 2021/04
  • 超音波で生体の壁を超える 超音波と気泡を併用する膀胱内注入療法の犬における安全性検討
    佐々木 東, 青柳 貞一郎, 池中 良徳, 工藤 信樹, 中村 健介, 滝口 満喜
    超音波医学 (公社)日本超音波医学会 48 (Suppl.) S195 - S195 1346-1176 2021/04
  • Ri Ichiro Shimizu, Ryo Suzuki, Nobuki Kudo
    IEEE International Ultrasonics Symposium, IUS 2020-September 1948-5719 2020/09/07 
    Mechanisms of BBB opening were investigated using a capillary model created by a three-dimensional cell culture technique. The model was made using human umbilical vein endothelial cells (HUVECs) suspended in collagen gel. Incubation with endothelial growth factor for one week resulted in the creation of capillary lumens, and a suspension of microbubbles supplemented with FITC-dextran, SYTOX Blue, and Calcein-AM was introduced inside the lumens. Bubble-cell interaction under exposure to short pulsed ultrasound of 1.0 MHz in center frequency and 0.4 MPa in peak negative pressure was captured using a high-speed camera, and lumen and endothelial cell damage was visualized using fluorescence microscopy. High-speed observation showed that non-uniform contraction of a bubble caused significant local deformation of the lumen beside the bubble, and strong extravasation from the lumen (FITC-dextran) and significant membrane damage of the endothelial cells (SYTOX Blue) were confirmed at this location. Lethal damage was also observed frequently (Calcein). On the other hand, cells on the opposite side of the lumen received stretching force during bubble expansion, and smaller extravasation and cell damage maintained the integrity of endothelial cells. These suggested the presence of different mechanisms of BBB opening.
  • Antoine Presset, Corentin Bonneau, Sasaoka Kazuyoshi, Lydie Nadal-Desbarats, Takigucho Mitsuyoshi, Ayache Bouakaz, Nobuki Kudo, Jean-Michel Escoffre, Noboru Sasaki
    Ultrasound in medicine & biology 46 (7) 1565 - 1583 2020/04/21 [Refereed][Not invited]
     
    Microbubble-assisted ultrasound has emerged as a promising method for local drug delivery. Microbubbles are intravenously injected and locally activated by ultrasound, thus increasing the permeability of vascular endothelium for facilitating extravasation and drug uptake into the treated tissue. Thereby, endothelial cells are the first target of the effects of ultrasound-driven microbubbles. In this review, the in vitro and in vivo bioeffects of this method on endothelial cells are described and discussed, including aspects on the permeabilization of biologic barriers (endothelial cell plasma membranes and endothelial barriers), the restoration of their integrity, the molecular and cellular mechanisms involved in both these processes, and the resulting intracellular and intercellular consequences. Finally, the influence of the acoustic settings, microbubble parameters, treatment schedules and flow parameters on these bioeffects are also reviewed.
  • Kazuhiro Nishida, Yuji Kato, Nobuki Kudo, Koichi Shimizu
    Optics and Lasers in Engineering 126 1 - 11 0143-8166 2020/03 [Refereed][Not invited]
     
    This report presents a proposal of a new technique to estimate the cross-sectional absorption distribution of turbid media from backscattered light by solving a nonlinear inverse problem. After illuminating a beam of light on the surface of a turbid object and measuring the backscattered light as a function of distance from the light incident point, we divide the object into multiple virtual layers to estimate the absorption distribution. The path lengths of photon propagation in the respective layers are calculated using Monte Carlo simulation. The absorption coefficient of each virtual layer can be estimated from the backscattered intensity and the path length distribution in a depth direction. For solving this inverse problem, the linear calculation results are useful as initial solutions. Then the final solutions are obtained from iteration of the nonlinear calculation. Convergence into a unique solution and robustness of the solution against the measurement noise were confirmed. The effectiveness of the proposed technique was verified through simulation and measurement. By lateral scanning of a source detector pair, we can reconstruct a cross-sectional image of the turbid medium to the depth to which the detected light reaches.
  • Johan Unga, Daiki Omata, Nobuki Kudo, Soki Ueno, Lisa Munakata, Tadamitsu Shima, Ryo Suzuki, Kazuo Maruyama
    Journal of liposome research 29 (4) 368 - 374 2019/12 [Refereed][Not invited]
     
    It is known that Phosphatidyl choline-Phosphatidyl glycerol mixtures can be used for liposome formulations, making them less leaky than liposomes with only one lipid. We hypothesized that this might also be the case for bubbles, which can be used as ultrasound (US) contrast agents. Therefore, we have compared a series of mixed distearoyl phosphatidylcholine-distearoyl phosphatidylglycerol (DSPC-DPSG) bubbles and with bubbles containing either DSPC or DSPG (and distearoyl ethanolamine-polyethyleneglycol 2000, DSPE-PEG2k). Here, we describe the development, examination of stability in vitro and attenuation of broad frequency US pulses. Novel lipid-stabilized freeze-dried formulations for US applications, using the phospholipids DSPC, DSPG, and PEGylated DSPE-PEG2k and perfluoropropane gas were developed. It was found that the bubbles could effectively be preserved by freeze-drying and then re-constituted by addition of water. Average bubble sizes were around 2 µm for all bubbles after re-constitution. Bubble stability was assessed by evaluating the decay of the US backscattering signal in vitro. Bubbles containing DSPG were more stable than bubbles with only DSPC. The composition DSPC:DSPG:DSPE-PEG2k 30:60:10 (molar ratio) was the most stable with an effective half-life of 9.12 min, compared to bubbles without DSPG, which had half-life of 2.05 min. Bubble attenuation of US depended highly on the compositions. Bubbles without DSPG had the highest attenuation indicating higher oscillation the most but were also destroyed by higher energy US. No bubbles with DSPG showed any indication of destruction but all had increased attenuations to varying degrees, DSPC:DSPG:DSPE-PEG2k 45:45:10 showed the least attenuation.
  • Sogo Toda, Yuji Kato, Nobuki Kudo, Koichi Shimizu
    Japanese Journal of Applied Physics Japan Society of Applied Physics 58 (3) 1 - 4 0021-4922 2019/03 [Refereed][Not invited]
     
    Far transillumination imaging of animal tissue, we have developed a technique to suppress the scattering effect in a turbid medium using the time-reversal principle of phase-conjugate light. In biomedical applications of this technique, the effects of absorption variation and the applicable tissue thickness must be clarified. Analysis of experimental data revealed that the scattering suppression capablity of the, proposed technique is independent of the absorption change of a turbid medium. Results also verified that the applicable thickness of animal tissue can be extended using a light source with greater coherence length. (C) 2019 The Japan Society of Applied Physics
  • Sogo Toda, Yuji Kato, Nobuki Kudo, Koichi Shimizu
    ADAPTIVE OPTICS AND WAVEFRONT CONTROL FOR BIOLOGICAL SYSTEMS V 10886 0277-786X 2019
  • Noboru Sasaki, Nobuki Kudo, Hiroshi Ohta, Mitsuyoshi Takiguchi
    2019 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS) 1308 - 1310 1948-5719 2019 
    Axon regeneration is crucial for the functional recovery after spinal cord injury. Myelin-related growth inhibitors, such as Nogo-A, inhibit neurites regrowth and elongation. Low-intensity pulsed ultrasound (LIPUS) is known to show neuroprotective effects in neurodegenerative diseases. In the present study, we evaluated the feasibility of LIPUS for enhancing axon regeneration in the presence of Nogo-A. Low-intensity pulsed ultrasound was exposed to rat cortical neurons in vitro after Nogo-A treatment. The total length of neurites per cell in LIPUS group was significantly larger than that of non-LIPUS group. There was no significant difference in the number of neurites. The results suggest that LIPUS may enhance the elongation of neurites in the presence of Nogo-A while may not affect on neurites sprouting and branching. This preliminary study implies the feasibility of LIPUS for axonal regeneration.
  • Iwaki Akiyama, Pak Kon Choi, Hiroyuki Hachiya, Akira Harata, Hideyuki Hasegawa, Kenya Hashimoto, Shoji Kakio, Nobuki Kudo, Subaru Kudo, Mami Matsukawa, Tatsuro Matsuoka, Koichi Mizutani, Kentaro Nakamura, Hirotsugu Ogi, Shinichi Takeuchi, Takao Tsuchiya, Shin ichiro Umemura, Yasuaki Watanabe, Ken Yamada, Kyuichi Yasui
    Japanese Journal of Applied Physics 57 (7) 0021-4922 2018/07 [Refereed][Not invited]
  • Sogo Toda, Yuji Kato, Nobuki Kudo, Koichi Shimizu
    Biomedical Optics Express 9 (4) 1570 - 1581 2156-7085 2018/04/01 [Refereed][Not invited]
     
    For transillumination imaging of animal tissues, we have attempted to suppress the scattering effect in a turbid medium using the time-reversal principle of phase-conjugate light. We constructed a digital phase-conjugate system to enable intensity modulation and phase modulation. Using this system, we clarified the effectiveness of the intensity information for restoration of the original light distribution through a turbid medium. By varying the scattering coefficient of the medium, we clarified the limit of time-reversal ability with intensity information of the phase-conjugate light. Experiment results demonstrated the applicability of the proposed technique to animal tissue.
  • Noboru Sasaki, Kazuhiro Ishi, Nobuki Kudo, Shouta M. M. Nakayama, Kensuke Nakamura, Keitaro Morishita, Hiroshi Ohta, Mayumi Ishizuka, Mitsuyoshi Takiguchi
    PLOS ONE 12 (11) e0188093  1932-6203 2017/11 [Refereed][Not invited]
     
    Non-muscle invasive bladder cancer is one of the most common tumors of the urinary tract. Despite the current multimodal therapy, recurrence and progression of disease have been challenging problems. We hereby introduced a new approach, ultrasound-assisted intravesical chemotherapy, intravesical instillation of chemotherapeutic agents and microbubbles followed by ultrasound exposure. We investigated the feasibility of the treatment for nonmuscle invasive bladder cancer. In order to evaluate intracellular delivery and cytotoxic effect as a function to the thickness, we performed all experiments using a bladder cancer mimicking 3D culture model. Ultrasound-triggered microbubble cavitation increased both the intracellular platinum concentration and the cytotoxic effect of cisplatin at the thickness of 70 and 122 mu m of the culture model. The duration of enhanced cytotoxic effect of cisplatin by ultrasound-triggered microbubble cavitation was approximately 1 hr. Based on the distance and duration of delivery, we further tested the feasibility of repetition of the treatment. Triple treatment increased the effective distance by 1.6-fold. Our results clearly showed spatial and temporal profile of delivery by ultrasound-triggered microbubble cavitation in a tumor-mimicking structure. Furthermore, we demonstrated that the increase in intracellular concentration results in the enhancement of the cytotoxic effect in a structure with the certain thickness. Repetition of ultrasound exposure would be treatment of choice in future clinical application. Our results suggest ultrasound-triggered microbubble cavitation can be repeatable and is promising for the local control of non-muscle invasive bladder cancer.
  • Akane Isono, Nobuki Kudo
    IEEE International Ultrasonics Symposium, IUS 1948-5727 2017/10/31 [Refereed][Not invited]
     
    It is widely accepted that cell membrane rupture induced by bubbles oscillating beside the cells is a maj or mechanism of sonoporation however, elucidation of bubble dynamics by high-speed observation is still important because the behavior is highly dependent on their surrounding conditions. In this study, a new observation chamber was developed. The observation chamber allows observation of bubble-cell interaction from a lateral direction without obstruction of the view by the oscillating bubbles themselves. Dynamics of bubbles beside cells cultured on a soft scaffold was investigated.
  • Akane Isono, Nobuki Kudo
    IEEE International Ultrasonics Symposium, IUS 1948-5727 2017/10/31 [Refereed][Not invited]
     
    A high-speed observation system for sonoporation study was improved for observation of bubble and cell dynamics under ultrasound exposure from a lateral direction. The effect of the presence of a scaffold mimicking an in vivo situation on the dynamics was investigated to study the mechanisms by which bubbles cause cell membrane damage. Observations showed that the stiffness of the scaffold has a significant effect on bubble dynamics: a microbubble on a hard scaffold remains on its hard surface, but a bubble on a soft scaffold make a translational movement in a direction away from the soft surface. The same movement was observed for bubbles adhering to cell membranes, and bubble-cell interaction was classified into four phenomena. Higher frequencies of cell membrane damage were found in two phenomena: a phenomenon in which a bubble moving in a separating direction drags the cell membrane, resulting in membrane damage, and a phenomenon in which a jet flow generated by bubble-bubble interaction causes local deformation of a cell, resulting in membrane damage. The results suggest that the efficiency of in vivo sonoporation can be improved by utilizing the mechanisms observed in the two phenomena.
  • Nobuki Kudo
    The Micro-World Observed by Ultra High-Speed Cameras: We See What You Don't See 391 - 405 2017/08/30 [Refereed][Not invited]
     
    Cavitation is an important phenomenon that has been intensively studied in the field of fluid dynamics. The formation of cavitation bubbles is induced under the condition of pressure fluctuations in a fluid, and the collapse of bubbles elicits strong effects in their surroundings. Normally, cavitation does not occur inside a biological body however, the use of an artificial organ and irradiation of acoustic energy may induce the formation of cavitation bubbles inside the body. In this chapter, medical equipment is introduced, that induces or utilizes cavitation phenomena. A mechanical heart valve is known to generate bubbles that may cause thrombosis and valve failure, and various types of ultrasound exposure are used for medical purposes such as surgical equipment, non-invasive therapy, and drug delivery. High-speed observation plays an important role in visualizing cavitation activities generated in various applications. Results of observations provide valuable insights into the mechanisms by which cavitation bubbles elicit effects and also insights into how the effects can be minimized or maximized.
  • Mami Matsukawa, Jun Kondoh, Keiji Sakai, Iwaki Akiyama, Pak Kon Choi, Hiroyuki Hachiya, Akira Harata, Hideyuki Hasegawa, Kenya Hashimoto, Shoji Kakio, Nobuki Kudo, Subaru Kudo, Tatsuro Matsuoka, Koichi Mizutani, Kentaro Nakamura, Hirotugu Ogi, Sinichi Takeuchi, Takao Tsuchiya, Shinichiro Umemura, Yasuaki Watanabe, Ken Yamada, Kyuichi Yasui
    Japanese Journal of Applied Physics 56 (7) 0021-4922 2017/07 [Refereed][Not invited]
  • Yukina Iijima, Nobuki Kudo
    JAPANESE JOURNAL OF APPLIED PHYSICS 56 (7) 0021-4922 2017/07 [Refereed][Not invited]
     
    Acoustic fields of a short-pulsed ultrasound propagating through a transparent medium with ultrasound attenuation were visualized by the focused shadowgraph technique. A brightness waveform and its spatial integrations were derived from a visualized field image and compared with a pressure waveform measured by a membrane hydrophone. The experimental results showed that first-order integration of the brightness wave has good agreement with the pressure waveforms. Frequency-dependent attenuation of the pulse propagating through castor oil was derived from brightness and pressure waveforms, and attenuation coefficients determined from focused shadowgraphy and hydrophone techniques showed good agreement. The results suggest the usefulness of the shadowgraph technique not only for the visualization of ultrasound fields but also for noncontact estimation of rough pressure waveforms and correct ultrasound attenuation. (C) 2017 The Japan Society of Applied Physics
  • KONDO Takashi, KUDO Nobuki
    Choonpa Igaku 一般社団法人 日本超音波医学会 2017
  • KUDO Nobuki
    Choonpa Igaku 一般社団法人 日本超音波医学会 44 (1) 37 - 39 2017
  • Imai Shinji, Kudo Nobuki
    Transactions of Japanese Society for Medical and Biological Engineering 公益社団法人 日本生体医工学会 55 (5) 405 - 405 2017 

    We have been studying sonoporation that promotes drug and gene delivery using ultrasound exposure in the presence of microbubbles. A sonoporation technique that utilizes drug-loaded microbubbles for efficient deliver is widely studied; however, their results showed low transduction rates of the technique. In this study, sonoporation phenomena under three types of exposure condition (continuous, repetitive, pulse) were observed in the presence of fluoresce dye-loaded microbubbles adjacent to cells using confocal microscopy. The results showed that different types of ultrasound exposure induce different types of membrane damage; however, the transduction was achieved only in one cell (3%), which was induced by exposure to pulsed ultrasound. In other cells, adhesion of the dye on cell membrane was frequently observed, suggesting that adhesion of bubble shell lipid to the cell bilayer lipid prevents the dye from transduction into cells. This suggests possibility for improving transduction rates by controlling affinity of microbubbles to cells.

  • Kadota Tomoaki, Kudo Nobuki
    Transactions of Japanese Society for Medical and Biological Engineering 公益社団法人 日本生体医工学会 55 (5) 403 - 403 2017 

    We have proposed a simple optical technique for visualization of ultrasound fields using the focused shadowgraphy. To improve the quality of the field images, effects of coherency in the illuminating light source were investigated using a laser diode (LD) and a light-emitting diode (LED). An acoustic field of a 2.5-MHz ultrasound pulse was visualized. The results showed that the effect of noise in the LD beam, which was generated by interference of light diffraction, was not removed by the image subtraction, while the effect of noise in LED beam containing no interference noise was successfully removed. Also, the first order integration of the brightness waveform evaluated using the LED field image showed good agreement with the pressure waveform only in the case with the pinhole, indicating the possibility for evaluation of pressure waveform from an optical image of an ultrasound fields.

  • Negishi Shota, Kudo Nobuki
    Transactions of Japanese Society for Medical and Biological Engineering 公益社団法人 日本生体医工学会 55 (5) 445 - 445 2017 

    We have been studying adverse effect of ultrasound exposure on pulsation of the heart using cardiomyocytes isolated from neonatal rats. Our previous study used cardiac myocytes cultured on a cover slip scaffold; however, the stiffness of the underlying layer is very different from that in in vivo conditions. In this study, cardiomyocytes were cultured on a soft gel scaffold, and their mechanosensitivity was compared with those cultured on a coverslip scaffold. In the experimental results, significant difference was found in the shape indices that represent circularity of cells (gel, 0.29 ± 0.08; cover slip, 0.11 ± 0.04), indicating that cytoskeleton is less developed in the cells cultured on the gel scaffold. Furthermore, a threshold of cycle numbers to induce pulsation disruption is about 10 times higher in the cardiomyocytes culltured on gel scaffold, suggesting the dependence of mechanosensitivity of cardiomyocytes on development of their cytoskeleton.

  • KONDO Takashi, KUDO Nobuki
    Choonpa Igaku 公益社団法人 日本超音波医学会 44 (6) 525 - 528 2017
  • Nobuki Kudo
    IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL 64 (1) 273 - 280 0885-3010 2017/01 [Refereed][Not invited]
     
    A high-speed in situ microscopic observation system developed for basic studies on mechanisms of sonoporation is introduced in this paper. The main part of the system is an inverted-type fluorescence microscope, and a high-speed camera of 20 MHz in a maximum framing rate was used to visualize the dynamics of cavitation bubbles that causes a sonoporation effect. Differential interference contrast and fluorescence techniques were used for sensitive visualization of cell changes during sonoporation. The system is also equipped with optical tweezers that can move a microbubble of several microns in size by using a donut-shaped light beam. In situ microscopic observation of sonoporation was carried out using a cell with a size-and position-controlled microbubble. The experimental results showed that the ability of cells to repair sonoporation-induced damage depends on their membrane tension, indicating the usefulness of the observation system as a basic tool for the investigation of sonoporation phenomena.
  • Norio Kato, Toshiaki Tanaka, Shunichi Sugihara, Koichi Shimizu, Nobuki Kudo
    ICCSE 2016 - 11th International Conference on Computer Science and Education 285 - 290 2016/10/03 [Refereed][Not invited]
     
    We developed a tele-rehabilitation system to improve community rehabilitation for patients who are discharged early from hospital. The developed tele-rehabilitation system consists of devices designed to reduce the physical and economic burden on users while promoting optimum user movement. A Backend-as-a-Service cloud computing service was used for the communication between terminals. A non-contact sensor, Kinect, was used to measure movement. In addition, we used a three-dimensional (3D) display to present 3D images using binocular parallax, to encourage smooth movement of patients. We used this system for stroke patients and found improvements in task-performance time, smoothness of movements, and range of motion in all patients. No major issues occurred during the tele-rehabilitation. These results demonstrated the high operability and efficacy of our cloud service-based 3D virtual reality tele-rehabilitation system.
  • Norio Kato, Toshiaki Tanaka, Syunichi Sugihara, Koichi Shimizu, Nobuki Kudo
    Journal of Physical Therapy Science 28 (4) 1134 - 1141 0915-5287 2016/04/01 [Refereed][Not invited]
     
    [Purpose] This study verified that the smoothness of reaching movements is able to quantitatively evaluate the effects of two- and three-dimensional images on movement in healthy people. In addition, clinical data of cerebrovascular accident patients were also analyzed by the same method. [Subjects] Ten healthy adult volunteers and two male patients with previous cerebrovascular accidents participated. [Methods] The subjects were tasked with reaching for objects shown on a display. The target and virtual limb, rendered with computer graphics, were shown on the display. Movements of the virtual limb were synchronized with those of the subject. Healthy subjects reached for targets with their dominant arm, and cerebrovascular accident patients used their paretic arm. A polarized display and polarized glasses were used when the subjects were shown three-dimensional images. In the present study, jerk cost was used to quantify the smoothness of movement. [Results] Six of the 10 healthy subjects had significantly smoother reaching movements when viewing the three-dimensional images. The two cerebrovascular accident patients tended to have smoother movements in response to the three-dimensional images. [Conclusion] Analysis of the smoothness of movement was able to detect the influence of the depth cue in vision on movement quantitatively for the healthy subjects and cerebrovascular accident patients.
  • KUDO Nobuki
    Choonpa Igaku 一般社団法人 日本超音波医学会 43 (5) 637 - 638 2016
  • KUDO Nobuki, KINOSHITA Yuto
    Choonpa Igaku 一般社団法人 日本超音波医学会 43 (2) 279 - 289 1346-1176 2016 
    Purpose: As basic studies to realize in vivo sonoporation, rates of cell membrane damage during sonoporation were evaluated using monolayer cells cultured on scaffolds withdifferent degrees of stiffness. Methods: Four types of scaffolds, constructed using collagen gel, 10 and 30% acrylamide gels, and a coverslip, were used for cultivation of monolayer cells. Young's moduli measured using an atomic force microscope were in the range 0.09-8.6 kPa for the gel scaffolds, whereas Young's modulus for living cells was 4.5 kPa. Cells with attached microbubbles were exposed to one-shot pulsed ultrasound of 8.0/-1.3 MPa in peak positive/negative pressures with durations of 3, 100, and 10,000 cycles. Results: Cell membrane damage was visualized by fluorescence microscopy using propidium iodide. The 3-cycle ultrasound pulse had no significant effect; however, the rates of damage caused by 100-cycle and 10,000-cycle pulses showed a strong tendency for higher rates of damage with a higher Young's modulus. Conclusion: The experimental results indicate that the stiffness of the underlying layer of adherent cells should be considered as an essential parameter of the sonoporation condition and that the optimum exposure conditions for in vivo sonoporation should be determined with consideration of the physical properties of underlying tissues.
  • UMEMURA Shinichiro, KUDO Nobuki
    Choonpa Igaku 一般社団法人 日本超音波医学会 43 (2) 255 - 263 1346-1176 2016 
    Three optical techniques for visualizing ultrasound acoustic fields used for medical applications are described. The first technique is a type of shadowgraphy that can be realized using a simple optical system consisting of only a point light source and a camera. Characteristics of the images acquired using this technique are compared to those acquired using the Schlieren technique, and the advantage of this technique is demonstrated by visualization of an acoustic field of diagnostic short-pulsed ultrasound. The other two techniques are quantitative shadowgraphy and the phase-contrast technique. These techniques are designed for visualization of three-dimensional (3D) pressure distributions to replace hydrophone measurements. Their principles are explained in detail, and experimental results for visualization of a focused ultrasound field are discussed. The acquired images were quantitatively investigated with comparison to hydrophone measurements, demonstrating the usefulness of the techniques in quantitative evaluation of 3D ultrasound fields.
  • Toda Sogo, Kato Yuji, Kudo Nobuki, Shimizu Koichi
    Transactions of Japanese Society for Medical and Biological Engineering 一般社団法人 日本生体医工学会 54 1T3 - 4-6-1-1T3-4-6-2 2016 

    The scattering effect in light propagation through random media can be suppressed with the phase-conjugate optics. We have applied this technique to the transillumination imaging of animal body using a digital phase-conjugate system. In the experiment, we attempted to restore various incident light patterns through a scattering medium. As a result, the feasibility of scattering suppression using digital phase-conjugate light was verified.

  • Sakaki Tsubasa, Kudo Nobuki
    Transactions of Japanese Society for Medical and Biological Engineering 一般社団法人 日本生体医工学会 54 1T3 - 4-1-1-1T3-4-1-2 2016 

    A high intensity focused ultrasound (HIFU) field of a transducer for ultrasound therapy was visualized using an image subtraction Schlieren technique. The transducer of 110 mm in diameter and 100 mm in focal length was driven by a burst pulse of 1.58 MHz in center frequency and of 10 W or 100 W in input electric power. 10 instantaneous HIFU fields were visualized at 10 different phases, and a beam profile was determined by superimposing the fields. FWHMs of the beam were 5.8 mm in a visualized field but was 7.3 mm in a field determined by hydrophone measurement.

  • KUDO Nobuki
    Choonpa Igaku 一般社団法人 日本超音波医学会 43 (6) 719 - 721 2016
  • Nobuki Kudo
    Handbook of Ultrasonics and Sonochemistry 207 - 238 2016/01/01 [Refereed][Not invited]
     
    In this section, optical techniques used for experimental observation of acoustic fields are reviewed. Acousto-optic interaction is discussed as a basic principle for visualizing inhomogeneity in refractive index fields. Light deflection and diffraction are also discussed as typical phenomena, especially in visualization of ultrasound fields. Three techniques, phase detection, Schlieren, and shadowgraph techniques, are mainly reviewed with discussion of the differences in the principles, optical systems, and acquired images. Background-oriented Schlieren technique, scanning laser Doppler vibrometry, and photoelastic techniques are also discussed as relatively new techniques for visualization of ultrasound fields. A technique that visualizes a distribution of temperature rise generated by ultrasound exposure is also introduced.
  • Aya Miwa, Nobuki Kudo
    2016 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS) 1948-5719 2016 [Refereed][Not invited]
     
    We have been studying experimental methods using cultured cardiomyocytes to evaluate the effect of short-pulsed ultrasound for generating disruption in pulsation such as premature contractions. In this study, we focused on the effect of ultrasound pulses with longer duration for a basic study on the safety of acoustic radiation force impulse (ARFI) imaging. Cardiomyocytes isolated from neonatal rats and cultured on a coverslip were used for this study. Pulsation of cardiomyocytes was controlled by an electric pacing signal, and the effect of ultrasound exposure on the pulsation was investigated by microscopic observation. Hanks' balanced salt solution degassed by using a vacuum chamber was used to eliminate cell damage caused by cavitation. To determine the parameter responsible for the induction of pulsation disruption, the effect of ultrasound exposure on cardiomyocyte pulsation was studied under exposure conditions combining different ultrasound pressures and pulse energies. The results indicated that the adverse effect of long duration pulses on cardiac pulsation is more dependent on ultrasound pressure, which determines the acoustic radiation force, than on pulse energy, which determines the temperature elevation of tissues.
  • Nobuki Kudo, Tomoaki Kadota, Yukina Iijima
    2016 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS) 1948-5719 2016 [Refereed][Not invited]
     
    We have proposed a simple optical technique for visualization of ultrasound fields using the focused shadowgraph technique. To improve the quality of field images, effects of coherency in the illuminating light source were investigated using a laser diode (LD) and a light-emitting diode (LED). An experimental system with the two light sources was developed, and an acoustic field of a 2.5-MHz ultrasound pulse was visualized. Two images were taken with and without ultrasound exposure, and the image taken without ultrasound exposure was subtracted from that with ultrasound exposure for sensitive detection and noise reduction. The results show that the effect of noise in the LD beam, which was generated by interference of light diffraction, was not removed by the image subtraction, while the effect of noise in LED beam containing no interference noise was successfully removed. Sharpness of the LED image was degraded, but its spatial resolution was still higher than one-tenth of the ultrasound wavelength, indicating the usefulness of an LED illuminating light source for improving the quality of acoustic field images acquired by using the focused shadowgraph technique.
  • Shogo Endo, Nobuki Kudo, Shigeru Yamaguchi, Koki Sumiyoshi, Hiroaki Motegi, Hiroyuki Kobayashi, Shunsuke Terasaka, Kiyohiro Houkin
    ULTRASOUND IN MEDICINE AND BIOLOGY 41 (9) 2458 - 2465 0301-5629 2015/09 [Refereed][Not invited]
     
    Because it is highly infiltrative, malignant glioma is a cancer with a poor prognosis despite multidisciplinary treatment strategies, such as aggressive surgery and chemoradiotherapy, necessitating new therapeutic approaches to control migration of tumor cells. In our study, we investigated the efficacy of sonodynamic therapy of glioma cells in vitro using porphyrin derivatives, including 5-aminolevulinic acid, protoporphyrin IX and talaporfin sodium, as sonosensitizers. These substances have been known to accumulate in glioma cells and are expected to have cytotoxic effects on sonication. Our study found that the cytotoxicity of sonication of glioma cells is enhanced by each sonosensitizer and that the efficacy of sonodynamic therapy may depend on the degree of intracellular accumulation of sonosensitizer. Also, the study suggests that induction of apoptosis is a major mechanism underlying cell death. Though further investigations are necessary, our preliminary result indicates a potential for sonodynamic therapy with sonosensitizers in glioma treatment. (C) 2015 World Federation for Ultrasound in Medicine & Biology.
  • Nobuki Kudo
    ULTRASOUND IN MEDICINE AND BIOLOGY 41 (7) 2071 - 2081 0301-5629 2015/07 [Refereed][Not invited]
     
    A simple technique designed for visualization of ultrasound fields without Schlieren optics is introduced. An optical system of direct shadowgraphy with diverging light, which consists of a point light source and a shadow screen, constituted the basic system, but the screen was replaced by focusing optics: a camera that makes a virtual screen at its focus plane. The proposed technique visualizes displacement of light deflected by ultrasound, and the use of focusing optics enables flexible settings of the virtual screen position and optical magnification. Insufficient sensitivity of shadowgraphy was overcome by elimination of non-deflecting light using image subtraction of shadowgrams taken with and without ultrasound exposure. A 1-MHz focused transducer for ultrasound therapy and a 20-MHz miniature transducer for intravascular imaging were used for experiments, and alternate pressure change in short-pulsed ultrasound was visualized, indicating the usefulness of the proposed technique for evaluation of medical ultrasound fields. (C) 2015 World Federation for Ultrasound in Medicine & Biology.
  • Nobuki Kudo
    JAPANESE JOURNAL OF APPLIED PHYSICS 54 (7) 07HA01  0021-4922 2015/07 [Refereed][Not invited]
     
    A brief review of optical techniques for visualizing ultrasound fields is given. Acousto-optic interaction is discussed as a basic principle for visualizing inhomogeneity in refractive index fields. Light diffraction and deflection are also discussed as important phenomena, especially for visualization of ultrasound fields. Three techniques, Schlieren, phase contrast, and shadowgraph techniques, used for visualization of ultrasound fields are reviewed with discussion of the differences in optical systems and visualized field images. A newly developed focused shadowgraph technique that achieves sensitive detection with simple optics is introduced, and its usefulness for visualization of very short pulses of diagnostic ultrasound equipment is shown. (C) 2015 The Japan Society of Applied Physics
  • 画像差分型シュリーレン法を用いた故障プローブ音場の定量評価
    関根 大輝, 西田 睦, 工藤 信樹
    超音波医学 (公社)日本超音波医学会 42 (1) 93 - 94 1346-1176 2015/01
  • Nobuki Kudo, Yuto Kinoshita
    JOURNAL OF MEDICAL ULTRASONICS 41 (4) 411 - 420 1346-4523 2014/10 [Refereed][Not invited]
     
    Purpose As basic studies to realize in vivo sonoporation, rates of cell membrane damage during sonoporation were evaluated using monolayer cells cultured on scaffolds with different degrees of stiffness. Methods Four types of scaffolds, constructed using collagen gel, 10 and 30 % acrylamide gels, and a coverslip, were used for cultivation of monolayer cells. Young's moduli measured using an atomic force microscope were in the range 0.09-8.6 kPa for the gel scaffolds, whereas Young's modulus for living cells was 4.5 kPa. Cells with attached microbubbles were exposed to one-shot pulsed ultrasound of 8.0/-1.3 MPa in peak positive/negative pressures with durations of 3, 100, and 10,000 cycles. Results Cell membrane damage was visualized by fluorescence microscopy using propidium iodide. The 3-cycle ultrasound pulse had no significant effect; however, the rates of damage caused by 100-cycle and 10,000-cycle pulses showed a strong tendency for higher rates of damage with a higher Young's modulus. Conclusion The experimental results indicate that the stiffness of the underlying layer of adherent cells should be considered as an essential parameter of the sonoporation condition and that the optimum exposure conditions for in vivo sonoporation should be determined with consideration of the physical properties of underlying tissues.
  • Koki Sumiyoshi, Daiki Sekine, Nobuki Kudo, Koichi Shimizu
    Transactions of Japanese Society for Medical and Biological Engineering 52 343 - O-344 1347-443X 2014/08/17 [Refereed][Not invited]
     
    We have been studying usefulness of image subtraction Schlieren technique that visualizes ultrasound fields. Also, in studies of the adverse effect of ultrasound exposure on cells, a culture dish is used as an exposure chamber with an ultrasound transducer placed beneath the dish. In this exposure setup, a standing wave field is produced inside the chamber, and change in shape of the chamber causes change in the standing wave fields. In this study, standing wave fields generated inside small chambers with different shapes were visualized using our technique, and the relation between acoustic fields and production of free radicals that cause cell damage was investigated.
  • Yasunobu Igarashi, Nobuki Kudo
    Transactions of Japanese Society for Medical and Biological Engineering 52 335 - O-336 1347-443X 2014/08/17 [Refereed][Not invited]
     
    It is widely accepted that the presence of microbubbles improves efficiency of sonoporation. We have been studying the mechanisms by using high-speed observation of bubble behavior. In this study, an observation chamber was improved to observe bubble behavior from a lateral direction. A pair of miniature mirrors was added to the chamber, and one mirror was used to illuminate bubbles from the lateral direction, and another was used to guide the lateral image to an objective lens. Observation results showed that the presence of a rigid wall or other bubble causes a bubbles to make non-spherical deformation that might induce cell membrane perforation.
  • Ryo Takada, Nobuki Kudo, Ryo Suzuki
    Transactions of Japanese Society for Medical and Biological Engineering 52 339 - O-340 1347-443X 2014/08/17 [Refereed][Not invited]
     
    Recently, much attention has been paid to dendritic cell (DC)-based cancer immunotherapy. Antigen delivery by sonoporation has been examined using microbubbles (MBs) loaded with antigen however, its mechanisms are not revealed yet. In this study, sonoporation effect was compared in three typical locations of MBs: (1) MBs in the vicinity of a cell, (2) MBs on a cell membrane, and (3) MBs endocytosed inside a cell, by using MBs conjugated with fluorescent dye. The results showed that antigen was transduced by ultrasound exposure in the cases (1) and (2) but not in the case (3), indicating that the positional relation between MBs and the cells strongly affects efficiency of antigen transduction.
  • Yuya Kudo, Nobuki Kudo
    Transactions of Japanese Society for Medical and Biological Engineering 52 347 - O-348 1347-443X 2014/08/17 [Refereed][Not invited]
     
    Membrane damage produced by sonicated bubbles is the mechanism of sonoporation for drug delivery. The low transduction efficacy is the main problem however, improvement can be expected by controlling a force that works between oscillating bubbles. High-speed observation was carried out in this study to elucidate interaction of oscillating two microbubbles. Two several -micron bubbles were trapped using optical tweezers and photographed under exposure to pulsed ultrasound at 4×10< sup> 6< /sup> fps. Generation of an attractive force between the bubbles and jetting to cause the bubbles to be fragmented were confirmed, indicating the possibility to control jetting and cell membrane damage.
  • Nobuki Kudo
    Journal of Medical Ultrasonics 41 (2) 137 - 138 1613-2254 2014/04/01 [Refereed][Not invited]
  • 画像差分シュリーレン装置を用いた故障プローブの音場可視化
    関根 大輝, 西田 睦, 清水 孝一, 工藤 信樹
    超音波医学 (公社)日本超音波医学会 41 (1) 56 - 56 1346-1176 2014/01
  • Noboru Sasaki, Nobuki Kudo, Kensuke Nakamura, Sue Yee Lim, Masahiro Murakami, W R Bandula Kumara, Yu Tamura, Hiroshi Ohta, Masahiro Yamasaki, Mitsuyoshi Takiguchi
    Journal of medical ultrasonics (2001) 41 (1) 11 - 21 2014/01 [Refereed][Not invited]
     
    PURPOSE: The aim of this study was to clarify whether ultrasound image-guided cisplatin delivery with an intratumor microbubble injection enhances the antitumor effect in a xenograft mouse model. METHODS: Canine thyroid adenocarcinoma cells were used for all experiments. Before in vivo experiments, the cisplatin and microbubble concentration and ultrasound exposure time were optimized in vitro. For in vivo experiments, cells were implanted into the back of nude mice. Observed by a diagnostic ultrasound machine, a mixture of cisplatin and ultrasound contrast agent, Sonazoid, microbubbles was injected directly into tumors. The amount of injected cisplatin and microbubbles was 1 μg/tumor and 1.2 × 10(7) microbubbles/tumor, respectively, with a total injected volume of 20 μl. Using the same diagnostic machine, tumors were exposed to ultrasound for 15 s. The treatment was repeated four times. RESULTS: The combination of cisplatin, microbubbles, and ultrasound significantly delayed tumor growth as compared with no treatment (after 18 days, 157 ± 55 vs. 398 ± 49 mm(3), P = 0.049). Neither cisplatin alone nor the combination of cisplatin and ultrasound delayed tumor growth. The treatment did not decrease the body weight of mice. CONCLUSION: Ultrasound image-guided anticancer drug delivery may enhance the antitumor effects of drugs without obvious side effects.
  • Naotaka Nitta, Nobuki Kudo, Tomoo Kamakura, Yasunao Ishiguro, Hideki Sasanuma, Nobuyuki Taniguchi, Iwaki Akiyama
    IEEE International Ultrasonics Symposium, IUS 386 - 389 1948-5719 2013 [Refereed][Not invited]
     
    Acoustic radiation force (ARF) has been recently used for the tissue elasticity measurement and imaging. On the other hand, it is predicted that the higher temperature rises occur. In vivo measurement of temperature rise in animal experiments is important, whereas the measurement using thermocouples have some problems such as position mismatch of a temperature measuring junction of thermocouple and a focal point of ultrasound and so on. Therefore, in vivo measurement system for solving the above problems was developed in this study. The feasibility of the developed system was verified by the experiments using a tissue mimicking materials (TMM), TMM with a bone mode, an extracted porcine liver and a bone of chicken. Moreover, relations between conditions of ultrasound irradiation and temperature rises were investigated using the system. These results showed that temperature rises at focus on the surface of bone may exceed an allowable temperature rise which WFUMB guideline recommends, even though the acoustic intensity is within the limits of acoustic output regulation in diagnostic ultrasound devices. © 2013 IEEE.
  • Nobuki Kudo, Yuto Tanaka, Kazuaki Uchida
    2013 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS) 53 - 56 2013 [Refereed][Not invited]
     
    We have been studying a sonoporation technique that uses one-shot exposure of short-pulsed ultrasound to cells with attached microbubbles. Here, we introduce a new observation system developed for elucidation of sonoporation mechanisms. An inverted-type microscope was equipped with optical tweezers that enable position control of a microbubble. A Laguerre-Gaussian (LG) beam, a Gaussian beam with a dark spot at the center, was used to trap a microbubble with a refractive index lower than that of the surrounding water. The LG beam was produced using a phase-only spatial light modulator and 1,065-nm laser light. Results of basic experiments showed that the tweezers can trap bubbles of 1-30 mu m in diameter suspended in water, and the minimum optical power for trapping bubbles of 5 m in diameter was around 10 mW. Sonoporation experiments were carried out using size-and position-controlled bubbles placed on cell membranes or placed at separated positions from cells, and the results indicated the importance of the newly developed system for elucidation of sonoporation mechanisms.
  • Yuto Tanaka, Nobuki Kudo
    IEEE International Ultrasonics Symposium, IUS 1777 - 1780 1948-5719 2013 [Refereed][Not invited]
     
    We have been studying a sonoporation technique and have reported that one-shot exposure of short-pulsed ultrasound can elicit a sonoporation effect in the presence of a microbubble attached to a cell. It is generally thought that sonoporation causes more severe damage to cells cultured on a rigid scaffold than to cells suspended in a medium or to cells of in vivo tissue. One possible explanation is that a higher damage rate is caused by higher membrane tension. Since the ability of cells to rescue themselves from membrane damage is strongly dependent on their membrane tension, cells cultured on a rigid scaffold, which have higher membrane tension, may have more severe sonoporation damage. In this study, cell membrane tension was controlled by changing osmolality of the culture medium and selecting shapes of cells cultured on a coverslip, and the effect of membrane tension on ability for membrane repair was investigated by fluorescence microscopic observation that visualizes severity of sonoporation-induced cell damage. Repair rates of cells treated under isotonic and hypertonic conditions of osmolality were 55±8%and 75±14% (means ± S.D.), respectively, indicating that lower membrane tension causes higher repair rate. The repair ability was also studied using cells with different shapes. The results showed that spherical-shaped cells, which have lower membrane tension, have a minimum lethal damage level five-times higher than that of spindle-shaped cells, also suggesting that lower membrane tension can increase the ability of cells to repair sonoporation-induced membrane damage. © 2013 IEEE.
  • Etsuo Takada, Nobuki Kudo, Nobuyuki Endoh, Hiroyuki Hachiya, Shin-ichi Takeuchi, Takenobu Tsuchiya, Michiya Natori
    JOURNAL OF MEDICAL ULTRASONICS 39 (3) 107 - 113 1346-4523 2012/07 [Not refereed][Not invited]
     
    The Ultrasound Equipment and Safety Committee of The Japan Society of Ultrasonics in Medicine performed experiments to confirm whether contrast-enhanced ultrasonography damages liver cells. Rats were injected with 0.1 ml of 300 mg/ml ultrasound contrast agent (UCA). Diagnostic ultrasound pulses with a center frequency of 6 MHz and a mechanical index of 1.9 were applied to rat livers with a water bag as a coupler to maintain a distance of 2-6 cm between the ultrasound probe surface and the liver. Contrast-enhanced ultrasonography was carried out for 10 s to visualize the entire liver. Then, specimens of liver tissue were fixed using two types of fixation: immersion and perfusion fixation. Although some variations were found in electron micrographs of liver tissue fixed using immersion fixation, none of three blinded readers found any significant differences between micrographs of liver tissue from rats receiving UCA with sonication and those from sham-treated control rats. Changes observed were not thought to be group-specific but instead due to differences between individual rats. When the livers were fixed using perfusion fixation and the hepatic vein was cut after injection of physiological saline for perfusion, a large number of vacuoles a parts per thousand yen2 mu m in diameter were observed. This finding suggested that hepatic cell damage observed in this study was caused by high perfusion pressure during the liver fixation process rather than by sonication with UCA. Blinded readings of electron micrographs showed no clear evidence that the use of Levovist in ADI mode ultrasonography causes significant damage to liver tissue.
  • Yusuke Oda, Ryo Suzuki, Shota Otake, Norihito Nishiie, Keiichi Hirata, Risa Koshima, Tetsuya Nomura, Naoki Utoguchi, Nobuki Kudo, Katsuro Tachibana, Kazuo Maruyama
    JOURNAL OF CONTROLLED RELEASE 160 (2) 362 - 366 0168-3659 2012/06 [Refereed][Not invited]
     
    Melanoma has an early tendency to metastasize, and the majority of the resulting deaths are caused by metastatic melanoma. It is therefore important to develop effective therapies for metastasis. Dendritic cell (DC)-based cancer immunotherapy has been proposed as an effective therapeutic strategy for metastasis and recurrence due to prime tumor-specific cytotoxic T lymphocytes. In this therapy, it is important that DCs present peptides derived from tumor-associated antigens on MHC class I molecules. Previously, we developed an innovative approach capable of directly delivering exogenous antigens into the cytosol of DCs using perfluoropropane gas-entrapping liposomes (Bubble liposomes, BLs) and ultrasound. In the present study, we investigated the prevention of melanoma lung metastasis via DC-based immunotherapy. Specifically, antigens were extracted from melanoma cells and used to treat DCs by BL and ultrasound. Delivery into the DCs by this route did not require the endocytic pathway. The delivery efficiency was approximately 74.1%. DCs treated with melanoma-derived antigens were assessed for in vivo efficacy in a mouse model of lung metastasis. Prophylactic immunization with BL/ultrasound-treated DCs provided a four-fold decrease in the frequency of melanoma lung metastases. These in vitro and in vivo results demonstrate that the combination of BLs and ultrasound is a promising method for antigen delivery system into DCs. Crown Copyright (C) 2011 Published by Elsevier B. V. All rights reserved.
  • Yusuke Oda, Ryo Suzuki, Shota Otake, Norihito Nishiie, Keiichi Hirata, Risa Koshima, Tetsuya Nomura, Naoki Utoguchi, Nobuki Kudo, Katsuro Tachibana, Kazuo Maruyama
    JOURNAL OF CONTROLLED RELEASE 160 (2) 362 - 366 0168-3659 2012/06 [Not refereed][Not invited]
     
    Melanoma has an early tendency to metastasize, and the majority of the resulting deaths are caused by metastatic melanoma. It is therefore important to develop effective therapies for metastasis. Dendritic cell (DC)-based cancer immunotherapy has been proposed as an effective therapeutic strategy for metastasis and recurrence due to prime tumor-specific cytotoxic T lymphocytes. In this therapy, it is important that DCs present peptides derived from tumor-associated antigens on MHC class I molecules. Previously, we developed an innovative approach capable of directly delivering exogenous antigens into the cytosol of DCs using perfluoropropane gas-entrapping liposomes (Bubble liposomes, BLs) and ultrasound. In the present study, we investigated the prevention of melanoma lung metastasis via DC-based immunotherapy. Specifically, antigens were extracted from melanoma cells and used to treat DCs by BL and ultrasound. Delivery into the DCs by this route did not require the endocytic pathway. The delivery efficiency was approximately 74.1%. DCs treated with melanoma-derived antigens were assessed for in vivo efficacy in a mouse model of lung metastasis. Prophylactic immunization with BL/ultrasound-treated DCs provided a four-fold decrease in the frequency of melanoma lung metastases. These in vitro and in vivo results demonstrate that the combination of BLs and ultrasound is a promising method for antigen delivery system into DCs. Crown Copyright (C) 2011 Published by Elsevier B. V. All rights reserved.
  • Noboru Sasaki, Nobuki Kudo, Kensuke Nakamura, Sue Yee Lim, Masahiro Murakami, W. R. Bandula Kumara, Yu Tamura, Hiroshi Ohta, Masahiro Yamasaki, Mitsuyoshi Takiguchi
    ULTRASOUND IN MEDICINE AND BIOLOGY 38 (1) 109 - 118 0301-5629 2012/01 [Refereed][Not invited]
     
    Ultrasound targeted microbubble destruction has succeeded in delivering drugs and genes. This study was designed to explore characteristics of ultrasound targeted microbubble destruction using short-pulsed diagnostic ultrasound. Canine thyroid adenocarcinoma cells were exposed to short-pulsed diagnostic ultrasound in the presence of cis-diamminedichloroplatinum (II) (cisplatin) and ultrasound contrast agent Sonazoid (R) microbubbles. The cytotoxic effect of cisplatin was enhanced by short-pulsed diagnostic ultrasound and microbubbles. Incubation time with microbubbles influenced the cytotoxic effect of cisplatin. However, exposure duration did not affect the cytotoxic effect of cisplatin. Therefore, short-pulsed diagnostic ultrasound may activate microbubbles near cells and deliver cisplatin into cells. In addition, activation of microbubbles may be concluded in a short time. Our results suggest that short exposure duration could be potentially sufficient to induce efficient drug delivery by ultrasound targeted microbubble destruction using short-pulsed diagnostic ultrasound. (E-mail: mtaki@vetmed.hokudai.ac.jp) (C) 2012 World Federation for Ultrasound in Medicine & Biology.
  • Naotaka Nitta, Nobuki Kudo, Iwaki Akiyama
    NONLINEAR ACOUSTICS: STATE-OF-THE-ART AND PERSPECTIVES (ISNA 19) 1474 264 - 267 0094-243X 2012 [Refereed][Not invited]
     
    Focused ultrasound with acoustic radiation force (ARF) is beginning to be used for imaging and measuring tissue elasticity. On the other hand, it was suggested that the temperature elevation near bone at focus may be significant within the limits of acoustic output regulation in diagnostic ultrasound devices (Herman; 2002). In this study, with the aim of obtaining the relationships between temperature elevations and parameters of ultrasound exposure with ARF, temperature elevations in two kinds of tissue models with or without bone were numerically evaluated. The results showed that the temperature elevation at focus on the surface of bone may exceed an allowable temperature elevation which WFUMB guideline recommends, even though the acoustic intensity is within the limits of acoustic output regulation in diagnostic ultrasound devices.
  • Nobuki Kudo, Yuto Kinoshita
    12TH INTERNATIONAL SYMPOSIUM ON THERAPEUTIC ULTRASOUND 1503 61 - 64 0094-243X 2012 [Refereed][Not invited]
     
    Efficiencies of sonoporation were investigated using four types of monolayer-cell samples: cells cultured directly on a cover slip, cells cultured on a cover slip coated with collagen gel of several mu m in thickness, and cells cultured on collagen gel scaffolds of 0.4 and 1.0 mm in thicknesses. Cell samples attached with Levovist microbubbles were irradiated by one shot of a three-or 10,000-cycle ultrasound pulse, and cell detachment and membrane perforation were investigated. Experimental results showed that rates of cell detachment and membrane damage were markedly decreased in the presence of soft gel layer of 0.4 and 1.0 mm in thicknesses under the cells and that these rates were inversely proportional to the thickness of the gel layer. These results indicate that optimum conditions of sonoporation in vitro should be carefully translated into those in vivo.
  • Shigeru Yamaguchi, Hiroyuki Kobayashi, Takuhito Narita, Koki Kanehira, Shuji Sonezaki, Nobuki Kudo, Yoshinobu Kubota, Shunsuke Terasaka, Kiyohiro Houkin
    ULTRASONICS SONOCHEMISTRY 18 (5) 1197 - 1204 1350-4177 2011/09 [Refereed][Not invited]
     
    Sonodynamic therapy is expected to be a novel therapeutic strategy for malignant gliomas. The titanium dioxide (TiO2) nanoparticle, a photosensitizer, can be activated by ultrasound. In this study, by using water-dispersed TiO2 nanoparticles, an in vitro comparison was made between the photodynamic and sonodynamic damages on U251 human glioblastoma cell lines. Water-dispersed TiO2 nanoparticles were constructed by the adsorption of chemically modified polyethylene glycole (PEG) on the TiO2 surface (TiO2/PEG). To evaluate cytotoxicity, U251 monolayer cells were incubated in culture medium including 100 mu g/ml of TiO2/PEG for 3 h and subsequently irradiated by ultraviolet light (5.0 mW/cm(2)) or 1.0 MHz ultrasound (1.0 W/cm(2)). Cell survival was estimated by MTT assay 24 h after irradiation. In the presence of TiO2/PEG, the photodynamic cytotoxic effect was not observed after 20 min of an ultraviolet light exposure, while the sonodynamic cytotoxicity effect was almost proportional to the time of sonication. In addition, photodynamic cytotoxicity of TiO2/PEG was almost completely inhibited by radical scavenger, while suppression of the sonodynamic cytotoxic effect was not significant. Results of various fluorescent stains showed that ultrasound-treated cells lost their viability immediately after irradiation, and cell membranes were especially damaged in comparison with ultraviolet-treated cells. These findings showed a potential application of TiO2/PEG to sonodynamic therapy as a new treatment of malignant gliomas and suggested that the mechanism of TiO2/PEG mediated sonodynamic cytotoxicity differs from that of photodynamic cytotoxicity. (C) 2011 Elsevier B.V. All rights reserved.
  • Shigeru Yamaguchi, Hiroyuki Kobayashi, Takuhito Narita, Koki Kanehira, Shuji Sonezaki, Nobuki Kudo, Yoshinobu Kubota, Shunsuke Terasaka, Kiyohiro Houkin
    ULTRASONICS SONOCHEMISTRY 18 (5) 1197 - 1204 1350-4177 2011/09 [Not refereed][Not invited]
     
    Sonodynamic therapy is expected to be a novel therapeutic strategy for malignant gliomas. The titanium dioxide (TiO2) nanoparticle, a photosensitizer, can be activated by ultrasound. In this study, by using water-dispersed TiO2 nanoparticles, an in vitro comparison was made between the photodynamic and sonodynamic damages on U251 human glioblastoma cell lines. Water-dispersed TiO2 nanoparticles were constructed by the adsorption of chemically modified polyethylene glycole (PEG) on the TiO2 surface (TiO2/PEG). To evaluate cytotoxicity, U251 monolayer cells were incubated in culture medium including 100 mu g/ml of TiO2/PEG for 3 h and subsequently irradiated by ultraviolet light (5.0 mW/cm(2)) or 1.0 MHz ultrasound (1.0 W/cm(2)). Cell survival was estimated by MTT assay 24 h after irradiation. In the presence of TiO2/PEG, the photodynamic cytotoxic effect was not observed after 20 min of an ultraviolet light exposure, while the sonodynamic cytotoxicity effect was almost proportional to the time of sonication. In addition, photodynamic cytotoxicity of TiO2/PEG was almost completely inhibited by radical scavenger, while suppression of the sonodynamic cytotoxic effect was not significant. Results of various fluorescent stains showed that ultrasound-treated cells lost their viability immediately after irradiation, and cell membranes were especially damaged in comparison with ultraviolet-treated cells. These findings showed a potential application of TiO2/PEG to sonodynamic therapy as a new treatment of malignant gliomas and suggested that the mechanism of TiO2/PEG mediated sonodynamic cytotoxicity differs from that of photodynamic cytotoxicity. (C) 2011 Elsevier B.V. All rights reserved.
  • Mariame A. Hassan, Yukihiro Furusawa, Qing-Li Zhao, Ichiro Takasaki, Loreto B. Feril, Katsuro Tachibana, Nobuki Kudo, Masami Minemura, Toshiro Sugiyama, Takashi Kondo
    JOURNAL OF MEDICAL ULTRASONICS 38 (2) 65 - 72 1346-4523 2011/04 [Not refereed][Not invited]
     
    Although sanazole has been used as a hypoxic radiosensitizer, we recently reported on its ability to sensitize U937 cells to hyperthermia and X-irradiation under aerobic conditions, enhancing apoptotic cell death following the combined treatment. The current study was undertaken to evaluate the effect of sanazole as a sonosensitizer under previously studied acoustic conditions of different pulse repetition frequencies, using two cell lines representative of solid tumours and haematopoietic cancers. Cells were treated with different doses of sanazole. Flow-cytometric analysis and DNA fragmentation assay were carried out at different times, and morphological features were also inspected. For ultrasound treatment, cells were pre-incubated with a non-cytotoxic dose of sanazole for 30 min before exposure. Evaluation of cell killing and a parallel examination of intracellular oxidative stress levels in both cell lines were performed using flow cytometry. Sanazole alone displayed selective cytotoxic effects towards solid tumour-derived cancer cells, resulting in complete cell death after 24 h of treatment, and enhanced the ultrasound-induced cell killing 6 h post-treatment. The enhancement seemed to be mediated by an additive increase in intracellular oxidative stress levels. Sanazole seems to be an efficient cytotoxic agent for the treatment of solid tumours and a promising sonosensitizer under aerobic conditions.
  • Nobuki Kudo, Ejsum, Koichi Shimizu
    Japanese Journal of Medical Ultrasonics 38 (1) 25 - 26 1346-1176 2011 [Not refereed][Not invited]
  • Nobuki Kudo, Ejsum, Koichi Shimizu
    Japanese Journal of Medical Ultrasonics 38 (1) 25 - 26 1346-1176 2011 [Not refereed][Not invited]
  • Risa Koshima, Ryo Suzuki, Yusuke Oda, Keiichi Hirata, Tetsuya Nomura, Yoichi Negishi, Naoki Utoguchi, Nobuki Kudo, Kazuo Maruyama
    10TH INTERNATIONAL SYMPOSIUM ON THERAPEUTIC ULTRASOUND (ISTU 2010) 1359 330 - + 0094-243X 2011 [Refereed][Not invited]
     
    The combination of nano/microbubbles and ultrasound is a novel technique for a non-viral gene deliver. We have previously developed novel ultrasound sensitive liposomes (Bubble liposomes) which contain the ultrasound imaging gas perfluoropropane. In this study, Bubble liposomes were compared with cationic lipid (CL)-DNA complexes as potential gene delivery carriers into tumors in vivo. The delivery of genes by bubble liposomes depended on the intensity of the applied ultrasound. The transfection efficiency plateaued at 0.7 W/cm(2) ultrasound intensity. Bubble liposomes efficiently transferred genes into cultured cells even when the cells were exposed to ultrasound for only 1 s. In addition, bubble liposomes were able to introduce the luciferase gene more effectively than CL-DNA complexes into mouse ascites tumor cells. We conclude that the combination of Bubble liposomes and ultrasound is a good method for gene transfer in vivo.
  • 貴田岡 正史, 熊田 卓, 松田 康雄, 飯島 尋子, 小川 眞広, 工藤 信樹, 小原 和史, 紺野 啓, 高倉 玲奈, 西田 睦, 南 康範, 森 秀明, 山田 昌彦
    Japanese journal of medical ultrasonics = 超音波医学 37 (2) 157 - 166 1346-1176 2010/03/15 [Not refereed][Not invited]
  • Mariame A. Hassan, Mikhail A. Buldakov, Ryohei Ogawa, Qing-Li Zhao, Yukihiro Furusawa, Nobuki Kudo, Takashi Kondo, Peter Riesz
    JOURNAL OF CONTROLLED RELEASE 141 (1) 70 - 76 0168-3659 2010/01 [Refereed][Not invited]
     
    Low modulation frequencies from 0.5 to 100 Hz were shown to alter the characteristics of the ultrasound field producing solution agitation (<5 Hz; region of "ultrasound streaming" prevalence) or stagnancy (>5 Hz; region of standing waves establishment) (Buldakov et al., Ultrason. Sonochem., 2009). In this study, the same conditions were used to depict the changes in exogenous DNA delivery in these regions. The luciferase expression data revealed that lower modulations were more capable of enhancing delivery at the expense of viability. On the contrary, the viability was conserved at higher modulations whereas delivery was found to be null. Cavitational activity and acoustic streaming were the effecters beyond the observed pattern and delivery enhancement was shown to be mediated mainly through sonopermeation. To promote transfection, the addition of calcium ions or an echo contrast agent (Levovist (R)) was proposed. Depending on the mechanism involved in each approach, differential enhancement was observed in both regions and at the interim zone (5 Hz). In both cases, enhancement in standing waves field was significant reaching 16.0 and 3.3 folds increase, respectively. Therefore, it is concluded that although the establishment of standing waves is not the only prerequisite for high transfection rates, yet, it is a key element in optimization when other factors such as proximity and cavitation are considered. (C) 2009 Elsevier B.V. All rights reserved.
  • Khai Jun Kek, Nobuki Kudo, Katsuyuki Yamamoto
    OXYGEN TRANSPORT TO TISSUE XXXI 662 199 - 204 0065-2598 2010 [Refereed][Not invited]
     
    Near-infrared spectroscopy (NIRS) enables noninvasive measurement of muscle oxygenation. However, since NIRS does not enable direct measurement of muscle metabolism, it is necessary to analyze the dynamic changes in metabolism during exercise using other methods in order to understand the relationship between NIRS measurements and muscle metabolism. A model of muscle metabolism that is composed of aerobic and anaerobic metabolic systems and 02 transport to tissue system was developed. Using the model, the temporal profiles of muscle oxygenation during exercise with different intensities (20, 40 and 70% maximum voluntary contraction), measured using NIRS in a single subject, were sufficiently reproduced. In addition, analyses of simulation results of (i) aerobic and anaerobic metabolic systems and (ii) O(2) consumption were performed, and the intensity-dependent differences in the temporal responses during exercise and recovery periods were estimated. The initial results show the usefulness of the model for simulating the kinetics of NIRS measurement data and for systematic interpretation of the relationship between NIRS data and muscle metabolism.
  • Khai Jun Kek, Nobuki Kudo, Katsuyuki Yamamoto
    OXYGEN TRANSPORT TO TISSUE XXXI 662 199 - 204 0065-2598 2010 [Not refereed][Not invited]
     
    Near-infrared spectroscopy (NIRS) enables noninvasive measurement of muscle oxygenation. However, since NIRS does not enable direct measurement of muscle metabolism, it is necessary to analyze the dynamic changes in metabolism during exercise using other methods in order to understand the relationship between NIRS measurements and muscle metabolism. A model of muscle metabolism that is composed of aerobic and anaerobic metabolic systems and 02 transport to tissue system was developed. Using the model, the temporal profiles of muscle oxygenation during exercise with different intensities (20, 40 and 70% maximum voluntary contraction), measured using NIRS in a single subject, were sufficiently reproduced. In addition, analyses of simulation results of (i) aerobic and anaerobic metabolic systems and (ii) O(2) consumption were performed, and the intensity-dependent differences in the temporal responses during exercise and recovery periods were estimated. The initial results show the usefulness of the model for simulating the kinetics of NIRS measurement data and for systematic interpretation of the relationship between NIRS data and muscle metabolism.
  • Mariame A. Hassan, Mikhail A. Buldakov, Ryohei Ogawa, Qing-Li Zhao, Yukihiro Furusawa, Nobuki Kudo, Takashi Kondo, Peter Riesz
    JOURNAL OF CONTROLLED RELEASE 141 (1) 70 - 76 0168-3659 2010/01 [Not refereed][Not invited]
     
    Low modulation frequencies from 0.5 to 100 Hz were shown to alter the characteristics of the ultrasound field producing solution agitation (<5 Hz; region of "ultrasound streaming" prevalence) or stagnancy (>5 Hz; region of standing waves establishment) (Buldakov et al., Ultrason. Sonochem., 2009). In this study, the same conditions were used to depict the changes in exogenous DNA delivery in these regions. The luciferase expression data revealed that lower modulations were more capable of enhancing delivery at the expense of viability. On the contrary, the viability was conserved at higher modulations whereas delivery was found to be null. Cavitational activity and acoustic streaming were the effecters beyond the observed pattern and delivery enhancement was shown to be mediated mainly through sonopermeation. To promote transfection, the addition of calcium ions or an echo contrast agent (Levovist (R)) was proposed. Depending on the mechanism involved in each approach, differential enhancement was observed in both regions and at the interim zone (5 Hz). In both cases, enhancement in standing waves field was significant reaching 16.0 and 3.3 folds increase, respectively. Therefore, it is concluded that although the establishment of standing waves is not the only prerequisite for high transfection rates, yet, it is a key element in optimization when other factors such as proximity and cavitation are considered. (C) 2009 Elsevier B.V. All rights reserved.
  • A. Hassan Mariame, Furusawa Yukihiro, Zhao Qing-Li, Takasaki Ichiro, Feril Loreto B., Tachibana Katsuro, Kudo Nobuki, Minemura Masami, Sugiyama Toshiro, Kondo Takashi
    Proceedings of the Annual Meeting of the Japan Society of Sonochemistry 日本ソノケミストリー学会 19 7 - 8 2010 
    The current study was undertaken to evaluate the effect of sanazole as a sonosensitizer at previously studied acoustic conditions of different pulse repetition frequencies using two cell lines representatives of solid tumors and hematopoietic cancers. Sanazole alone displayed selective cytotoxic effects towards solid tumor-derived cancer cells resulting in complete cell death after 24 hr treatment and enhanced the ultrasound-induced cell killing after 6 hr post-treatment. The enhancement seemed to be mediated by an additive increase in intracellular oxidative stress levels. Sanazole seems to be an efficient cytotoxic agent for the treatment of solid tumors and a promising sonosensitizer under aerobic conditions.
  • Mariame A. Hassan, Loreto B. Feril, Nobuki Kudo, Katsuro Tachibana, Takashi Kondo, Peter Riesz
    JAPANESE JOURNAL OF APPLIED PHYSICS 49 (7) 0021-4922 2010 [Refereed][Not invited]
     
    The encapsulation of gas bubbles has resulted in improved stability and added a binding capacity to shells for ultrasound-guided targeted delivery. However, this has also changed the physical and acoustical properties of the final formulation. In this study, we have evaluated three clinically-used contrast agents of different compositions, namely, Levovist, Sonazoid, and SonoVue, with respect to their sonochemical and biological effects at different concentrations. The results showed that both shell elasticity and reactivity played a role in modulating both effects influencing the extent of ultrasound-induced free-radical formation. Microbubbles with elastic shells were found to be more capable of inducing delayed symptoms of cell killing, whereas the combined use of chemically reactive robust shells and high-density gases, such as perfluorocarbons, could exert a protective effect on cells. These conclusions offer new perspectives on how microbubbles interact with biological systems and might be useful in tailoring novel microbubbles in the future. (C) 2010 The Japan Society of Applied Physics
  • Naoki Hirokawa, Kazumitsu Koito, Futoshi Okada, Nobuki Kudo, Katsuyuki Yamamoto, Katsuhiko Fujimoto, Mutsumi Nishida, Takeshi Ichimura, Masakazu Hori, Taishi Satoh, Masato Hareyama
    JOURNAL OF MEDICAL ULTRASONICS 36 (4) 177 - 185 1346-4523 2009/12 [Not refereed][Not invited]
     
    The purpose of the present study is to investigate anticancer efficacy and apoptosis confirmed by caspase under several exposure conditions of high-intensity focused ultrasound (HIFU). Twenty-five rats with KDH-8 hepatoma were treated by HIFU at several acoustic energies to evaluate treatment efficacy. Apoptosis was examined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and Hoechst 33258 staining, and caspase 3, 8, and 9/6 activity was respectively assayed. The KDH-8 subcutaneous tumors were reduced by HIFU, and these rats survived longer than the nontreatment rats (P < 0.01). The minimal threshold of HIFU energy was 30 W x 1.0 s for tumor control and long-term survival. The tumors exposed to HIFU exhibited marked apoptotic features under conditions of less than 10 W x 1.0 s. In cultured KDH-8 cells, apoptosis was caused at less than 30 W x 1.0 s (P < 0.01), and more was induced as the energy went down. Caspase 3, 8, and 9/6 were more activated at low energy under 10 W x 1.0 s (P < 0.01), and caspase 8, which is death receptor dependent, was significantly more activated than caspase 9/6, which is mitochondria dependent (P < 0.01). HIFU-induced apoptosis in vivo and in vitro is one of the mechanisms for tumor control and is mediated by caspase 3, 8, and 9/6. The significantly greater activation of caspase 8 than of caspase 9/6 suggests that the apoptosis pathway induced by HIFU might be more mitochondria dependent than death receptor dependent. However, further examination will be needed.
  • Takashi Kondo, Toru Yoshida, Ryohei Ogawa, Mariame A. Hassan, Yukihiro Furusawa, Qing-Li Zhao, Akihiko Watanabe, Akihiro Morii, Loreto B. Feril, Katsuro Tachibana, Hiroshi Kitagawa, Yoshiaki Tabuchi, Ichiro Takasaki, Mohammad H. Shehata, Nobuki Kudo, Kazuhiro Tsukada
    JOURNAL OF MEDICAL ULTRASONICS 36 (2) 61 - 68 1346-4523 2009/06 [Not refereed][Not invited]
     
    In this study, the effects of low-intensity pulsed ultrasound (LIU) as an adjuvant to doxorubicin (DOX) treatment was further investigated in comparison to hyperthermia as another widely used adjuvant. The effects were compared with respect to cell killing and apoptosis induction in U937 cells. Human primary liver cancer (PLC) cells were also used to evaluate the effects of the combinations. The use of an echo contrast agent was investigated for further enhancement of cytotoxicity. Finally, the acoustic mechanisms involved were investigated. The effects of different treatment regimens on cell viability were determined using the Trypan blue dye-exclusion test. Apoptosis induction was detected by flow cytometry using fluorescein isothiocyanate-annexin V and propidium iodide staining. The mechanistic study involved electron paramagnetic spin trapping for detecting free radical formation as an indicator of the occurrence of inertial cavitation and spectrophotometry for sucrose hydrolysis as an indicator for noncavitational effects. The combination treatments exerted synergistic effects on cytotoxicity depending on the acoustic conditions used. The use of LIU as an adjuvant to DOX treatment was shown to be superior to the use of hyperthermia as an adjuvant. Moreover, the combination seems to be promising for other cancer types provided that the acoustic conditions are properly selected with respect to drug concentration. The key ultrasound mechanism responsible for the synergism observed was shown to be the production of free radicals by inertial cavitation. Non-cavitational forces were also shown to contribute to the effect. This study is motivating to engage in in vivo research with various cancer types as a step toward clinical applicability and is emphasizing on the importance of developing therapeutic protocols for setting LIU parameters with respect to other therapeutic conditions.
  • Nobuki Kudo, Kengo Okada, Katsuyuki Yamamoto
    BIOPHYSICAL JOURNAL 96 (12) 4866 - 4876 0006-3495 2009/06 [Refereed][Not invited]
     
    In this article, membrane perforation of endothelial cells with attached microbubbles caused by exposure to single-shot short pulsed ultrasound is described, and the mechanisms of membrane damage and repair are discussed. Real-time optical observations of cell-bubble interaction during sonoporation and successive scanning electron microscope observations of the membrane damage with knowledge of bubble locations revealed production of micron-sized membrane perforations at the bubble locations. High-speed observations of the microbubbles visualized production of liquid microjets during nonuniform contraction of bubbles, indicating that the jets are responsible for cell membrane damage. The resealing process of sonoporated cells visualized using fluorescence microscopy suggested that Ca(2+)-independent and Ca(2+)-triggered resealing mechanisms were involved in the rapid resealing process. In an experimental condition in which almost all cells have one adjacent bubble, 25.4% of the cells were damaged by exposure to single-shot pulsed ultrasound, and 15.9% (similar to 60% of the damaged cells) were resealed within 5 s. These results demonstrate that single-shot pulsed ultrasound is sufficient to achieve sonoporation when microbubbles are attached to cells.
  • Takashi Kondo, Toru Yoshida, Ryohei Ogawa, Mariame A. Hassan, Yukihiro Furusawa, Qing-Li Zhao, Akihiko Watanabe, Akihiro Morii, Loreto B. Feril, Katsuro Tachibana, Hiroshi Kitagawa, Yoshiaki Tabuchi, Ichiro Takasaki, Mohammad H. Shehata, Nobuki Kudo, Kazuhiro Tsukada
    JOURNAL OF MEDICAL ULTRASONICS 36 (2) 61 - 68 1346-4523 2009/06 [Not refereed][Not invited]
     
    In this study, the effects of low-intensity pulsed ultrasound (LIU) as an adjuvant to doxorubicin (DOX) treatment was further investigated in comparison to hyperthermia as another widely used adjuvant. The effects were compared with respect to cell killing and apoptosis induction in U937 cells. Human primary liver cancer (PLC) cells were also used to evaluate the effects of the combinations. The use of an echo contrast agent was investigated for further enhancement of cytotoxicity. Finally, the acoustic mechanisms involved were investigated. The effects of different treatment regimens on cell viability were determined using the Trypan blue dye-exclusion test. Apoptosis induction was detected by flow cytometry using fluorescein isothiocyanate-annexin V and propidium iodide staining. The mechanistic study involved electron paramagnetic spin trapping for detecting free radical formation as an indicator of the occurrence of inertial cavitation and spectrophotometry for sucrose hydrolysis as an indicator for noncavitational effects. The combination treatments exerted synergistic effects on cytotoxicity depending on the acoustic conditions used. The use of LIU as an adjuvant to DOX treatment was shown to be superior to the use of hyperthermia as an adjuvant. Moreover, the combination seems to be promising for other cancer types provided that the acoustic conditions are properly selected with respect to drug concentration. The key ultrasound mechanism responsible for the synergism observed was shown to be the production of free radicals by inertial cavitation. Non-cavitational forces were also shown to contribute to the effect. This study is motivating to engage in in vivo research with various cancer types as a step toward clinical applicability and is emphasizing on the importance of developing therapeutic protocols for setting LIU parameters with respect to other therapeutic conditions.
  • Nobuki Kudo, Kengo Okada, Katsuyuki Yamamoto
    BIOPHYSICAL JOURNAL 96 (12) 4866 - 4876 0006-3495 2009/06 [Not refereed][Not invited]
     
    In this article, membrane perforation of endothelial cells with attached microbubbles caused by exposure to single-shot short pulsed ultrasound is described, and the mechanisms of membrane damage and repair are discussed. Real-time optical observations of cell-bubble interaction during sonoporation and successive scanning electron microscope observations of the membrane damage with knowledge of bubble locations revealed production of micron-sized membrane perforations at the bubble locations. High-speed observations of the microbubbles visualized production of liquid microjets during nonuniform contraction of bubbles, indicating that the jets are responsible for cell membrane damage. The resealing process of sonoporated cells visualized using fluorescence microscopy suggested that Ca(2+)-independent and Ca(2+)-triggered resealing mechanisms were involved in the rapid resealing process. In an experimental condition in which almost all cells have one adjacent bubble, 25.4% of the cells were damaged by exposure to single-shot pulsed ultrasound, and 15.9% (similar to 60% of the damaged cells) were resealed within 5 s. These results demonstrate that single-shot pulsed ultrasound is sufficient to achieve sonoporation when microbubbles are attached to cells.
  • Kengo Okada, Nobuki Kudo, Mariame A. Hassan, Takashi Kondo, Katsuyuki Yamamoto
    ULTRASONICS SONOCHEMISTRY 16 (4) 512 - 518 1350-4177 2009/04 [Refereed][Not invited]
     
    To understand the underlying concepts required for the determination of thresholds for free radical generation, effects of gas dissolution in and microbubble addition to sonicated solutions were investigated. Four solutions with different gaseous conditions, air-saturated and degassed solutions with and without microbubbles of 20 pm in diameter with shells, were studied in the presence of an air-liquid interface. These test solutions were exposed to 1 MHz ultrasound of 0.06 MPa(p-p) at various pulse durations (PDs) from 0.1 to 5 ms and pulse repetition frequencies from 0.1 to 2 kHz. Generation of free radicals was evaluated using the electron spin resonance (ESR) spin trapping method and starch-iodine method. Thresholds of duty ratio (DR) corresponding to temporal average intensity of ultrasound for free radical generation were significantly greater in degassed solutions than in air-saturated solutions. Microbubbles had no significant effects in air-saturated solutions but caused a slight decrease in the threshold in degassed solutions. In all of these results, the DR of a threshold curve against pulse repetition period (PRP) was not constant but linearly decreased with it, suggesting that a balance between bubble growth and shrinkage during the ON and OFF times of burst ultrasound is the primary parameter for the interpretation of thresholds. The effect of an air-liquid interface of the solution was also examined, and it was revealed that gas transport from the air is a predominant factor determining the amount of free radicals. (c) 2008 Elsevier B.V. All rights reserved.
  • Kengo Okada, Nobuki Kudo, Mariame A. Hassan, Takashi Kondo, Katsuyuki Yamamoto
    ULTRASONICS SONOCHEMISTRY 16 (4) 512 - 518 1350-4177 2009/04 [Not refereed][Not invited]
     
    To understand the underlying concepts required for the determination of thresholds for free radical generation, effects of gas dissolution in and microbubble addition to sonicated solutions were investigated. Four solutions with different gaseous conditions, air-saturated and degassed solutions with and without microbubbles of 20 pm in diameter with shells, were studied in the presence of an air-liquid interface. These test solutions were exposed to 1 MHz ultrasound of 0.06 MPa(p-p) at various pulse durations (PDs) from 0.1 to 5 ms and pulse repetition frequencies from 0.1 to 2 kHz. Generation of free radicals was evaluated using the electron spin resonance (ESR) spin trapping method and starch-iodine method. Thresholds of duty ratio (DR) corresponding to temporal average intensity of ultrasound for free radical generation were significantly greater in degassed solutions than in air-saturated solutions. Microbubbles had no significant effects in air-saturated solutions but caused a slight decrease in the threshold in degassed solutions. In all of these results, the DR of a threshold curve against pulse repetition period (PRP) was not constant but linearly decreased with it, suggesting that a balance between bubble growth and shrinkage during the ON and OFF times of burst ultrasound is the primary parameter for the interpretation of thresholds. The effect of an air-liquid interface of the solution was also examined, and it was revealed that gas transport from the air is a predominant factor determining the amount of free radicals. (c) 2008 Elsevier B.V. All rights reserved.
  • Mariame A. Hassan, Loreto B. Feril, Kosho Suzuki, Nobuki Kudo, Katsuro Tachibana, Takashi Kondo
    ULTRASONICS SONOCHEMISTRY 16 (3) 372 - 378 1350-4177 2009/03 [Refereed][Not invited]
     
    Three novel lipid-shell-type microbubbles (MBs), AS-0100, BG6356A and BG6356B, have been evaluated for their impact on ultrasound (US)-induced cell death and free radicals production. Previously studied and well-characterized US exposure conditions were employed in which human myelomonocytic lymphoma U937 cells were exposed to 1 MHz pulsed US beam (0.3 W/cm(2), 10% duty factor) for 1 min with or without MBs. Three different concentrations of each MB were used. Apoptosis and cell lysis were assessed by examining phosphatidylserine externalization and by counting viable cells, respectively, 6 h post-exposure. Free radicals production and scavenging activities were evaluated using electron paramagnetic resonance (EPR)-spin trapping. The results showed that only AS-0100 and BG6356A were able to enhance the US-induced apoptosis, mainly by increasing the secondary necrosis. Apoptosis and cell lysis seemed to depend more on mechanical forces exerted by oscillating MBs while free radicals played a trivial role. BG series MBs exhibited pronounced scavenging activities. Generally, despite the need for further optimization, AS-0100 and BG6356A appear to be promising as adjuncts in cases where US-induced cell death is required. (c) 2008 Published by Elsevier B.V.
  • Mikhail A. Buldakov, Mariame A. Hassan, Qing-Li Zhao, Loreto B. Feril, Nobuki Kudo, Takashi Kondo, Nikolai V. Litvyakov, Mikhail A. Bolshakov, Vladislav V. Rostov, Nadejda V. Cherdyntseva, Peter Riesz
    ULTRASONICS SONOCHEMISTRY 16 (3) 392 - 397 1350-4177 2009/03 [Refereed][Not invited]
     
    This study was undertaken to examine ultrasound (US) mechanisms and their impact on chemical and biological effects in vitro as a function of changing pulse repetition frequency (PRF) from 0.5 to 100 Hz using a 1 MHz-generator at low-intensities and 50% duty factor (DF). The presence of inertial cavitation was detected by electron paramagnetic resonance (EPR) spin-trapping of hydroxyl radicals resulting from sonolysis of water. Non-cavitational effects were evaluated by studying the extent of sucrose hydrolysis measured by UV spectrophotometry. Biological effects were assessed by measuring the extent of cell killing and apoptosis induction in U937 cells using Trypan blue dye exclusion test and flow cytometry, respectively. The results indicate significant PRF dependence with respect to hydroxyl radical formation, cell killing and apoptosis induction. The lowest free radical formation and cell killing and the highest cell viability were found at 5 Hz (100 ms pulse duration). On the other hand, no correlation was found between sucrose hydrolysis and PRF. To our knowledge, this is the first report to be devoted to study the impact of low PRFs at low-intensities on US-induced chemical and biological effects and the mechanisms involved. This study has introduced the role of "US streaming" (convection); a forgotten factor in optimization studies, and explored its importance in comparison to standing waves. (c) 2008 Published by Elsevier B.V.
  • Mikhail A. Buldakov, Mariame A. Hassan, Qing-Li Zhao, Loreto B. Feril, Nobuki Kudo, Takashi Kondo, Nikolai V. Litvyakov, Mikhail A. Bolshakov, Vladislav V. Rostov, Nadejda V. Cherdyntseva, Peter Riesz
    ULTRASONICS SONOCHEMISTRY 16 (3) 392 - 397 1350-4177 2009/03 [Not refereed][Not invited]
     
    This study was undertaken to examine ultrasound (US) mechanisms and their impact on chemical and biological effects in vitro as a function of changing pulse repetition frequency (PRF) from 0.5 to 100 Hz using a 1 MHz-generator at low-intensities and 50% duty factor (DF). The presence of inertial cavitation was detected by electron paramagnetic resonance (EPR) spin-trapping of hydroxyl radicals resulting from sonolysis of water. Non-cavitational effects were evaluated by studying the extent of sucrose hydrolysis measured by UV spectrophotometry. Biological effects were assessed by measuring the extent of cell killing and apoptosis induction in U937 cells using Trypan blue dye exclusion test and flow cytometry, respectively. The results indicate significant PRF dependence with respect to hydroxyl radical formation, cell killing and apoptosis induction. The lowest free radical formation and cell killing and the highest cell viability were found at 5 Hz (100 ms pulse duration). On the other hand, no correlation was found between sucrose hydrolysis and PRF. To our knowledge, this is the first report to be devoted to study the impact of low PRFs at low-intensities on US-induced chemical and biological effects and the mechanisms involved. This study has introduced the role of "US streaming" (convection); a forgotten factor in optimization studies, and explored its importance in comparison to standing waves. (c) 2008 Published by Elsevier B.V.
  • Mariame A. Hassan, Loreto B. Feril, Kosho Suzuki, Nobuki Kudo, Katsuro Tachibana, Takashi Kondo
    ULTRASONICS SONOCHEMISTRY 16 (3) 372 - 378 1350-4177 2009/03 [Not refereed][Not invited]
     
    Three novel lipid-shell-type microbubbles (MBs), AS-0100, BG6356A and BG6356B, have been evaluated for their impact on ultrasound (US)-induced cell death and free radicals production. Previously studied and well-characterized US exposure conditions were employed in which human myelomonocytic lymphoma U937 cells were exposed to 1 MHz pulsed US beam (0.3 W/cm(2), 10% duty factor) for 1 min with or without MBs. Three different concentrations of each MB were used. Apoptosis and cell lysis were assessed by examining phosphatidylserine externalization and by counting viable cells, respectively, 6 h post-exposure. Free radicals production and scavenging activities were evaluated using electron paramagnetic resonance (EPR)-spin trapping. The results showed that only AS-0100 and BG6356A were able to enhance the US-induced apoptosis, mainly by increasing the secondary necrosis. Apoptosis and cell lysis seemed to depend more on mechanical forces exerted by oscillating MBs while free radicals played a trivial role. BG series MBs exhibited pronounced scavenging activities. Generally, despite the need for further optimization, AS-0100 and BG6356A appear to be promising as adjuncts in cases where US-induced cell death is required. (c) 2008 Published by Elsevier B.V.
  • Kengo Okada, Nobuki Kudo, Takashi Kondo, Katsuyuki Yamamoto
    JOURNAL OF MEDICAL ULTRASONICS 35 (4) 169 - 176 1346-4523 2008/12 [Not refereed][Not invited]
     
    The objective was to investigate the contributions of mechanical effects due to kinetic force induced by the dynamic behavior of microbubbles and sonochemical effects due to free radicals produced by inertial cavitation to cell membrane damage under sonoporation conditions in which cells with adjacent microbubbles were irradiated with single-shot pulsed ultrasound. The free radical scavenger cysteamine was used to control the occurrence of sonochemical effects, and the ratios of cells with membrane damage to intact cells were compared in the presence and absence of cysteamine. To determine the optimal dose of cysteamine, free radical production on exposure to burst pulse ultrasound was investigated using KI-starch solutions with different concentrations (0-5 mM) of cysteamine. High-speed observation of the dynamic behavior of Levovist microbubbles during ultrasound exposure was also carried out in the presence and absence of cysteamine, and the difference in the ratios of the maximum bubble diameter to the initial diameter was evaluated. Next, human prostate cancer cells with adjacent Levovist microbubbles were exposed to single-shot pulsed ultrasound with a center frequency of 1 MHz, a peak negative pressure of 1.1 MPa, and a pulse width of 3 mu s, and the percentages of cells with membrane damage were evaluated by fluorescent microscopy using propidium iodide in the presence and absence of cysteamine. It was confirmed that cysteamine at a concentration of 5 mM completely suppressed sonochemical effects without causing a change in the dynamic response of microbubbles to pulsed ultrasound. The percentages of cells with membrane damage in the presence and absence of cysteamine (5 mM) were 10.3% +/- 4.1% (n = 13) and 8.7% +/- 3.9% (n = 9), respectively. No significant difference was found (P = 0.36). The results indicate that cell membrane damage induced by single-shot pulsed ultrasound with adjacent microbubbles was due mainly to mechanical effects, not to sonochemical effects.
  • KUDO Nobuki, YAMAMOTO Katsuyuki
    Japanese journal of medical ultrasonics = 超音波医学 35 (6) 623 - 629 1346-1176 2008/11/15 [Not refereed][Not invited]
  • Khai Jun Kek, Ryuta Kibe, Masatsugu Niwayama, Nobuki Kudo, Katsuyuki Yamamoto
    OPTICS EXPRESS 16 (22) 18173 - 18187 1094-4087 2008/10 [Refereed][Not invited]
     
    An imaging instrument based on spatially resolved spectroscopy that enables temporal and spatial analyses of muscle oxygenation was designed. The instrument is portable and can be connected to 32 compact and separate-type optical probes. Its measurement accuracy of O-2 saturation and hemoglobin concentration was evaluated using a tissue-equivalent phantom. Imaging and multi-point measurements of tissue oxygen saturation (StO2) in the quadriceps muscle were also performed, and dynamic changes in StO2 in response to increase in exercise intensity (within the rectus femoris region) and variation in exercise protocol (among the rectus femoris, vastus lateralis and vastus medialis) were clearly shown. (C) 2008 Optical Society of America
  • Khai Jun Kek, Ryuta Kibe, Masatsugu Niwayama, Nobuki Kudo, Katsuyuki Yamamoto
    OPTICS EXPRESS 16 (22) 18173 - 18187 1094-4087 2008/10 [Not refereed][Not invited]
     
    An imaging instrument based on spatially resolved spectroscopy that enables temporal and spatial analyses of muscle oxygenation was designed. The instrument is portable and can be connected to 32 compact and separate-type optical probes. Its measurement accuracy of O-2 saturation and hemoglobin concentration was evaluated using a tissue-equivalent phantom. Imaging and multi-point measurements of tissue oxygen saturation (StO2) in the quadriceps muscle were also performed, and dynamic changes in StO2 in response to increase in exercise intensity (within the rectus femoris region) and variation in exercise protocol (among the rectus femoris, vastus lateralis and vastus medialis) were clearly shown. (C) 2008 Optical Society of America
  • YOSHIDA TORU, KONDO TAKASHI, OGAWA RYOHEI, ZHAO QING-LI, HASSAN MARIAME A, WATANABE AKIHIKO, TAKASAKI ICHIRO, TABUCHI YOSHIAKI, SHOJI MIKI, KUDO NOBUKI, FERIL LORETO B. JR, TACHIBANA KATSURO, BULDAKOV MIKHAIL A, HONDA TAKASHI, TSUKADA KAZUHIRO, RIESZ PETER
    Thermal Medicine(Japanese Journal of Hyperthermic Oncology) Japanese Society for Thermal Medicine 23 (3) 113 - 122 1882-2576 2007/09/20 [Not refereed][Not invited]
     
    Interest in molecular imaging and in molecularly-targeted therapy has grown tremendously, and ultrasound may offer new tools for modern cancer therapy. To understand how therapeutic ultrasound works, it is necessary to understand its biological effects at the molecular level. In this review, investigations on the molecular aspects of ultrasound are discussed, with emphasis on apoptosis induction, gene expression, and gene transfection. In these studies, apoptosis induction was assayed with flow cytometry and with other methods targeting indicators of apoptosis. Gene expression was evaluated using western blotting, real-time polymerase chain reaction, and microarray analysis. Gene transfection was investigated using a luciferase assay and other methods. The reported results show that low intensity ultrasound can induce apoptosis in cancer cell lines, and that this effect can be optimized using pulsed ultrasound. Exposure to ultrasound can result in the down-regulation or up-regulation of some genes. Of particular interest is the striking up-regulation of the heme oxygenase-1 gene, a gene usually associated with oxidative stress in human lymphoma U937 cells. Introducing genes using ultrasound with or without microbubbles also exhibited promising results. Membrane damage is pivotal to biological effects, and using ultrasound to modify or affect cell membranes can either promote or inhibit desired effects. In summary, it is concluded that ultrasound has the potential to help develop useful methods which can be utilized in therapies which require apoptosis induction, gene introduction into cells, alterations in gene regulation, and drug-activation.
  • Loreto B. Feril, Takashi Kondo, Yoshiaki Tabuchi, Ryohei Ogawa, Qing-Li Zhao, Tetsuo Nozaki, Toru Yoshida, Nobuki Kudo, Katsuro Tachibana
    JAPANESE JOURNAL OF APPLIED PHYSICS PART 1-REGULAR PAPERS BRIEF COMMUNICATIONS & REVIEW PAPERS 46 (7B) 4435 - 4440 0021-4922 2007/07 [Refereed][Not invited]
     
    Biological effects of low-intensity ultrasound (US) focusing on US-induced programmed cell death (apoptosis), regulation of gene expression, and US-mediated gene transfection (sonotransfection) are reviewed. Studies have shown that US can induce apoptosis and that certain conditions can provide an optimal apoptosis induction. Sonotransfection of different cell lines in vitro and target tissues in vivo have been reported. Several genes can also be up-regulated or down-regulated by sonication. As to the potential therapeutic applications, apoptosis induction by US may induce direct and fast ways of treating tumor or cancer tissues. Systemic or local sonotransfection might also be a safe and effective gene therapy method in effecting the cure of local and systemic disorders. Gene regulation of target cells may be utilized in modifying cellular response to a treatment, such as increasing the sensitivity of diseased cells while making normal cells resistant to the side effects of the treatment. In addition, gene regulation by US may also play an important part in the enhanced healing of damaged tissues.
  • Yoshiaki Tabuchi, Hidetaka Ando, Ichiro Takasaki, Loreto B. Feril, Qing-Li Zhao, Ryohei Ogawa, Nobuki Kudo, Katsuro Tachibana, Takashi Kondo
    CANCER LETTERS 246 (1-2) 149 - 156 0304-3835 2007/02 [Refereed][Not invited]
     
    We examined the gene expression of human leukemia Molt-4 cells treated with non-thermal low intensity pulsed ultrasound. Six hours after 0.3 W/cm(2) pulsed ultrasound treatment, apoptosis (24 +/- 3.3%, mean +/- SD) with minimal cell lysis was observed. Of approximately 16,600 genes analyzed, BCL2-associated athanogene 3 (BAG3), Dual (Hsp40) homolog, subfamily B, member I (DNAJB1), heat shock 70 kDa protein 113 (HSPA1B), and heat shock 70 kDa protein 6 (HSPA6) showed increased levels of expression while isopentenyl-diphosphate delta isomerase (IDII) and 3-hydroxy-3-methylglutaryl-coenzyme A synthase I (HMGCS1) showed decreased levels in the cells 3 h after the ultrasound treatment. The expression levels of these six genes were confirmed by a real-time quantitative polymerase chain reaction. To our knowledge, this is the first report of DNA microarray analysis of genes that are differentially expressed in response to apoptosis induced by non-thermal low intensity pulsed ultrasound in human leukemia cells. The present results will provide a basis for further understanding of the molecular mechanisms of effects of not only low intensity pulsed ultrasound but also that of mechanical shear stress in the cells. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
  • Yoshiaki Tabuchi, Hidetaka Ando, Ichiro Takasaki, Loreto B. Feril, Qing-Li Zhao, Ryohei Ogawa, Nobuki Kudo, Katsuro Tachibana, Takashi Kondo
    CANCER LETTERS 246 (1-2) 149 - 156 0304-3835 2007/02 [Not refereed][Not invited]
     
    We examined the gene expression of human leukemia Molt-4 cells treated with non-thermal low intensity pulsed ultrasound. Six hours after 0.3 W/cm(2) pulsed ultrasound treatment, apoptosis (24 +/- 3.3%, mean +/- SD) with minimal cell lysis was observed. Of approximately 16,600 genes analyzed, BCL2-associated athanogene 3 (BAG3), Dual (Hsp40) homolog, subfamily B, member I (DNAJB1), heat shock 70 kDa protein 113 (HSPA1B), and heat shock 70 kDa protein 6 (HSPA6) showed increased levels of expression while isopentenyl-diphosphate delta isomerase (IDII) and 3-hydroxy-3-methylglutaryl-coenzyme A synthase I (HMGCS1) showed decreased levels in the cells 3 h after the ultrasound treatment. The expression levels of these six genes were confirmed by a real-time quantitative polymerase chain reaction. To our knowledge, this is the first report of DNA microarray analysis of genes that are differentially expressed in response to apoptosis induced by non-thermal low intensity pulsed ultrasound in human leukemia cells. The present results will provide a basis for further understanding of the molecular mechanisms of effects of not only low intensity pulsed ultrasound but also that of mechanical shear stress in the cells. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
  • Kudo Nobuki, Yamamoto Katsuyuki
    Proceedings of the Annual Meeting of the Japan Society of Sonochemistry 日本ソノケミストリー学会 2007 41 - 41 2007
  • Kondo Takashi, Tabuchi Yoshiaki, Takasaki Ichiro, Feril Loreto B. Jr., Tachibana Katsuro, Kudo Nobuki, Zhao Qing-Li, Ogawa Ryohei
    Proceedings of the Annual Meeting of the Japan Society of Sonochemistry 日本ソノケミストリー学会 2007 48 - 48 2007
  • Khai Jun Kek, Takahiro Miyakawa, Nobuki Kudo, Katsuyuki Yamamoto
    Progress in Biomedical Optics and Imaging - Proceedings of SPIE 6434 1605-7422 2007 [Refereed][Not invited]
     
    In this study, we showed that exercise type- and intensity-dependent regional differences in muscle oxygenation and oxygen consumption rate (V̇o2) of the knee extensor muscles could be imaged in real time with a multi-channel spatially resolved near-infrared spectroscopy (SR-NIRS) imaging device. Healthy subjects performed isometric knee extension exercise for 30 s (without- or with-leg-press action) at different exercise intensities [10%, 40% and 70% of maximum voluntary contraction (MVC)]. "Separation- type" probes were attached to the skin over the major knee extensor muscles: vastus lateralis (VL), rectus femoris (RF) and vastus medialis (VM). Placement of the probes enabled simultaneously measurement of 12 sites over a skin area of about 30 cm2 (temporal resolution = 0.25 s). Local V̇o2 of each muscle, resting V̇o2 (V̇o 2,rest) and recovery V̇o2 (V̇o2,rec ), were determined with arterial occlusion before the start and after the end of contraction, respectively. There was no significant difference between the values of V̇o2,rest in the muscles. However, during knee extension exercise without-leg-press action, V̇o2,rec value of the RF was significantly greater than the values of the VL and VM at all exercise intensities. In contrast, during exercise with-leg-press action, V̇o2,rec values of the RF and VM were greater than those of the VL, especially during exercise at 40% and 70% MVC. In summary, the regional differences in muscle oxygenation and V̇o2 of the knee extensor muscles, probably due to the differences in relative contributions of muscles to exercise and in muscle architecture, were imaged using SR-NIRS.
  • Khai Jun Kek, Takahiro Miyakawa, Nobuki Kudo, Katsuyuki Yamamoto
    OPTICAL TOMOGRAPHY AND SPECTROSCOPY OF TISSUE VII 6434 0277-786X 2007 [Refereed][Not invited]
     
    In this study, we showed that exercise type- and intensity-dependent regional differences in muscle oxygenation and oxygen consumption rate ((V) over dotO(2)) of the knee extensor muscles could be imaged in real time with a multi-channel spatially resolved near-infrared spectroscopy (SR-NIRS) imaging device. Healthy subjects performed isometric knee extension exercise for 30 s (without- or with-leg-press action) at different exercise intensities [10%, 40% and 70% of maximum voluntary contraction (MVC)]. "Separation-type" probes were attached to the skin over the major knee extensor muscles: vastus lateralis (VL), rectus femoris (RF) and vastus medialis (VM). Placement of the probes enabled simultaneously measurement of 12 sites over a skin area of about 30 cm(2) (temporal resolution = 0.25 s). Local (V) over dotO(2) of each muscle, resting (V) over dotO(2) ((V) over dotO(2), rest) and recovery (V) over dotO(2) ((V) over dotO(2), rec), were determined with arterial occlusion before the start and after the end of contraction, respectively. There was no significant difference between the values of (V) over dotO(2),rest in the muscles. However, during knee extension exercise without-leg-press action, (V) over dotO(2),rec value of the RF was significantly greater than the values of the VL and VM at all exercise intensities. In contrast, during exercise with-leg-press action, (V) over dotO(2),rec values of the RF and VM were greater than those of the VL, especially during exercise at 40% and 70% MVC. In summary, the regional differences in muscle oxygenation and (V) over dotO(2) of the knee extensor muscles, probably due to the differences in relative contributions of muscles to exercise and in muscle architecture, were imaged using SR-NIRS.
  • Wakako Hiraoka, Hidemi Honda, Loreto B. Feril, Nobuki Kudo, Takashi Kondo
    ULTRASONICS SONOCHEMISTRY 13 (6) 535 - 542 1350-4177 2006/09 [Refereed][Not invited]
     
    Although enhancement of ultrasound-induced cell killing by photodynamic reagents has been shown, the sonochemical mechanism in detail is still not clear. Here, comparison between sonodynamic effect and photodynamic effect with photosensitizers at a concentration of 10 mu M on free radical formation and cell killing was made. When electron paramagnetic-resonance spectroscopy (EPR) was used to detect 2,2,6,6-tetramethyl-4-piperidone-N-oxyl (TAN) after photo-irradiation or sonication with 2,2,6,6-tetramethyl-4-piperidone (TMPD), the order of TAN formation in the photo-irradiated samples was as follows: thodamine 6G (R6) > sulforhodamine B (SR) > hematoporphyrin (Hp) > rhodamine 123 (R 123) > rose bengal (RB) > erythrosine B (Er) = 0; although there was time-dependent TAN formation when the samples were sonicated, no significant difference among these agents were observed. All these agents suppressed ultrasound-induced OH radical formation detected by EPR-spin trapping. Sensitizer-derived free radicals were markedly observed in SR, RB and Er, while trace level of radicals derived from R6 and R123 were observed. Enhancement of ultrasound-induced decrease of survival in human lymphoma U937 cells was observed at 1.5 W/cm(2) (less than inertial cavitation threshold) for R6, R123, SR and Er, and at 2.3 W/cm(2) for R6, R123, Er, RB and SR. On the other hand, photo-induced decrease of survival was observed for R6, Hp and RB at the same concentration (10 mu M). These comparative results suggest that (1) O-1(2) is not involved in the enhancement of ultrasound-induced loss of cell survival, (2) OH radicals and sensitizer-derived free radicals do not take part in the enhancement, and (3) the mechanism is mainly due to certain mechanical stress such as augmentation of physical disruption of cellular membrane by sensitizers in the close vicinity of cells and/or cavitation bubbles. (C) 2005 Elsevier B.V. All rights reserved.
  • KUDO Nobuki, HIRAO Norifumi, OKADA Kengo, YAMAMOTO Katsuyuki
    The Transactions of the Institute of Electronics, Information and Communication Engineers. A 一般社団法人電子情報通信学会 89 (9) 746 - 753 0913-5707 2006/09/01 [Not refereed][Not invited]
     
    超音波造影法では,造影剤の種類によって最適な造影効果を得るための超音波照射条件が異なることが知られている.このような特徴は,造影剤の微小気泡を包むシェルの力学的な特性に強く影響されると考えられている.そこで本論文では,音圧振幅が異なる超音波パルス列を一つの微小気泡に連続的に照射し,気泡の振舞いを高速度撮影することによりシェル特性を可視化する手法について検討した.更に,これを実現するシステムを開発して2種類の造影剤気泡の高速度観察を行い,本手法によりシェルの力学的特性の違いが可視化できることを確認した.また,広帯域超音波パルスを用いて微小気泡懸濁液の消失係数の音圧依存性を測定し,高速度カメラで可視化されたシェル特性の違いが音響計測でも確認できることを確認した.これらの評価によって明らかにされた各造影剤気泡の特徴は,臨床で報告されている特徴と一致しており,開発したシェル特性評価手法の有用性が確認された.
  • Wakako Hiraoka, Hidemi Honda, Loreto B. Feril, Nobuki Kudo, Takashi Kondo
    ULTRASONICS SONOCHEMISTRY 13 (6) 535 - 542 1350-4177 2006/09 [Not refereed][Not invited]
     
    Although enhancement of ultrasound-induced cell killing by photodynamic reagents has been shown, the sonochemical mechanism in detail is still not clear. Here, comparison between sonodynamic effect and photodynamic effect with photosensitizers at a concentration of 10 mu M on free radical formation and cell killing was made. When electron paramagnetic-resonance spectroscopy (EPR) was used to detect 2,2,6,6-tetramethyl-4-piperidone-N-oxyl (TAN) after photo-irradiation or sonication with 2,2,6,6-tetramethyl-4-piperidone (TMPD), the order of TAN formation in the photo-irradiated samples was as follows: thodamine 6G (R6) > sulforhodamine B (SR) > hematoporphyrin (Hp) > rhodamine 123 (R 123) > rose bengal (RB) > erythrosine B (Er) = 0; although there was time-dependent TAN formation when the samples were sonicated, no significant difference among these agents were observed. All these agents suppressed ultrasound-induced OH radical formation detected by EPR-spin trapping. Sensitizer-derived free radicals were markedly observed in SR, RB and Er, while trace level of radicals derived from R6 and R123 were observed. Enhancement of ultrasound-induced decrease of survival in human lymphoma U937 cells was observed at 1.5 W/cm(2) (less than inertial cavitation threshold) for R6, R123, SR and Er, and at 2.3 W/cm(2) for R6, R123, Er, RB and SR. On the other hand, photo-induced decrease of survival was observed for R6, Hp and RB at the same concentration (10 mu M). These comparative results suggest that (1) O-1(2) is not involved in the enhancement of ultrasound-induced loss of cell survival, (2) OH radicals and sensitizer-derived free radicals do not take part in the enhancement, and (3) the mechanism is mainly due to certain mechanical stress such as augmentation of physical disruption of cellular membrane by sensitizers in the close vicinity of cells and/or cavitation bubbles. (C) 2005 Elsevier B.V. All rights reserved.
  • Go Kagiya, Yoshiaki Tabuchi, Loreto B Feril Jr, Ryohei Ogawa, Qing-Li Zhao, Nobuki Kudo, Wakako Hiraoka, Katsuro Tachibana, Shin-Ichiro Umemura, Takashi Kondo
    Journal of medical ultrasonics (2001) 33 (1) 3 - 10 1346-4523 2006/03 [Not refereed][Not invited]
     
    PURPOSE: The present study was undertaken to reconfirm heme oxygenase-1 (HO-1) induction by ultrasound, and elucidate the mechanism by which this occurs. METHODS: After exposure of human lymphoma U937 cells to 1 MHz continuous ultrasound (US), gene profiling by using cDNA microarray analysis, cell viability by using the trypan blue dye exclusion test, mRNA expression by using real-time quantitative polymerase chain reaction, and protein expression by using Western blotting were examined. As an indicator of cavitation, hydroxyl radical formation was studied by using electron paramagnetic resonance-spin trapping. RESULTS: The cDNA microarray analysis reconfirmed HO-1 induction in human lymphoma U937 cells after exposure to US, and further identified one upregulated and two downregulated genes. When U937 cells were exposed to US for 1 min, HO-1 induction, as examined by real-time quantitative polymerase chain reaction and Western blotting, was observed at intensities higher than the cavitational threshold. When a potent antioxidant, N-acetyl-L-cysteine, was added to the culture medium before or after sonication, the induction was attenuated, indicating that reactive oxygen species are involved in HO-1 induction. A decrease in mitochondrial membrane potential and generation of superoxide anion radicals were also observed in the cells exposed to US. CONCLUSION: We used a cDNA microarray system to confirm upregulation of the HO-1 gene and to discover new genes that respond to ultrasonic cavitation. Increased intracellular oxidative stress secondary to the sonomechanical effects arising from ultrasonic cavitation is suggested to be the mechanism of enhancement of HO-1 expression.
  • 光学的高速度観測による超音波造影剤気泡のシェル特性の評価
    電子情報通信学会和文誌 J89-A (9) 746 - 753 2006 [Not refereed][Not invited]
  • Nobuki Kudo, Hideki Miyashita, Katsuyuki Yamamoto
    THERAPEUTIC ULTRASOUND 829 (829) 614 - + 0094-243X 2006 [Not refereed][Not invited]
     
    We have proposed a new simple Schlieren method for visualizing an acoustic field without the requirement of a complex optical system. In this study, we developed an experimental system of the simple Schlieren method and investigated the possibility of applying this technique to visualization of an acoustic field of a HIFU transducer. Since visualized acoustic fields showed typical non-linear distortion of high-intensity ultrasound, we concluded that the proposed simple Schlieren method is useful for evaluating a HIFU field.
  • Kudo Nobuki
    Proceedings of the Annual Meeting of the Japan Society of Sonochemistry 日本ソノケミストリー学会 15 9 - 10 2006 
    Single bubble sonoluminescence was discovered in 1989, and the following studies on this phenomenon greatly contributed to elucidate the mechanisms of cavitation phenomena. However, several important problems of the phenomenon are still under investigation. Non-spherical behavior of a single or multi bubbles is one of the unsettled problem. As part of our studies on the safety of diagnostic ultrasound using an ultrasound contrast agent, dynamics of microbubbles of several microns in diameter have been studied using high-speed photography method. This paper introduces our observation system and a collection of high-speed photos especially focusing on non-spherical bubble behavior.
  • K. J. Kek, T. Miyakawa, S. Yoneyama, N. Kudo, K. Yamamoto
    Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings 5101 - 5104 0589-1019 2006 [Refereed][Not invited]
     
    Near-infrared spectroscopy (NIRS) is a useful technique for noninvasive measurement of muscle oxygenation. However, analyses of the dynamic changes in muscle metabolism based only on experimental observations of NIRS are difficult. Therefore, we constructed a mathematical model of muscle metabolism, comprising of the ATP synthesizing systems and O2 diffusion system, to identify the mechanisms responsible for those observations. A customized NIRS instrument was used to measure the changes in muscle oxygenation of the forearm flexor muscles during intermittent and continuous isometric flexion exercises when healthy male subjects participated in exercises tests. The exercise-dependent difference in changes could be distinguished and the simulated results agreed well with that measured experimentally. Although the contraction intensity for both exercises was identical, the magnitude of energy needed to perform the respective exercises was different This difference was reflected by the changes in the ATP synthesizing systems, in which the energy needed during the latter-half of continuous exercise was mostly supplied by anaerobic system, whereas that during intermittent exercise was supplied by the aerobic and anaerobic systems that operated synergisti-cally. From the results, we conclude that the model could be a useful tool for the elucidation of the relationship between experimental observations of NIRS and muscle metabolism. © 2006 IEEE.
  • OKADA Kengo, KUDO Nobuki, NIWA Koichi, YAMAMOTO Katsuyuki
    Japanese journal of medical ultrasonics = 超音波医学 32 (5) 461 - 470 1346-1176 2005/09/15 [Not refereed][Not invited]
  • OKADA Kengo, KUDO Nobuki, NIWA Koichi, YAMAMOTO Katsuyuki
    Journal of medical ultrasonics = 超音波医学 32 (5) 461 - 470 1346-1176 2005/09/15 [Not refereed][Not invited]
  • KUDO Nobuki, YAMAMOTO Katsuyuki
    Transactions of the Japanese Society for Medical and Biological Engineering : BME 社団法人日本生体医工学会 43 (2) 231 - 237 1347-443X 2005/06/10 [Not refereed][Not invited]
  • Kengo Okada, Nobuki Kudo, Koichi Niwa, Katsuyuki Yamamoto
    Journal of Medical Ultrasonics 32 (1) 3 - 11 1346-4523 2005/03 [Not refereed][Not invited]
     
    Purpose. Sonoporation is an ultrasound technique that enables large molecules that normally do not penetrate the cell membrane to pass through it. Recent studies show that pulsed ultrasound in the presence of microbubbles increases the permeability of the cell membrane. However, the mechanism and basic properties of this sonoporation remain unclear. We thus investigated the mechanism of generation and frequency of occurrence of sonoporation, as well as the repair of a cell membrane damaged by microbubbles. Methods. The spatial relationship between microbubbles and cells was observed microscopically when cells were sonicated with pulsed ultrasound. Effects of microbubbles on the cells were observed with a high-speed camera, and the ratio of cell membrane damage and repair was examined using fluorescent microscopy. Results. Damage to the cell membrane, caused mainly by mechanical effects of the expansion and contraction of microbubbles, significantly increased the permeability of the cell membrane. The frequency of cell membrane damage was closely associated with the presence of microbubbles and increased with increase in acoustic pressure. The ratio of repair of damaged cells was about 70% during 3 min after a single shot of pulsed ultrasound, indicating that repair of damaged cell membranes requires little time. Conclusion. We examined the frequency of occurrence of cell membrane damage and repair in sonoporation using pulsed ultrasound and microbubbles. Our results should prove useful for improving pulsed-ultrasound sonoporation. © The Japan Society of Ultrasonics in Medicine 2005.
  • S Yamada, K Komuro, T Mikami, N Kudo, H Onozuka, K Goto, S Fujii, K Yamamoto, A Kitabatake
    HEART 91 (2) 183 - 188 1355-6037 2005/02 [Not refereed][Not invited]
     
    Objective: To test the hypothesis that the power of the received signal of harmonic power Doppler imaging ( HPDI) is proportional to the bubble concentration under conditions of constant applied acoustic pressure, and to determine whether a new quantitative method can overcome the acoustic field inhomogeneity during myocardial contrast echocardiography (MCE) and identify perfusion abnormalities caused by myocardial infarction. Methods: The relation between Levovist concentration and contrast signal intensity (CI) of HPDI was investigated in vitro under conditions of constant acoustic pressure. MCE was performed during continuous infusion of Levovist with intermittent HPDI every sixth cardiac cycle in 11 healthy subjects and 25 patients with previous myocardial infarction. In the apical views myocardial CI (CImyo) was quantified in five myocardial segments. The CI from the left ventricular blood pool adjacent to the segment was also measured in dB and subtracted from the CImyo ( relative CI (RelCI)). Results: CI had a logarithmic correlation and the calculated signal power a strong linear correlation with Levovist concentration in vitro. Thus, a difference in CI of X dB indicates a microbubble concentration ratio of 10(X/10). In normal control subjects, CImyo differed between the five segments (p< 0.0001), with a lower CImyo in deeper segments. However, RelCI did not differ significantly between segments ( p = 0.083). RelCI was lower ( p, 0.0001) in the 39 infarct segments (mean (SD) -18.6 (2.8) dB) than in the 55 normal segments (mean (SD) -15.1 (1.6) dB). RelCI differed more than CImyo between groups. Conclusions: The new quantitative method described can overcome the acoustic field inhomogeneity in evaluation of myocardial perfusion during MCE. RelCI represents the ratio of myocardium to blood microbubble concentrations and may correctly reflect myocardial blood volume fraction.
  • パルス超音波による微小気泡存在下でのsonoporationに関する基礎的検討
    超音波医学 32 461 - 470 2005 [Not refereed][Not invited]
  • N Kobayashi, T Yasu, S Yamada, N Kudo, M Kuroki, K Miyatake, M Kawakami, M Saito
    CIRCULATION JOURNAL 67 (7) 630 - 636 1346-9843 2003/07 [Not refereed][Not invited]
     
    Microbubbles have been reported to enhance ultrasound (US)-related side effects in animal systems. The present study investigated the influence of contrast ultrasonography (US) with perflutren lipid microspheres, a recently developed second-generation contrast agent, on microvessels. Rat mesentery was exposed to 1.8-MHz pulsed US with intravenous injection of perflutren (0.1 or 1.0ml/kg) or Levovist(R) (300mg/kg), and the microvessel bleeding and endothelial cell injury was examined. Impaired endothelial cells were identified by the fluorescence of propidium iodide. Microvessel bleeding was examined also in the rat myocardium. The interaction between 0.1 ml/kg of perflutren and US exposure did not cause microvessel bleeding, and did not increase endothelial cell injury compared with the sham operation, unless frequent, strong US exposure occurred. When the dose was increased to 1.0ml/kg, the combination of perflutren and US exposure resulted in capillary bleeding and increased endothelial cell injury in capillaries and venules (p<0.01). However, the incidence of microvessel bleeding and endothelial cell injury did not exceed that with Levovist(R) microbubbles. In the myocardium, microvessel bleeding was not observed under any conditions. In conclusion, perflutren lipid microspheres enhanced US-related microvessel injury as with other contrast agents at the dose of 1.0 ml/kg, but not with 0.1 ml/kg and the appropriate US setting.
  • Loreto B. Feril Jr., Takashi Kondo, Qing-Li Zhao, Ryohei Ogawa, Katsuro Tachibana, Nobuki Kudo, Shinichi Fujimoto, Shinobu Nakamura
    Ultrasound in Medicine and Biology 29 (2) 331 - 337 0301-5629 2003/02/01 [Refereed][Not invited]
     
    To determine the effects of echo-contrast agents (ECAs) on ultrasound (US)-induced apoptosis and cell lysis, human myelomonocytic lymphoma U937 cells in suspension were exposed to 1 MHz continuous waves US for 1 min at an intensity of 0.5, 1.0, 2.0 or 4.0 W/cm2 with or without non-shell type ECA, Levovist™ (2 mg/ml), and shell type, Optison™ (1 μl/ml) or YM454 (1 μl/ml). Levovist™ minimally enhanced the US-induced apoptosis at 1.0 W/cm2 while Optison™ and YM454 did at 2.0 and 4.0 W/cm2, as detected by flow cytometry. Cell lysis was also augmented when Levovist™ was combined with US at 2.0 W/cm2, and when Optison™ was combined with US at 2.0 and 4.0 W/cm2. YM454 showed the highest rate of enhanced cell lysis at 1.0, 2.0 and 4.0 W/cm2. Therefore, this study shows that Optison™ and YM454 are effective in augmenting the US-induced cell killing, but not Levovist™. Another result indicates that cavitation plays a role in the augmented effects and that inertial cavitation appears necessary for Optison™ and YM454 to effect their actions. In addition, results show that the rate of apoptosis is lower in the presence of ECAs with higher free radical scavenging activity, suggesting a possible role for free radicals in apoptosis. These findings suggest that some ECAs have potential to be adjuncts in cases wherein augmented US-induced cell killing is needed, such as in cancer therapy with US. © 2003 World Federation for Ultrasound in Medicine & Biology.
  • N Kobayashi, T Yasu, S Yamada, N Kudo, M Kuroki, M Kawakami, K Miyatake, M Saito
    ULTRASOUND IN MEDICINE AND BIOLOGY 28 (7) 949 - 956 0301-5629 2002/07 [Not refereed][Not invited]
     
    The aim of the present study was to test the hypothesis that microvascular endothelial cells (EC) are subject to the bioeffects induced by contrast ultrasound (US) because of their proximity to the circulating microbubbles. We examined EC injury in each microvessel section (arteriole, capillary or venule) in rat mesenteries among the following five groups: three controls (sham operation, microbubble injection alone, US exposure with saline injection), and two contrast-US groups (US exposure at a 1-Hz or 30-Hz frame rate with microbubble injection). Propidium iodide (PI), a fluorescent indicator of cell injury, was employed to visualize impaired EC. PI-positive nuclei were equally few among the three controls. Contrast-US increased PI-positive cells in capillaries (1-Hz frame rate, 2.4 +/- 2.2 cells per 0.1-mm vessel length, p = 0.09; 30-Hz frame rate, 4.3 +/- 1.8 cells, p < 0.01) and in venules (1-Hz frame rate, 4.1 +/- 2.5 cells, p < 0.05; 30-Hz frame rate, 13.8 +/- 3.6 cells, p < 0.01) compared with sham operation (0.10 +/- 0.22 cells). The finding indicates that diagnostic contrast US potentially causes EC injury, particularly in venules and capillaries. (E-mail: tyasu@omiya.jichi.ac.jp) (C) 2002 World Federation for Ultrasound in Medicine Biology.
  • M Niwayama, K Yamamoto, D Kohata, K Hirai, N Kudo, T Hamaoka, R Kime, T Katsumura
    IEICE TRANSACTIONS ON INFORMATION AND SYSTEMS E85D (1) 115 - 123 0916-8532 2002/01 [Not refereed][Not invited]
     
    We have developed a 200-channel imaging system that enables measurement of changes in oxygenation and blood volume and that covers a wider area (45 cm x 15 cm) than that covered by conventional systems. This system consisted of 10 probes of five channels, a light-emitting diode (LED) driver, multiplexers and a personal computer. Each probe was cross-shaped and consisted of an LED, five photo diodes, and a current-to-volt age (I-V) converter. Lighting of the LEDs and acquisition of 200-channel data were time-multiplexed. The minimum data acquisition time for 200 channels, including the time required for calculation of oxygenation and monitoring of a few traces of oxygenation on a computer display, was about 0.2 s. We carried out exercise tests and measured the changes in oxy- and deoxy-hemoglobin concentrations in the thigh. Working muscles in exercises could be clearly imaged, and spatio-temporal changes in muscle oxygenation during exercise and recovery were also shown. These results demonstrated that the 200-channel imaging system enables observation of the distribution of muscle metabolism and localization of muscle function.
  • H. Lee, K. Yamamoto, N. Kudo, T. Shimooka, Y. Mitamura, T. Yuhta
    Journal of Artificial Organs 5 (3) 193 - 199 1434-7229 2002 [Not refereed][Not invited]
     
    Recently, cavitation on the surface of mechanical heart valves has been studied as a cause of fractures that occur in implanted mechanical heart valves. Several factors, including peak dp/dt of the ventricular pressure, maximum closing velocity of the leaflet, and squeeze flow, have been studied as indices of the cavitation threshold. In the present study, cavitation erosion on the surface of a mechanical valve was examined by focusing on squeeze flow and the water-hammer phenomenon during the closing period of the valve. A simple solenoid-actuated test device that can directly control the valve closing velocity was developed, and opening - closing tests of 3000 and 40000 cycles were performed at various closing velocities. The results showed that there was a closing velocity threshold above which erosion pitting was induced and that the threshold was about 0.4m/s in the valves used in this study. Cavitation-induced erosion pits were observed only in regions where squeeze flow occurred immediately before valve closure. On the other hand, the number of the pits was found to be closely related to the area of the water hammer-induced pressure were below the critical pressure defined by water vapor pressure. Therefore, it was concluded that cavitation is initiated and augmented by the two pressure drops due to squeeze flow and the water-hammer phenomenon, respectively.
  • J Shao, L Lin, M Niwayama, N Kudo, K Yamamoto
    OPTICAL ENGINEERING 40 (10) 2293 - 2301 0091-3286 2001/10 [Not refereed][Not invited]
     
    In spite of the usefulness of continuous-wave near-infrared spectroscopy (CW-NIRS) for noninvasive measurement of oxygenation of the brain and muscle, no theoretically derived algorithms for this technique have yet been presented, although an algorithm can be theoretically determined on the basis of diffusion. We derive the theoretical mean optical pathlength based on diffusion theory, and we develop linear and nonlinear algorithms for CW-NIRS. Both algorithms are validated by the results of experiments using a phantom consisting of Intralipid and hemoglobin solutions. An extra absorber is also used to examine the effects of background absorption in tissues, except for blood. The changes in concentrations of oxy- and deoxyhemoglobin, calculated using both algorithms, agree well with those obtained by experiments around an operating point determined by the optical pathlength. The results of the phantom experiments and theoretical analyses show that the nonlinear algorithm can be used in a wider range of variation in absorption than the linear algorithm. The results also suggest that if the operating point is inappropriately given, the accuracy of both algorithms is greatly reduced. The errors in actual measurements of muscle oxygenation using the linear and nonlinear algorithms are also estimated, assuming a variation of +/-50% in blood volume, and are found to be less than 12 and 6%, respectively, if the operating point is set appropriately. (C) 2001 Society of Photo-Optical Instrumentation Engineers.
  • 超音波照射下における微小気泡のふるまいの高速度カメラによる観察
    電子情報通信学会論文誌Ａ J84-A 1492 - 1499 2001 [Not refereed][Not invited]
  • 超音波変調光による生体の光イメージングに関する基礎的検討 ‐スペックルパターンの変動を利用した変調光の検出‐
    電子情報通信学会論文誌Ａ J84-A 2293 - 2301 2001 [Not refereed][Not invited]
  • M Niwayama, L Lin, J Shao, N Kudo, K Yamamoto
    REVIEW OF SCIENTIFIC INSTRUMENTS 71 (12) 4571 - 4575 0034-6748 2000/12 [Not refereed][Not invited]
     
    The inhomogeneity of tissue structure greatly affects the sensitivity of tissue oxygenation measurement by reflectance near-infrared spectroscopy. In this study, we investigated the influence of a fat layer on muscle oxygenation measurement by in vivo tests and Monte Carlo simulation, and we propose a method for correcting the influence. In the simulation, a three-dimensional model consisting of the epidermis, dermis, fat, and muscle layers was used. In in vivo tests, measurement sensitivity was examined by measuring oxygen consumption of the forearm muscle and the peak-to-peak variation of oxygenation in periodic exercise tests on the vastus lateralis using a newly developed multisensor type of tissue oximeter. Fat layer thickness was also measured by ultrasonography. The correction curve of measurement sensitivity against fat layer thickness was obtained from the results of simulation and in vivo tests. The values of corrected oxygen consumption were almost the same and had less variation between individuals (0.13 +/-0.02 ml 100 g(-1) min(-1)) than did the uncorrected values (0.08 +/-0.04 ml 100 g(-1) min(-1)). (C) 2000 American Institute of Physics. [S0034-6748(00)02812-4].
  • NIRSによる筋組織酸素計測における脂肪層の影響補正 ‐ 31P-NMRお よびPETによる筋酸素消費量との比較‐
    セラピューティックリサーチ 21 (6) 1520 - 1523 2000 [Not refereed][Not invited]
  • Influence of a fat layer on muscle oxygenation measurement using near-IR spectroscopy: quantitative analysis based on two-layered phantom experiments and Monte Carlo simulation
    Frontiers Med. Biol. Eng. 10 43 - 58 2000 [Not refereed][Not invited]
  • LEE H.S, KUDO N, SHIMOOKA S, MITAMURA Y, YAMAMOTO K
    Jinko Zoki JAPANESE SOCIETY FOR ARTIFICIAL ORGANS 28 (2) 436 - 441 0300-0818 1999/04/15 [Not refereed][Not invited]
     
    Since the discovery, in the 1980 s, of erosion-pit-induced fractures in implanted mechanical heart valves, cavitation on the surface of mechanical heart valves has been widely studied as a possible cause of pitting. We previously performed accelerated fatigue tests on artificial valves and found that both the number and diameter of pits were increased by compliance of a vessel wall near the valve. In this study, we measured pressure waveforms near a valve and closing velocities of a disk, which were placed in a holder with and without compliance. It was found that negative peak pressure near the valve with compliance was smaller than that of the rigid holder, but that the duration of the low pressure was longer. It was also found that the closing velocity of the disk increased and that cavitation erosion was enhanced in the rigid valve holders. These results suggest that disk closing velocity during the closing phase has significant effects on pitting erosion.
  • 張旭
    超音波医学 25 167 - 178 1998 [Not refereed][Not invited]
  • 超音波ＲＦエコー解析による頸動脈壁厚計測に関する検討
    超音波医学 25 155 - 166 1998 [Not refereed][Not invited]
  • 庭山 雅嗣, 志賀 利一, 林 凌, 工藤 信樹, 高橋 誠, 山本 克之
    医用電子と生体工学 36 (1) 41 - 48 0021-3292 1998 [Not refereed][Not invited]
  • N Kudo, M Yoshida, K Yamamoto, T Mikami, A Kitabatake, Y Ito
    1998 IEEE ULTRASONICS SYMPOSIUM - PROCEEDINGS, VOLS 1 AND 2 1479 - 1482 1051-0117 1998 [Refereed][Not invited]
     
    To investigate the effects of a myofibrous structure of biological tissue on ultrasound attenuation, the frequency-dependence of attenuation in bovine muscle tissue was measured in the frequency range of 10-40 MHz. The frequency-dependence of attenuation was approximated by a power-low, af(b), in the measured frequency range. The exponent value 'b' of the sliced samples was 1.2 for parallel insonification with respect to the direction of myofibers and 1.9 for normal insonification, while it was 1.5 for the supernatant liquid extracted from the homogenized tissue suspension. These results suggest that the exponent value 'b' of fibrous structure is changed by the angle of insonification. It is well known that ultrasound attenuation of fibrous tissue at frequencies below 10 MHz depends on the direction of the fibrous structure. Our results suggest that this angular dependence of attenuation is caused by a change in the exponent value of frequency-dependent attenuation.
  • M Niwayama, T Shiga, L Lin, N Kudo, M Takahashi, K Yamamoto
    PROCEEDINGS OF THE 20TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOL 20, PTS 1-6 20 1849 - 1850 1094-687X 1998 [Refereed][Not invited]
     
    The inhomogeneity of tissue structure greatly affects the sensitivity of tissue oxygenation measurement by reflectance NIRS. We have proposed a method for correcting the influence of a subcutaneous fat layer on muscle oxygenation measurement. The correction is based on an inverse realtionship between the measurement sensitivity and detected light intensity. In this study, this method was validated by measuring the peak-to-peak variation of muscle oxygenation in periodic exercise tests on the vastus lateralis. A multisensor probe consisting of a light source and four photodiodes with source-detector distances of 7-40 mm was newly developed. A proximal detector with a 7-mm separation was used to eliminate the effect of skin. The fat layer thickness was also measured by ultrasonography. Results of the tests clearly showed that the presence of a fat layer greatly decreases the sensitivity of measurement and increases the light intensity at the detectors. Sensitivity correction by detected light intensity resulted in almost the same changes in muscle oxygention due to periodic exercise among subjects regardless of different fat layer thicknesses. The proximal detector was also effective for reducing the effect of skin.
  • M OYANAGI, N KUDO, Y YANAGIDA, N IWAMA, K OKAZAKI
    JAPANESE JOURNAL OF APPLIED PHYSICS PART 1-REGULAR PAPERS SHORT NOTES & REVIEW PAPERS 33 (5B) 3155 - 3158 0021-4922 1994/05 [Not refereed][Not invited]
     
    A new, method for evaluating shock wave pressure distribution of extracorporeal shock wave lithotripters, using pressure-sensitive paper has been developed. It is a simple method to visualize the shock wave pressure distribution and has a better spatial resolution than the hydrophone. The pressure-sensitive paper can be used to visually detect whether the focal point is on the correct position, and to detect changes of pressure distribution. Additionally, the relationship between lithotripter power and integrated density, as a new evaluating value shows linearity. Therefore, this method is useful for quality assurance of lithotripters at hospitals.
  • Development of the robust hydrophone for extracorporeal shock wave lithotripters
    Jpn. J. Endourology and ESWL 7 (2) 153 - 158 1994 [Not refereed][Not invited]
  • KUDO N.
    Frontiers Med. Biol. Eng. 1 (1) 19 - 28 1988 [Not refereed][Not invited]
  • Nobuki Kudo, Koichi Shimizu, Goro Matsumoto
    Japanese journal of medical electronics and biological engineering 25 (2) 91 - 98 0021-3292 1987 [Not refereed][Not invited]
     
    The optical biotelemetry using free-space light transmission in a closed space has many advantages over the conventional telemetry techniques using radio waves. There are some reports on the optical telemeters using direct light transmission, but few are found which use the indirect light scattered from a ceiling, a floor and walls. Since the latter technique does not require the line-of-sight transmission, it enables us to realize the non-restraint measurement of biological signals. In order to examine the possibility of this technique, the distribution of the indirect light in a room was calculated by a computer simulation. The distribution is uniform enough to carry out the telemetry with one receiver in the room with the dimension of W4.2XL6.4XH2.7m. The minimum received power was -28.0dBm with the transmitter power of 1 watt, which was about a half of the maximum power. To verify the possibility shown in the theoretical analysis, an optical biotelemetry system using the indirect light transmission was developed. 3 ECG's and a body temperature are multiplexed in time domain and modulated into a PIM pulse sequence. Light emitters placed on both shoulders emit the light of about 1 watt when the pulse is on. The system can be operated over 100 hours without replacing batteries. To examine the practical usefulness of this technique in clinical application, the optical biotelemetry from a freely moving subject is carried out with the developed system. A stable data acquisition was demonstrated even from the subject in exercise. © 1987, Japanese Society for Medical and Biological Engineering. All rights reserved.
  • Optical biotelemetry using indirect light transmission
    Biotelemetry IX 55 - 58 1987 [Not refereed][Not invited]
  • Nobuki Kudo, Koichi Shimizu, Goro Matsumoto
    Japanese journal of medical electronics and biological engineering 23 (3) 194 - 198 0021-3292 1985 [Not refereed][Not invited]
     
    A new method of biotelemetry is proposed, which realizes nonrestrained acquisition of biological signals using the infrared light diffused out from animal skin. This technique is fundamentally different from conventional telemetry techniques which use radio-frequency electromagnetic waves. An optical transmitter which consists of some LED's is implanted beneath the skin. Biological information such as ECO signal is collected in vivo and the light emitted from the LED's is modulated by the signal. The light transmitted through the skin is strongly diffused and spread out in a wide angle. The light is collected by the remotely located optical receivers and the biological information is obtained by demodulating the signal. Thus, the biological information in vivo is obtained without restraining the object with cables or optical fibers. In order to verify the possibility of the above technique, a system, which obtains an ECG from laboratory animals, has been developed. An infrared light was chosen due to its invisibility and high transmittance through the skin. Considering the stability of the communication link and the power consumption of the implanted transmitter, PFM (Pulse Frequency Modulation) technique was used. Using the system, the transcutaneous ECG telemetry was performed successfully. In the experiment, the indirect light reflected and scattered by the walls, the ceiling and the floor was shown to be useful in the optical telemetry. Light transmission patterns through the skin of a mouse were measured. The results suggest the possibility of telemetry even from the deep part of the body cavity. It is concluded that recent progress of optical and electronic technologies have reached the point, where transcutaneous optical telemetry of biological signals has become practically possible. © 1985, Japanese Society for Medical and Biological Engineering. All rights reserved.

MISC

  • 超音波で生体の壁を超える 超音波と気泡を併用する膀胱内注入療法の犬における安全性検討
    佐々木 東, 青柳 貞一郎, 池中 良徳, 工藤 信樹, 中村 健介, 滝口 満喜  超音波医学  48-  (Suppl.)  S195  -S195  2021/04
  • 鈴木亮, 島忠光, 丸山保, 小俣大樹, 宗像理紗, 工藤信樹, 丸山一雄  超音波医学 Supplement  48-  2021
  • 佐々木東, 青柳貞一郎, 池中良徳, 工藤信樹, 中村健介, 滝口満喜  超音波医学 Supplement  48-  2021
  • 低強度パルス超音波照射による毛髪細胞刺激
    佐々木 東, 工藤 信樹, 大田 寛, 滝口 満喜  超音波医学  46-  (Suppl.)  S579  -S579  2019/04  [Not refereed][Not invited]
  • 今井慎司, UNGA Johan, 鈴木亮, 丸山一雄, 工藤信樹  超音波医学  46-  (Supplement (CD-ROM))  2019
  • 佐々木東, 工藤信樹, 大田寛, 滝口満喜  超音波医学  45-  (Suppl.)  S575  -S575  2018/04  [Not refereed][Not invited]
  • 佐々木 東, 工藤 信樹, 中山 翔太, 滝口 満喜  超音波techno  29-  (4)  27  -30  2017/07  [Not refereed][Not invited]
  • 佐々木東, 工藤信樹, 中村健介, 森下啓太郎, 大田寛, 滝口満喜  再生医療  16-  348  2017/02/01  [Not refereed][Not invited]
  • 佐々木東, 工藤信樹, 森下啓太郎, 大田寛, 滝口満喜  日本超音波医学会光超音波画像研究会プログラム・抄録集  2017-  (2nd)  66‐67  2017  [Not refereed][Not invited]
  • Sogo Toda, Yuji Kato, Nobuki Kudo, Koichi Shimizu  Proceedings of SPIE - The International Society for Optical Engineering  10251-  2017/01/01  [Not refereed][Not invited]
     
    © 2017 SPIE. For transillumination imaging of an animal body, we have attempted to suppress the scattering effect in a turbid medium. It is possible to restore the optical image before scattering using phase-conjugate light. We examined the effect of intensity information as well as the phase information for the restoration of the original light distribution. In an experimental analysis using animal tissue, the contributions of the phase-and the intensity-information to the image restoration through turbid medium were demonstrated.
  • 工藤 信樹  光アライアンス  27-  (9)  6  -10  2016/09
  • 超音波による細胞周期変動を利用した増感放射線療法の可能性
    藤沢 眞代, 佐々木 東, 安井 博宣, 工藤 信樹, 滝口 満喜  超音波医学  43-  (5)  679  -679  2016/09  [Not refereed][Not invited]
  • 膀胱癌を模した3次元培養系でのシスプラチンデリバリー
    佐々木 東, 工藤 信樹, 滝口 満喜  超音波医学  43-  (5)  679  -679  2016/09  [Not refereed][Not invited]
  • 佐々木東, 工藤信樹, 中村健介, 森下啓太郎, 大田寛, 滝口満喜  超音波医学  43-  (Suppl.)  S544  -S544  2016/04  [Not refereed][Not invited]
  • 髙田 亮, 小田 雄介, 鈴木 亮, 工藤 信樹  電子情報通信学会技術研究報告 = IEICE technical report : 信学技報  115-  (513)  33  -38  2016/03/22
  • 佐々木東, 工藤信樹, 中山翔太, 滝口満喜  日本超音波医学会光超音波画像研究会プログラム・抄録集  2016-  (2nd)  22‐24  2016  [Not refereed][Not invited]
  • Igarashi Yasunobu, Kudo Nobuki  Proceedings of Symposium on Ultrasonic Electronics  36-  "1J2  -2-1"-"1J2-2-2"  2015/11/05
  • 住吉 洸城, 工藤 信樹  電子情報通信学会技術研究報告 = IEICE technical report : 信学技報  115-  (116)  1  -6  2015/06/26
  • SHIRAHATA You, SHIGETOMI (KURIBAYASHI) Kaori, KUDO Nobuki  IEICE technical report. ME and bio cybernetics  114-  (514)  19  -23  2015/03/16  
    We have been studying a sonoporation technique that transduces drugs into cells by exposure of the cells with adjacent bubbles to short-pulsed ultrasound. In the research process, it was found that efficiency of the cell membrane repair after sonoporation is affected by the cell membrane tension. In this study, micron-sized wells that can culture several tens of cells were designed and fabricated to control cell membrane tension by changing extension state of the cells. The wells were manufactured using a conventional photolithography technique with thick photoresist SU-8. The wells are designed to be 15-200 μm in diameter and about 40 μm in depth. The developed wells were used for 1-week cell culture, and it was confirmed that adherent areas of cells can be controlled by controlling number of the cells cultured inside a well, indicating that the developed wells are useful tools for future studies on in vivo sonoporation.
  • 遠藤将吾, 工藤信樹, 山口秀, 住吉洸城, 茂木洋晃, 金子貞洋, 小林浩之, 寺坂俊介, 寳金清博  日本超音波医学会光超音波画像研究会プログラム・抄録集  2015-  (2nd)  25  -26  2015  [Not refereed][Not invited]
  • Kudo Nobuki  Proceedings of Symposium on Ultrasonic Electronics  35-  397  -398  2014/12/03
  • 吉松幸里, 工藤信樹, 鈴木亮, 丸山一雄  超音波医学  40-  (4)  427  2013/07/15  [Not refereed][Not invited]
  • SEKINE Daiki, KUDO Nobuki, SHIMIZU Koichi  IEICE technical report. ME and bio cybernetics  113-  (103)  39  -44  2013/06/21  
    We have proposed a novel technique for acquiring Schlieren-like images of ultrasound fields using a simple optics. This technique takes two shadowgraphs with and without ultrasound exposure and visualizes an acoustic field by subtraction of the images. In this study, a Schlieren system was improved to visualize diagnostic ultrasound fields. A pressure sensor that receives ultrasound pulses was added to the system, and the detected signal was used for a timing signal to visualize instantaneous fields of propagating ultrasound. Various diagnostic ultrasound fields were visualized, such as the propagating fields from near-field to focal regions, and the fields in M mode and pulse Doppler mode. In these results, the importance of the proposed method for evaluation of aged deterioration and malfunction of a diagnostic ultrasound probe was confirmed. The relation between pressure and image brightness was investigated, and a good correlation was found between the pulse-averaged square values of the pressure and brightness. This suggests the usefulness of this method for the determination of output intensities of diagnostic ultrasound equipment.
  • 吉松幸里, 工藤信樹, 鈴木亮, 丸山一雄  超音波医学  40-  (2)  230  2013/03/15  [Not refereed][Not invited]
  • KUDO Nobuki  Japanese journal of medical ultrasonics = 超音波医学  39-  (6)  567  -568  2012/11/15  [Not refereed][Not invited]
  • Obara Hiroki, Kudo Nobuki, Shimizu Koichi  Proceedings of Symposium on Ultrasonic Electronics  33-  249  -250  2012/11/13
  • 吉松幸里, 工藤信樹, 鈴木亮, 丸山一雄  日本DDS学会学術集会プログラム予稿集  28th-  143  2012/06/05  [Not refereed][Not invited]
  • 熊田 卓, 松田 康雄, 飯島 尋子, 小川 眞広, 工藤 信樹, 小原 和史, 紺野 啓, 高倉 玲奈, 西田 睦, 南 康範, 森 秀明, 山田 昌彦  Japanese journal of medical ultrasonics = 超音波医学  39-  (3)  317  -326  2012/05/15  [Not refereed][Not invited]
  • KUDO NOBUKI, SASAKI NOBORU, TAKIGUCHI MITSUYOSHI  超音波医学  39-  (Suppl.)  S174  -S174  2012/04/15  [Not refereed][Not invited]
  • SASAKI NOBORU, NAKAMURA KENSUKE, KUDO NOBUKI, TAKIGUCHI MITSUYOSHI  超音波医学  39-  (2)  226  -227  2012/03/15  [Not refereed][Not invited]
  • 宇留賀仁史, 鈴木亮, 小田雄介, 工藤信樹, 根岸洋一, 平田圭一, 野村鉄也, 宇都口直樹, 丸山一雄  日本薬学会年会要旨集  132nd-  (4)  321  2012/03/05  [Not refereed][Not invited]
  • SASAKI NOBORU, NAKAMURA KENSUKE, KUDO NOBUKI, TAKIGUCHI MITSUYOSHI  超音波医学  38-  (6)  674  -674  2011/11/15  [Not refereed][Not invited]
  • 吉松幸里, 工藤信樹, 鈴木亮, 丸山一雄  超音波医学  38-  (6)  671  2011/11/15  [Not refereed][Not invited]
  • KUDO Nobuki  Japanese journal of medical ultrasonics = 超音波医学  38-  (6)  623  -624  2011/11/15  [Not refereed][Not invited]
  • Obara Hiroki, Kudo Nobuki, Shimizu Koichi  IEICE technical report. Ultrasonics  111-  (88)  31  -35  2011/06/16  [Not refereed][Not invited]
     
    Recently, there has been considerable interest in sonoporation, a technique to transduct drugs or genes into cells by ultrasound exposure. In typical studies of sonoporation using cultured cells, the cells and microbubbles are suspended in a culture dish with medium, and exposed to continuous ultrasound waves. In this situation, reflection of ultrasound at a medium-air interface and dish walls produces complex acoustic fields with various standing waves. In this study, the pressure fields of therapeutic ultrasound in a small chamber are visualized using a newly proposed technique called image-subtraction Schlieren. Observation results revealed that brightness of visualized fields is doubled in the presence of reflection and that brightness is decreased adjacent to the chamber wall. It was also confirmed that perturbation of water surface by acoustic streaming causes decrease in pressure amplitudes at antinodes. The linear relation found between brightness of the Schlieren images and acoustic pressure indicates the importance of the image-subtraction Schlieren technique for dosimetry of complex acoustic fields generated inside small chambers.
  • OKUYAMA Manabu, KUDO Nobuki, SHIMIZU Koichi  IEICE technical report. ME and bio cybernetics  111-  (84)  7  -12  2011/06/10  [Not refereed][Not invited]
     
    Sonoporation is a promising technique that temporally increases membrane permeability by exposure of cells to ultrasound. We have been studying a sonoporation technique that uses short-pulsed ultrasound and reported that this exposure condition also can initiate sonoporation effects in the case with microbubbles attached to the cells. In order to clarify the roles of the bubbles for this technique, it is essential to study sonoporation phenomena under control of the size and position of bubbles adjacent cells, which is difficult to achieve by our conventional experimental system. In this study, we developed optical tweezes system that can trap micron-sized bubbles of an ultrasound contrast agent. A spatial liquid modulation device was used to generate a phase hologram for producing doughnut-shaped light beam (Laguerre-Gaussian beam). In the results, it was shown that the tweezers can generate the transverse trapping force of about 20 pN for a bubble of 2.5μm in radius using 1-W laser light. It was also confirmed that the tweezers can manipulate contrast-agent bubbles of 0.5-2.5μm in radius, which are widely used for sonoporation studies.
  • SASAKI NOBORU, NAKAMURA KENSUKE, MURAKAMI MASAHIRO, OTA HIROSHI, YAMASAKI MASAHIRO, KUDO NOBUKI, TAKIGUCHI MITSUYOSHI  超音波医学  38-  (3)  338  -338  2011/05/15  [Not refereed][Not invited]
  • SASAKI NOBORU, NAKAMURA KENSUKE, MURAKAMI MASAHIRO, KUMARA BADULA, OTA HIROSHI, YAMASAKI MASAHIRO, KUDO NOBUKI, TAKIGUCHI MITSUYOSHI  超音波医学  38-  (Suppl.)  S316  -S316  2011/04/15  [Not refereed][Not invited]
  • LI Xin, KUDO Nobuki, SHIMIZU Koichi, KURIKI Shinya  電気学会研究会資料. MBE, 医用・生体工学研究会  2011-  (1)  71  -76  2011/01/27  [Not refereed][Not invited]
  • LI Xin, KUDO Nobuki, SHIMIZU Koichi, KURIKI Shinya  IEICE technical report. ME and bio cybernetics  110-  (399)  71  -76  2011/01/20  [Not refereed][Not invited]
     
    A magnetic detection technique was devised to noninvasively detect the tip position of the nasal feeding tube that delivers liquid diet to the patient's stomach through a transnasal tube. We have designed an AC magnetic susceptibility measurement system that consists of an excitation coil and a pair of differential detection coils. To attain practical sensitivity, a technique to maximize the excitation field at a specific depth in the patient's body has been newly developed. In experimental analyses, the effectiveness of the developed technique was verified.
  • Nobuki Kudo, Masaya Yamamoto  10TH INTERNATIONAL SYMPOSIUM ON THERAPEUTIC ULTRASOUND (ISTU 2010)  1359-  318  -321  2011  [Not refereed][Not invited]
     
    It is known that use of a contrast agents in echocardiography increases the probability of generation of premature ventricular contractions (PVCs). As a basic study to elucidate the mechanisms and to reduce adverse effects, the generation of PVCs was investigated using cultured cardiac myocytes instead of the intact heart in vivo. Cardiac myocytes were isolated from neonatal rats and cultured on a cover slip. The myocyte sample was exposed to pulsed ultrasound with microbubbles adjacent to the myocytes, and generation of PVCs was examined with ultrasound exposure at various delay times after onset of myocyte contraction. The experimental results showed that generation of PVCs had a stable threshold delay time and that PVCs were generated only when myocytes were exposed to ultrasound with delay times longer than the threshold. The results indicate that the model used in this study is useful for revealing the mechanisms by which PVCs are induced by ultrasound exposure.
  • SASAKI AZUMA, NAKAMURA KENSUKE, MURAKAMI MASAHIRO, BANDULA KUMARA, TAMURA YU, OTA HIROSHI, YAMASAKI MASAHIRO, KUDO NOBUKI, TAKIGUCHI MITSUYOSHI  日本獣医学会学術集会講演要旨集  150th-  297  -297  2010/09/01  [Not refereed][Not invited]
  • KUDO Nobuki, SHIMIZU Koichi  IEICE technical report. ME and bio cybernetics  110-  (111)  13  -16  2010/06/23  [Not refereed][Not invited]
     
    A suspension of microbubbles of about one micron in diameter is now widely used as a contrast agent for diagnostic ultrasound and as an enhancer for therapeutic ultrasound. In this study, five types of gas-encapsulated liposomes (bubble liposomes) were produced and their stability was studied under static and dynamic pressure conditions. Five types of phosphatidylcholine, DOPC, POPC, DMPC, DPPC and DSPC, with different transition temperatures between liquidcrystalline and gel phases in the range of -22℃ to +55℃, were used as a main component of the liposomes. Static stability of these bubbles was evaluated by observations of temporal change in turbidity of their suspension, and dynamic stability was evaluated by measurements of pressure-dependent ultrasound transmission. The results showed that both stabilities have strong dependence on temperature of the bubble suspensions, suggesting that phase of the shell material is one of the main parameters for determining bubble stabilities. Bubbles with shells in gel phase have higher stability under the condition of exposure to ultrasound, suggesting that the intact shell in this phase can be restored immediately after bubble oscillation.
  • 工藤信樹, 八木智史, 萩沢康介, 鈴木亮, 丸山一雄, 山本克之  超音波医学  37-  (3)  368  2010/05/15  [Not refereed][Not invited]
  • 八木智史, 工藤信樹, 鈴木亮, 丸山一雄  超音波医学  37-  (3)  372  -373  2010/05/15  [Not refereed][Not invited]
  • SASAKI NOBORU, NAKAMURA KENSUKE, MURAKAMI MASAHIRO, KUMARA BANDULA, OTA HIROSHI, YAMASAKI MASAHIRO, KUDO NOBUKI, TAKIGUCHI MITSUYOSHI  超音波医学  37-  (Suppl.)  S322  -S322  2010/04/15  [Not refereed][Not invited]
  • 八木智史, 工藤信樹, 鈴木亮, 丸山一雄  超音波医学  37-  (1)  45  2010/01/15  [Not refereed][Not invited]
  • Nobuki Kudo  JOURNAL OF MEDICAL ULTRASONICS  37-  (1)  1  -2  2010/01  [Not refereed][Not invited]
  • Nobuki Kudo, Yoshiaki Sanbonmatsu, Koichi Shimizu  Proceedings - IEEE Ultrasonics Symposium  829  -832  2010  [Not refereed][Not invited]
     
    We have proposed a new technique for visualization of an ultrasound fieldthat enables acquisition of Schlieren images by subtraction of two shadowgraphstaken in the presence and absence of ultrasound exposure. This technique can beeasily applied to other optical methods because there is no need to use aconventional Schlieren optics. This paper shows the possibility of applying thetechnique to microscopic observation of high-frequency ultrasound fields. Alight source of short pulsed light of 0.11 ns and a CCD camera with a 15 bitdynamic range were installed in an inverted-type microscope. High-frequencyultrasound fields of a miniature 20-MHz transducer for intravascular ultrasoundimaging and a 50-MHz wideband transducer were visualized using 4 and 10objective lenses. Observation results showed that the high-frequency fields weresuccessfully visualized at the maximum spatial resolution of 0.93 m.Transmission and reflection of pulsed ultrasound at a water-Plexiglas interfacewere also observed, and the acquired movie image of ultrasound propagationdemonstrated the importance of this technique for direct understanding ofcomplex acoustic fields. © 2010 IEEE.
  • 坂口克至, 工藤信樹, 鈴木亮, 丸山一雄, 山本克之  超音波医学  36-  (3)  384  2009/05/15  [Not refereed][Not invited]
  • 八木智史, 岡田健吾, 工藤信樹, 萩沢康介, 鈴木亮, 丸山一雄, 山本克之  超音波医学  36-  S315  2009/04/15  [Not refereed][Not invited]
  • 八木智史, 岡田健吾, 工藤信樹, 萩沢康介, 鈴木亮, 丸山一雄, 山本克之  超音波医学  36-  (1)  67  -68  2009/01/15  [Not refereed][Not invited]
  • Nobuki Kudo, Katsuji Sakaguchi, Ryo Suzuki, Kazuo Maruyama  Proceedings - IEEE Ultrasonics Symposium  1255  -1258  2009  [Not refereed][Not invited]
     
    Five types of gas-encapsulated liposomes (bubble liposomes) were produced and their stability was studied under static pressure and dynamic pressure conditions. Five types of phosphatidylcholine, DOPC, POPC, DMPC DPPC and DSPC, with different transition temperatures between liquid-crystalline and gel phases in the range from ! 22°C to +55°C were used as a main component of the liposomes. Static stability of these BLs was evaluated by observations of turbidity of their suspension, and dynamic stability was evaluated by measurements of pressure-dependent ultrasound transmission. The results showed that both stabilities have strong dependence on temperature of bubble suspensions, suggesting that the phase of the shell material is one of the main parameters to determine bubble stabilities. Bubbles with shells in gel phase have higher stability under exposure to ultrasound, suggesting that the intact shell in this phase can be restored immediately after bubble oscillation. ©2009 IEEE.
  • Okada Kengo, Kudo Nobuki, Hassan Mariame A, Kondo Takashi, Yamamoto Katsuyuki  Proceedings of Symposium on Ultrasonic Electronics  29-  (29)  419  -420  2008/11/11  [Not refereed][Not invited]
  • SUZUKI Ryosuke, KUDO Nobuki, YAMAMOTO Katsuyuki  Japanese journal of medical ultrasonics = 超音波医学  35-  S280  2008/04/15
  • KUDO Nobuki, WATANABE Hiroshi, GOTO Shingo, OKADA Kengo, YAMAMOTO Katsuyuki  Japanese journal of medical ultrasonics = 超音波医学  35-  S289  2008/04/15
  • KUDO Nobuki, YAMAMOTO Katsuyuki  Japanese journal of medical ultrasonics = 超音波医学  35-  S181  2008/04/15
  • 坂口克至, 工藤信樹, 鈴木亮, 丸山一雄, 山本克之  超音波医学  35-  S555  2008/04/15  [Not refereed][Not invited]
  • 八木智史, 岡田健吾, 工藤信樹, 鈴木亮, 丸山一雄, 山本克之  超音波医学  35-  S560  2008/04/15  [Not refereed][Not invited]
  • Katsuji Sakaguchi, Nobuki Kudo, Katsuyuki Yamamoto, Ryo Suzuki, Kazuo Maruyama  Proceedings - IEEE Ultrasonics Symposium  1675  -1678  2008  [Not refereed][Not invited]
     
    Two types of gas-encapsulated liposomes (Bubble liposomes) with different shell compositions were evaluated by measurements of pressure-dependent ultrasound attenuation of bubble suspensions and by high-speed observations of bubble behaviors under exposure to pulsed ultrasound. Attenuation peaks were observed at the frequency range\\ of 16-19 MHz, suggesting that the size of Bubble liposomes is around 400 nm. There was a large difference between threshold pressures of bubble collapse in the two types of Bubble liposomes, indicating that decrease in shell fluidity by addition of cholesterol to a lipid bilayer and increase in surface area by bubble fragmentation have strong effects for facilitating bubble disappearance. ©2008 IEEE.
  • N. Kudo, N. Hirao, K. Okada, K. Yamamoto  ACOUSTICAL IMAGING, VOL 29  29-  107  -+  2008  [Not refereed][Not invited]
     
    This paper describes a method for measuring extinction coefficients of a microbubble suspension at different probing pulse pressures. The experimental results demonstrated the usefulness of this method for evaluating acoustic properties of microbubbles of ultrasound contrast agents and also for finding the optimum exposure conditions of ultrasound.
  • KIBE Ryuta, KEK Khai Jun, KUDO Nobuki, YAMAMOTO Katsuyuki  IEICE technical report  2007-  (36)  13  -16  2007/06/29  [Not refereed][Not invited]
     
    We have been developing a device for imaging muscle oxygenation using spatially resolved spectroscopy. To validate the measurement reliability of the device, we previously used tissue-mimicking liquid phantoms using red blood cells. However, validation could not be sufficiently performed due to unstable optical properties and poor reproducibility of the liquid phantoms. Therefore, we constructed plastic phantoms that mimic the optical properties of backscattered light from muscles with the aim of establishing a more stable and simple method for validation. Clear plastic was used as the base resin, and the concentrations of absorber and scatterer were adjusted accordingly to mimic the absorption and scattering of light in muscle and adipose tissues. Values of absorption coefficient μ'_s and reduced scatter coefficient μ'_s of the muscle tissue phantoms (μ_a=0.019-0.047 mm^<-1>, μ'_s=0.53-0.68 mm^<-1>) and adipose tissue phantoms (μ_a=0.0002-0.0052 mm^<-1>, μ'_s=0.83-1.05 mm^<-1>) were measured using time-resolved spectroscopy, and the values showed good agreement with those of actual tissues.
  • SUZUKI Ryosuke, SOSEKHA Ly, KUDO Nobuki, YAMAMOTO Katsuyuki  IEICE technical report  2007-  (36)  17  -20  2007/06/29  [Not refereed][Not invited]
     
    We have proposed a novel simple method for visualizing acoustic fields of diagnostic pulsed ultrasound without using a conventional Schlieren optical system. Based on the proposed method, we have developed an experimental system and have evaluated its practical usefulness experimentally. In this study, we developed a new low-cost system using a consumer digital camera and an inexpensive laser diode. We also successfully visualized an acoustic field of a diagnostic ultrasound probe using this system. The results indicate the possibility of applying the proposed method to routine inspection of ultrasound probe function in a hospital.
  • KIBE Ryuta, KEK Khai Jun, KUDO Nobuki, YAMAMOTO Katsuyuki, YAMAMOTO Katsuyuki  IEICE technical report. ME and bio cybernetics  107-  (126)  13  -16  2007/06/22  [Not refereed][Not invited]
     
    We have been developing a device for imaging muscle oxygenation using spatially resolved spectroscopy. To validate the measurement reliability of the device, we previously used tissue-mimicking liquid phantoms using red blood cells. However, validation could not be sufficiently performed due to unstable optical properties and poor reproducibility of the liquid phantoms. Therefore, we constructed plastic phantoms that mimic the optical properties of backscattered light from muscles with the aim of establishing a more stable and simple method for validation. Clear plastic was used as the base resin, and the concentrations of absorber and scatterer were adjusted accordingly to mimic the absorption and scattering of light in muscle and adipose tissues. Values of absorption coefficient μ'_s and reduced scatter coefficient μ'_s of the muscle tissue phantoms (μ_a=0.019-0.047 mm^<-1>, μ'_s=0.53-0.68 mm^<-1>) and adipose tissue phantoms (μ_a=0.0002-0.0052 mm^<-1>, μ'_s=0.83-1.05 mm^<-1>) were measured using time-resolved spectroscopy, and the values showed good agreement with those of actual tissues.
  • SUZUKI Ryosuke, SOSEKHA Ly, KUDO Nobuki, YAMAMOTO Katsuyuki  IEICE technical report. ME and bio cybernetics  107-  (126)  17  -20  2007/06/22  [Not refereed][Not invited]
     
    We have proposed a novel simple method for visualizing acoustic fields of diagnostic pulsed ultrasound without using a conventional Schlieren optical system. Based on the proposed method, we have developed an experimental system and have evaluated its practical usefulness experimentally. In this study, we developed a new low-cost system using a consumer digital camera and an inexpensive laser diode. We also successfully visualized an acoustic field of a diagnostic ultrasound probe using this system. The results indicate the possibility of applying the proposed method to routine inspection of ultrasound probe function in a hospital.
  • GOTO Shingo, OKADA Kengo, KUDO Nobuki, YAMAMOTO Katsuyuki  Journal of medical ultrasonics = 超音波医学  34-  S272  2007/04/15
  • 江本 精, 工藤 信樹  Journal of medical ultrasonics = 超音波医学  34-  S164  2007/04/15
  • WATANABE Hiroshi, GOTO Shingo, OKADA Kengo, KUDO Nobuki, YAMAMOTO Katsuyuki  Journal of medical ultrasonics = 超音波医学  34-  S167  2007/04/15
  • OKADA Kengo, KUDO Nobuki, YAMAMOTO Katsuyuki  Journal of medical ultrasonics = 超音波医学  34-  S333  2007/04/15
  • 鈴木 亮, 滝澤 知子, 根岸 洋一, 宇都口 直樹, 門脇 則光, 工藤 信樹, 立花 克郎, 丸山 一雄  Journal of medical ultrasonics = 超音波医学  34-  2007/04/15  [Not refereed][Not invited]
  • KEK Khai Jun, YONEYAMA Satoko, MIYAKAWA Takahiro, KUDO Nobuki, YAMAMOTO Katsuyuki  IEICE technical report  106-  (127)  25  -28  2006/06/16  
    Near-infrared spectroscopy (NIRS) is a technique for noninvasive measurement of muscle oxygenation. However, analyses of the dynamic changes in metabolism based only on NIRS measurements are difficult because the changes in muscle oxygenation could be affected by different factors of the complex metabolic system. Therefore, we constructed a model of muscle metabolism to identify the mechanisms responsible for experimental observation of NIRS measurements. Simulations that were performed with the model sufficiently reproduced the characteristic temporal changes of NIRS measurements. The results demonstrate the usefulness of the model for elucidation of the relationship between muscle metabolism and NIRS measurements.
  • MIYAKAWA Takahiro, KEK Khai Jun, KUDO Nobuki, YAMAMOTO Katsuyuki  IEICE technical report. ME and bio cybernetics  106-  (127)  21  -24  2006/06/16  [Not refereed][Not invited]
     
    Near-infrared spectroscopy (NIRS) is a useful technique for noninvasive and real-time measurement of muscle oxygenation. In this study, we constructed a continuous-wave NIRS (CWS) instrument with high temporal resolution. Using the instrument, we measured the changes in local muscle oxygen consumption rate (Vo_2) during exercise with rapid arterial occlusion method. We also investigated the exercise- (continuous and intermittent isometric contraction exercises) and measurement site-dependent (forearm flexor and tibialis anterior muscles) differences in local Vo_2. The results show that local Vo_2 could be measured almost instantaneously and that the exercise and measurement site-dependent differences in local Vo_2 could be clearly distinguished using NIRS.
  • MIYASHITA Hideki, KUDO Nobuki, YAMAMOTO Katsuyuki  IEICE technical report. ME and bio cybernetics  106-  (127)  5  -8  2006/06/16  [Not refereed][Not invited]
     
    Previously, we proposed a novel simple Schlieren method that eliminates the use of complex optical system for visualizing acoustic fields of diagnostic pulsed ultrasound. Based on the proposed method, we developed an experiment system and evaluated its applicability experimentally. In this study, we successfully visualized the acoustic field of high-intensity focused ultrasound (HIFU) transducer with the developed experiment system. The input power of the transducer was changed in the range of 10-100W, and the visualized acoustic fields showed typical non-linear distortion at higher input powers. The results show that the proposed simple Schlieren method is useful for evaluating an acoustic field of a HIFU transducer.
  • 宮下 英樹, 工藤 信樹, 山本 克之  生体医工学 : 日本エム・イー学会誌  44-  (2)  315  -316  2006/06/10
  • 郭 凱俊, 宮川 崇拓, 佐溝 正輝, 工藤 信樹, 山本 克之  Transactions of the Japanese Society for Medical and Biological Engineering : BME  44-  (2)  315  -315  2006/06/10
  • 岡田 健吾, 工藤 信樹, 山本 克之  生体医工学 : 日本エム・イー学会誌  44-  (2)  311  -311  2006/06/10
  • 岡田健吾, 工藤信樹, 鈴木亮, 滝澤知子, 丸山一雄, 山本克之  日本生体医工学会大会プログラム・論文集  45th-  528  2006/05/15  [Not refereed][Not invited]
  • 工藤 信樹, 山本 克之  細胞  38-  (4)  129  -132  2006/04
  • YOKOYAMA Goya, OKADA Kengo, KUDO Nobuki, KAWAHARA Koichi, YAMAMOTO Katsuyuki  電気学会研究会資料. MBE, 医用・生体工学研究会  2005-  (7)  21  -24  2005/06/17  [Not refereed][Not invited]
  • IKEBUCHI Masayasu, OKADA Kengo, KUDO Nobuki, YAMAMOTO Katsuyuki  IEICE technical report. ME and bio cybernetics  105-  (122)  25  -28  2005/06/10  [Not refereed][Not invited]
     
    Sonoporation is a technique that increases drug uptake of cells using ultrasound exposure. Recently, it has been shown that exposure of cells to pulsed ultrasound with microbubbles attached to the cells can improve efficiency of sonoporation; however, the mechanisms of this phenomenon have not yet been revealed. In this study, we carried out sonoporation of cultivated endothelial cells using pulsed ultrasound in the presence of bubbles, and the cell slight damage and repair was evaluated using fluorescence and scanning electron microscopes. Based on the results, we concluded that mechanical damage of cell membrane induced by mechanical bubble effects can enhance cell membrane permeability and that damage of cell membrane is repaired within 20 seconds.
  • YOKOYAMA Goya, OKADA Kengo, KUDO Nobuki, KAWAHARA Koichi, YAMAMOTO Katsuyuki  IEICE technical report. ME and bio cybernetics  105-  (122)  21  -24  2005/06/10  [Not refereed][Not invited]
     
    Recent study in human volunteers has shown that exposure to ultrasound during contrast echocardiography can cause premature ventricular contractions (PVCs). To elucidate its mechanism, we carried out experiments using cultivated cardiac myocytes and investigated the dependence of PVC production on timing and pressure amplitude of ultrasound irradiation with and without microbubbles. In the results, PVCs were observed only in the period after the end of myocyte contraction, suggesting that this time-dependent phenomenon was caused by a refractory period of myocytes. Threshold pressure to produce PVCs decreased in the presence of microbubbles attached to the cells, reflecting that the ultrasound-induced bubble behavior can give mechanical stress to myocytes greater than that produced by exposure to ultrasound without microbubbles.
  • IKEBUCHI Masayasu, OKADA Kengo, KUDO Nobuki, YAMAMOTO Katsuyuki  電子情報通信学会技術研究報告. MBE, MEとバイオサイバネティックス  105-  (122)  25  -28  2005/06/10  [Not refereed][Not invited]
  • YOKOYAMA Goya, OKADA Kengo, KUDO Nobuki, YAMAMOTO Katsuyuki  Japanese journal of medical ultrasonics = 超音波医学  32-  S286  2005/04/15
  • OKADA Kengo, KUDO Nobuki, NIWA Koichi, YAMAMOTO Katsuyuki  Japanese journal of medical ultrasonics = 超音波医学  32-  S284  2005/04/15
  • KUDO Nobuki, OKADA Kengo, YAMAMOTO Katsuyuki  Japanese journal of medical ultrasonics = 超音波医学  32-  S285  2005/04/15
  • KUDO Nobuki, MIYASHITA Hideki, OUCHI Hiroyuki, YAMAMOTO Katsuyuki, SEKIMIZU Hidemasa  Japanese journal of medical ultrasonics = 超音波医学  32-  S250  2005/04/15
  • IKEBUCHI Masayasu, OKADA Kengo, KUDO Nobuki, YAMAMOTO Katsuyuki  Japanese journal of medical ultrasonics = 超音波医学  32-  S210  2005/04/15
  • HIROKAWA Naoki, KOITO Kazumitsu, NISHIDA Mutsumi, SATOH Taishi, KAWAI Yuriko, SOMEYA Masanori, SYONAI Takaharu, YAMA Naoya, HYODO Hideki, KUDO Nobuki, YAMAMOTO Katsuyuki, HAREYAMA Masato  Japanese journal of medical ultrasonics = 超音波医学  32-  S242  2005/04/15  [Not refereed][Not invited]
  • 工藤 信樹, 山本 克之  超音波techno  17-  (1)  13  -16  2005/01  [Not refereed][Not invited]
  • N Kudo, K Yamamoto  4th International Symposium on Therapeutic Ultrasound  754-  (754)  211  -213  2005  [Not refereed][Not invited]
     
    To study the mechanisms of sonoporation caused by exposure of cells to pulsed ultrasound in the presence of microbubbles, microscopic observations of bubble behaviour and cell-bubble interaction were carried out using a high-speed camera and a video camera. In the highspeed observation of bubble behaviour, symmetric radial oscillation of bubbles with spherical shape was mainly observed at lower pressure-amplitudes of ultrasound, but asymmetric contraction was frequently observed at higher pressure-amplitudes. The asymmetric contraction of a microbubble generates a small stream in the surrounding liquid, resulting in bubble fragmentation. In the next series of experiments, interactions with bubbles with cells exposed to pulsed ultrasound were observed using bovine endothelial cells with microbubbles attached to the cell membranes, and the repair of cell membrane damage caused by the small streams was investigated. Damage to the membrane was found at the locations where bubble collapse was observed. Using fluorescence microscopy, repair of the membrane was observed in about 70% of damaged cells within three minutes. These observational results suggest that the mechanical stress from a small liquid stream caused by asymmetric contraction of a bubble is responsible for membrane damage in our experimental conditions and that most damaged cells are repaired in a few minutes.
  • OUCHI Hiroyuki, KUDO Nobuki, YAMAMOTO Katsuyuki, SEKIMIZU Hidemasa  IEICE technical report. Ultrasonics  104-  (142)  9  -12  2004/06/18  [Not refereed][Not invited]
     
    A new Schlieren method for visualizing an acoustic field of pulsed ultrasound was proposed, and a system was developed to evaluate the validity of the proposed method by visualizing an acoustic field of a focused ultrasound field of diagnostic frequency range. A conventional Schlieren optical system is not used in the developed system. The system consists of a short-pulsed laser, a CCD camera with a wide dynamic range, and a PC that processes images captured by the CCD camera. In the proposed method, extraction of light diffracted by ultrasound is carried out by subtraction of images captured with and without ultrasound exposure. The usefulness of the developed system was confirmed by experiments in which acoustic fields of a 5-MHz focused transducer and 20-MHz non-focused transducer were visualized.
  • YONEYAMA Satoko, KUDO Nobuki, YAMAMOTO Katsuyuki  IEICE technical report. ME and bio cybernetics  104-  (129)  5  -8  2004/06/11  [Not refereed][Not invited]
     
    In recent years, many studies on muscle oxygenation measurement using near-infrared spectroscopy (NIRS) have been conducted. However, it is difficult to estimate the tissue metabolic kinetics from NIRS measurements because many factors are related to muscle energy metabolism. In this study, we made a model of muscle metabolism that was consisted of an ATP production system and an oxygen diffusion system. The former was modeled with an aerobic system, phosphocreatine system and glycolysis, and the latter was modeled with blood and tissue compartments. Steady and transient responses to exercise were simulated and compared with experimental results. It was strongly suggested that temporal responses of NIRS mainly reflect changes in oxygenation of hemoglobin and myoglobin at high and low tissue oxygenation levels, respectively.
  • MAEKAWA Kota, KUDO Nobuki, YAMAMOTO Katsuyuki  IEICE technical report. ME and bio cybernetics  104-  (129)  9  -12  2004/06/11  [Not refereed][Not invited]
     
    Near-infrared spectroscopy (NIRS) is a useful technique for noninvasive and real-time measurement of tissue oxygenation. However, it is difficult to measure independently the oxygen concentrations of hemoglobin (Hb) and myoglobin (Mb) because the absorption spectrum of Hb is almost the same as that of Mb. In this study, we performed a basic study on measurement of oxygen saturation in skeletal muscles using microspectrophotometry, aiming to find the contribution rates of Hb and Mb to NIRS measurements. Oxygen saturation of small vessels of about 30μm in diameter was able to be measured in the mesentery and cremaster muscles of small animals. However, the conventional microspectrophotometry using transmitted light is restricted to measurement for thin tissues. Therefore, a reflective lighting technique that is applicable to thick skeletal muscles was also studied.
  • 米山 聡子, 工藤 信樹, 山本 克之  生体医工学 : 日本エム・イー学会誌  42-  (2)  133  -133  2004/06/10
  • OUCHI Hiroyuki, KUDO Nobuki, YAMAMOTO Katsuyuki, SEKIMIZU Hidemasa  Journal of medical ultrasonics = 超音波医学  31-  S104  2004/04/15
  • KUDO Nobuki, IKEBUCHI Masayasu, OKADA Kengo, YAMAMOTO Katsuyuki, TANIYAMA Yoshiaki  Journal of medical ultrasonics = 超音波医学  31-  S127  2004/04/15
  • N Kudo, H Ouchi, K Yamamoto, H Sekimizu  AMUM 2004: ADVANCED METROLOGY FOR ULTRASOUND IN MEDICINE 2004  1-  (1)  146  -149  2004  [Not refereed][Not invited]
     
    A new Schlieren method for visualizing an acoustic field of pulsed ultrasound was proposed, and a system was developed to evaluate the validity of the proposed method by visualizing an acoustic field of a focused ultrasound field of diagnostic frequency range. A conventional Schlieren optical system is not used in the developed system. The system uses a short-pulsed laser, a CCD camera with a wide dynamic range, and a PC that processes images captured by the CCD camera. In the proposed method, extraction of light diffracted by ultrasound is carried out by subtraction of images captured with and without ultrasound exposure. The usefulness of the developed system was confirmed by an experiment in which acoustic fields of a 5-MHz focused transducer were visualized. Good agreement was found between the visualized and simulated ultrasound fields.
  • N Kudo, G Yokoyama, M Ikebuchi, K Okada, K Kawahara, K Yamamoto  AMUM 2004: Advanced Metrology for Ultrasound in Medicine 2004  1-  (1)  118  -121  2004  [Not refereed][Not invited]
     
    It has been shown that diagnostic ultrasound examination using a contrast agent can cause premature ventricular contractions (PVCs). In this study, we investigated a usefulness of a new technique using cultured cardiac myocytes to study mechanisms of PVC production. Cardiac myocytes were isolated from neonatal rats and cultured on a cover glass. The cover glass was attached to an observation chamber in which it was possible to observe changes in myocytes during ultrasound exposure. In the experiments, cardiac myocytes were exposed to pulsed ultrasound in the presence and absence of microbubbles. The pressure amplitudes (peak-negative pressures) were set at 5 steps, -0.28, -0.55, -0.73, -0.92 and -1.1 MPa, and threshold pressure to produce a PVC was recorded. The results showed that the presence of microbubbles attached to a cell reduces threshold pressure for producing PVCs, and it was concluded that our method is useful for studying the mechanisms of PVC production.
  • N Kudo, K Yamamoto  STATE OF THE ART: ULTRASONICS IN MEDICINE  1274-  (1274)  129  -132  2004  [Not refereed][Not invited]
     
    Microbubbles in a medium function to concentrate the energy of the ultrasound to which it is exposed, and the focused energy has thermal, chemical and mechanical effects on surrounding biological tissue. Thermal effects: When a microbubble vibrates. it extracts energy from the ultrasound to which it is exposed. Part of this power is used for re-radiation of acoustic waves, but most of the extracted power is converted into heat due to adiabatic compression of encapsulated gas, viscosity of surrounding water and friction of the shell. Generated heat can cause an additional temperature rise in biological tissue. Chemical effects: The presence of microbubbles reduces the pressure threshold to produce inertial cavitation bubbles. Symmetrical contraction of an inertial cavitation bubble will result in very high temperature and pressure inside the bubble and generate highly reactive sonochemicals. Mechanical effects: Behavior of microbubbles exposed to ultrasound can cause mechanical stress to the surrounding tissue. Asymmetric contraction of an inertial cavitation bubble generates a microjet-like small stream that has a localized but unfavorable mechanical effect, such as membrane damage of a cell. (C) 2004 Elsevier B.V. All rights reserved.
  • AE Takada, N Kudo, N Endoh, H Hachiya, S Takeuchi, T Tuchiya, M Natori, K Yamaguchi  STATE OF THE ART: ULTRASONICS IN MEDICINE  1274-  (1274)  147  -150  2004  [Not refereed][Not invited]
     
    To confirm whether the microbubble activated by sonication causes liver damage. the authors performed two experiments. Experiment 1 followed Shigeta's experiment As an ultrasound contrast agent (UCA), Levovist was used and sonicated by Acuson Sequoia(TM) 512 by Siemens. Wister rats of 300 g were divided into four groups: (A) administration of ultrasonic contrast agent (UCA) and ultrasonic exposure, (B) administration of UCA, (C) ultrasonic exposure, and (D) control. Experiment 1 did not show the evidence of hepatic damage such as Shigeta et al. reported. Hence, we conducted Experiment 2 with a much higher acoustic output. But no clear damage was observed in both optical and electron microscopic specimens. (C) 2004 Elsevier B.V. All rights reserved.
  • N Kudo, G Yokoyama, M Ikebuchi, K Okada, K Kawahara, K Yamamoto  2004 IEEE Ultrasonics Symposium, Vols 1-3  1820  -1823  2004  [Not refereed][Not invited]
     
    It has been shown that diagnostic ultrasound examination using a contrast agent can cause premature ventricular contractions (PVCs). In this study, we investigated the usefulness of a new technique using cultured cardiac myocytes to study mechanisms of PVC production. Cardiac myocytes isolated from neonatal rats were cultured on a cover glass. Synchronized autonomous pulsation of myocytes started after incubation for one week. The cover glass was then attached to an observation chamber so that it was possible to observe changes in myocytes during exposure to ultrasound. In the experiments, cardiac myocytes were exposed to pulsed ultrasound with and without microbubbles. The peak negative pressure amplitudes were set at five steps (-0.28, -0.55, -0.73, -0.92 and -1.1 MPa), and threshold pressure to produce a PVC was recorded. The results showed that the presence of microbubbles attached to a cell reduces the threshold pressure for producing PVCs, and it was concluded that our method is useful for studying the mechanisms of PVC production.
  • N Kudo, K Yamamoto  STATE OF THE ART: ULTRASONICS IN MEDICINE  1274-  (1274)  49  -52  2004  [Not refereed][Not invited]
     
    It has recently been shown that the new generation of contrast agents has suitable pressure ranges and driving pulse sequences for optimal imaging. Differences in imagine conditions are due to differences in physical properties of microbubbles of the ultrasound contrast agents: mechanical properties of shell materials and diffusion of encapsulated gases. In this study, bubble behaviors of two types of contrast agents were observed using a high-speed camera and differences in mechanical properties of the shells and diffusion of the encapsulated gases were investigated. A microbubble was exposed to five ultrasound pulses with constant or increasing pressures with a pulse interval of 20 us, and the bubbles exposed to each pulse were photographed using a high-speed camera. Definity(R) and Levovist(R) were used in the experiments. In the case of Definity(R), amplitude of bubble oscillation increased with an increase in pulse pressure. In the case of Levovist(R), discontinuous expansion of the bubble was observed during exposure to five pulses with increasing pressure, and it is thought that the strong non-linear relationship between oscillation amplitude and ultrasound pressure in the case of Levovist(R) is caused by the presence of bubble shells, which cannot be treated with a simple elastic model. Furthermore, shrinkage of bubble fragments seas observed in the case of Levovist(R), and it is thought that diffusion of encapsulated gas is accelerated by exposure to pulsed ultrasound. (C) 2004 Elsevier B.V. All rights reserved.
  • 広川直樹, 小井戸一光, 市村健, 西田睦, 晴山雅人, 岡田太, 工藤信樹, 藤本克彦  超音波医学  30-  (6)  J809  -J809  2003/11  [Not refereed][Not invited]
  • 工藤 信樹, 山本 克之  超音波techno  15-  (5)  61  -64  2003/09  [Not refereed][Not invited]
  • 工藤 信樹, 山本 克之  超音波techno  15-  (5)  65  -68  2003/09  [Not refereed][Not invited]
  • OKADA Kengo, KUDO Nobuki, NIWA Koichi, WADA Shigeo, YAMAMOTO Katsuyuki  IEICE technical report. ME and bio cybernetics  103-  (133)  49  -54  2003/06/13  [Not refereed][Not invited]
     
    Sonoporation is a technique that increases drag uptake of cells by ultrasound exposure. Ultrasound exposure of continuous wave has beens mainly used in this technique, and it is well known that existence of microbubbles around cells improves efficiency of sonoporation. Recent studies have shown that cell permeability can be increased by exposure of pulsed ultrasound with microbubbles; however, the mechanism of is not yet clear. In this study, cell-bubble behavior and cell damage were observed using a high-speed camera and a fluorescence microscope, and the mechanism of sonoporation was discussed. Based on observation results, we concluded that the cell membrane damage was mainly caused by mechanical stress induced by the bubble behavior. Cell viability was also studied under various conditions of ultrasound exposure, and it was shown that cell damage strongly depends on the presence of microbubbles and that cell damage increases with increase in pulse pressure.
  • 平井 甲亮, 工藤 信樹, 山本 克之  生体医工学 : 日本エム・イー学会誌  41-  (1)  63  -63  2003/03/10
  • N Kudo, K Okada, K Yamamoto  2003 IEEE ULTRASONICS SYMPOSIUM PROCEEDINGS, VOLS 1 AND 2  1507  -1510  2003  [Not refereed][Not invited]
     
    New methods for ultrasound contrast imaging that use amplitude-encoded ultrasound pulses have recently been developed. An understanding of various behaviors of bubbles exposed to ultrasound pulses with different pressures is important for using these methods. In order to study the dependence of bubble behavior on pressure, a high-speed observation system was improved to generate pulses that have various pressures at pulse intervals of several tens of microseconds. A microbubble was exposed to five ultrasound pulses with increasing pressures (normalized pressures of 1.0, 1.2, 1.4, 1.6 and 1.8 at pulse intervals of 20 mus). The total frame number of the high-speed camera is 24, and 5 frames were assigned to the first 4 pulses and 4 frames were assigned to the last pulse. The ultrasound contrast agents Definity and Levovist were used in the experiments, and the center frequency of ultrasound pulses was set at 1 MHz. It was found that the amplitude of bubble oscillation generally increased with increase in pulse pressure, though discontinuous increase in oscillation amplitude was frequently observed in the results obtained using Levovist. This strong nonlinear relationship between pressure of ultrasound pulse and amplitude of radial oscillation should be considered in amplitude-encoded contrast imaging methods.
  • HIRAI Kosuke, MAEGAWA Kazuya, KOHATA Daisuke, KUDO Nobuki, YAMAMOTO Katsuyuki  生体・生理工学シンポジウム論文集  17-  341  -344  2002/09/09  [Not refereed][Not invited]
  • OGIHARA Makoto, KUDO Nobuki, YAMAMOTO Katsuyuki  IEICE technical report. ME and bio cybernetics  102-  (137)  13  -16  2002/06/14  [Not refereed][Not invited]
     
    Recently, there has been further progress of the performance of diagnostic ultrasound equipment due to improvement of focusing techniques of ultrasound. This means that ultrasound intensity increases at a focal point, and therefore adverse effect of ultrasound exposure has become a topic again among users of this equipment. In this study, we developed a system to accurately measure temperature rise caused by ultrasound exposure and discussed effects of blood perfusion on temperature rise in a soft tissue. To simulate blood perfusion of an in vivo soft tissue, we used an excised fresh liver that was perfused with saline using a circulation pump. Temperature rises were measured at a focal point of exposed ultrasound and a point at 5 mm far from the focus under various conditions of perfusion rate. In the measurements at perfusion rates of 0.30 and 0.68 l/min, temperature rises decreased by 25% and 55%, respectively, compared to those with no perfusion. From these results, we concluded that the effects of blood perfusion should be adequately taken in account in estimating a temperature rise in soft tissues.
  • 工藤 信樹, 山本 克之  映像情報medical  34-  (6)  572  -574  2002/05  [Not refereed][Not invited]
  • Nakamura Kazuaki, Kitama Masataka, Misawa Kenji, Arisawa Junji, Shao Jun, Kudo Nobuki, Yamamoto Katsuyuki  Memoirs of the Hokkaido Institute of Technology  30-  261  -266  2002/03  [Not refereed][Not invited]
  • N Kudo, T Miyaoka, K Okada, K Yamamoto, K Niwa  2002 IEEE ULTRASONICS SYMPOSIUM PROCEEDINGS, VOLS 1 AND 2  1383  -1386  2002  [Not refereed][Not invited]
     
    To elucidate the mechanisms of cell damage caused by microbubbles exposed to ultrasound, two series of experiments were carried out. In one series of experiments, microbubbles and cells were exposed to 1-MHz pulsed ultrasound and observed using a high-speed camera. In another series of experiments, endothelial cells were exposed to ultrasound with and without microbubbles, and the viabilities of the cells were evaluated by fluorescent staining. In the high-speed images, generation of a small stream of the surrounding liquid caused by non-uniform contraction of a microbubble and deformation of a cell beside the bubble were observed. In the cell viability test, the percentage of damaged cells in the presence of microbubbles that had been exposed to ultrasound was significantly higher than that of cells without microbubbles that had been exposed to ultrasound. These results indicated that bubbles exposed to ultrasound causes mechanical stress to act on cells and that this mechanical stress may cause cell injury.
  • KUDO Nobuki, KURIBAYASHI Kaori, NATORI Michiya, MORIYASU Fuminori, YAMAMOTO Katsuyuki  The Transactions of the Institute of Electronics, Information and Communication Engineers. A  84-  (12)  1492  -1499  2001/12/01  [Not refereed][Not invited]
     
    超音波照射下での超音波造影剤の振舞いの解明を目的として, 高速度カメラを用いた観察システムを開発し, キャビテーション気泡と, 20〜100μmの含気気泡の振舞いを観察した.キャビテーション気泡では, 収縮時に気泡の崩壊と考えられる現象が観察され, 高温高圧状態が発生していることが示唆された.これに対し, 含気気泡では収縮時にもある程度の大きさが保たれており, 気泡の崩壊現象は起きていないと考えられたが, 気泡の分割が観察されており, これは気泡の非等方的な収縮により生じた微小な流れによるものと考えられた.
  • NAKAMURA Kazuaki, SHAO Jun, KUDO Nobuki, KITAMA Masataka, MISAWA Kenji, ARISAWA Junju, YAMAMOTO Katsuyuki  The Transactions of the Institute of Electronics, Information and Communication Engineers. A  84-  (12)  1525  -1532  2001/12/01  [Not refereed][Not invited]
     
    近年, 生体の光イメージングの空間分解能の向上を目指して, 超音波変調光を利用する方法が検討されている.本論文では, 光のスペックルパターンの変動に着目した超音波変調光の検出方法について基礎的検討を行った.まず, パルスレーザ光を散乱体に入射させ, 連続集束超音波を用いて局所的に光を変調し, スペックルパターンの変動をCCDカメラで検出した.パスル光を超音波の位相と同期させることにより, 変調成分を一般的なCCDカメラで検出可能とした.更に, 超音波のパルス化により空間分解能を向上させる手法についても検討し, 提案手法により, 連続及びパルス超音波を用いて散乱光から超音波変調成分を効率的に検出できることを確認した.
  • NAKAMURA Kazuaki, SHAO Jun, KUDO Nobuki, KITAMA Masataka, MISAWA Kenji, ARISAWA Junji, YAMAMOTO Katsuyuki  IEICE technical report. ME and bio cybernetics  101-  (478)  87  -92  2001/11/22  [Not refereed][Not invited]
     
    Ultrasound-modulated light has recently been utilized to improve a spatial resolution of optical imaging of biological tissues. This paper describes a method for detecting the ultrasound-modulated light by using variations in speckle patterns. A pulsed laser beam was injected into a turbid medium and modulated by an ultrasound pulse. The pulsed loght was synchronized with the ultrasound, and a phase inversion technique was used so that a modulated component could be detected using a conventional CCD camera. To evaluate the usefulness of this technique, one-dimensional imaging of absorbing object embedded in a turbid medium was carried out in both of transmission and reflection methods. It was found that a modulated component can be extracted from scattered light by the proposed technique in both cases.
  • Hirai Kousuke, Niwayama Masatsugu, Kohata Daisuke, Maekawa Kazuya, Kudo Nobuki, Hamaoka Takafumi, Katsumura Toshihito, Yamamoto Katsuyuki  IEICE technical report. ME and bio cybernetics  101-  (130)  1  -8  2001/06/15  [Not refereed][Not invited]
     
    In recent years, continuous wave near-infrared spectroscopy (CW-NIRS) has been applied to in vivo reflectance imaging of muscle oxygenation. We previously developed a 200-channel imaging system that enables measurement of change in oxygenation and blood volume. However, we obtained the images of change in oxygenation and blood volume in an off-line mode after data processing. In this study, we have developed a real-time imaging system. Using the new system, we have imaged the change in oxygenation and blood volume in muscles of the whole thigh during various exercises at a rate of 5 frames/s. The results showed that difference in muscle function and fast changes in blood volume can be imaged and that this system is applicable to clinical medicine.
  • MIYAOKA Takehiro, FURUYA Junji, KUDO Nobuki, NIWA Kouichi, YAMAMOTO Katsuyuki  IEICE technical report. ME and bio cybernetics  101-  (130)  83  -89  2001/06/15  [Not refereed][Not invited]
     
    Recently, it has been reported that activation of contrast agent gas bodies by ultrasound exposure can damage the cell membrane. To elucidate mechanisms of such cell damage, we improved an high-speed and high-magnification observation system using a new high-speed camera and an inverted microscope. microbubbles of 3 to several tens microns in diameter were exposed to 1 MHz or 250 kHz ultrasound, and their dynamic behaviors were observed in 24-frame sequential high-speed photographs at the maximum frame rate of 8 million frames per second. Typical movements of a bubble, such as rapid contraction resulting in destruction of the microbubble and non-uniform contraction accompanied with generation of a small stream, were observed. To study the possibility that these bubble movements can cause cell damage, bovine arterial endothelial cells and microbubbles were exposed to ultrasound. Non-uniform contraction of a microbubble and deformation of the cell beside the bubble were observed. It was suggested that a small stream generated by non-uniform contraction of a bubble could cause mechanical damage to a cell.
  • KUDO Nobuki, MIYAOKA Takehiro, OGIHARA Makoto, NATORI Michiya, YAMAMOTO Katsuyuki  Journal of medical ultrasonics = 超音波医学  28-  (3)  J363  2001/04/15  [Not refereed][Not invited]
  • MIYAOKA T, HURUYA J, KUDO N, NATORI M, YAMAMOTO K  Journal of medical ultrasonics = 超音波医学  28-  (3)  J411  2001/04/15  [Not refereed][Not invited]
  • Nakamura Kazuaki, Kitama Masataka, Misawa Kenji, Arisawa Junji, Sibayama Kaichiro, Shao Jun, Kudo Nobuki, Yamamoto Katsuyuki  Memoirs of the Hokkaido Institute of Technology  29-  217  -223  2001/03/26  [Not refereed][Not invited]
  • K Yamamoto, M Niwayama, D Kohata, N Kudo, T Hamaoka, R Kime, T Katsumura  OPTICAL TOMOGRAPHY AND SPECTROSCOPY OF TISSUE IV  4250-  (4250)  142  -152  2001  [Not refereed][Not invited]
     
    Functional imaging of muscle oxy enation using NIRS is a promising technique for evaluation of the heterogeneity of muscle function and diagnosis of peripheral vascular disease or muscle injury. We have developed a 200-channel imaging system that can measure the changes in oxygenation and blood volume of muscles and that covers a wider area than do previously reported systems. Our system consists of 40 probes, a multiplexer for switching signals to and from the probes, and a personal computer for obtaining images. In each probe, one two-wavelength light-emitting diode (770 and 830 mn) and five photodiodes were mounted on a flexible substrate. In order to eliminate the influence of a subcutaneous fat layer, a correction method, which we previously developed, was also used in imaging. Thus, quantitative changes in concentrations of oxy- and deoxy-hemoglobin were obtained. Temporal resolution was 1.5 s and spatial resolution was about 20 mm, depending on probe separations. Exercise tests (isometric contraction of 50% MVC) on the thigh with and without arterial occlusion were conducted. and changes in muscle oxygenation were imaged using our system. Results showed that the heterogeneity of deoxygenation and reoxygenation during exercise and recovery periods, respectively, were clearly observed. These results suggest that optical imaging of dynamic change in muscle oxygenation using MRS would be useful not only for basic physiological studies but also for clinical applications with respect to muscle functions.
  • KUDO Nobuki, ARITA Naoki, YAMAMOTO Katsuyuki  Symposium on ultrasonic electronics  (21)  347  -348  2000/11/06  [Not refereed][Not invited]
  • Yamamoto Katsuyuki, Niwayama Masatsugu, Kudo Nobuki  IEICE technical report.  100-  (287)  19  -23  2000/09/07  [Not refereed][Not invited]
     
    In this talk, several new techniques for biomedical functional imaging using ultrasound and light will be presented. High-resolution imaging of tissues and blood flow in micro-vessels using a miniaturized ultrasound probe could be used for in vivo examination during biopsy and surgical operation. Vibration and rapture of micro-bubbles of ultrasound contrast agents can be observed by a ultra-high-speed camera, and results on dynamics of the bubbles give valuable, basic data for establishing highly efficient and safe contrast agents. Functional imaging of muscle oxygenation using near-infrared spectroscopy is one of the most useful techniques applicable to rehabilitation and sport medicine.
  • Kohata D, Niwayama M, Shao J, Kudo N, Hamaoka T, Katsumura T, Yamamoto K  IEICE technical report. ME and bio cybernetics  100-  (163)  33  -38  2000/06/23  [Not refereed][Not invited]
     
    In recent years, continuous wave near-infrared spectroscopy(CW-NIRS)has been applied to in vivo reflectance imaging of muscle oxygenation. However, conventional mapping systems do not have a sufficient measurement area at present. In this study, we developed a 200-channel mapping system that enables measurement of change in oxygenation and blood volume and that covers a wider area(30cm×20cm)than do traditional systems. Using the new system, we obtained the images of change in oxygenation and blood volume in muscles of the whole thigh during two kinds of exercises. The results showed that difference in muscle function and tissue heterogeneity can be imaged.
  • Maegawa K, Niwayama M, Shao J, Kudo N, Yamamoto K  IEICE technical report. ME and bio cybernetics  100-  (163)  39  -44  2000/06/23  [Not refereed][Not invited]
     
    Spatially resolved spectroscopy(SRS)is a method for measuring the optical properties of a medium using spatial profiles of reflectance. This method is useful for quantitative measurement of tissue oxygenation with continuous wave light in real time. However, conventional SRS theory is based on the assumption that tissue structure is homogeneous. This assumption can not be applied to actual inhomogeneous structures, and there might be great errors due to the inappropriate assumption. Therefore, we studied the influences of overlying tissues on muscle oxygenation measurement by 4-layer Monte Carlo simulations and proposed a correction method. There were great differences in in vivo measurements between conventional SRS and our correction method. This result suggested that correction is needed for quantitative measurement using SRS.
  • KUDO Nobuki, KURIBAYASHI Kaori, NATORI Michiya, MORIYASU Fuminori, YAMAMOTO Katsuyuki  Journal of medical ultrasonics = 超音波医学  27-  (4)  416  -416  2000/04/15  [Not refereed][Not invited]
  • KUDO Nobuki, KURIBAYASHI Kori, YAMAMOTO Katsuyki, NATORI Michiya, MORIYASU Fuminori  Journal of medical ultrasonics = 超音波医学  27-  (4)  517  -517  2000/04/15  [Not refereed][Not invited]
  • 山本 克之, 庭山 雅嗣, 工藤 信樹, 川初 清典  計測と制御 = Journal of the Society of Instrument and Control Engineers  39-  (4)  283  -286  2000/04/10  [Not refereed][Not invited]
  • KUDO Nobuki, KURIBAYASHI Kaori, YAMAMOTO Katsuyuki, NATORI Michiya, MORIYASU Fuminori  日本音響学会研究発表会講演論文集  2000-  (1)  1057  -1058  2000/03/01  [Not refereed][Not invited]
  • M Niwayama, D Kohata, J Shao, N Kudo, T Hamaoka, T Katsumura, K Yamamoto  OPTICAL SENSING, IMAGING, AND MANIPULATION FOR BIOLOGICAL AND BIOMEDICAL APPLICATIONS  4082-  (4082)  48  -56  2000  [Not refereed][Not invited]
     
    Near-infrared spectroscopy (NIRS) is a very useful technique for noninvasive measurement of tissue oxygenation. Among various methods of NIRS, continuous wave near-infrared spectroscopy (CW-NIRS) is especially suitable for real-time measurement and for practical use. CW-NIRS has recently been applied to in vivo reflectance imaging of muscle oxygenation and brain activity. However, conventional mapping systems do not have a sufficient mapping area at present. Moreover, they do not enable quantitative measurement of tissue oxygenation because conventional MRS is based on the inappropriate assumption that tissue is homogeneous. In this study we developed a 200-channel mapping system that enables measurement of changes in oxygenation and blood volume and that covers a wider area (30 cm x 20 cm) than do conventional systems. The spatial resolution (source-detector separation) of this system is 15 mm. As for the effects of tissue inhomogeneity on muscle oxygenation measurement, subcutaneous adipose tissue greatly reduces measurement sensitivity. Therefore, we also used a correction method for the influence of the subcutaneous fat layer so that we could obtain quantitative changes in concentrations of oxy- and deoxy-hemoglobin. We conducted exercise tests and measured the changes in hemoglobin concentration in the thigh using the new system. The working muscles in the exercises could be imaged, and the heterogeneity of the muscles was shown. These results demonstrated the new 200-channel mapping system enables observation of the distribution of muscle metabolism and localization of muscle function.
  • M Niwayama, T Hamaoka, L Lin, J Shao, N Kudo, C Katoh, K Yamamoto  BIOMEDICAL DIAGNOSTIC, GUIDANCE, AND SURGICAL-ASSIST SYSTEMS II  3911-  (3911)  256  -265  2000  [Not refereed][Not invited]
     
    The inhomogeneity of tissue structure greatly affects the sensitivity of tissue oxygenation measurement by near-infrared spectroscopy (NIRS). We have proposed a method for correcting the influence of a subcutaneous fat layer on muscle oxygenation measurements. In this study, we validated our correction method by measuring oxygen consumption rates of the forearm muscle (Vo(2)mus) and comparing the measurements with those obtained by other techniques: P-31-magnetic resonance spectroscopy (P-31-NMR) and positron emission tomography (PET). In NIRS, Vo2mus was obtained from the falling rate of oxygenation in ischemia tests. The values of Vo(2)mus were corrected using a curve of measurement sensitivity against fat layer thicknesses, which were measured by ultrasonography. The corrected Vo(2)mus showed greater values and less variation between individuals (0.21 +/-0.03 ml 100g(-1) min(-1)) than did the uncorrected one (0.17+/-0.04 ml 1000g(-1) min(-1)). In the P-31-NMR measurements on 10 subjects, Vo(2)mus was estimated from changes in phosphocreatine (PCr). The corrected Vo(2)mus in NIRS correlated well with the measurements by P-31-NMR (r = 0.61), compared to the uncorrected Vo(2)mus (r=-0.26). This result suggested that our correction method is valid. Vo2mus was also measured using PET in one of the authors. The measured values by NIRS (with correction), P-31-NMMR, and PET were 0.22, 0.17, 0.24 ml 100g(-1) min(-1) respectively. The measurement by NIRS using our correction method was in an acceptable range.
  • J Shao, L Lin, M Niwayama, N Kudo, K Yamamoto  OPTICAL SENSING, IMAGING, AND MANIPULATION FOR BIOLOGICAL AND BIOMEDICAL APPLICATIONS  4082-  (4082)  76  -86  2000  [Not refereed][Not invited]
     
    Near-infrared spectroscopy (NIRS) is a useful technique for noninvasive measurement of oxygenation of the brain and muscle. However, no accurate, quantitative algorithms for continuous wave NIRS (CW-NIRS) have yet been presented dute to the following two problems. The first is that inhomogeneous tissue structure greatly affects measurement sensitivity. We previously reported on the influence of a fat layer on muscle oxygenation measurement and proposed a method for correcting the sensitivity. The second problem is that almost all algorithms for CW-NIRS have been experimentally determined, although an algorithm can be theoretically determined on the basis of diffusion theory if the mean optical pathlength in muscle in an in vivo state is known. In this study, we derived basic equations for a CW-NIRS algorithm based on diffusion theory, and we determined linear and nonlinear algorithms from mean optical pathlengths and validated them by results obtained from phantom experiments. For the determination of pathlength, the absorption and scattering coefficients of the muscle must be obtained by taking into account the influence of a fat layer. Laser pulses of 752 and 871 nm were applied to the forearms of subjects, and the temporal point spread function (TPSF) was obtained by using a streak camera. The absorption and scattering coefficients of the muscle were determined by fitting the measured TPSF with that obtained by a Monte Carlo model consisting of skin, fat and muscle layers. From these coefficients, the mean optical pathlengths at two wavelengths were obtained and the algorithms were determined.
  • IKEDA Takefumi, KUDO Nobuki, YAMAMOTO Katsuyuki  電気学会研究会資料. MBE, 医用・生体工学研究会  1999-  (21)  31  -35  1999/06/26  [Not refereed][Not invited]
  • KUDO Nobuki, SHIBAYAMA Kaichiro, SHAO Jun, YAMAMOTO Katsuyuki  電気学会研究会資料. MBE, 医用・生体工学研究会  1999-  (21)  37  -42  1999/06/26  [Not refereed][Not invited]
  • SHAO Jun, LIN Ling, NIWAYAMA Masatsugu, KUDO Nobuki, YAMAMOTO Katsuyuki  IEICE technical report. ME and bio cybernetics  99-  (138)  15  -22  1999/06/24  
    Near-infrared spectroscopy (NIRS) has been proved to be a useful technique for noninvasive monitoring of tissue oxygenation. But until now there is no clearly quantitative algorithm for tissue oxygenation measurement. We deduced a quantitative algorithm for the tissue oxygenation, based on diffusion theory. The algorithm was confirmed by tissue-like phantom experiments. The experimental results showed that the relationship between optical density and absorption coefficient can be well described by diffusion theory. The experimental results also showed that the oxygenation can be correctly calculated when the change in absorption coefficient is not too large.
  • LEE Hwansung, KUDO Nobuki, SHIMOOKA Toshiyuki, MITAMURA Yoshinori, YUHTA Toshio, YAMAMOTO Katsuyuki  IEICE technical report. ME and bio cybernetics  99-  (138)  7  -13  1999/06/24  
    Recently, cavitation on a surface of mechanical heart valves has been studied as a cause of fractures in implanted mechanical heart valves. Several factors such as peak dp/dt of the ventricular pressure and mean closing velocity of leaflet have been studied as an index for the cavitation threshold. In our previous studies, we suggested that disk closing velocity immediately before closing has significant effects on pitting erosion. In the present study, the effects of the disk closing velocity on surface erosion were further studied. The results showed that there is a threshold in the closing velocity inducing erosion cavitation and it was about 0.4 m/s in the mechanical heart valves used in this study.
  • IKEDA Takefumi, KUDO Nobuki, YAMAMOTO Katsuyuki  Journal of medical ultrasonics = 超音波医学  26-  (4)  693  -693  1999/04/15  [Not refereed][Not invited]
  • KURIBAYASHI Kaori, KUDO Nobuki, NATORI Michiya, YAMAMOTO Katsuyuki  Journal of medical ultrasonics = 超音波医学  26-  (4)  695  -695  1999/04/15  [Not refereed][Not invited]
  • M Niwayama, L Lin, J Shao, T Shiga, N Kudo, K Yamamoto  OPTICAL TOMOGRAPHY AND SPECTROSCOPY OF TISSUE III, PROCEEDINGS OF  3597-  (3597)  291  -299  1999  [Not refereed][Not invited]
     
    The inhomogeneity of tissue structure greatly affects the sensitivity of tissue oxygenation measurement by reflectance NIRS. We have examined the influence of a subcutaneous fat layer on muscle oxygenation measurements. In this study, the influences of a fat layer and skin on muscle oxygenation measurement were investigated using Monte Carlo simulation and in vivo tests. Based on the experimental results, a correction curve for measurement sensitivity was determined. In the simulation, a 3-D model consisting of the epidermis, dermis, fat and muscle layers was used. In in vivo tests, measurement sensitivity was examined by measuring the falling rate of oxygenation in ischemia tests on the forearm using a newly developed multisensor type of oximeter with source-detector distances of 3-40 mm. Fat layer thickness was also measured by ultrasonography. The correction curve of measurement sensitivity against fat layer thickness was obtained from the results of simulation and in vivo tests. The measurements of oxygen consumption, calculated from the falling rates of oxygenation without correction, varied widely due to different thicknesses of fat layers. In contrast, the measurements of oxygen consumption with correction were almost the same (0.21 +/- 0.03 ml 100g(-1) min(-1)). In this correction, the effect of skin on change in optical density was also taken into account using a detector with a short separation.
  • K Kuribayashi, N Kudo, M Natori, K Yamamoto  1999 IEEE ULTRASONICS SYMPOSIUM PROCEEDINGS, VOLS 1 AND 2  1755  -1758  1999  [Not refereed][Not invited]
     
    Clinical applications of ultrasound contrast agent (UCA) have been widely studied in recent years, but the behavior of microbubbles exposed to ultrasound is not fully understood yet. We developed a high-magnification and high-speed observation system, and we studied the dynamic behavior of cavitation bubbles, air-contained microbubbles, and UCA under ultrasound exposure. The dynamic behavior of cavitation was observed at the frame rate of 2 x 10(6) frames/s with magnification of x 15, and periodic expansion and shrinkage due to exposure to ultrasound were observed. The maximum diameter of a bubble was around 10 mu m in the expansion phase, and it was too small to observe in the compression phase. Air-contained microbubbles of 20-100 mu m in diameter and UCA of 3-5 mu m in diameter were also observed at the maximum imaging rate of 1 x 10(7) frames/s and maximum magnification of x 100. Typically, microbubbles exposed to ultrasound pressure undergo repeated expansion and shrinkage and reach a critical size, then collapse.
  • K Nakajima, N Kudo, K Yamamoto, T Mikami, A Kitabatake  1999 IEEE ULTRASONICS SYMPOSIUM PROCEEDINGS, VOLS 1 AND 2  1381  -1384  1999  [Not refereed][Not invited]
     
    We have been measuring ultrasound attenuation of biological tissues in the frequency range of 2.5-40 MHz using a multi-resonance transducer [1, 2]. In this study, we used two additional wide-band transducers of 5 and 10 MHz, and we measured liquid-type samples to improve the accuracy of the measurement, especially at frequencies below 10 MHz. Homogenized swine liver tissue was centrifuged to separate it into two samples: a supernatant liquid sample containing water-soluble proteins of liver cells and a sediment sample containing the constituents of the tissue structure. Specific attenuations of both samples were almost the same at frequencies around 10 MHz. However, the exponent values of the two samples were clearly different; the exponent value of the supernatant liquid sample was 1.3 in the entire frequency range of 2-40 MHz, while the exponent value of the sediment sample was 0.7. This result suggests that there is a turning point of the exponent value of the whole liver tissue at about 10 MHz.
  • YOSHIDA Makoto, KUDO Nobuki, YAMAMOTO Katsuyuki, MIKAMI Taisei, KITABATAKE Akira  IEICE technical report. ME and bio cybernetics  1998-  (5)  75  -80  1998/06/19  [Not refereed][Not invited]
     
    In order to verify the contribution of a fibrous structure of biological tissue to ultrasound attenuation, we measured ultrasound attenuation coefficients of bovine muscular tissue in the frequency range of 10-40 MHz. Measurements were performed on a homogenized sample and a sliced sample, In the homogenized sample, supermatant of a muscular tissue suspension homogenized with a physiological saline was used. The sliced samples were cut in the normal and the parallel directions to a fibrous structure. An attenuation coefficient of homogenized sample increased proprtionally to the 1.5 power of frequency, while the attenuation coefficients of the sliced samples increased proportionally to the 1.9 power of frequency for the normal sample and the 1.2 power for the parallel sample, respectively. It is well known in a lower frequency than 10 MHz that ultrasound attenuation of fibrous tissue depends on a direction of the fibrous structure. Our results suggest that this angular dependence of the attenuation is caused by the change in the exponent value of frequency-dependent attenuation.
  • NIWAYAMA Masatsugu, SHIGA Toshikazu, LIN Ling, KUDO Nobuki, TAKAHASHI Makoto, YAMAMOTO Katsuyuki  IEICE technical report. ME and bio cybernetics  1998-  (5)  81  -88  1998/06/19  [Not refereed][Not invited]
     
    The inhomogeneity of tissue structure greatly affects the sensitivity of tissue oxygenation measurement by reflectance NIRS. We have proposed a method for correcting the influence of a subcutaneous fat layer on muscle oxygenation measurement. In this study, this method was validated by measuring the peak-to-peak variation of muscle oxygenation in periodic exercise tests on the vastus lateralis. A multisensor probe including a proximal detector was newly developed. A proximal detector was used to eliminate the effect of skin. Results of the tests clearly showed that the presence of a fat layer greatly decreases the sensitivity of measurement and increases the light intensity at the detectors. Sensitivity correction by detected light intensity resulted in almost the same changes in muscle oxygention among subjects regardless of different fat layer thicknesses. The proximal detector was also effective for reducing the effect of skin.
  • YOSHIDA Makoto, KUDO Nobuki, YAMAMOTO Katsuyuki, MIKAMI Taisei, KITABATAKE Akira  IEICE technical report. ME and bio cybernetics  98-  (135)  75  -80  1998/06/19  [Not refereed][Not invited]
     
    In order to verify the contribution of a fibrous structure of biological tissue to ultrasound attenuation, we measured ultrasound attenuation coefficients of bovine muscular tissue in the frequency range of 10-40 MHz. Measurements were performed on a homogenized sample and a sliced sample, In the homogenized sample, supermatant of a muscular tissue suspension homogenized with a physiological saline was used. The sliced samples were cut in the normal and the parallel directions to a fibrous structure. An attenuation coefficient of homogenized sample increased proprtionally to the 1.5 power of frequency, while the attenuation coefficients of the sliced samples increased proportionally to the 1.9 power of frequency for the normal sample and the 1.2 power for the parallel sample, respectively. It is well known in a lower frequency than 10 MHz that ultrasound attenuation of fibrous tissue depends on a direction of the fibrous structure. Our results suggest that this angular dependence of the attenuation is caused by the change in the exponent value of frequency-dependent attenuation.
  • NIWAYAMA Masatsugu, SHIGA Toshikazu, LIN Ling, KUDO Nobuki, TAKAHASHI Makoto, YAMAMOTO Katsuyuki  IEICE technical report. ME and bio cybernetics  98-  (135)  81  -88  1998/06/19  [Not refereed][Not invited]
     
    The inhomogeneity of tissue structure greatly affects the sensitivity of tissue oxygenation measurement by reflectance NIRS. We have proposed a method for correcting the influence of a subcutaneous fat layer on muscle oxygenation measurement. In this study, this method was validated by measuring the peak-to-peak variation of muscle oxygenation in periodic exercise tests on the vastus lateralis. A multisensor probe including a proximal detector was newly developed. A proximal detector was used to eliminate the effect of skin. Results of the tests clearly showed that the presence of a fat layer greatly decreases the sensitivity of measurement and increases the light intensity at the detectors. Sensitivity correction by detected light intensity resulted in almost the same changes in muscle oxygention among subjects regardless of different fat layer thicknesses. The proximal detector was also effective for reducing the effect of skin.
  • KUDO N, YOSHIDA M, YAMAMOTO K, MIKAMI T, KITABATAKE A, ITO Y, KANDA H  Journal of medical ultrasonics = 超音波医学  25-  (4)  495  -495  1998/04/15  [Not refereed][Not invited]
  • KUDO Nobuki, ZHANG Xu, YAMAMOTO Katsuyuki  Journal of medical ultrasonics = 超音波医学  25-  (3)  1  -12  1998/03/15  [Not refereed][Not invited]
  • ZHANG Xu, KUDO Nobuki, YAMAMOTO Katsuyuki  J Med Ultrasonics  25-  (3)  13  -24  1998/03/15  [Not refereed][Not invited]
  • NIWAYAMA Masatsugu, SHIGA Toshikazu, LIN Ling, KUDO Nobuki, TAKAHASHI Makoto, YAMAMOTO Katsuyuki  Japanese journal of medical electronics and biological engineering  36-  (1)  41  -48  1998/03/10  [Not refereed][Not invited]
  • K Yamamoto, M Niwayama, L Lin, T Shiga, N Kudo, M Takahashi  INFRARED SPECTROSCOPY: NEW TOOL IN MEDICINE, PROCEEDINGS OF  3257-  (3257)  146  -155  1998  [Not refereed][Not invited]
     
    The inhomogeneity of tissue structure greatly affects the sensitivity of tissue oxygenation measurement by reflectance NIRS. We have proposed a method for correcting the influence of a subcutaneous fat layer an muscle oxygenation measurement. In this study, this method was validated by measuring the peak-to-peak variation of muscle oxygenation in periodic exercise tests an the vastus lateralis and the ailing rate of oxygenation in ischemia tests on the forearm. A newly developed multisensor probe with source-detector distances of 7-40 mm was used. The probe, consisting of a two-wavelength LED and four photodiodes, was connected to a 4-channel tissue oxygen monitor. The fat layer thickness was also measured by ultrasonography. Results of the tests clearly showed that the presence of a fat layer greatly decreases the sensitivity of measurement and increases the light intensity at a detector. The correction factors of sensitivity were determined from this relationship and Monte Carlo simulation. The corrected oxygenation levels were quantitatively compared among subjects in spite of different fat layer thicknesses.
  • K Yamamoto, M Niwayama, L Lin, T Shiga, N Kudo, M Takahashi  PHOTON PROPAGATION IN TISSUES III, PROCEEDINGS OF  3194-  (3194)  166  -173  1998  [Not refereed][Not invited]
     
    Although the inhomogeneity of tissue structure affects the sensitivity of tissue oxygenation measurement by reflectance near-infrared spectroscopy (NIRS), few analyses of this effect have been reported. In this study, the influence of a subcutaneous fat layer on muscle oxygenation measurement was investigated by Monte Carlo simulation and experimental studies. In the experiments, measurement sensitivity was examined by measuring the falling rate of oxygenation in occlusion tests on the forearm using a tissue oxygen monitor. The fat layer thickness was measured by ultrasonography. Results of the simulation and occlusion tests clearly showed that the presence of a fat layer greatly decreases the measurement sensitivity and increases the light intensity at the detector. The correction factors of sensitivity were obtained from this relationship and were successfully validated by experiments on 12 subjects whose fat layer thickness ranged from 3.5 to 8 mm.
  • L Lin, M Niwayama, T Shiga, N Kudo, M Takahashi, K Yamamoto  INFRARED SPECTROSCOPY: NEW TOOL IN MEDICINE, PROCEEDINGS OF  3257-  (3257)  156  -166  1998  [Not refereed][Not invited]
     
    Two-layered phantom experiments were performed to examine the influence of a Eat layer on measurement of muscle oxygenation using near-infrared spectroscopy (NIRS). Tire phantom consisted of a fat-like layer and a muscle-like layer which were a mixture of agar and TiO2 powder and a suspension of washed bovine blood into 0.55% Intralipid solution. An LED including 760 and 840 nm elements was used as the optical source,( )and the reflectance light was detected by photodiodes at source-detector distances of 20, 30 and 40 mm, Curves of optical density changes versus blood volume ratio were obtained with fat-like layer thickness of 0, 5, 10, and 15 mm. It was found that the change in optical density is significantly decreased and that the linearity of measurement characteristics clearly deteriorated by the presence of a fat layer. This strongly suggests that a new algorithm is needed for muscle oxygenation measurement to eliminate the influence of a fat layer. In addition to the phantom experiments, Monte Carlo simulations corresponding to the experiments were performed. Although the simulations showed similar results concerning the influence of a fat layer, it was noted that the changes in optical density obtained from simulations were lower than those of the phantom experiments. This discrepancy was thought to be due to the light scattering caused by blood cells.
  • M Natori, T Tsuchiya, S Umemura, T Shiina, Y Takeuchi, N Kudo  1998 IEEE ULTRASONICS SYMPOSIUM - PROCEEDINGS, VOLS 1 AND 2  1435  -1438  1998  [Not refereed][Not invited]
     
    Echo enhancers are consisted of microballoons and we aimed to investigate the thresholds of microballoon collapse of two different shell types. PVC-AN microballoon is a mimicking echo enhancer with a hard shell and Albunex(R) that is a commercially available albumin shelled echo enhancer. The thresholds of the microballoon collapse were analyzed by detecting subharmonic wave production. Scattered waveforms by PVC-AN that was diluted to 1/1000 with normal saline. The scattered waves from the microballoon were detected by the hydrophone and analyzed by the digital oscilloscope with 10 bit A/D conversion rate. The spectrum was calculated with Fast Fourier Transform applied to the leading 5 microseconds of the waveform. We concluded that the threshold of PVC-AN collapse exists between 1.5 to 2.25 W/cm(2) of ultrasound intensity. We however, could not determine the threshold of Albunex(R) that was diluted to 1/100 with normal saline, since subharmonics were recognized even by 0.1 W/cm(2) irradiation which was the lowest intensity in our system.
  • Ultrasound attenuation measurement of tissue in frequency range 2.5-40 MHz using a multi-resonance transducer
    1998 IEEE UFFC Ultrasound Symposium Proc.  1479  -1482  1998  [Not refereed][Not invited]
  • KUDO N, YAMAMOTO K, ONOZUKA H, MIKAMI T, KITABATAKE A  Journal of medical ultrasonics = 超音波医学  24-  (9)  148  -148  1997/09/15  [Not refereed][Not invited]
  • KUDO Nobuki, KANENARI Tetsuya, ZHANG Xu, YAMAMOTO Katsuyuki  Journal of medical ultrasonics = 超音波医学  24-  (9)  291  -291  1997/09/15  [Not refereed][Not invited]
  • KUDO N, YOSHIDA M, YAMAMOTO K, MIKAMI T, KITABATAKE A, ITO Y, KANDA H  Journal of medical ultrasonics = 超音波医学  24-  (9)  425  -425  1997/09/15  [Not refereed][Not invited]
  • HACHIKUBO Takahiro, KUDO Nobuki, YAMAMOTO Katsuyuki  IEICE technical report. ME and bio cybernetics  97-  (124)  1  -8  1997/06/20  
    In recent years, ultrasound imaging becomes a very important diagnostic method in clinical examinations because it realizes a non-invasive diagnosis without any damages to biological tissues. But a spatial resolution of a typical ultrasound imaging system is inferior to the other diagnostic method such as X-ray CT or MRI. Though higher frequency ultrasound imaging provides a good spatial resolution, an observed region is restricted to a superficial area because of larger attenuation. In this paper, we propose a new method to realize a high spatial resolution and a deep region imaging capability using a miniaturized needle probe which enables the imaging from a puncturing needle inserted into a body. We have developed the miniaturized needle probe and a peripheral system to obtain linear-scan B-mode images. The fabricated transducer is 0.8×1.2×0.3mm in dimension, 23 MHz in center frequency, 0.15 mm in axial resolution and 0.5 mm in lateral resolution. This transducer can be introduced into the lumen of 18 gauge self-retaining needle. We have acquired in vitro B-mode images of swine lever using this miniaturized needle probe.
  • KANENARI Tetsuya, KUDO Nobuki, ZHANG Xu, TAKAHASHI Makoto, YAMAMOTO Katsuyuki  IEICE technical report. ME and bio cybernetics  1997-  (16)  9  -16  1997/06/20  [Not refereed][Not invited]
     
    Intravascular ultrasound (IVUS) imaging has recently been used widely in clinical examinations. Clear discrimination of vascular lumen using IVUS is important to quantify a degree of Vascular stenosis. But, in many cases, it is difficult to detect the boundary between lumen and a thrombosis because the difference of an acoustic impedance id small. In this paper, we propose a new IVUS method which enables us to discriminate the vessel lumen by detecting movement in regions of blood flow and a thrombosis. The Doppler technique can not detect this movement, because the blood flow is transverse to an ultrasound beam in a conventional IVUS system. We, therefore, used a newly developed correlation technique to detect the movement. Constructing an experimental system, we obtained correlation images of a vascular phantom. Experimental results showed that the blood flow was clearly discriminated from the thrombus, whereas the discrimination was difficult in conventional M-mode and B-mode images.
  • KANENARI Tetsuya, KUDO Nobuki, ZHANG Xu, TAKAHASHI Makoto, YAMAMOTO Katsuyuki  IEICE technical report. ME and bio cybernetics  97-  (124)  9  -16  1997/06/20  [Not refereed][Not invited]
     
    Intravascular ultrasound (IVUS) imaging has recently been used widely in clinical examinations. Clear discrimination of vascular lumen using IVUS is important to quantify a degree of Vascular stenosis. But, in many cases, it is difficult to detect the boundary between lumen and a thrombosis because the difference of an acoustic impedance id small. In this paper, we propose a new IVUS method which enables us to discriminate the vessel lumen by detecting movement in regions of blood flow and a thrombosis. The Doppler technique can not detect this movement, because the blood flow is transverse to an ultrasound beam in a conventional IVUS system. We, therefore, used a newly developed correlation technique to detect the movement. Constructing an experimental system, we obtained correlation images of a vascular phantom. Experimental results showed that the blood flow was clearly discriminated from the thrombus, whereas the discrimination was difficult in conventional M-mode and B-mode images.
  • KUDO N, KAMATAKI T, YAMAMOTO K, ONOZUKA H, MIKAMI T, KITABATAKE A, ITO Y, KANDA H  Journal of medical ultrasonics = 超音波医学  24-  (3)  567  -567  1997/03/15  [Not refereed][Not invited]
  • N Kudo, T Kamataki, K Yamamoto, H Onozuka, T Mikami, A Kitabatake, Y Ito, H Kanda  1997 IEEE ULTRASONICS SYMPOSIUM PROCEEDINGS, VOLS 1 & 2  1181  -1184  1997  [Not refereed][Not invited]
     
    We developed a measurement system of ultrasound attenuation in the frequency range of 2.5 to 40 MHz and measured the ultrasound attenuation coefficients of normal, infarcted, and dilated cardiomyopathy samples of a human formalized myocardium. Results of attenuation measurements showed that the attenuation coefficients increased proportionally to the n-th power of frequency in the measured frequency range. Attenuation coefficients in the myocardium specimens increased proportionally to the 1.3 power for the infarction and 1.2 power for the dilated cardiomyopathy of frequency, respectively, while the attenuation coefficient increased proportionally to the 1.6 power for the normal myocardium. These results suggest that an exponent of frequency-dependent attenuation could be used as an index of tissue characterization.
  • YAMAMOTO Katsuyuki, KUDO Nobuki  Journal of the Japan Society of Precision Engineering  62-  (11)  1541  -1544  1996/11/05  [Not refereed][Not invited]
  • KAMATAKI Takahisa, KUDO Nobuki, TAKAHASHI Makoto, YAMAMOTO Katsuyuki, ONOZUKA Hisao, MIKAMI Taisei, KITABATAKE Akira  IEICE technical report. ME and bio cybernetics  96-  (114)  65  -70  1996/06/21  
    In this study, we developed a measurement system of ultrasound attenuation coefficients in the frequency range of 5-40MHz. First, we confirmed the basic performance of the measurement system, then measured the ultrasound attenuation in normal and infarctional human myocardium. As the results, we observed the change of ultrasound attenuation coefficients of the pig myocardium in a formalize process. In the measurements of the human myocardium, attenuation coefficients of infarctional myocardium was larger than that of normal myocardium. However, it is expected that the attenuation coefficients of normal myocardium will be greater than that of infarctional myocardium in a much higher frequency range because the normal myocardium showed steep increase of attenuation coefficient as the frequency increased.
  • NIWAYAMA Masatsugu, SHIGA Toshikazu, LIN Ling, KUDO Nobuki, TAKAHASHI Makoto, YAMAMOTO Katsuyuki  IEICE technical report. ME and bio cybernetics  96-  (114)  51  -56  1996/06/21  [Not refereed][Not invited]
     
    Near-infrared spectroscopy (NIRS) has been found to be a useful technique for noninvasive monitoring of tissue oxygenation. Although the inhomogeneity of tissue structure may affect the sensitivity of the measurement, few analyses of this effect have been perfomed. In the present study, the influence of a subcutaneous fat layer on muscle oxygenation measurement using NIRS was examined by Monte Carlo simulation and experimental studies. From the results of the simulation, it was predicted that the sensitivity of the measurement greatly decreased with the increase of the fat layer thickness. In the experimental studies, the measurement sensitivity was examined by occlusion tests at the forearm and ergometer exercise at the vastus lateralis muscle, in which the fat thickness was measured by a diagnostic ultrasound equipment. The experimenrtal results also clearly showed the great decrease of the measurement sensitivity due to the presence of a fat layer.
  • 川上 芳明, 志村 尚宣, 郷 秀人, 武田 正之, 工藤 信樹  日本泌尿器科學會雜誌  86-  (1)  237  -237  1995/01/20  [Not refereed][Not invited]
  • Oyanagi M, Kudo N, Yanagida Y, Iwama N, Okazaki K  Symposium on ultrasonic electronics  (14)  165  -166  1993/12/07  [Not refereed][Not invited]
  • Nobuki Kudo, Koichi Shimizu, Goro Matsumoto  Japanese journal of medical electronics and biological engineering  25-  (2)  91  -98  1987  [Not refereed][Not invited]
     
    The optical biotelemetry using free-space light transmission in a closed space has many advantages over the conventional telemetry techniques using radio waves. There are some reports on the optical telemeters using direct light transmission, but few are found which use the indirect light scattered from a ceiling, a floor and walls. Since the latter technique does not require the line-of-sight transmission, it enables us to realize the non-restraint measurement of biological signals. In order to examine the possibility of this technique, the distribution of the indirect light in a room was calculated by a computer simulation. The distribution is uniform enough to carry out the telemetry with one receiver in the room with the dimension of W4.2XL6.4XH2.7m. The minimum received power was -28.0dBm with the transmitter power of 1 watt, which was about a half of the maximum power. To verify the possibility shown in the theoretical analysis, an optical biotelemetry system using the indirect light transmission was developed. 3 ECG's and a body temperature are multiplexed in time domain and modulated into a PIM pulse sequence. Light emitters placed on both shoulders emit the light of about 1 watt when the pulse is on. The system can be operated over 100 hours without replacing batteries. To examine the practical usefulness of this technique in clinical application, the optical biotelemetry from a freely moving subject is carried out with the developed system. A stable data acquisition was demonstrated even from the subject in exercise. © 1987, Japanese Society for Medical and Biological Engineering. All rights reserved.

Books etc

  • 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

Presentations

Association Memberships

  • 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 Projects

  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2022/06 -2025/03 
    Author : 橋本 守, 工藤 信樹, 加藤 祐次
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2020/04 -2023/03 
    Author : 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：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2020/04 -2023/03 
    Author : 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。
  • 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
    文部科学省：科学研究費補助金（基盤研究（A））
    Date (from‐to) : 2017 -2021 
    Author : 工藤 信樹
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2016/04 -2019/03 
    Author : 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：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2016/04 -2018/03 
    Author : 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：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2014/04 -2017/03 
    Author : 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：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2014/04 -2016/03 
    Author : 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：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2013/04 -2016/03 
    Author : 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：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2013 -2014 
    Author : 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：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2011 -2012 
    Author : 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：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2011 -2012 
    Author : 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：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2011 -2012 
    Author : 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：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2009 -2012 
    Author : 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.
  • Ministry of Education, Culture, Sports, Science and Technology：Grants-in-Aid for Scientific Research(基盤研究(A))
    Date (from‐to) : 2008 -2010 
    Author : 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：Grants-in-Aid for Scientific Research(基盤研究(C))
    Date (from‐to) : 2007 -2008 
    Author : 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.
  • 文部科学省：科学研究費補助金(萌芽研究)
    Date (from‐to) : 2006 -2007 
    Author : 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...
  • Ministry of Education, Culture, Sports, Science and Technology：Grants-in-Aid for Scientific Research(基盤研究(B))
    Date (from‐to) : 2004 -2006 
    Author : 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：Grants-in-Aid for Scientific Research(基盤研究(B))
    Date (from‐to) : 2004 -2006 
    Author : 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...
  • 文部科学省：科学研究費補助金(萌芽研究)
    Date (from‐to) : 2004 -2005 
    Author : 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...
  • Ministry of Education, Culture, Sports, Science and Technology：Grants-in-Aid for Scientific Research(基盤研究(B))
    Date (from‐to) : 2001 -2003 
    Author : 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：Grants-in-Aid for Scientific Research(基盤研究(C))
    Date (from‐to) : 2001 -2002 
    Author : 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...
  • 文部科学省：科学研究費補助金(萌芽的研究, 萌芽研究)
    Date (from‐to) : 2001 -2002 
    Author : 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...
  • Ministry of Education, Culture, Sports, Science and Technology：Grants-in-Aid for Scientific Research(基盤研究(B))
    Date (from‐to) : 1999 -2001 
    Author : 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：Grants-in-Aid for Scientific Research(基盤研究(B))
    Date (from‐to) : 1998 -2000 
    Author : 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：Grants-in-Aid for Scientific Research(基盤研究(B))
    Date (from‐to) : 1998 -2000 
    Author : 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：Grants-in-Aid for Scientific Research(基盤研究(B))
    Date (from‐to) : 1998 -2000 
    Author : 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...
  • 文部科学省：科学研究費補助金(萌芽的研究)
    Date (from‐to) : 1998 -1999 
    Author : 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.
  • Ministry of Education, Culture, Sports, Science and Technology：Grants-in-Aid for Scientific Research(基盤研究(A))
    Date (from‐to) : 1996 -1998 
    Author : 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：Grants-in-Aid for Scientific Research(基盤研究(C))
    Date (from‐to) : 1996 -1998 
    Author : 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：Grants-in-Aid for Scientific Research(基盤研究(C))
    Date (from‐to) : 1996 -1997 
    Author : 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：Grants-in-Aid for Scientific Research(基盤研究(B))
    Date (from‐to) : 1996 -1997 
    Author : 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：Grants-in-Aid for Scientific Research(基盤研究(C))
    Date (from‐to) : 1996 -1997 
    Author : 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...
  • 光および超音波による生体計測
    Date (from‐to) : 1995
  • Measurements of biomedical parameters using optical and ultrasonic techniques
    Date (from‐to) : 1995

Industrial Property Rights

  • 超音波プローブ及び超音波診断装置
    特許公開平９−５２２
  • 衝撃波治療装置
    特許公開平８−３０８８４９
  • 衝撃波治療装置
    特許公開平８−２９９３５０
  • 超音波診断装置
    特許公開平８−２９４４９０
  • 衝撃波治療装置
    特許公開平８−２５２２５９
  • 超音波探触子
    特許公開平８−１９１８３５
  • Heat measurement apparatus for inspecting therapeutic energy waves
    US-A1-005465625
  • 結石破砕装置
    特許公開平６−３２７６９１
  • 超音波測定用ハイドロホン
    特許公開平６−２４１８８５
  • Shockwave treatment apparatus
    US-A1-005174294
  • 音圧測定装置
    特許公開平５−３０６９６１
  • Pressure measurement apparatus for inspecting therapeutic energy waves
    US-A1-005357805
  • A pressure measurement apparatus for inspecting therapeutic energy waves (DE,FR)
    EP-A2-000509800
  • 圧力測定装置
    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
    US-A1-00521310
  • 超音波治療装置
    特許公開平５−１９２３４３
  • 超音波結石破砕装置
    特許公開平５−３１１１９
  • Acoustic wave therapy apparatus (DE,NL)
    EP-A1-000404121
  • Acoustic wave therapy apparatus
    US-A1-005095907
  • 衝撃波治療装置及び温熱治療装置
    第２９６８５６１号
  • Shock wave generating apparatus capable of setting moving direction of shock wave generating source to ultrasonic tomographic image plane (DE,FR)
    EP-A1-000397056
  • Shock wave treatment apparatus (DE,FR)
    EP-A1-000548048
  • Shock wave treatment apparatus (FR, DE)
    EP-A1-000367116
  • 超音波治療装置
    第２９３７３４４号
  • 衝撃波治療装置
    1867287
  • 衝撃波治療装置
    第２６４５０３８号

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