Researcher Database

Nobuki Kudo
Faculty of Information Science and Technology Bioengineering and Bioinformatics Bioengineering
Associate Professor

Researcher Profile and Settings

Affiliation

  • Faculty of Information Science and Technology Bioengineering and Bioinformatics Bioengineering

Job Title

  • Associate Professor

Degree

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

URL

J-Global ID

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

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

Academic & Professional 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

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 Activities

Published Papers

  • 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.
  • Miwa A, Kudo N
    2016 IEEE Ultrasonics Symposium Proceedings 2016 [Refereed][Not invited]
  • Kudo N, Kadota T, Iijima Y
    2016 IEEE Ultrasonics Symposium Proceedings 2016 [Refereed][Not invited]
  • 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
  • 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.
  • 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.
  • Relation between cell membrane tension and repair of membrane damaged during sonoporation
    Tanaka Y, Kudo N
    2013 IEEE Ultrasonics Symposium Proceedings 1777 - 1789 2013 [Refereed][Not invited]
  • 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.
  • 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]
  • 工藤 信樹, 清水 孝一
    超音波医学 38 (1) 25 - 26 1346-1176 2011 [Not refereed][Not invited]
  • 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.
  • 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
  • Optics Express 15 18173 - 18187 2008 [Not refereed][Not invited]
  • 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
    日本ハイパーサーミア学会誌 = Japanese journal of hyperthermic oncology 23 (3) 113 - 122 1882-2576 2007/09/20 [Not refereed][Not invited]
  • 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.
  • 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]
  • AIP Conference Proceedings (829) 614 - 617 2006 [Not refereed][Not invited]
  • 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]
  • 岡田 健吾, 工藤 信樹, 丹羽 光一, 山本 克之
    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.
  • 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.
  • Ultrasound Med. Biol. 29 949 - 956 2002 [Not refereed][Not invited]
  • 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]
  • 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]
  • NIWAYAMA M, LIN L, SHAO J, KUDO N, YAMAMOTO K
    Rev. Sci. Instrum. 71 (12) 4571 - 4575 0034-6748 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 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.
  • 相関法を用いた単一集束超音波ビームによる変位・流速ベクトルの計測特性の理論解析
    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]
  • Development of the robust hydrophone for extracorporeal shock wave lithotripters
    Jpn. J. Endourology and ESWL 7 (2) 153 - 158 1994 [Not refereed][Not invited]
  • Fundamental Study on transcutaneous biotelemetry using diffused light
    Frontiers of Medical and Biological Engineering 1 (1) 19 - 28 1988 [Not refereed][Not invited]
  • 医用電子と生体工学 25 (2) 91 - 98 1987 [Not refereed][Not invited]
  • Optical biotelemetry using indirect light transmission
    Biotelemetry IX 55 - 58 1987 [Not refereed][Not invited]
  • 工藤 信樹, 清水 孝一, 松本 伍良
    医用電子と生体工学 23 (3) 194 - 198 0021-3292 1985 [Not refereed][Not invited]

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

Conference Activities & Talks

MISC

  • KUDO Nobuki  Japanese journal of medical ultrasonics = 超音波医学  39-  (6)  567  -568  2012/11/15  [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  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.
  • 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.
  • 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.
  • 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.
  • An experimental model using cultured cardiac myocytes for a study on generation of premature ventricular contractions under ultrasound exposure
    AIP Conference Proceedings  318  -321  2010  [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)  419  -420  2008/11/11  [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.
  • Measurement of pressure-dependent attenuation of ultrasound contrast agents
    Acoustical Imaging  29-  107  -113  2008  [Not refereed][Not invited]
  • KIBE Ryuta, KEK Khai Jun, KUDO Nobuki, YAMAMOTO Katsuyuki  電気学会研究会資料. MBE, 医用・生体工学研究会  2007-  (36)  13  -16  2007/06/29  [Not refereed][Not invited]
  • SUZUKI Ryosuke, SOSEKHA Ly, KUDO Nobuki, YAMAMOTO Katsuyuki  電気学会研究会資料. MBE, 医用・生体工学研究会  2007-  (36)  17  -20  2007/06/29  [Not refereed][Not invited]
  • 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.
  • 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.
  • 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]
  • Behavior of microbubbles exposed to pulsed ultrasound and its mechanical effect on a cell
    AIP Conference Proceedings  (754)  211  -213  2005  [Not refereed][Not invited]
  • 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.
  • A simple Schlieren system for visualizing a sound field of pulsed ultrasound
    Journal of Physics: Conference Series  (1)  146  -149  2004  [Not refereed][Not invited]
  • A study on premature ventricular contractions caused by ultrasound exposure with microbubbles using cultured ventricular muscle cells
    Journal of Physics: Conference Series  (1)  118  -121  2004  [Not refereed][Not invited]
  • Impact of bubbles on ultrasound safety
    International Congress Series  (1274)  129  -132  2004  [Not refereed][Not invited]
  • Does contrast ultrasonography damage liver cell
    International Congress Series  (1274)  147  -150  2004  [Not refereed][Not invited]
  • 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.
  • Physical properties of ultrasound contrast agents
    International Congress Series  (1274)  49  -52  2004  [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.
  • 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]
  • Study on mechanisms of cell damage caused by microbubbles exposed to ultrasound
    2002 IEEE Ultrasonics Symposium Proceedings  1351  -1354  2002  [Not refereed][Not invited]
  • 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, KUOD 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)  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)  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]
  • Proc. SPIE  (4250)  142  -152  2001  [Not refereed][Not invited]
  • 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)  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)  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]
  • Development of 200-channel mapping system for tissue oxygenation measured by near-infrared spectroscopy
    Proceedings of SPIE, 4082:48-56(2000)  (4082)  48  -56  2000  [Not refereed][Not invited]
  • 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.
  • Determination of a quantitative algorithm for the measurement of muscle oxygenation using CW near-infrared spectroscopy ─Mean optical pathlength without the influence of the adipose tissue─
    Proceedings of SPIE  (4082)  76  -86  2000  [Not refereed][Not invited]
  • 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]
  • IKEDA Takefumi, KUDO Nobuki, YAMAMOTO Katsuyuki  Journal of medical ultrasonics = 超音波医学  26-  (4)  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)  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  電気学会研究会資料. MBE, 医用・生体工学研究会  1998-  (5)  75  -80  1998/06/19  [Not refereed][Not invited]
  • NIWAYAMA Masatsugu, SHIGA Toshikazu, LIN Ling, KUDO Nobuki, TAKAHASHI Makoto, YAMAMOTO Katsuyuki  電気学会研究会資料. MBE, 医用・生体工学研究会  1998-  (5)  81  -88  1998/06/19  [Not refereed][Not invited]
  • 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)  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, KUDOH Nobuyuki, YAMAMOTO Katsuyuki  J Med Ultrasonics  25-  (3)  13  -24  1998/03/15  [Not refereed][Not invited]
  • NIWAYAMA Masatsugu, SHIGA Toshikazu, LIN Ling, KUDOU Nobuki, TAKAHASHI Makoto, YAMAMOTO Katsuyuki  Japanese journal of medical electronics and biological engineering  36-  (1)  41  -48  1998/03/10  [Not refereed][Not invited]
  • Proc. SPIE  (3257)  146  -155  1998  [Not refereed][Not invited]
  • Proc. SPIE  (3194)  166  -173  1998  [Not refereed][Not invited]
  • 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)  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)  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)  1997/09/15  [Not refereed][Not invited]
  • KANENARI Tetsuya, KUDO Nobuki, ZHANG Xu, TAKAHASHI Makoto, YAMAMOTO Katsuyuki  電気学会研究会資料. MBE, 医用・生体工学研究会  1997-  (16)  9  -16  1997/06/20  [Not refereed][Not invited]
  • 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)  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]
  • 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)  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]
  • 工藤 信樹, 清水 孝一, 松本 伍良  医用電子と生体工学  25-  (2)  p91  -98  1987/06  [Not refereed][Not invited]

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

Awards & Honors

  • 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)
  • 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

Research Grants & Projects

  • 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
  • 文部科学省:科学研究費補助金(挑戦的萌芽研究)
    Date (from‐to) : 2013 -2014 
    Author : 工藤 信樹
  • 文部科学省:科学研究費補助金(基盤研究(B))
    Date (from‐to) : 2011 -2012 
    Author : 工藤 信樹
  • 文部科学省:科学研究費補助金(挑戦的萌芽研究)
    Date (from‐to) : 2011 -2012 
    Author : 工藤 信樹
  • 文部科学省:科学研究費補助金(基盤研究(A))
    Date (from‐to) : 2009 -2012 
    Author : 清水 孝一, 加藤 祐次, 工藤 信樹, 北間 正崇, 千葉 仁志
     
    本研究は、生体内部の構造情報および機能情報を光により3次元的に透視イメージングすることをめざし、新原理に基づく新たな手法を創出するとともに、それを具現化するシステムを開発しようとするものである。第二年度は、初年度の基礎的検討の成果を受け、3次元光透視原理を具現化するシステムの基本構成を設計した。具体的内容は、次のとおりである。1.生体に対する光入射部分の設計と改良を繰り返し、透視可能な生体の厚みを大きく増加させた。これにより、従来は手掌程度の厚さにとどまっていた透過型透視を、成人上腕部全域にまで拡大することに成功した。2.静脈認証と言われるように、光で透視できる血管は体表近くの静脈とされてきた。これに対し、透視システムの改良により、これまで不可能と思われてきた動脈の透視を、成人前腕部において初めて可能とした。この成果は、現在のところ世界初のものと考えられる。3.透過光方式CTのシミュレーションを繰り返し、光CTによる3次元構造再構成を可能とするシステム条件を明らかにした。4.マウスやラット胴体を模擬する実験ファントムを作成し、体内吸光構造の3次元光透視の可能性を実証した。研究成果の発表:学術誌(Ann.Clin.Biochem.,超音波医学)、国際会議、国内会議(invited talk 2件、シンポジスト2件を含む)において、本研究の成果を発表した。
  • 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

Educational Activities

Teaching Experience

  • Medical Systems Engineering
    開講年度 : 2020
    課程区分 : 修士課程
    開講学部 : 情報科学研究科
    キーワード : 医用システム,医用計測,医用画像,診断・治療機器,医用情報,医用安全,生体医工学.
  • Medical Systems Engineering
    開講年度 : 2020
    課程区分 : 修士課程
    開講学部 : 情報科学院
    キーワード : 医用システム,医用計測,医用画像,診断・治療機器,医用情報,医用安全,生体医工学.
  • Bioengineering
    開講年度 : 2020
    課程区分 : 修士課程
    開講学部 : 情報科学研究科
    キーワード : 遺伝情報, genetic information, バイオインフォマティクス, bioinformatics, イメージング, imaging, 生体医工学, biomedical engineering, 細胞力学, cell mechanics
  • Medical Systems Engineering
    開講年度 : 2020
    課程区分 : 博士後期課程
    開講学部 : 情報科学研究科
    キーワード : 医用システム,医用計測,医用画像,診断・治療機器,医用情報,医用安全,生体医工学.
  • Medical Systems Engineering
    開講年度 : 2020
    課程区分 : 博士後期課程
    開講学部 : 情報科学院
    キーワード : 医用システム,医用計測,医用画像,診断・治療機器,医用情報,医用安全,生体医工学.
  • Bioengineering
    開講年度 : 2020
    課程区分 : 博士後期課程
    開講学部 : 情報科学研究科
    キーワード : 遺伝情報, genetic information, バイオインフォマティクス, bioinformatics, イメージング, imaging, 生体医工学, biomedical engineering, 細胞力学, cell mechanics
  • Exercise in Bioengineering and Bioinformatics Ⅰ
    開講年度 : 2020
    課程区分 : 学士課程
    開講学部 : 工学部
    キーワード : 電磁気学,線形システム論,信号処理,電気・電子・ディジタル回路
  • Bioengineering and Bioinformatics Laboratory Ⅱ
    開講年度 : 2020
    課程区分 : 学士課程
    開講学部 : 工学部
    キーワード : 遺伝情報,生体電気現象,生体機能情報,生体計測,バイオエレクトロニクス
  • Applied Electric Circuits
    開講年度 : 2020
    課程区分 : 学士課程
    開講学部 : 工学部
    キーワード : 非周期波,周波数応答,過渡応答,分布定数回路
  • Scientific Measurements and Instrumentation
    開講年度 : 2020
    課程区分 : 学士課程
    開講学部 : 工学部
    キーワード : 電気計測,電子計測,波形分析,センサ,応用計測


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