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Last Updated :2024/08/23

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Master

Affiliation (Master)

  • Faculty of Information Science and Technology　Bioengineering and Bioinformatics　Bioengineering

Affiliation (Master)

  • Faculty of Information Science and Technology　Bioengineering and Bioinformatics　Bioengineering

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Profile and Settings

Profile and Settings

  • Name (Japanese)

    Hirata

  • Name (Kana)

    Hiroshi

  • Name

    201301058669114396

Alternate Names

Achievement

Research Interests

  • 電子スピン共鳴   イメージング   生体計測   共振器   電子常磁性共鳴   ニトロキシルラジカル   MRI   画像再構成   マイクロ波共振器   周波数変調   サーフェイス・コイル   自動マッチング制御   磁界変調   共振尖鋭度   磁気共鳴   安定性   高周波磁界発生効率   空洞共振器   スライス選択画像   実験動物   線形制御理論   平衡線路   pH   帰還制御   マイクロ波発振器   マウス   脳   分光   スペクトル   一酸化窒素   

Research Areas

  • Manufacturing technology (mechanical, electrical/electronic, chemical engineering) / Measurement engineering
  • Life sciences / Radiology
  • Life sciences / Pharmacology
  • Nanotechnology/Materials / Crystal engineering
  • Nanotechnology/Materials / Applied materials
  • Life sciences / Pharmaceuticals - analytical and physicochemistry

Research Experience

  • 2019/04 - Today Faculty of Information Science and Technology Proessor
  • 2008/10 - 2019/03 Hokkaido University Graduate School of Information Science and Technology
  • 2015/03 - 2015/03 Jagiellonian University, Poland Faculty of Biochemistry, Biophysics and Biotechnology Visiting Professor
  • 2007/04 - 2008/09 Yamagata University Graduate School of Science and Engineering
  • 1996/04 - 2007/03 Yamagata University Faculty of Engineering
  • 2006/09 - 2006/09 The Ohio State University, USA Davis Heart and Lung Research Institute Visiting Scholar
  • 2003/06 - 2005/07 Ministry of Education,Culture,Sports,Science and Technology
  • 1999/04 - 2000/03 Dartmouth Medical School EPR Center for the Study of Viable Systems Research Associate
  • 1993/04 - 1996/03 Yamagata University Faculty of Engineering

Education

  • 1990/04 - 1993/03  Tokyo Institute of Technology  Graduate School of Multidisciplinary Science and Technology  Department of Applied Electronics
  • 1988/04 - 1990/03  Yamagata University  Graduate School of Engineering  Department of Electrical Engineering
  • 1984/04 - 1988/03  Tohoku Institute of Technology  Department of Communication Engineering

Committee Memberships

  • 2024/07 -2025/03   ENC-ISMAR Joint Conference 2025   Program Committee Member
  • 2022/02 -2024/02   The Society of Electron Spin Science and Technology   Vice President

Awards

  • 2024/01 International EPR/ESR Society IES Medal in Instrumentation and Methods Development
  • 2019/06 International Society for Magnetic Resonance in Medicine Distinguished Reviewer, Magnetic Resonance in Medicine
     
    受賞者: Hiroshi Hirata
  • 2018/07 International Society for Magnetic Resonance in Medicine Distinguished Reviewer for Magnetic Resonance in Medicine
     
    受賞者: Hiroshi Hirata
  • 2003/10 電子スピンサイエンス学会 奨励賞
     生命科学研究のための電子スピン共鳴装置の開発 
    受賞者: 平田 拓

Published Papers

  • Jeonghun Oh, Chang Uk Koo, Jong In Park, Kwon Choi, Junyoung Lee, Hiroshi Hirata, Sung-Joon Ye
    Radiation Measurements 176 107185  1350-4487 2024/08 [Refereed][Not invited]
  • Koudai Sawami, Tatsuya Naganuma, Hana Yabe, Toshihiko Taki, Neil J. Stewart, Yoshiki Uchio, Norihiko Takeda, Noriyuki Hatae, Takuya Hashimoto, Hiroshi Hirata, Shingo Matsumoto
    IEEE Transactions on Biomedical Engineering 71 (7) 2224 - 2231 0018-9294 2024/07 [Refereed][Not invited]
  • Misa Oba, Mai Taguchi, Yohei Kudo, Koya Yamashita, Hironobu Yasui, Shingo Matsumoto, Igor A. Kirilyuk, Osamu Inanami, Hiroshi Hirata
    Molecular Imaging and Biology 26 (3) 459 - 472 1536-1632 2024/06 [Refereed][Not invited]
  • Hideo Sato-Akaba, Tsukasa Sakai, Hiroshi Hirata
    Journal of Magnetic Resonance 360 107633  1090-7807 2024/03 [Refereed][Not invited]
  • Chang Uk Koo, Jong In Park, Jeonghun Oh, Kwon Choi, Joanne Yoon, Hiroshi Hirata, Sung-Joon Ye
    Journal of Magnetic Resonance 353 107520  1090-7807 2023/08 [Refereed][Not invited]
  • Ririko Nakaoka, Kazuhiro Kato, Kumiko Yamamoto, Hironobu Yasui, Shingo Matsumoto, Igor A. Kirilyuk, Valery V. Khramtsov, Osamu Inanami, Hiroshi Hirata
    Analytical Chemistry 95 (8) 3940 - 3950 0003-2700 2023/02 [Refereed][Not invited]
     
    Extracellular acidification indicates a metabolic shift in cancer cells and is, along with tissue hypoxia, a hallmark of tumor malignancy. Thus, non-invasive mapping of extracellular pH (pHe) is essential for researchers to understand the tumor microenvironment and to monitor tumor response to metabolism-targeting drugs. While electron paramagnetic resonance (EPR) has been successfully used to map pHe in mouse xenograft models, this method is not sensitive enough to map pHe with a moderate amount of exogenous pH-sensitive probes. Here, we show that a modified EPR system achieves twofold higher sensitivity by using the multiple harmonic detection (MHD) method and improves the robustness of pHe mapping in mouse xenograft models. Our results demonstrate that treatment of a mouse xenograft model of human-derived pancreatic ductal adenocarcinoma cells with the carbonic anhydrase IX (CAIX) inhibitor U-104 delays tumor growth with a concurrent tendency toward further extracellular acidification. We anticipate that EPR-based pHe mapping can be expanded to monitor the response of other metabolism-targeting drugs. Furthermore, pHe monitoring can also be used for the development of improved metabolism-targeting cancer treatments.
  • R. Sato, A. Utagawa, K. Fushimi, F. Li, T. Isono, K. Tajima, T. Satoh, S. Sato, H. Hirata, Y. Kikkawa, T. Yamamoto
    Polymers 15 (3) 666  2023/01 [Refereed][Not invited]
     
    The redox behaviors of macrocyclic molecules with an entirely π-conjugated system are of interest due to their unique optical, electronic, and magnetic properties. In this study, defect-free cyclic P3HT with a degree of polymerization (DPn) from 14 to 43 was synthesized based on our previously established method, and its unique redox behaviors arising from the cyclic topology were investigated. Cyclic voltammetry (CV) showed that the HOMO level of cyclic P3HT decreases from –4.86 eV (14 mer) to –4.89 eV (43 mer), in contrast to the linear counterparts increasing from –4.94 eV (14 mer) to –4.91 eV (43 mer). During the CV measurement, linear P3HT suffered from electro-oxidation at the chain ends, while cyclic P3HT was stable. ESR and UV–Vis–NIR spectroscopy suggested that cyclic P3HT has stronger dicationic properties due to the interactions between the polarons. On the other hand, linear P3HT showed characteristics of polaron pairs with multiple isolated polarons. Moreover, the dicationic properties of cyclic P3HT were more pronounced for the smaller macrocycles.
  • Kwon Choi, ChangUk Koo, JeongHun Oh, Jong In Park, Hiroshi Hirata, Sung-Joon Ye
    Concepts in Magnetic Resonance Part B, Magnetic Resonance Engineering 2022 7332324  2022/05 [Refereed][Not invited]
  • Hiroshi Hirata, Harold M. Swartz
    Applied Magnetic Resonance 53 (1) 167 - 191 0937-9347 2022/01 [Refereed][Not invited]
  • Yasuhiro Nakai, Ichiro Yamaguchi, Hiroshi Hirata, Harold M. Swartz, Ann Barry Flood, Benjamin B. Williams, Wilson Schreiber, Minoru Miyake
    Applied Magnetic Resonance 53 (1) 305 - 318 0937-9347 2022/01 [Refereed][Not invited]
  • Neil J. Stewart, Tatsuyuki Sato, Norihiko Takeda, Hiroshi Hirata, Shingo Matsumoto
    Antioxidants & Redox Signaling 36 (1-3) 81 - 94 1523-0864 2022/01 [Refereed][Invited]
     
    Significance: Magnetic resonance imaging (MRI) with hyperpolarized (HP) 13C-labeled redox-sensitive metabolic tracers can provide noninvasive functional imaging biomarkers, reflecting tissue redox state, oxidative stress, and inflammation, among others. The capability to use endogenous metabolites as 13C-enriched imaging tracers without structural modification makes HP 13C MRI a promising tool to evaluate redox state in patients with various diseases. Recent Advances: Recent studies have demonstrated the feasibility of in vivo metabolic imaging of 13C-labeled tracers polarized by parahydrogen-induced polarization techniques, which offer a cost-effective alternative to the more widely used dissolution dynamic nuclear polarization-based hyperpolarizers. Critical Issues: Although the fluxes of many metabolic pathways reflect the change in tissue redox state, they are not functionally specific. In the present review, we summarize recent challenges in the development of specific 13C metabolic tracers for biomarkers of redox state, including that for detecting reactive oxygen species. Future Directions: Applications of HP 13C metabolic MRI to evaluate redox state have only just begun to be investigated. The possibility to gain a comprehensive understanding of the correlations between tissue redox potential and metabolism under different pathological conditions by using HP 13C MRI is promoting its interest in the clinical arena, along with its noninvasive biomarkers to evaluate the extent of disease and treatment response.
  • Kota Kimura, Nami Iguchi, Hitomi Nakano, Hironobu Yasui, Shingo Matsumoto, Osamu Inanami, Hiroshi Hirata
    Antioxidants & Redox Signaling 36 (1-3) 57 - 69 1523-0864 2022/01 [Refereed][Not invited]
     
    Aims: This work aimed to establish an accelerated imaging system for redox-sensitive mapping in a mouse tumor model using electron paramagnetic resonance (EPR) and nitroxyl radicals. Results: Sparse sampling of EPR spectral projections was demonstrated for a solution phantom. The reconstructed three-dimensional (3D) images with filtered back-projection (FBP) and compressed sensing image reconstruction were quantitatively assessed for the solution phantom. Mouse xenograft models of a human-derived pancreatic ductal adenocarcinoma cell line, MIA PaCa-2, were also measured for redox-sensitive mapping with the sparse sampling technique. Innovation: A short-lifetime redox-sensitive nitroxyl radical (15N-labeled perdeuterated Tempone) could be measured to map the decay rates of the EPR signals for the mouse xenograft models. Acceleration of 3D EPR image acquisition broadened the choices of nitroxyl radical probes with various redox sensitivities to biological environments. Conclusion: Sparse sampling of EPR spectral projections accelerated image acquisition in the 3D redox-sensitive mapping of mouse tumor-bearing legs fourfold compared with conventional image acquisition with FBP. Antioxid. Redox Signal. 36, 57-69.
  • Fan Cheng, Takayuki Shibata, Yoshifumi Aoki, Hiroshi Hirata
    Journal of Magnetic Resonance 332 107081 - 107081 1090-7807 2021/11 [Refereed][Not invited]
  • Denis A. Komarov, Alexandre Samouilov, Hiroshi Hirata, Jay L. Zweier
    Journal of Magnetic Resonance 329 107024  1090-7807 2021/08 [Refereed][Not invited]
  • Neil J. Stewart, Hitomi Nakano, Shuto Sugai, Mitsushi Tomohiro, Yuki Kase, Yoshiki Uchio, Toru Yamaguchi, Yujirou Matsuo, Tatsuya Naganuma, Norihiko Takeda, Ikuya Nishimura, Hiroshi Hirata, Takuya Hashimoto, Shingo Matsumoto
    ChemPhysChem 22 (10) 915 - 923 1439-4235 2021/05 [Refereed]
     
    Hyperpolarized [1-13 C]fumarate is a promising magnetic resonance imaging (MRI) biomarker for cellular necrosis, which plays an important role in various disease and cancerous pathological processes. To demonstrate the feasibility of MRI of [1-13 C]fumarate metabolism using parahydrogen-induced polarization (PHIP), a low-cost alternative to dissolution dynamic nuclear polarization (dDNP), a cost-effective and high-yield synthetic pathway of hydrogenation precursor [1-13 C]acetylenedicarboxylate (ADC) was developed. The trans-selectivity of the hydrogenation reaction of ADC using a ruthenium-based catalyst was elucidated employing density functional theory (DFT) simulations. A simple PHIP set-up was used to generate hyperpolarized [1-13 C]fumarate at sufficient 13 C polarization for ex vivo detection of hyperpolarized 13 C malate metabolized from fumarate in murine liver tissue homogenates, and in vivo 13 C MR spectroscopy and imaging in a murine model of acetaminophen-induced hepatitis.
  • Jong In Park, Kwon Choi, Chang Uk Koo, Jeonghun Oh, Hiroshi Hirata, Harold M. Swartz, Sung-Joon Ye
    Health Physics 120 (2) 152 - 162 0017-9078 2021/02 [Refereed][Not invited]
  • Akihiro Taguchi, Stephen DeVience, Benoit Driesschaert, Valery V. Khramtsov, Hiroshi Hirata
    The Analyst 145 (9) 3236 - 3244 0003-2654 2020/05 [Refereed][Not invited]
     

    A simultaneous mapping method was established for the partial pressure of oxygen, pH and inorganic phosphate using electron paramagnetic resonance.

  • Takahito Yokoyama, Akihiro Taguchi, Harue Kubota, Neil J. Stewart, Shingo Matsumoto, Igor A. Kirilyuk, Hiroshi Hirata
    Journal of Magnetic Resonance 305 122 - 130 1090-7807 2019/08 [Refereed]
  • Ririko Nakaoka, Hiroshi Hirata
    AIP Advances 9 (7) 075312 - 075312 2019/07 [Refereed][Not invited]
  • Denis A Komarov, Yuki Ichikawa, Kumiko Yamamoto, Neil J Stewart, Shingo Matsumoto, Hironobu Yasui, Igor A Kirilyuk, Valery V Khramtsov, Osamu Inanami, Hiroshi Hirata
    Analytical Chemistry 90 (23) 13938 - 13945 2018/12 [Refereed][Not invited]
     
    An electron paramagnetic resonance (EPR)-based method for noninvasive three-dimensional extracellular pH mapping was developed using a pH-sensitive nitroxyl radical as an exogenous paramagnetic probe. Fast projection scanning with a constant magnetic field sweep enabled the acquisition of four-dimensional (3D spatial +1D spectral) EPR images within 7.5 min. Three-dimensional maps of pH were reconstructed by processing the pH-dependent spectral information on the images. To demonstrate the proposed method of pH mapping, the progress of extracellular acidosis in tumor-bearing mouse legs was studied. Furthermore, extracellular pH mapping was used to visualize the spatial distribution of acidification in different tumor xenograft mouse models of human-derived pancreatic ductal adenocarcinoma cells. The proposed EPR-based pH mapping method enabled quantitative visualization of regional changes in extracellular pH associated with altered tumor metabolism.
  • Ririko Nakaoka, Denis A. Komarov, Shingo Matsumoto, Hiroshi Hirata
    Applied Magnetic Resonance 49 (8) 853 - 867 0937-9347 2018/08 [Refereed][Not invited]
  • Tatsuya Amida, Ririko Nakaoka, Denis A Komarov, Kumiko Yamamoto, Osamu Inanami, Shingo Matsumoto, Hiroshi Hirata
    IEEE Transactions on Biomedical Engineering 65 (5) 1124 - 1132 2018/05 [Refereed][Not invited]
     
    OBJECTIVE: The purpose of this work was to develop an electronically tunable resonator operating at 750 MHz for continuous-wave electron paramagnetic resonance (CW-EPR) imaging of a mouse tumor-bearing leg. METHODS: The resonator had a multi-coil parallel-gap structure with a sample space of 16 mm in diameter and 20 mm in length. Microstrip line couplers were used in conjunction with varactor diodes to enable resonance frequency adjustment and to reduce the nonlinear effects of the varactor diodes. The resonator was modeled by the finite-element method and a microwave circuit simulation was performed to clarify its radiofrequency characteristics. RESULTS: A tunable resonator was evaluated in terms of its resonance frequency, tunable frequency band, and conversion efficiency of the RF magnetic field. The developed resonator provided a tunable frequency band of 4 MHz at a central frequency of 747 MHz and a conversion efficiency of 34 μT/W1/2. To demonstrate the application of this tunable resonator to EPR imaging, three-dimensional EPR images of a sample solution and a mouse tumor-bearing leg were obtained. CONCLUSION: The developed tunable resonator satisfied our initial requirements for in vivo EPR imaging and may be able to be further improved using the present finite-element and circuit models if any problems arise during future practical applications. SIGNIFICANCE: This work may help to promote EPR imaging of tumor-bearing mice in cancer-related studies.
  • Hideo Sato-Akaba, Miho C. Emoto, Hiroshi Hirata, Hirotada G. Fujii
    JOURNAL OF MAGNETIC RESONANCE 284 48 - 58 1090-7807 2017/11 [Refereed][Not invited]
     
    This paper describes the development of a digital console for three-dimensional (3D) continuous wave electron paramagnetic resonance (CW-EPR) imaging of a small animal to improve the signal-to-noise ratio and lower the cost of the EPR imaging system. A RF generation board, an RF acquisition board and a digital signal processing (DSP) & control board were built for the digital EPR detection. Direct sampling of the reflected RF signal from a resonator (approximately 750 MHz), which contains the EPR signal, was carried out using a band-pass subsampling method. A direct automatic control system to reduce the reflection from the resonator was proposed and implemented in the digital EPR detection scheme. All DSP tasks were carried out in field programmable gate array ICs. In vivo 3D imaging of nitroxyl radicals in a mouse's head was successfully performed. (C) 2017 Elsevier Inc. All rights reserved.
  • Michitaka Umakoshi, Ichiro Yamaguchi, Hiroshi Hirata, Naoki Kunugita, Benjamin B. Williams, Harold M. Swartz, Minoru Miyake
    HEALTH PHYSICS 113 (4) 262 - 270 0017-9078 2017/10 [Refereed][Not invited]
     
    In vivo L-band electron paramagnetic resonance tooth dosimetry is a newly developed and very promising method for retrospective biodosimetry in individuals who may have been exposed to significant levels of ionizing radiation. The present study aimed to determine the relationships among enamel thickness, enamel area, and measured electron paramagnetic resonance signal amplitude with a view to improve the quantitative accuracy of the dosimetry technique. Ten isolated incisors were irradiated using well-characterized doses, and their radiation-induced electron paramagnetic resonance signals were measured. Following the measurements, the enamel thickness and area of each tooth were measured using micro-focus computed tomography. Linear regression showed that the enamel area at each measurement position significantly affected the radiation-induced electron paramagnetic resonance signal amplitude (p < 0.001). Simulation data agreed well with this result. These results indicate that it is essential to properly consider enamel thickness and area when interpreting electron paramagnetic resonance tooth dosimetry measurements to optimize the accuracy of dose estimation.
  • Denis A. Komarov, Hiroshi Hirata
    JOURNAL OF MAGNETIC RESONANCE 281 44 - 50 1090-7807 2017/08 [Refereed][Not invited]
     
    In this paper, we introduce a procedure for the reconstruction of spectral-spatial EPR images using projections acquired with the constant sweep of a magnetic field. The application of a constant field-sweep and a predetermined data sampling rate simplifies the requirements for EPR imaging instrumentation and facilitates the backprojection-based reconstruction of spectral-spatial images. The proposed approach was applied to the reconstruction of a four-dimensional numerical phantom and to actual spectral-spatial EPR measurements. Image reconstruction using projections with a constant field sweep was three times faster than the conventional approach with the application of a pseudo-angle and a scan range that depends on the applied field gradient. Spectral-spatial EPR imaging with a constant field-sweep for data acquisition only slightly reduces the signal-to-noise ratio or functional resolution of the resultant images and can be applied together with any common backprojection-based reconstruction algorithm. (C) 2017 Elsevier Inc. All rights reserved.
  • Harue Kubota, Denis A. Komarov, Hironobu Yasui, Shingo Matsumoto, Osamu Inanami, Igor A. Kirilyuk, Valery V. Khramtsov, Hiroshi Hirata
    MAGNETIC RESONANCE MATERIALS IN PHYSICS BIOLOGY AND MEDICINE 30 (3) 291 - 298 0968-5243 2017/06 [Refereed][Not invited]
     
    Objectives The aim of this study was to demonstrate the feasibility of in vivo three-dimensional (3D) relaxation time T-2* mapping of a dicarboxy-PROXYL radical using continuous-wave electron paramagnetic resonance (CW-EPR) imaging. Materials and methods Isotopically substituted dicarboxy-PROXYL radicals, 3,4-dicarboxy-2,2,5,5-tetra(H-2(3)) methylpyrrolidin-( 3,4-H-2(2))-(1-N-15)-1-oxyl (H-2, N-15-DCP) and 3,4-dicarboxy-2,2,5,5-tetra(H-2(3)) methylpyrrolidin-(3,4-H-2(2))1- oxyl (H-2-DCP), were used in the study. A clonogenic cell survival assay was performed with the H-2-DCP radical using squamous cell carcinoma (SCC VII) cells. The time course of EPR signal intensities of intravenously injected H-2, N-15-DCP and H-2-DCP radicals were determined in tumor-bearing hind legs of mice (C3H/HeJ, male, n = 5). CW-EPR-based single-point imaging (SPI) was performed for 3D T-2* mapping. Results H-2-DCP radical did not exhibit cytotoxicity at concentrations below 10 mM. The in vivo half-life of H-2, N-15-DCP in tumor tissues was 24.7 +/- 2.9 min (mean +/- standard deviation [SD], n = 5). The in vivo time course of the EPR signal intensity of the H-2, N-15-DCP radical showed a plateau of 10.2 +/- 1.2 min (mean +/- SD) where the EPR signal intensity remained at more than 90% of the maximum intensity. During the plateau, in vivo 3D T-2* maps with H-2, N-15-DCP were obtained from tumor-bearing hind legs, with a total acquisition time of 7.5 min. Conclusion EPR signals of H-2, N-15-DCP persisted long enough after bolus intravenous injection to conduct in vivo 3D T-2* mapping with CW-EPR-based SPI.
  • Minoru Miyake, Yasuhiro Nakai, Ichiro Yamaguchi, Hiroshi Hirata, Naoki Kunugita, Benjamin B. Williams, Harold M. Swartz
    RADIATION PROTECTION DOSIMETRY 172 (1-3) 248 - 253 0144-8420 2016/12 [Refereed][Not invited]
     
    The aim of this study was to make direct measurements of the possible radiation-induced EPR signals in the teeth of volunteers who were residents in Fukushima within 80 km distance from the Fukushima Nuclear Power plant at the time of the disaster, and continued to live there for at least 3 month after the disaster. Thirty four volunteers were enrolled in this study. These measurements were made using a portable L-band EPR spectrometer, which was originally developed in the EPR Center at Dartmouth. All measurements were performed using surface loop resonators that have been specifically designed for the upper incisor teeth. Potentially these signals include not only radiation-induced signals induced by the incident but also background signals including those from prior radiation exposure from the environment and medical exposure. We demonstrated that it is feasible to transport the dosimeter to the measurement site and make valid measurements. The intensity of the signals that were obtained was not significantly above those seen in volunteers who had not had potential radiation exposures at Fukushima.
  • Xiaolei Wang, Miho Emoto, Yusuke Miyake, Kaori Itto, Shu Xu, Hirotada Fujii, Hiroshi Hirata, Hirokazu Arimoto
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 26 (20) 4947 - 4949 0960-894X 2016/10 [Refereed][Not invited]
     
    A novel blood-brain barrier (BBB)-permeable compound 10 was discovered, wherein the nitroxide moiety was linked to a nicotine acetylcholine receptor ligand. It was applied as a probe for electron paramagnetic resonance (EPR) imaging of the mouse brain. The results demonstrated that the newly synthesized compound 10 exhibited BBB permeability. These findings provide an essential discovery for in vivo EPR imaging. (C) 2016 Elsevier Ltd. All rights reserved.
  • Ann Barry Flood, The EPR Center Tooth Dosimetry Project Team, Benjamin B. Williams, Wilson Schreiber, Gaixin Du, Victoria A. Wood, Maciej M. Kmiec, Sergey V. Petryakov, Eugene Demidenko, Harold M. Swartz, Holly K. Boyle, Ruhong Dong, Shireen Geimer, Lesley A. Jarvis, Kyo Kobayashi, Roberto J. Nicolalde, Jason Crist, Ankit Gupta, Timothy Raynolds, Spencer Brugger, Pawel Budzioh, Brandon Carr, Matthew Feldman, Barjor Gimi, Oleg Grinberg, Vladimir Krymov, Piotr Lesniewski, Michael Mariani, Paul M. Meaney, Kevin M. Rychert, Ildar Salikhov, Dmitriy S. Tipikin, Mark Tseytlin, Brian R. Edwards, Christopher D. Herring, Catherine Lindsay, Traci Rosenbaum, Arif Ali, David Carlson, Wojciech Froncisz, Hiroshi Hirata, Jason Sidabras, Steven G. Swarts, Paul Calderone, Jamie Kennedy, Joseph Ianotti, Eric Elder, Barry Sands
    Radiation Protection Dosimetry 172 (1-3) 72 - 80 1742-3406 2016 [Refereed][Not invited]
     
    Several important recent advances in the development and evolution of in vivo Tooth Biodosimetry using Electron Paramagnetic Resonance (EPR) allow its performance to meet or exceed the U.S. targeted requirements for accuracy and ease of operation and throughput in a large-scale radiation event. Ergonomically based changes to the magnet, coupled with the development of rotation of the magnet and advanced software to automate collection of data, have made it easier and faster to make a measurement. From start to finish, measurements require a total elapsed time of 5 min, with data acquisition taking place in less than 3 min. At the same time, the accuracy of the data for triage of large populations has improved, as indicated using the metrics of sensitivity, specificity and area under the ROC curve. Applying these standards to the intended population, EPR in vivo Tooth Biodosimetry has approximately the same diagnostic accuracy as the purported 'gold standard' (dicentric chromosome assay). Other improvements include miniaturisation of the spectrometer, leading to the creation of a significantly lighter and more compact prototype that is suitable for transporting for Point of Care (POC) operation and that can be operated off a single standard power outlet. Additional advancements in the resonator, including use of a disposable sensing loop attached to the incisor tooth, have resulted in a biodosimetry method where measurements can be made quickly with a simple 5-step workflow and by people needing only a few minutes of training (which can be built into the instrument as a training video). In sum, recent advancements allow this prototype to meet or exceed the US Federal Government's recommended targets for POC biodosimetry in large-scale events.
  • Ayano Enomoto, Keita Saito, Sankaran Subramanian, Murali C. Krishna, Hiroshi Hirata, Nallathamby Devasahayam
    APPLIED MAGNETIC RESONANCE 46 (6) 671 - 683 0937-9347 2015/06 [Refereed][Not invited]
     
    This article describes a four-channel coil array for in vivo time-domain electron paramagnetic resonance (EPR) imaging applications. Decoupling of the individual element coils was achieved with the low-quality factors required in pulsed EPR at radiofrequency to accommodate the imaging bandwidth. No active decoupling method was used in the coil array. Remote control of a coaxial switch connected to the four-channel coil array was performed with voltage signals from a personal computer. To verify the operation of this four-channel coil array, a phantom tube filled with a solution of paramagnetic triarylmethyl radicals (OX063) was visualized by pulsed EPR imaging based on the single-point method involving pure phase encoding. In an in vivo experiment, OX063 in a mouse tumor-bearing right hind leg was visualized by pulsed EPR imaging. Even without active decoupling circuits, there was no shift in resonances for individual coils when those were tuned to the same frequency due to low quality factors and low coupling coefficients with neighboring coils. The coil assembly allowed us to study an object that was larger than an individual coil element, enabling the imaging of larger subjects with reduced overall specific absorption rate. Such strategies should be useful for studying larger objects by EPR imaging.
  • Wataru Takahashi, Yusuke Miyake, Hiroshi Hirata
    JOURNAL OF MAGNETIC RESONANCE 247 (10) 31 - 37 1090-7807 2014/10 [Refereed][Not invited]
     
    This article describes an improved method for suppressing image artifacts in the visualization of N-14- and N-15-labeled nitroxyl radicals in a single image scan using electron paramagnetic resonance (EPR). The purpose of this work was to solve the problem of asymmetric EPR absorption spectra in spectral processing. A hybrid function of Gaussian and Lorentzian lineshapes was used to perform spectral line-fitting to successfully separate the two kinds of nitroxyl radicals. This approach can process the asymmetric EPR absorption spectra of the nitroxyl radicals being measured, and can suppress image artifacts due to spectral asymmetry. With this improved visualization method and a 750-MHz continuous-wave EPR imager, a temporal change in the distributions of a two-phase paraffin oil and water/glycerin solution system was visualized using lipophilic and hydrophilic nitroxyl radicals, i.e., 2-(14-carboxytetradecy1)-2-ethyl-4, 4-dimethyl-3-oxazolidinyloxy (16-DOXYL stearic acid) and 4-hydroxyl-2,2,6,6-tetramethylpiperidine-d(17)-1-N-15-1-oxyl (TEMPOL-d(17)-N-15). The results of the two-phase separation experiment verified that reasonable artifact suppression could be achieved by the present method that deals with asymmetric absorption spectra in the EPR imaging of N-14- and N-15-labeled nitroxyl radicals. (C) 2014 Elsevier Inc. All rights reserved.
  • Wataru Takahashi, Andrey A. Bobko, Ilirian Dhimitruka, Hiroshi Hirata, Jay L. Zweier, Alexandre Samouilov, Valery V. Khramtsov
    APPLIED MAGNETIC RESONANCE 45 (9) 817 - 826 0937-9347 2014/09 [Refereed][Not invited]
     
    Variable radio frequency proton-electron double-resonance imaging (VRF PEDRI) enables extracting a functional map from a limited number of images acquired at pre-selected EPR frequencies using specifically designed paramagnetic probes with high-quality spatial resolution and short acquisition times. In this work we explored the potential of VRF PEDRI for pH mapping of aqueous samples using recently synthesized pH-sensitive phosphonated trityl radical, pTR. The ratio of Overhauser enhancements measured at each pixel at two different excitation frequencies corresponding to the resonances of protonated and deprotonated forms of pTR probe allows for a pH map extraction. Long relaxation times of pTR allow for pH mapping at EPR irradiation power as low as 1.25 W during 130 s acquisition time with spatial resolution of about 1 mm. This is particularly important for in vivo applications enabling one to avoid sample overheating by reducing RF power deposition.
  • Miho C. Emoto, Hideo Sato-Akaba, Hiroshi Hirata, Hirotada G. Fujii
    FREE RADICAL BIOLOGY AND MEDICINE 74 222 - 228 0891-5849 2014/09 [Refereed][Not invited]
     
    Electron paramagnetic resonance (EPR) imaging using nitroxides as redox-sensitive probes is a powerful, noninvasive method that can be used under various physiological conditions to visualize changes in redox status that result from oxidative damage. Two blood-brain barrier-permeative nitroxides, 3-hydroxymethy1-2,2,5,5-tetramethylpyrrolidine-1-oxyl (HMP) and 3-methoxycarbony1-2,2,5,5-tetramethy (MCP), have been widely used as redox-sensitive probes in the brains of small animals, but their in vivo distribution and properties have not yet been analyzed in detail. In this study, a custom-made continuous-wave three-dimensional (3D) EPR imager was used to obtain 3D EPR images of mouse heads using MCP or HMP. This EPR imager made it possible to take 3D EPR images reconstructed from data from 181 projections acquired every 60 s. Using this improved EPR imager and magnetic resonance imaging, the distribution and reduction time courses of HMP and MCP were examined in mouse heads. EPR images of living mice revealed that HMP and MCP have different distributions and different time courses for entering the brain. Based on the pharmacokinetics of the reduction reactions of HMP and MCP in the mouse head, the half-lives of HMP and MCP were clearly and accurately mapped pixel by pixel. An ischemic mouse model was prepared, and the half-life of MCP was mapped in the mouse head. Compared to the half-life in control mice, the half-life of MCP in the ischemic model mouse brain was significantly increased, suggesting a shift in the redox balance. This in vivo EPR imaging method using BBB-permeative MCP is a useful noninvasive method for assessing changes in the redox status in mouse brains under oxidative stress. (C) 2014 Elsevier Inc. All rights reserved.
  • Hirotaka Sugawara, Hiroshi Hirata, Sergey Petryakov, Piotr Lesniewski, Benjamin B. Williams, Ann Barry Flood, Harold M. Swartz
    IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING 61 (6) 1894 - 1901 0018-9294 2014/06 [Refereed][Not invited]
     
    This paper describes an optimized design of a surface coil resonator for in vivo electron paramagnetic resonance (EPR)-based tooth dosimetry. Using the optimized resonator, dose estimates with the standard error of the mean of approximately 0.5 Gy were achieved with irradiated human teeth. The product of the quality factor and the filling factor of the resonator was computed as an index of relative signal intensity in EPR tooth dosimetry by the use of 3-D electromagnetic wave simulator and radio frequency circuit design environment (ANSYS HFSS and Designer). To verify the simulated results of the signal intensity in our numerical model of the resonator and a tooth sample, we experimentally measured the radiation-induced signals from an irradiated tooth with an optimally designed resonator. In addition to the optimization of the resonator design, we demonstrated the improvement of the stability of EPR spectra by decontamination of the surface coil resonator using an HCl solution, confirming that contamination of small magnetic particles on the silver wire of the surface coil had degraded the stability of the EPR spectral baseline.
  • Jonathan Goodwin, Katsuya Yachi, Masaki Nagane, Hironobu Yasui, Yusuke Miyake, Osamu Inanami, Andrey A. Bobko, Valery V. Khramtsov, Hiroshi Hirata
    NMR IN BIOMEDICINE 27 (4) 453 - 458 0952-3480 2014/04 [Refereed][Not invited]
     
    The in vivo quantification of extracellular pH (pH(e)) in tumours may provide a useful biomarker for tumour cell metabolism. In this study, we assessed the viability of continuous-wave electron paramagnetic resonance (CW-EPR) spectroscopy with a pH-sensitive nitroxide for the measurement of extracellular tumour pH in a mouse model. CW-EPR spectroscopy (750 MHz) of C3H HeJ mice hind leg squamous cell tumour was performed after intravenous tail vein injection of pH-sensitive nitroxide (R-SG, 2-(4-((2-(4-amino-4-carboxybutanamido)-3-(carboxymethylamino)-3-oxoproylthio)methyl)phenyl)-4-pyrrolidino-2,5,5-triethyl-2,5-dihydro-1H-imidazol-1-oxyl) during stages of normal tumour growth and in response to a single 10-Gy dose of X-ray irradiation. An inverse relationship was observed between tumour volume and pH(e) value, whereby, during normal tumour growth, a constant reduction in pH(e) was observed. This relationship was disrupted by X-ray irradiation and, from 2-3 days post-exposure, a transitory increase in pH(e) was observed. In this study, we demonstrated the viability of CW-EPR spectroscopy using R-SG nitroxide to obtain high-sensitivity pH measurements in a mouse tumour model with an accuracy of <0.1 pH units. In addition, the measured changes in pH(e) in response to X-ray irradiation suggest that this may offer a useful method for the assessment of the physiological change in response to existing and novel cancer therapies. Copyright (c) 2014 John Wiley & Sons, Ltd.
  • Xiaolei Wang, Miho Emoto, Atsushi Sugimoto, Yusuke Miyake, Kaori Itto, Mitsuo Amasaka, Shu Xu, Hiroshi Hirata, Hirotada Fujii, Hirokazu Arimoto
    TETRAHEDRON LETTERS 55 (13) 2146 - 2149 0040-4039 2014/03 [Refereed][Not invited]
     
    A scalable synthetic route for N-15-labeled 4-oxo-2,2,6,6-tetraethylpiperidine nitroxide (N-15-TEEPONE) is described. This N-15-labeled nitroxide is suitable for electron paramagnetic resonance imaging of brain, and its higher sensitivity compared with that of its N-14-counterpart is an important advantage of the labeled derivative. (C) 2014 Elsevier Ltd. All rights reserved.
  • Ayano Enomoto, Hiroshi Hirata, Shingo Matsumoto, Keita Saito, Sankaran Subramanian, Murali C. Krishna, Nallathamby Devasahayam
    MAGNETIC RESONANCE IN MEDICINE 71 (2) 853 - 858 0740-3194 2014/02 [Refereed][Not invited]
     
    Time-domain electron paramagnetic resonance imaging is currently a useful preclinical molecular imaging modality in experimental animals such as mice and is capable of quantitatively mapping hypoxia in tumor implants. The microseconds range relaxation times (T-1 and T-2) of paramagnetic tracers and the large bandwidths (tens of MHz) to be excited by electron paramagnetic resonance pulses for spatial encoding makes imaging of large objects a challenging task. The possibility of using multiple array coils to permit studies on large sized object is the purpose of the present work. Toward this end, the use of planar array coils in different configurations to image larger objects than cannot be fully covered by a single resonator element is explored. Multiple circular surface coils, which are arranged in a plane or at suitable angles mimicking a volume resonator, are used in imaging a phantom and a tumor-bearing mouse leg. The image was formed by combining the images collected from the individual coils with suitable scaling. The results support such a possibility. By multiplexing or interleaving the measurements from each element of such array resonators, one can scale up the size of the subject and at the same time reduce the radiofrequency power requirements and increase the sensitivity. Magn Reson Med 71:853-858, 2014. (c) 2013 Wiley Periodicals, Inc.
  • Ayano Enomoto, Hiroshi Hirata
    JOURNAL OF MAGNETIC RESONANCE 239 29 - 33 1090-7807 2014/02 [Refereed][Not invited]
     
    This article describes a feasibility study of parallel image-acquisition using a two-channel surface coil array in continuous-wave electron paramagnetic resonance (CW-EPR) imaging. Parallel EPR imaging was performed by multiplexing of EPR detection in the frequency domain. The parallel acquisition system consists of two surface coil resonators and radiofrequency (RF) bridges for EPR detection. To demonstrate the feasibility of this method of parallel image-acquisition with a surface coil array, three-dimensional EPR imaging was carried out using a tube phantom. Technical issues in the multiplexing method of EPR detection were also clarified. We found that degradation in the signal-to-noise ratio due to the interference of RF carriers is a key problem to be solved. (C) 2013 Elsevier Inc. All rights reserved.
  • Ayano Enomoto, Miho Emoto, Hirotada Fujii, Hiroshi Hirata
    JOURNAL OF MAGNETIC RESONANCE 234 (1) 21 - 29 1090-7807 2013/09 [Refereed][Not invited]
     
    This article describes a four-channel surface coil array to increase the area of visualization for continuous-wave electron paramagnetic resonance (CW-EPR) imaging. A 776-MHz surface coil array was constructed with four independent surface coil resonators and three kinds of switches. Control circuits for switching the resonators were also built to sequentially perform EPR image acquisition for each resonator. The resonance frequencies of the resonators were shifted using PIN diode switches to decouple the inductively coupled coils. To investigate the area of visualization with the surface coil array, three-dimensional EPR imaging was performed using a glass cell phantom filled with a solution of nitroxyl radicals. The area of visualization obtained with the surface coil array was increased approximately 3.5-fold in comparison to that with a single surface coil resonator. Furthermore, to demonstrate the applicability of this surface coil array to animal imaging, three-dimensional EPR imaging was performed in a living mouse with an exogenously injected nitroxyl radical imaging agent. (C) 2013 Elsevier Inc. All rights reserved.
  • Tadatsugu Haga, Hiroshi Hirata, Piotr Lesniewski, Kevin M. Rychert, Benjamin B. Williams, Ann B. Flood, Harold M. Swartz
    CONCEPTS IN MAGNETIC RESONANCE PART B-MAGNETIC RESONANCE ENGINEERING 43B (1) 32 - 40 1552-5031 2013/02 [Refereed][Not invited]
     
    A surface-coil resonator that is capable of voltage-control for impedance-matching is described in the context of its application in electron paramagnetic resonance (EPR)-based tooth dosimetry. Varactor-based coupling of an 1,150 MHz surface-coil resonator was achieved to supply RF power. The developed resonator consists of a single-turn loop, 9 mm in mean diameter; a capacitor made of a polytetrafluoroethylene (PTFE) substrate; a quarter-wavelength parallel transmission line; a half-wave line balun, and varactors. The surface coil and the PTFE substrate capacitor were connected to a quarter-wavelength parallel transmission line. For the newly developed resonator, an RF magnetic field-generation efficiency of 130 T/W1/2 was achieved, and the sensitivity of the surface-coil resonator was investigated with an irradiated tooth. Measurements consisting of six sets of EPR spectra on a 10 Gy irradiated tooth using this newly developed resonator achieved a standard error of the mean (SEM) of 1.1 Gy. This level of accuracy of dose measurements was comparable to the SEM with a previously developed resonator; however, the previous resonator was not capable of voltage-control for impedance-matching adjustment, which represents a significant advance in facilitating automation. (c) 2013 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 43B:3240, 2013
  • Yusuke Miyake, Xiaolei Wang, Mitsuo Amasaka, Kaori Itto, Shu Xu, Hirokazu Arimoto, Hirotada Fujii, Hiroshi Hirata
    Analytical Chemistry 85 (2) 985 - 990 0003-2700 2013/01/15 [Refereed][Not invited]
     
    This Article describes the simultaneous imaging of chiral nitroxyl radicals using electron paramagnetic resonance (EPR). Chiral nitroxyl radicals could be simultaneously visualized with the labeling of isotopic nitrogen. Chiral nitroxyl radicals, hydroxylmethyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl, were visualized using the method of simultaneous EPR imaging, which refers to the visualization of two kinds of molecules with unpaired electrons in a single image scan. EPR spectra of a racemic mixture of chiral nitroxyl radicals and those of the respective R and S configurations confirmed labeling by isotopic nitrogen. 1H nuclear magnetic resonance (NMR) imaging and simultaneous imaging of solutions of chiral nitroxyl radicals were performed. The advantages and limitations of simultaneous imaging using EPR are also discussed. Simultaneous imaging with chiral-labeled nitroxyl radicals is a new application of EPR imaging and may be useful for biological studies involving biologically active chiral molecules. © 2012 American Chemical Society.
  • Hirotada G Fujii, Hideo Sato-Akaba, Miho C Emoto, Kouichi Itoh, Yasuhiro Ishihara, Hiroshi Hirata
    Magnetic resonance imaging 31 (1) 130 - 8 0730-725X 2013/01 [Refereed][Not invited]
     
    Increased reactive oxygen species (ROS) contribute to numerous brain disorders, and ROS generation has been examined in diverse experimental models of lipopolysaccharide (LPS)-induced inflammation. The in vivo electron paramagnetic resonance (EPR)/nitroxide spin probe method has been used to analyze the redox status in animal models modulated by ROS generation. In this study, a blood-brain barrier (BBB)-permeable nitroxide spin probe, 3-hydroxymethyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (HMP), was used as a redox-sensitive nitroxide probe. Magnetic resonance images of mouse head after the injection of HMP showed that HMP was distributed throughout all regions of the mouse head including the brain, suggesting that HMP can reveal redox information in all regions of the mouse head. After the injection of HMP through the mouse tail vein 6 h after the injection of LPS, three-dimensional (3D) EPR images were obtained each minute under a field scanning of 0.3 s and with 81 projections. The reduction reaction of HMP in septic mouse heads was remarkably accelerated compared to that in control mice, and this accelerated reaction was inhibited by aminoguanidine and allopurinol, which inhibit enzymatic activities of induced nitric oxide synthase and xanthine oxidase, respectively. Based on the pharmacokinetics of HMP in mouse heads, the half-life mapping of HMP was performed in LPS-treated mouse head. Half-life maps clearly show a difference in the redox status induced by ROS generation in the presence or absence of inhibitors of ROS-generating enzymes. The present results suggest that a 3D in vivo EPR imaging system combined with BBB-permeable HMP is a useful noninvasive tool for assessing changes in the redox status in rodent models of brain disease under oxidative stress.
  • Kouichi Nakagawa, Yasunori Ohba, Boris Epel, Hitoshi Hirata
    JOURNAL OF OLEO SCIENCE 61 (8) 451 - 456 1345-8957 2012/08 [Refereed][Not invited]
     
    A 9 GHz EPR imager that is capable of the imaging surface area of thin materials has been built. The EPR imager resolved samples spaced 1 mm apart. The developed TEIII cavity was able to detect easily similar to 1.0 mM aqueous TEMPOL solution in similar to 1.0 mm (i.d.) glass capillary placed just above the cavity. The sensitivity measured using the TEMPOL solution showed similar to 0.3 of that for the modified JEOL cavity, which was in a qualitative agreement with the calculations considering the difference in the filling factors of the cavities. The relatively low measured sensitivity of the TEIII cavity is due to utilization of the microwave field from similar to 3 mm aperture (hole) in the cavity wall. More importantly, the TEIII cavity does not require inserting the sample into the cavity and placing samples into EPR tubes.
  • Shunichi Koda, Jonathan Goodwin, Valery V. Khramtsov, Hirotada Fujii, Hiroshi Hirata
    ANALYTICAL CHEMISTRY 84 (8) 3833 - 3837 0003-2700 2012/04 [Refereed][Not invited]
     
    The development of electron paramagnetic resonance (EPR)-based mapping of pH is an important advancement for the field of diagnostic imaging. The ability to accurately quantify pH change in vivo and monitor spatial distribution is desirable for the assessment of a number of pathological conditions in the human body as well as the monitoring of treatment response. In this work we introduce a method for EPR-based pH mapping utilizing a method of spectral-spatial imaging of sequentially scanned spectra to decrease the missing gradient rotation angle, without increasing the spatial field of view. Repeated in vitro measurements of pH phantom tubes demonstrated higher precision measurements of the hyperfine coupling constant (HFC) compared to previous EPR-based methods, resulting in mean pH values accurate to less than 0.1 pH across a range of physiologically observed values.
  • Miho Emoto, Fumiya Mito, Toshihide Yamasaki, Ken-Ichi Yamada, Hideo Sato-Akaba, Hiroshi Hirata, Hirotada Fujii
    FREE RADICAL RESEARCH 45 (11-12) 1325 - 1332 1071-5762 2011/11 [Refereed][Not invited]
     
    The loss of paramagnetism of nitroxide radicals due to reductant reactions in biological systems, places a fundamental time constraint on their application as an imaging probe in in vivo EPR imaging studies. However, in vitro studies of the newly synthesized tetraethyl-substituted piperidine nitroxide radical demonstrated high resistivity to paramagnetic reduction when exposed to ascorbic acid, a common reduction agent in biological systems. In this work we investigated the use of these nitroxides as an imaging probe in EPR imaging of small rodents. 2,2,6,6-Tetraethyl-piperidine nitroxide (TEEPONE) is not highly soluble in aqueous media, thus a lipid-based emulsion system of lecithin was used to solubilize TEEPONE. The obtained solution was homogenous and with low viscosity, allowing smooth intravenous injection into mice tail vein. Acquired three dimensional (3D) EPR images of mouse head clearly showed TEEPONE distributed in all tissues including brain tissues, with an average measurable signal half-life of more than 80 min, thus demonstrating high resistivity to reduction due to ascorbic acid in in vivo animal studies, and the potential for use of this compound in in vivo studies of animal model systems.
  • Masashi Ohfuchi, Jonathan Goodwin, Hirotada Fujii, Hiroshi Hirata
    CONCEPTS IN MAGNETIC RESONANCE PART B-MAGNETIC RESONANCE ENGINEERING 39B (4) 180 - 190 1552-5031 2011/10 [Refereed][Not invited]
     
    The coregistration of electron paramagnetic resonance (EPR) and nuclear magnetic resonance (NMR) images in three-dimensional (3D) data space typically involves a process of visual inspection and manual alignment of the images. This is due primarily to the use of separate scanners, which can result in a number of potential differences between the two image types, such as resolution, field-of-view, and image orientation. In this article, we describe recently developed methodology and software that enables automatic coregistration of EPR and NMR acquired images without the need for manual alignment. The technique requires the use of fiducial markers during both EPR and NMR image acquisition, which contain a solution of free radical spin probes, and allow adjustment of the positions and the fields-of-view of the measured images. In this work we present results for EPR/NMR image coregistration using an isoflurane-anesthetized mouse, injected with triarylmethyl radical (Oxo63) spin probes. The same spin probes were also used inside the fiducial markers and in plastic tubes used for phantom measurements. Using our MATLAB-based software, we were able to successfully coregister EPR/NMR images in approximately 60 s. (C) 2011 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 39B: 180-190, 2011
  • Ayano Enomoto, Hiroshi Hirata
    JOURNAL OF MAGNETIC RESONANCE 209 (2) 244 - 249 1090-7807 2011/04 [Refereed][Not invited]
     
    This paper describes the development of a surface coil array that consists of two inductively coupled surface-coil resonators, for use in continuous-wave electron paramagnetic resonance (CW-EPR) imaging at 760 MHz. To make sequential EPR image acquisition possible, we decoupled the surface coils using PIN-diode switches, to enable the shifting of the resonators resonance frequency by more than 200 MHz. To assess the effectiveness of the surface coil array in CW-EPR imaging, two-dimensional images of a solution of nitroxyl radicals were measured with the developed coil array. Compared to equivalent single coil acquired images, we found the visualized area to be extended approximately 2-fold when using the surface coil array. The ability to visualize larger regions of interest through the use of a surface coil array, may offer great potential in future EPR imaging studies. (C) 2011 Elsevier Inc. All rights reserved.
  • Hirotada Fujii, Hideo Sato-Akaba, Katsuya Kawanishi, Hiroshi Hirata
    MAGNETIC RESONANCE IN MEDICINE 65 (1) 295 - 303 0740-3194 2011/01 [Refereed][Not invited]
     
    Electron paramagnetic resonance imaging using nitroxides is a powerful method for visualizing the redox status modulated by oxidative stress in vivo. Typically, however, data acquisition times have been too slow to obtain a sufficient number of projections for three-dimensional images, when using continuous wave-electron paramagnetic resonance imager in small rodents, using nitroxides with comparatively short T(2) and a half-life values. Because of improvements in imagers that enable rapid data-acquisition, the feasibility of three-dimensional electron paramagnetic resonance imaging with good quality in mice was tested with nitroxides. Three-dimensional images of mice were obtained at an interval of 15 sec under field scanning of 0.3 sec and with 46 projections in the case of strong electron paramagnetic resonance signals. Three-dimensional electron paramagnetic resonance images of a blood brain barrier-permeable nitroxide, 3-hydroxymethyl-2,2,5,5- tetramethylpyrrolidine-1-oxyl, in the mouse head clearly showed that 3-hydroxymethyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl was distributed within brain tissues, and this was confirmed by MRI observations. Based on the pharmacokinetics of nitroxides in mice, half-life mapping was demonstrated in an ischemia-reperfusion model mouse brain. Inhomogeneous half-lives were clearly mapped pixel-by-pixel in mouse head under oxidative stress by the improved continuous wave-electron paramagnetic resonance imager noninvasively. Magn Reson Med 65: 295-303, 2011. (C) 2010 Wiley-Liss, Inc.
  • Anna Pawlak, Ryohei Ito, Hirotada Fujii, Hiroshi Hirata
    CHEMICAL COMMUNICATIONS 47 (11) 3245 - 3247 1359-7345 2011 [Refereed][Not invited]
     
    The major advancement outlined in this communication is the simultaneous visualisation of two kinds of nitroxyl radicals using electron paramagnetic resonance (EPR) spectroscopy and imaging.
  • Yusuke Ikebata, Hideo Sato-Akaba, Takashi Aoyama, Hirotada Fujii, Kouichi Itoh, Hiroshi Hirata
    MAGNETIC RESONANCE IN MEDICINE 62 (3) 788 - 795 0740-3194 2009/09 [Refereed][Not invited]
     
    A method of post-processing to enhance the image resolution of the distribution of free radical molecules obtained with continuous-wave electron paramagnetic resonance (CW-EPR) Imaging is reported. The low spatial resolution of EPR imaging, which has created difficulties in biomedical applications, was overcome by the method of resolution-recovery for EPR imaging. High spatial resolution images for the distribution of free radical molecules with a very short relaxation time were obtained with this method. The method's two-step postprocessing consists of conventional deconvolution and filtered back-projection and a process of iterative deconvolution. The resolution-recovery method was demonstrated with three-dimensional (3D) imaging of stable nitroxyl radicals in mouse head. In phantom experiments with a solution of triarylmethyl (TAM) radicals, the spatial resolution was improved by a factor of 7 with the resolution-recovery method. Magn Reson Med 62:788-795, 2009. (C) 2009 Wiley-Liss, Inc.
  • Hideo Sato-Akaba, Yoko Kuwahara, Hirotada Fujii, Hiroshi Hirata
    ANALYTICAL CHEMISTRY 81 (17) 7501 - 7506 0003-2700 2009/09 [Refereed][Not invited]
     
    This technical note reports, a continuous-wave electron paramagnetic resonance (CW-EPR) imager that can visualize the distribution of free radicals with a half-life of subminutes in three-dimensional (3D) space. A total of 46 EPR spectra under magnetic field gradients, called projections, were obtained for image reconstruction at an interval of 3.6 s. A shortened data-acquisition time was achieved with the use of analog signals that drove field gradient coils in the imager. 3D mapping of the half-lives of nitroxyl radicals (4-hydroxyl-2,2,6,6-tetramethyl-piperidinyl-1-oxyl) was demonstrated in their reduction reaction with ascorbic acid. Inhomogeneous half-lives were clearly mapped pixel-by-pixel in a sample tube.
  • Hideo Sato-Akaba, Hirotada Fujii, Hiroshi Hirata
    REVIEW OF SCIENTIFIC INSTRUMENTS 79 (12) 123701  0034-6748 2008/12 [Refereed][Not invited]
     
    This paper describes improved temporal resolution for three-dimensional (3D) continuous-wave electron paramagnetic resonance (EPR) imaging. To improve temporal resolution, the duration of magnetic filed scanning that is used to obtain an EPR spectrum for each projection was reduced to 40 ms. The Helmholtz coil pair for field scanning was driven by triangular waves. The uniform distribution of projections was also used to reduce the number of projections for 3D image reconstruction. The reduction reaction of 4-hydroxy-2,2,6,6-tetramethyl-piperidinooxy with ascorbic acid was visualized by improved 3D EPR imaging techniques with a temporal resolution of 5.8 s.
  • Hideo Sato-Akaba, Hirotada Fujii, Hiroshi Hirata
    JOURNAL OF MAGNETIC RESONANCE 193 (2) 191 - 198 1090-7807 2008/08 [Refereed][Not invited]
     
    This article describes a method for reducing the acquisition time in three-dimensional (3D) continuous-wave electron paramagnetic resonance (CW-EPR) imaging. To visualize nitroxyl spin probes, which have a short lifetime in living organisms, the acquisition time for a data set of spectral projections should be Shorter than the lifetime of the spin probes. To decrease the total time required for data acquisition, the duration of magnetic field scanning was reduced to 0.5 s. Moreover, the number of projections was decreased by using the concept Of a uniform distribution. To demonstrate this faster data acquisition, two kinds of nitroxyl radicals with different decay rates were measured in mice. 3D EPR imaging of 4-hydroxy-2,2,6,6-tetramethylpiperidine-d(17)-1-N-15-1-oxyl in mouse head was Successfully carried out. 3D EPR imaging of nitroxyl spin probes with a half-life of a few minutes was achieved for the first time in live animals. (c) 2008 Elsevier Inc. All rights reserved.
  • Hideo Sato-Akaba, Haruhiko Abe, Hirotada Fujii, Hiroshi Hirata
    MAGNETIC RESONANCE IN MEDICINE 59 (4) 885 - 890 0740-3194 2008/04 [Refereed][Not invited]
     
    Continuous wave (CW) electron paramagnetic resonance (EPR) imaging can be used to obtain slice-selective images of free radicals without measuring three-dimensional (3D) projection data. A method that incorporated a modulated magnetic field gradient (MFG) was combined with polar field gradients to select a slice in the subject noninvasively. The slice-selective in vivo EPR imaging of triarylmethyl radicals in the heads of live mice is reported. 3D surface-rendered images were successfully obtained from slice-selective images. In the experiment in mice, a slice thickness of 1.8 mm was achieved.
  • Hirotada Fujii, Koh-ichi Sakata, Yoshihiro Katsumata, Rikiya Sato, Makoto Kinouchi, Masanori Someya, Shin-ichiro Masunaga, Masato Hareyama, Harold M. Swartz, Hiroshi Hirata
    RADIOTHERAPY AND ONCOLOGY 86 (3) 354 - 360 0167-8140 2008/03 [Refereed][Not invited]
     
    Purpose: The goal of this study was to clarify the dynamics of oxygenation (partial pressure of oxygen, PO2) in SCC VII murine tumors in mice after X-ray irradiation. Materials and methods: Changes in PO2 in tumors were measured by 1.2-GHz electron paramagnetic resonance (EPR) spectroscopy after they were exposed to various doses of irradiation. The PO2 in tumors was followed for up to six days after irradiation at doses of 0, 5, 10, 15, and 20 Gy. Paramagnetic crystals were used as an oximetry probe and implanted into normal or tumor tissues in mice for prolonged periods. Results: The pattern of tumor oxygen after a single dose of radiation with the 5-Gy dose was different from those with other doses (10, 15, and 20 Gy). After 5 Gy, pO(2) increased rapidly (P < 0.01, Student's t test) and then returned to the level observed before irradiation by 12 h (P < 0.01). In contrast, after 10, 15, or 20 Gy, PO2 increased rapidly by 6 h after irradiation, continued to increase until at least 24 h (P < 0.01), and then gradually decreased. Conclusions: In tumors that received 5 Gy, post-irradiation increases in PO2 at 4 h after irradiation were detected by EPR oximetry (P < 0.01) noninvasively. (c) 2007 Elsevier Ireland Ltd. All rights reserved.
  • Shingo Matsumoto, Michael Graham Espey, Hideo Utsumi, Nallathamby Devasahayam, Ken-Ichiro Matsumoto, Atsuko Matsumoto, Hiroshi Hirata, David A. Wink, Periarman Kuppusamy, Sankaran Subramanian, James B. Mitchell, Murali C. Krishna
    MAGNETIC RESONANCE IN MEDICINE 59 (3) 619 - 625 0740-3194 2008/03 [Refereed][Not invited]
     
    Oxygenation status is a key determinant in both tumor growth and responses to therapeutic interventions. The oxygen partial pressure (1302) was assessed using a novel pulsed electron paramagnetic resonance (EPR) spectroscopy at 750 MHz. Crystals of lithium phthalocyanine (LiPc) implanted into either squamous cell carcinoma (SCC) tumor or femoral muscle on opposing legs of mice were tested by pulsed EPR. The results showed pO(2) of SCC tumor was 2.7 +/- 0.4 mmHg, while in the femoral muscle it was 6.1 +/- 0.9 mmHg. A major advantage of pulsed EPR oximetry over conventional continuous-wave (CW) EPR oximetry is the lack of influence from subject motion, while avoiding artifacts associated with modulation or power saturation. Resonators in pulsed EPR are overcoupled to minimize recovery time. This makes changes in coupling associated with object motion minimal without influencing spectral quality. Consequently, pulsed EPR oximetry enables approximately a temporal resolution of similar to one second in pO(2) monitoring in conscious subjects, avoiding significant influence of anesthetics on the physiology being studied. The pO(2) in SCC tumor and muscle was found to be higher without anesthesia (3.9 +/- 0.5 mmHg for tumor, 8.8 +/- 1.2 mmHg for muscle). These results support the advantage of pulsed EPR in examining pO(2) in conscious animals with LiPc chronically implanted in predetermined regions.
  • Hiroshi Hirata, Guanglong He, Yuanmu Deng, Ildar Salikhov, Sergey Petryakov, Jay L. Zweier
    JOURNAL OF MAGNETIC RESONANCE 190 (1) 124 - 134 1090-7807 2008/01 [Refereed][Not invited]
     
    A loop resonator was developed for 300 MHz continuous-wave electron paramagnetic resonance (CW-EPR) spectroscopy and imaging in live rats. A single-turn loop (55 mm in diameter) was used to provide sufficient space for the rat body. Efficiency for generating a radiofrequency magnetic field of 38 mu T/W-1/2 was achieved at the center of the loop. For the resonator itself, an unloaded quality factor of 430 was obtained. When a 350 g rat was placed in the resonator at the level of the lower abdomen, the quality factor decreased to 18. The sensitive volume in the loop was visualized with a bottle filled with an aqueous solution of the nitroxide spin probe 3-carbamoyl-2,2,5,5-tetramethyl-3-pyrrolin-1-yloxy (3-CP). The resonator was shown to enable EPR imaging in live rats. Imaging was performed for 3-CP that had been infused intravenously into the rat and its distribution was visualized within the lower abdomen. (c) 2007 Elsevier Inc. All rights reserved.
  • Hiroshi Hirata, Hirotada Fujii
    MEASUREMENT SCIENCE AND TECHNOLOGY 18 (5) N27 - N31 0957-0233 2007/05 [Refereed][Not invited]
     
    This note describes an automatic matching control (AMC) circuit for use in in vivo continuous-wave (CW) electron paramagnetic resonance (EPR) spectroscopy. This AMC circuit is based on a phase-sensitive detection scheme, and can automatically stabilize the input impedance of a 1.1 GHz tunable resonator, even if the subject moves during data acquisition. The AMC circuit was designed for measuring small animals such as mice or rats. Noise suppression with the AMC circuit was investigated with a motion phantom and a live mouse. Experimental findings support the notion that the feedback loop in the developed AMC circuit is stable and provides good noise suppression. Moreover, AMC can improve the stability of the baselines in EPR spectra with an animal subject.
  • Shingo Matsumoto, Kenichi Yamada, Hiroshi Hirata, Keiji Yasukawa, Fuminori Hyodo, Kazuhiro Ichikawa, Hideo Utsumi
    MAGNETIC RESONANCE IN MEDICINE 57 (4) 806 - 811 0740-3194 2007/04 [Refereed][Not invited]
     
    The present study describes the advantageous application of a surface coil to electron paramagnetic resonance (EPR) irradiation in Overhauser-enhanced MRI (OMRI). OMRI is a double-resonance method for imaging free radicals based on the Over-hauser effect. Proton NMR images are recorded without and with EPR irradiation of the free radical resonance, which results in a difference proton image that shows signal enhancement in spatial regions that contain the free radical. To obtain good signal enhancement in OMRI, very high RF power and a long EPR irradiation time are required. To improve sensitivity and shorten the image acquisition time, especially for localized (and topical) applications, we developed and tested a surface-coil-type EPR irradiation coil. Theoretical calculations and experimental data showed that EPR irradiation through the surface coil could ameliorate the localized Overhauser enhancement, which was related to the ratio of 8, surface coil/B-1 volume coil in the region of interest (ROI), as expected. The increased sensitivity could also be converted into a shortened EPR irradiation time, resulting in fast data acquisition. For biomedical applications, the use of a surface coil (as opposed to a conventional volume coil) could decrease the total RF power deposition in the sample required to obtain the same Overhauser enhancement in the ROI.
  • Rizwan Ahmad, Bradley Clymer, Deepti S. Vikram, Yuanmu Deng, Hiroshi Hirata, Jay L. Zweier, Periannan Kuppusamy
    JOURNAL OF MAGNETIC RESONANCE 184 (2) 246 - 257 1090-7807 2007/02 [Refereed][Not invited]
     
    The broad spectrum of spin probes used for electron paramagnetic resonance imaging (EPRI) result in poor spatial resolution of the reconstructed images. Conventional deconvolution procedures can enhance the resolution to some extent but obtaining high resolution EPR images is still a challenge. In this work, we have implemented and analyzed the performance of a postacquisition deblurring technique to enhance the spatial resolution of the EPR images. The technique consists of two steps; noniterative deconvolution followed by iterative deconvolution of the acquired projections which are then projected back using filtered backprojection (FBP) to reconstruct a high resolution image. Further, we have proposed an analogous technique for iterative reconstruction algorithms such as multiplicative simultaneous iterative reconstruction technique (MSIRT) which can be a method of choice for many applications. The performance of the suggested deblurring approach is evaluated using computer simulations and EPRI experiments. Results suggest that the proposed procedure is superior to the standard FBP and standard iterative reconstruction algorithms in terms of mean-square-error (MSE), spatial resolution, and visual judgment. Although the procedure is described for 2D imaging, it can be readily extended to 3D imaging. (c) 2006 Elsevier Inc. All rights reserved.
  • Yuuki Kawada, Hiroshi Hirata, Hirodata Fujii
    JOURNAL OF MAGNETIC RESONANCE 184 (1) 29 - 38 1090-7807 2007/01 [Refereed][Not invited]
     
    This article reports experimental investigations on the use of RF resonators for continuous-wave electron paramagnetic resonance (cw-EPR) and proton nuclear magnetic resonance (NMR) imaging. We developed a composite resonator system with multi-coil parallel-gap resonators for co-registration EPR/NMR imaging. The resonance frequencies of each resonator were 21.8 MHz for NMR and 670 MHz for EPR. A smaller resonator (22 mm in diameter) for use in EPR was placed coaxially in a larger resonator (40 mm in diameter) for use in NMR. RF magnetic fields in the composite resonator system were visualized by measuring a homogeneous 4-hydroxy-2,2,6,6-tetramethyl-piperidinooxy (4-hydroxy-TEMPO) solution in a test tube. A phantom of five tubes containing distilled water and 4-hydroxy-TEMPO solution was also measured to demonstrate the potential usefulness of this composite resonator system ill biomedical science. An image of unpaired electrons was obtained for 4-hydroxy-TEMPO in three tubes, and was successfully mapped oil the proton image for five tubes. Technical problems in the implementation of a composite resonator system are discussed with regard to co-registration EPR/NMR imaging for animal experiments. (c) 2006 Elsevier Inc. All rights reserved.
  • Hirotada Fujii, Kouichi Itoh, Ramasamy P. Pandian, Motomichi Sakata, Periannan Kuppusamy, Hiroshi Hirata
    Magnetic Resonance in Medical Sciences 6 (2) 83 - 89 1347-3182 2007 [Refereed][Not invited]
     
    The in vivo measurement of oxygen in tissues is of great interest because of oxygen's fundamental role in life. Many methods have been developed for such measurement, but all have been limited, especially with regard to repeated measurement, degree of invasive-ness, and sensitivity. We describe electron spin resonance (ESR) oximetry with paramagnetic oxygen-sensing probe for in vivo measurement of oxygen in brain tissues by homemade ESRWMR dual imaging spectroscopy. Lithium 5, 9, 14, 18, 23, 27, 32, 36-octa-n-butoxy-2,3-naphthlocyanine (LiNc-BuO) radical was employed as the solid oxygen-sensing probe, and we confirmed its ability to report partial pressure of oxygen (pO2) in brain tissues of live animals under normal and pathological conditions for more than a month. pO2 measurements could also be made repeatedly on the same animal and at the same location. The implantation site of LiNc-BuO in examined rats was verified by 0.5T magnetic resonance (MR) imaging. Septic-shock rats were used to monitor tissue oxygenation during pathological state. A decline in pO2 levels from severe hypotension during sepsis was detected, and generation of nitric oxide (NO) in brain tissues was confirmed by NO spin trapping. ESR oximetry using oxygen-sensing probe and NO spin-trapping can be used to monitor pO2 change and NO production simultaneously and repeatedly at the same site in examined animals.
  • Hiroshi Hirata, Michi Wakana, Hitoshi Susaki
    APPLIED PHYSICS LETTERS 88 (25) 254103  0003-6951 2006/06 [Refereed][Not invited]
     
    In this letter, we report that superresolution continuous-wave electron paramagnetic resonance (cw-EPR) imaging is feasible for enhancing spatial resolution in images of unpaired electrons. We demonstrate one-dimensional superresolution EPR imaging for phantoms of 1,1-diphenyl-2-picrylhydrazyl (DPPH) powder with a 650 MHz cw-EPR imager. The spatial resolution was improved up to fivefold with iterative deconvolution techniques. Our superresolution EPR imaging includes two-stage postprocessing, i.e., noniterative deconvolution for measured EPR spectra and iterative deconvolution processing for a blurred EPR image profile with the point spread function of the low-pass window function being applied. (c) 2006 American Institute of Physics.
  • Hiroshi Hirata, Hirotada Fujii
    Current Organic Chemistry 10 (5) 521 - 534 1385-2728 2006/03 [Refereed]
  • K Takeshita, CP Chi, H Hirata, M Ono, T Ozawa
    FREE RADICAL BIOLOGY AND MEDICINE 40 (5) 876 - 885 0891-5849 2006/03 [Refereed][Not invited]
     
    Although free radicals may be involved in various types of UV-induced injuries, only a few in vivo studies of the generation of free radicals, including oxygen radicals, during exposure to ultraviolet light (UV) have been reported. In this study, the nitroxyl probe 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-N-oxyl was intravenously injected into hairless mice, and its decay was monitored in the skin with an in vivo EPR spectrometer equipped with a surface-coil-type resonator. The rate of decay of the EPR signal increased during UV (UVA+B) irradiation. This increase in signal decay was suppressed by preadministration of a spin trap, N-tert-butyl-alpha-phenylnitrone (PBN). PBN did not change the rate of signal decay in nonirradiated mice. The correlation between signal decay rate and physiological parameters such as blood velocity, blood mass, or skin temperature was low. The decay rate responded rapidly and reversibly to starting and stopping the UV illumination. Hydroxyl and peroxyl radicals caused reduction of the probe signal in vitro, and PBN inhibited only the peroxyl radical-induced signal reduction. These observations suggest that peroxyl radicals are generated in the skin of live mice during UVA+B irradiation. (c) 2005 Elsevier Inc. All rights reserved.
  • H Hirata, T Itoh, K Hosokawa, Y Deng, H Susaki
    JOURNAL OF MAGNETIC RESONANCE 175 (2) 177 - 184 1090-7807 2005/08 [Refereed][Not invited]
     
    This article describes a systematic method for determining the cutoff frequency of the low-pass window function that is used for deconvolution in two-dimensional continuous-wave electron paramagnetic resonance (EPR) imaging. An evaluation function for the criterion used to select the cutoff frequency is proposed, and is the product of the effective width of the point spread function for a localized point signal and the noise amplitude of a resultant EPR image. The present method was applied to EPR imaging for a phantom.. and the result of cutoff frequency selection was compared with that based on a previously reported method for the same projection data set. The evaluation function has a global minimum point that gives the appropriate cutoff frequency. Images with reasonably good resolution and noise suppression can be obtained from projections with an automatically selected cutoff frequency based on the present method. (c) 2005 Elsevier Inc. All rights reserved.
  • A composition resonator assembly suitable for EPR/NMR co-registration imaging
    Matsumoto S, Nagai M, Yamada K, Hyodo F, Yasukawa K, Muraoka M, Hirata H, Ono M, Utsumi H
    Concepts in Magnetic Resonance Part B Magnetic Resonance Engineering 25B (1) 1 - 11 2005/01 [Refereed][Not invited]
  • H Hirata, H Watanabe, M Kumada, K Itoh, H Fujii
    NMR IN BIOMEDICINE 17 (5) 295 - 302 0952-3480 2004/08 [Refereed][Not invited]
     
    This article describes a systematic approach to decoupling automatic tuning control (ATC) and automatic matching control (AMC) systems in continuous-wave (CW) electron paramagnetic resonance (EPR) spectroscopy for animal experiments. This technique enables us to improve the stability of CW-EPR spectroscopy even if the animal is moving during the data acquisition of EPR spectra. The control systems are formulated to allow the behavior of interference between them to be investigated, since they are generally coupled due to the characteristics of the microwave resonator. The stability of the entire control system in a 1.1 GHz CW-EPR spectrometer is evaluated with the generalized Nyquist stability criterion. We compare the EPR spectra of a triarylmethyl (TAM) radical that is dosed in anesthetized mice in terms of the signal-to-noise ratio (SNR) to test the precompensator for decoupling the ATC and AMC systems. The experimental findings suggest that the present technique is useful for improving the SNR of E-PR spectra in animal experiments. The SNR of the measured EPR spectra was improved by about 50% with the precompensator. Copyright (C) 2004 John Wiley Sons, Ltd.
  • H Hirata, T Kuyama, M Ono, Y Shimoyama
    JOURNAL OF MAGNETIC RESONANCE 168 (2) 252 - 258 1090-7807 2004/06 [Refereed][Not invited]
     
    We report a difference in the spectral lineshapes of continuous-wave (CW) electron paramagnetic resonance (EPR) spectroscopy between field and frequency modulation. This finding addresses the long-standing question of the effect of modulation in EPR absorption. We compared the first-derivative EPR spectra at 1.1 GHz for lithium phthalocyanine crystals, which have a single narrow linewidth in the EPR absorption spectrum, using field and frequency modulation. The experimental findings suggest that unpaired electrons have different behaviors under perturbation due to field and frequency modulation. (C) 2004 Elsevier Inc. All rights reserved.
  • K Takeshita, T Takajo, H Hirata, M Ono, H Utsumi
    JOURNAL OF INVESTIGATIVE DERMATOLOGY 122 (6) 1463 - 1470 0022-202X 2004/06 [Refereed][Not invited]
     
    Although oxygen radicals are thought to play a key role in the skin injury that is caused by protoporphyria, there is no direct evidence of generation of these radicals in vivo. This study measured the generation of oxygen radicals caused by visible light non-invasively in the skin of griseofulvin-induced protoporphyria model mice, using an in vivo electron spin resonance spectrometer equipped with a surface-coil-type resonator that could detect radicals within about 0.5 mm of the skin surface. A durable nitroxyl radical was administered intravenously as a probe. Light irradiation enhanced the decay of the nitroxyl signal in griseofulvin-treated mice, whereas light irradiation did not enhance the signal decay in control mice. The enhanced signal decay was completely suppressed by intravenous administration of hydroxyl radical scavengers, superoxide dismutase or catalase, or the intraperitoneal administration of desferrioxamine. The enhanced signal decay with illumination was reversible, and quickly responded to turning the light on and off. These observations suggest that the hydroxyl radical is generated via an iron-catalyzed reaction in the skin. This paper demonstrates, for the first time, the specific generation of oxygen radicals in response to light irradiation of the skin of protoporphyria model mice.
  • H Hirata, T Kuyama, M Ono, Y Shimoyama
    JOURNAL OF MAGNETIC RESONANCE 164 (2) 233 - 241 1090-7807 2003/10 [Refereed][Not invited]
     
    A frequency modulation (FM) method was developed to measure electron paramagnetic resonance (EPR) absorption. The first-derivative spectrum of 1,1-diphenyl-2-picrylhydrazyl (DPPH) powder was measured with this FM method. Frequency modulation of up to 1.6 MHz (peak-to-peak) was achieved at a microwave carrier frequency of 1.1 GHz. This corresponds to a magnetic field modulation of 57 muT (peak-to-peak) at 40.3 mT. By using a tunable microwave resonator and automatic control systems, we achieved a practical continuous-wave (CW) EPR spectrometer that incorporates the FM method. In the present experiments, the EPR signal intensity was proportional to the magnitude of frequency modulation. The background signal at the modulation frequency (1 kHz) for EPR detection was also proportional to the magnitude of frequency modulation. An automatic matching control (AMC) system reduced the amplitude of noise in microwave detection and improved the baseline stability. Distortion of the spectral lineshape was seen when the spectrometer settings were not appropriate, e.g., with a lack of the open-loop gain in automatic tuning control (ATC). FM is an alternative to field modulation when the side-effect of field modulation is detrimental for EPR detection. The present spectroscopic technique based on the FM scheme is useful for measuring the first derivative with respect to the microwave frequency in investigations of electron-spin-related phenomena. (C) 2003 Elsevier Inc. All rights reserved.
  • Salikhov, I, H Hirata, T Walczak, HM Swartz
    JOURNAL OF MAGNETIC RESONANCE 164 (1) 54 - 59 1090-7807 2003/09 [Refereed][Not invited]
     
    An improved external loop resonator (ELR) used for L-band electron paramagnetic resonance (EPR) spectroscopy is reported. This improvement is achieved by shortening the parallel coaxial line. The resonant structure is formed by two single turn coils (10 mm in diameter) that are connected to a parallel coaxial line. A resonance frequency of 1197 MHz and a quality factor of 466 were obtained in the absence of biological tissue and similar to1130 MHz and similar to50 with a living animal, respectively. The sensitivity of the new ELR was compared to the previously developed ELR using three types of EPR samples: (1) paramagnetic material with no biological tissue, (2) paramagnetic material in a leg and in the peritoneal cavity of a dead rat, and (3) paramagnetic material in the back of an anesthetized rat. The sensitivity was 1.2-1.6 times greater in the rat and 4.2 times without tissue. (C) 2003 Elsevier Science (USA). All rights reserved.
  • H Hirata, Y Yamaguchi, T Takahashi, ZW Lu
    MAGNETIC RESONANCE IN MEDICINE 50 (1) 223 - 227 0740-3194 2003/07 [Refereed][Not invited]
     
    A method for estimating the characteristics of an automatic matching control (AMC) system for in vivo electron paramagnetic resonance (EPR) spectroscopy is described. AMC is also known as automatic coupling control (ACC) and is used to compensate for perturbation due to movement of the subject animal. The open-loop function of the AMC system is derived and the characteristics (gain, phase margin, steady-state error, system bandwidth, and disturbance rejection) of the system are examined. The proposed method is supported by experimental findings. The frequency response of perturbation due to the movement of an anesthetized rat was measured with a 1.1-GHz continuous-wave EPR spectrometer. Disturbance rejection with the AMC system was also considered for respiratory motion and the heartbeat of the anesthetized rat, and these perturbations were reduced by about 40 dB in the power spectrum of the output of the diode detector in the spectrometer. (C) 2003 Wiley-Liss, Inc.
  • GL He, SP Evalappan, H Hirata, YM Deng, S Petryakov, P Kuppusamy, JL Zweier
    MAGNETIC RESONANCE IN MEDICINE 48 (6) 1057 - 1062 0740-3194 2002/12 [Refereed][Not invited]
     
    Surface coil resonators have been widely used to perform topical EPR spectroscopy. They are usually positioned adjacent to or implanted within the body. For EPR applications these resonators have a number of important advantages over other resonator designs due to their ease of sample accessibility, mechanical fabrication, implementation of electronic tuning and coupling functions, and low susceptibility to sample motions. However, a disadvantage is their B-1 field inhomogeneity, which limits their usefulness for 3D imaging applications. We show that this problem can be addressed by mapping and correcting the B-1 field distribution. We report the use of EPR imaging (EPRI) to map the B-1 distribution of a surface coil resonator. We show that EPRI provides a fast, accurate, and reliable technique to evaluate the B-1 distribution. 3D EPRI was performed on phantoms, prepared using three different saline concentrations, to obtain the B-1 distribution. The information obtained from the phantoms was used to correct the images of living animals. With the use of this B-1 correction technique, surface coil resonators can be applied to perform 3D mapping of the distribution of free radicals in biological samples and living systems.
  • H Hirata, M Ueda, N Ono, Y Shimoyama
    JOURNAL OF MAGNETIC RESONANCE 155 (1) 140 - 144 1090-7807 2002/03 [Refereed][Not invited]
     
    Continuous-wave EPR spectroscopy using a frequency modulation (FM) scheme was developed. An electronically tunable resonator and an automatic tuning control (ATC) system were used. Using the FM scheme instead of magnetic field modulation, we detected EPR absorption at the first derivative mode. We used a microwave frequency of 1.1 GHz in the present experiment. Similar signal-to-noise ratios were obtained with conventional field modulation and the FM method, and a low-quality factor EPR resonator was not necessary to suppress the significant microwave reflection from the resonator. The FM method with a tunable resonator may be an alternative solution to achieving phase-sensitive detection, when the side-effects of magnetic field modulation, such as microphonic noise and mechanical vibration, are detrimental for EPR detection. (C) 2002 Elsevier Science (USA).
  • M Ono, A Suenaga, H Hirata
    MAGNETIC RESONANCE IN MEDICINE 47 (2) 415 - 419 0740-3194 2002/02 [Refereed][Not invited]
     
    The relationship between an RF magnetic field and an electric shielding plate called a bridge in a bridged loop-gap resonator (BLGR), which is used for EPR spectroscopy and imaging, is examined. The magnetic field in a BLGR is perturbed due to discontinuity of the conductive loop and electric fringing fields near the gaps. The magnetic field homogeneity in the BLGR can be improved with a bridge. The optimum angle for such bridges can be found by measuring the RF magnetic field. In this study, the RF magnetic field was measured for BLGRs 70 mm in diameter, with a resonance frequency of 302 +/- 5 MHz. The field uniformity on a circle with a radius of 27 mm was improved by 8% with bridges at optimal angles. Improved RF magnetic field homogeneity associated with a BLGR is demonstrated. Magn Reson Med 47:415-419, 2002. (C) 2002 Wiley-Liss, Inc.
  • H Hirata, ZW Luo
    MAGNETIC RESONANCE IN MEDICINE 46 (6) 1209 - 1215 0740-3194 2001/12 [Refereed][Not invited]
     
    Stability analysis and design of an automatic frequency control (AFC) system for in vivo continuous-wave EPR spectroscopy is described. The open-loop function of the feedback control system for the AFC was derived and the stability of the feedback loop systematically examined. A stability analysis of the system is demonstrated and a systematic design procedure is proposed. The design is started from the required system specifications (phase margin, steady-state error, and system bandwidth) and clear guidelines for designing an AFC system are given. A case study of the design is presented based on the specific needs of in vivo EPR measurements. A phase margin of 53 degrees, a steady-state error of 1.6%, and a system bandwidth of up to 1.8 kHz were obtained in the designed AFC system. The system specifications defined in advance are satisfied in this case study. (C) 2001 Wiley-Liss, Inc.
  • H Hirata, T Walczak, HM Swartz
    REVIEW OF SCIENTIFIC INSTRUMENTS 72 (6) 2839 - 2841 0034-6748 2001/06 [Refereed][Not invited]
     
    This note describes considerable additional information on the key parameters of an electronically tunable surface-coil-type resonator for L-band continuous-wave electron paramagnetic resonance (EPR) spectroscopy [Hirata , J. Magn. Reson. 142, 159 (2000)]. For the 1.1 GHz prototype tunable surface coil (10.6 mm in diameter), the measured efficiency for generating the rf magnetic field is 77 muT/W-1/2. The unloaded quality factor of the tunable surface coil is in the range of 260-310. In absence of an EPR sample, 57% of the magnetic energy in the system is stored in the parallel coaxial line, 16% in the surface coil, and a half of the energy is dissipated in the parallel coaxial line. The energy dissipation for the surface coil occurs mainly through radiation (25% of the total energy dissipation). The level of the second harmonic in the reflected microwaves generated by the tunable surface coil was measured. The varactor diodes used in the matching and tuning circuits are the dominant source of the second harmonic. (C) 2001 American Institute of Physics.
  • H Hirata, T Walczak, HM Swartz
    JOURNAL OF MAGNETIC RESONANCE 142 (1) 159 - 167 1090-7807 2000/01 [Refereed][Not invited]
     
    The automatic frequency control (AFC) circuit in conventional electron paramagnetic resonance (EPR) spectrometers automatically tunes the microwave source to the resonance frequency of the resonator. The circuit works satisfactorily for samples stable enough that the geometric relations in the resonance structure do not change in a significant way. When EPR signals are measured during in vivo experiments with small rodents, however, the distance between the signal source and the surface-coil detector can change rapidly. When a conventional AFC circuit keeps the oscillator tuned to the resonator under those conditions, the resultant frequency change may exceed +/- 5 MHz and markedly shift the position of the EPR signal. Such a shift results in unacceptable effects on the spectra, especially when the experimenter is dealing with narrow EPR lines. The animal movement also causes a mismatching of the resonator and the 50-ohm transmission line. Direct results of this mismatching are increased noise; shifts in the position of the baseline; and a high probability of overdriving the signal preamplifier with consequent loss of the EPR signal. We therefore designed, built, and tested a new surface-coil resonator using varactor diodes for tuning the resonance frequency to the fixed frequency oscillator and for capacitive matching of the resonator to the 50-ohm transmission line. The performance of the automatic matching system was tested in vivo by measuring EPR spectra of lithium phthalocyanine implanted in rats. Stability and sensitivity of the spectrometer were evaluated by measuring EPR spectra with and without the use of the automatic matching system. The overall experimental performance of the spectrometer was found to significantly improve during in vivo experiments using the automatic matching system. Excellent matching between the 50-ohm transmission line and the resonator was maintained under all experimental circumstances that were tested. This should allow us now to carry out experiments that previously were not possible. (C) 2000 Academic Press.
  • H Hirata, M Ono
    REVIEW OF SCIENTIFIC INSTRUMENTS 68 (9) 3595 - 3596 0034-6748 1997/09 [Refereed][Not invited]
     
    This note describes a newly developed flexible surface-coil-type resonator (FSCR) used for electron paramagnetic resonance (EPR) measurements. A conventional FSCR has used a balanced transmission line made by coaxial lines. The new resonator uses triaxial cable in order to avoid anisotropy of flexure of the transmission line. Experimental results show that the EPR signal measured with the triaxial FSCR is 35% stronger than that measured with the conventional FSCR. (C) 1997 American Institute of Physics.
  • H Hirata, M Ono
    REVIEW OF SCIENTIFIC INSTRUMENTS 68 (9) 3528 - 3532 0034-6748 1997/09 [Refereed][Not invited]
     
    This article describes an impedance-matching system for a flexible surface-coil-type resonator (FSCR) used in electron paramagnetic resonance (EPR) experiments. To design the matching system, the input impedance of the FSCR was formulated using transmission line theory, and then the parameters of a matching circuit using varicap diodes were calculated. Experimental measurements of input impedance showed the validity of the formulation and the usefulness of the matching system. The matching circuit made by the varicap diodes 1SV186 offered the tunable bandwidth of 50 MHz for the prototype FSCR. Such a matching system also offers the possibility of remotely tuning EPR resonators electronically. (C) 1997 American Institute of Physics.
  • H Hirata, T Walczak, HM Swartz
    REVIEW OF SCIENTIFIC INSTRUMENTS 68 (8) 3187 - 3191 0034-6748 1997/08 [Refereed][Not invited]
     
    The development of in vivo electron paramagnetic resonance spectrometers has generated a need for a better method of inductive coupling between a microwave resonator and a transmission Line, We describe here an approach, based on introducing an additional impedance transformer between a coupling loop and the transmission line. This additional transformer decreases (by a factor of 20) the resonance frequency shift that occurs during adjustment of the coupling. The calculated optimal length is slightly greater than a quarter of the wavelength of the electromagnetic waves. Experimental measurements of the return loss for the matching circuit has shown the validity of the calculations and the usefulness of the proposed theoretical model. (C) 1997 American Institute of Physics.
  • H Hirata, M Ono
    REVIEW OF SCIENTIFIC INSTRUMENTS 67 (1) 73 - 78 0034-6748 1996/01 [Refereed][Not invited]
     
    This paper presents a method for estimating the resonance frequency of a bridged loop-gap resonator (BLGR). It first describes the structure of the BLGR and its equivalent electrical circuit, and then a procedure for calculating the resonance frequency is revealed. In this procedure, node analysis, which is a circuit theory, is applied to calculate the branch voltages of the equivalent circuit. Finally, this paper reports on the calculations and measurements of the resonance frequency, and the validity of the method for estimating resonance frequency. (C) 1996 American Institute of Physics.
  • H HIRATA, H IWAI, M ONO
    REVIEW OF SCIENTIFIC INSTRUMENTS 66 (9) 4529 - 4534 0034-6748 1995/09 [Refereed][Not invited]
     
    This paper presents a method for analyzing the sensitivity of a flexible surface-coil-type resonator (FSCR). It first describes the configuration and the operation principle of the FSCR and then a method for estimating relative sensitivity of the FSCR. In this estimation, the quality factor and the filling factor of the FSCR are formulated because the strength of electron spin resonance (ESR) signals is proportional to the product of these factors. Finally, this paper reports experiments, measuring the ESR spectra of 1,1-Diphenyl-2-picrylhydrazyl powder, confirming the validity of the proposed method. (C) 1995 American Institute of Physics.
  • Y SAKAMOTO, H HIRATA, M ONO
    IEEE TRANSACTIONS ON MICROWAVE THEORY AND TECHNIQUES 43 (8) 1840 - 1847 0018-9480 1995/08 [Refereed][Not invited]
     
    The purpose of the present paper is to establish a method of design for a multicoupled loop-gap resonator used for pulsed electron paramagnetic resonance measurements, For the design of resonator characteristics, the method has an advantage of a systematic approach without iterative calculations, In this design, the number of loop-gap resonators used is first determined from the pass band required as the specifications of the resonator, To satisfy the specifications, electrical parameters of an equivalent circuit and the dimensions of the resonator are estimated, By the proposed method, a prototype resonator which has the operation frequency of 1,3 GHz is designed and fabricated, For the prototype resonator, the characteristics of the return loss agree with the required ones, As a result, the validity of the design method is experimentally confirmed.
  • Hiroshi Hirata, Sadayuki Ueha
    IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control 42 (2) 225 - 231 0885-3010 1995 [Refereed][Not invited]
     
    The purpose of the present paper is to establish a method of design for a traveling wave type ultrasonic motor. This method is based on two models for the ultrasonic motor. A two-dimensional elastic contact model is used for estimating the friction drive between the rotor and vibrator of the motor. Moreover, an electrical equivalent circuit is used to estimate the interaction between the electrical and mechanical parts of the vibrator. The proposed method is applied to the design of a prototype motor. To determine applicability of the method, the load characteristics of the prototype motor are measured. The measured characteristics agree with the required ones which are specified in advance. As a result, the validity of the proposed method is experimentally confirmed. 0885-3010/95$04.00 © 1995 IEEE
  • M ONO, K ITO, N KAWAMURA, KC HSIEH, H HIRATA, N TSUCHIHASHI, H KAMADA
    JOURNAL OF MAGNETIC RESONANCE SERIES B 104 (2) 180 - 182 1064-1866 1994/06 [Refereed][Not invited]
  • Hiroshi Hirata, Sadayuki Ueha
    IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control 40 (4) 402 - 406 0885-3010 1993/07 [Refereed][Not invited]
     
    The purpose of the present paper is to propose a method of calculation of load characteristics for a traveling wave type ultrasonic motor (TWUM). A method using an equivalent circuit is proposed for estimating the performance of the motor. Using this method, a systematic approach is achieved for estimating the performance, including the electrical and the mechanical parts of the motor. In the proposed method, a governing equation of the motor is derived to describe the relation between the applied voltage at an electrical terminal, vibration velocities, and the external forces at mechanical of a vibrator. An estimation method of the forces between the rotor and the vibrator o the motor is revealed to calculate the load characteristics. On the basis of the proposed method, the load characteristics are numerically calculated and compared with the measured ones. Since the calculated load characteristics curves agree well with the measured ones, the validity of the proposed method for estimating the load characteristics is confirmed.
  • Hiroshi Hirata, Sadayuki Ueha
    Journal of the Acoustical Society of Japan (E) 13 (2) 77 - 84 0388-2861 1992 [Refereed][Not invited]
     
    A piezoelectric circular plate, which vibrates in non-axisymmetric or flexural vibration mode, is used for the stator vibrator of an ultrasonic motor. To design the stator vibrator adequately, the force factor of the vibrator should be estimated in advance. The theoretically calculated force factors for the two vibration modes are compared with the measured ones to obtain good agreement. In order to study how to control the force factor, the relation between the shape of the vibrator and the force factor is also considered. © 1992, Acoustical Society of Japan. All rights reserved.
  • H HIRATA, S UEHA
    JAPANESE JOURNAL OF APPLIED PHYSICS PART 1-REGULAR PAPERS SHORT NOTES & REVIEW PAPERS 31 (Suppl. 31-1) 248 - 250 0021-4922 1992 [Refereed][Not invited]
     
    Using a two-dimensional elastic contact theory, the pressure distribution on the area of contact between the rotor and the stator vibrator of an ultrasonic motor is calculated. In this calculation, the stator vibrator and the rotor are assumed to be a rigid body and an elastic half-space, respectively. The no-load revolution speed of the motor using the calculated pressure distribution is estimated, and is compared with the measured speed. As a result, it is proved that the revolution speed can be estimated by using the calculated pressure distribution if the assumption is satisfied.
  • Takehiro Takano, Hiroshi Hirata, Yoshiro Tomikawa
    Journal of the Acoustical Society of Japan (E) 11 (3) 161 - 172 0388-2861 1990 [Refereed][Not invited]
     
    The mathematical analysis of non-axisymmetric vibration of a piezoelectric annular plate and its application to an ultrasonic motor had previously been reported. In this paper, analysis of the annular plate clamped on its inside or outside circumferences is stated from the view point of its application to an ultrasonic motor. Calculated results reveal the potential usage of the vibration modes for a thin-type ultrasonic motor. © 1990, Acoustical Society of Japan. All rights reserved.
  • Y TOMIKAWA, K ADACHI, H HIRATA, T SUZUKI, T TAKANO
    JAPANESE JOURNAL OF APPLIED PHYSICS PART 1-REGULAR PAPERS SHORT NOTES & REVIEW PAPERS 29 (Suppl. 29-1) 179 - 181 0021-4922 1990 [Refereed][Not invited]
     
    Excitation of a progressive wave in a straight and thin bar vibrating in the flexural mode can be utilized to construct a transport device such as a parts-feeder. A new method to excite the progressive wave is proposed herein which has been proved possible by simulation and experiment. Excitation of a progressive wave without utilizing the concept of impedance matching in a transmission line is done using two adjacent modes of flexural vibration.
  • Takehiro Takano, Hiroshi Hirata, Yoshiro Tomikawa
    IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control 37 (6) 558 - 565 0885-3010 1990 [Refereed][Not invited]
     
    The development of an ultrasonic motor using nonaxisymmetric vibration modes of a piezoelectric annular plate is described. A piezoelectric annular plate is analyzed to And its mode patterns, elliptic motions of displacement for the motor, distributions of the induced charge on the plate surface, and calculate electromechanical coupling factors. Then, on the basis of the analyzed results, motors using the annular plate have been built and their characteristics measured. © 1990, IEEE
  • Y TOMIKAWA, T TAKANO, H HIRATA, T OGASAWARA
    JAPANESE JOURNAL OF APPLIED PHYSICS PART 1-REGULAR PAPERS SHORT NOTES & REVIEW PAPERS 28 (suppl. 28-1) 161 - 163 0021-4922 1989 [Refereed][Not invited]
  • T TAKANO, Y TOMIKAWA, T OGASAWARA, H HIRATA
    JAPANESE JOURNAL OF APPLIED PHYSICS PART 1-REGULAR PAPERS SHORT NOTES & REVIEW PAPERS 28 (Suppl. 28-2) 202 - 205 0021-4922 1989 [Refereed][Not invited]

MISC

  • Electron paramagnetic resonance imaging and its biomedical applications
    Hiroshi Hirata  Bunsei  2019-  (12)  538  -544  2019/12  [Refereed][Invited]
  • Hiroshi Hirata  Bunkou Kenkyu  64-  (6)  573  -581  2015/12  [Refereed][Invited]
  • HIRATA Hiroshi  Folia Pharmacologica Japonica  140-  (4)  146  -150  2012  [Not refereed][Not invited]
     
    不対電子のエネルギー吸収を特異的に検出することができる電子常磁性共鳴（EPR）分光（電子スピン共鳴，ESRとも呼ばれる）は，フリーラジカル分子の研究において強力な計測手法となっている．EPR分光は，核磁気共鳴（NMR）とは兄弟関係にある磁気共鳴分光法であり，NMRイメージング（核スピンの可視化）同様に電子スピンの分布を可視化するイメージング法も30年来研究されてきた．近年になり，短時間で電子スピンの3次元空間分布を計測する技術が開発された．本稿では，高速EPRイメージングを用いて，生体内の酸化還元状態を可視化する，レドックス計測について紹介する．電子スピンの緩和時間は，ナノ秒からマイクロ秒のオーダーであり，NMRと同様のパルス法による計測は容易ではない．特に，生体を対象とする低周波・低磁場のEPR計測では，連続波を用いた計測が主に用いられている．高速に磁場を掃引するEPRイメージング装置の開発により，生体内で寿命が短いフリーラジカル種の検出，測定が可能になった．また，ニトロキシルラジカルの寿命は溶液または生体中の還元作用の強さを反映するため，ニトロキシルラジカルの信号の消失速度を測定することにより，酸化還元状態（レドックス）をマッピングする方法を説明する．通常，3次元画像計測は長い計測時間が必要とされ，生体内でのレドックスマップを得ることは容易ではなかったが，計測技術の進歩に...
  • H Hirata, ZW Luo  MAGNETIC RESONANCE IN MEDICINE  49-  (5)  977  -977  2003/05  [Not refereed][Not invited]

Books etc

Presentations

  • R. Nakaoka, K. Kato, K. Yamamoto, H. Yasui, S. Matsumoto, I. A. Kirilyuk, V. V. Khramtsov, O. Inanami, H. Hirata
    23rd International Society of Magnetic Resonance Conference (ISMAR 2023)  2023/08
  • Technological advances in resonators for in vivo and clinical EPR  [Invited]
    H. Hirata
    EPR 2023: International Conference on EPR Spectroscopy and Imaging of Biological Systems  2023/05
  • H. Hirata
    Asia-Pacific EPR/ESR Symposium 2022 (APES 2022)  2022/11
  • R. Nakaoka, K. Kato, K. Yamamoto, H. Yasui, S. Matsumoto, I. A. Kirilyuk, V. V. Khramtsov, O. Inanami, H. Hirata
    XIIth International Workshop on EPR in Biology and Medicine  2022/10
  • Hiroshi Hirata
    Modern Development of Magnetic Resonance (MDMR) 2021  2021/11
  • A. Taguchi, S. DeVience, B. Driesschaert, V. V. Khramtsov, H. Hirata
    22nd International Society of Magnetic Resonance Conference (ISMAR 2021)  2021/08
  • Overview of Electron Paramagnetic Resonance-Based Human Tooth Dosimetry  [Invited]
    H. Hirata, I. Yamaguchi, M. Miyake
    4th Conference on Nuclear Analytical Techniques (NAT2020) Jointed with 6th Symposium on Radiation in Medicine, Space, and Power (RMSP-VI),  2020/11
  • Recent Progress in 3D Extracellular pH Mapping of Tumors Using EPR  [Invited]
    Hiroshi Hirata
    International Conference “Magnetic Resonance–Current Status and Future perspectives” (EPR-75)  2019/09
  • In vivo three-dimensional extracellular pH mapping of tumors using EPR  [Invited]
    Hiroshi Hirata
    Joint Conference of 21st International Society for Magnetic Resonance (ISMAR) and 15th European Magnetic Resonance Congress (EUROMAR)  2019/07
  • In vivo extracellular pH mapping of tumors using EPR imaging  [Invited]
    Hiroshi Hirata
    Joint Conference of Asia-Pacific EPR/ESR Symposium 2018 and 3rd International EPR (ESR) Society Symposium (APES-IES 2018)  2018/09
  • In vivo extracellular pH mapping of tumors using electron paramagnetic resonance  [Invited]
    Hiroshi Hirata
    46th Annual Meeting of International Society on Oxygen Transport to Tissue (ISOTT 2018)  2018/07
  • Three-dimensional oxygen mapping using a pair of isotopic nitroxyl radicals and CW-EPR-based single-point imaging  [Invited]
    Hiroshi Hirata
    EPR 2017: International Conference on Electron Paramagnetic Resonance Spectroscopy and Imaging of Biological Systems  2017/07
  • CW-EPR-based oxygen mapping technique using a pair of isotopic nitroxyl radicals  [Invited]
    Hiroshi Hirata
    Xth International Workshop on EPR in Biology and Medicine  2016/10
  • Development of a CW-EPR-based oxygen-mapping technique using a pair of isotopic nitroxyl radicals  [Invited]
    Hiroshi Hirata
    Asia-Pacific EPR/ESR Symposium 2016  2016/08
  • In vivo tumor extracellular pH monitoring using EPR spectroscopy  [Invited]
    Hiroshi Hirata
    Magnetic Resonance: Fundamental research and pioneering applications (MR-70)  2014/06
  • MR imaging of oxidative stress: Electron paramagnetic resonance imaging –Challenges to functional imaging–  [Invited]
    Hiroshi Hirata
    COST Action BM1203 EU-ROS Working Group Meeting  2013/05

Association Memberships

  • THE INSTITUTE OF ELECTRONICS, INFORMATION AND COMMUNICATION ENGINEERS.   International EPR (ESR) Society   International Society for Magnetic Resonance in Medicine   THE SOCIETY OF ELECTRON SPIN SCIENCE AND TECHNOLOGY   International Society of Magnetic Resonance (ISMAR)   International Society on Oxygen Transport to Tissue (ISOTT)   

Research Projects

  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
    Date (from‐to) : 2022/04 -2026/03 
    Author : 平田 拓, 安井博宣
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2022/04 -2025/03 
    Author : 安井 博宣, 稲波 修, 平田 拓, 久下 裕司
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2020/04 -2025/03 
    Author : 稲波 修, 平岡 和佳子, 安井 博宣, 平田 拓, 滝口 満喜, 岡松 優子
     
    本年度はインビトロの培養細胞の系の実験で、以下の四つの結果が明らかとなった。 1）グルタミン要求性の強いヒト肺がんA549細胞やH460細胞では、放射線照射により、これらの細胞でのグルタミンの取り込みの増大とグルタメートの増大、すなわちグルタミナーゼの活性化を起こす事を明らかにした。さらに、グルタミン代謝阻害剤添加あるいはグルタミン欠乏培地下で培養すると治療線量レベルの放射線照射によって多くの老化様細胞死とSASPの培養液中への分泌を増強させることが可能である事が明らかとなった。 2）グルタミノリシス阻害条件下で放射線による老化様細胞死の誘発機構には活性酸素種の生成量、グルタチオン量の変化DNA損傷の量、さらにはDNA損傷に伴う伴うp53やp21、p16の発現変化などの既知のメカニズムの関与は殆ど無く、未知の機構の関与が示唆されている。 3）更にグルタミノリシス阻害条件下で放射線誘発する老化様細胞死を起こす条件で、Bcl-XL阻害剤ABT-737によって、この増大した老化様細胞死の多くはアポトーシスに変換できること、いわゆるセノリシスを起こせることを明らかにした。 4）一方では、同じ肺がん由来細胞でも786-o細胞ではグルタミン代謝阻害が老化様細胞の増強を起こさず、A549やH460細胞と同様の現象は観察されず、全ての肺がん細胞に於いて同様の機構が働いていない事も明らかとなった。また、脂質代謝阻害剤は老化様細胞増強には関与しなかった。 以上の結果はグルタミン要求性の強い肺がん細胞を中心にその亜致死レベルのグルタミノリシス阻害条件下で治療線量レベルの放射線照射をすると、多量の老化様細胞死の増大が起こす事を示しており、さらに、アポトーシス抑制因子の阻害剤で効率よく老化様細胞死をアポトーシスに変換できることが明確になった。
  • 日本学術振興会：科学研究費助成事業 (挑戦的研究(開拓))
    Date (from‐to) : 2021/07 -2025/03 
    Author : 平田拓, 稲波修
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2018/04 -2023/03 
    Author : 三宅 実, 山口 一郎, 平田 拓, 大林 由美子
     
    ①EPR (Electron Paramagnetic Resonance 電子常磁性体共鳴）分光計を用いた生体内の歯の計測は、診断領域のX線に対して感度が高く、患者や医療従事者の放射線曝露歴を把握できる可能性がある。しかし、歯を試料として用いることから歯科での審美治療により象牙質内の有機物を化学処理により分解する際に、歯のエナメル質のハイドロキシアパタイトにも影響を与え、放射線照射により生成される安定な炭酸ラジカルの保持に影響を与える可能性がある。また、紫外線を照射するなどすることでEPR計測に影響を与える可能性がある。紫外線による信号形成：280nm以下の波長のUV-Cでは比較的高率にEPR信号が形成されるが、UVA (400－315nm)、UVB(315-280nm)でも、長時間照射によりL-band でも検出可能な信号について実験を行った。地球で緯度的な差異による直接的な太陽光の曝露量の違いについて文献的な考察も加え、実際紫外線の曝露を受ける可能性のある前歯で、L-bandEPR計測値に有意差を与える信号強度でないことを確認した。この結果はApplied Magnetic Resonanceにて発表を行った。(Nakai,Y.,et al.2021) ②改良EPR装置の評価：昨年と同様に制御用PCの制御プログラムの改良を実施し動作安定性の向上を図った。ソフトウエアーやPCメインプログラムを、共同研究機関であるダートマス大学に協力で更新を実施した。③解離性放射線には種々のエネルギーの異なる線源が存在する。そこでエネルギーの異なる線源（60COγ線、X線(60kV,250kv)，中性子線）を、抜去歯（智歯）に段階的に照射し、EPR測定を実施する計画であったが広島大学原爆放射線医学研究所においてガンマセル使用ができず、今年度に再度追加照射、分析を計画している。
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2019/04 -2022/03 
    Author : YASUI HIRONOBU
     
    In this study, (1) we searched for a point of action that can effectively induce ferrotosis with various candidate drugs, (2) we show evidence of the obtained mechanism of radiosensitizing action, and (3) therapeutic effect at the biological level. The ultimate goal was to develop an imaging method that could support this. Toward this goal, during this study, ferroptosis inducers were shown to increase radiosensitivity by reducing antioxidants in cancer cells, and intracellular iron metabolism in cancer cells by transferrin probes. Focusing on the mechanism, we succeeded in developing a method that makes it possible to predict the therapeutic effect of ferrotosis-induced cancer in advance.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    Date (from‐to) : 2019/04 -2022/03 
    Author : Hirata Hiroshi
     
    We aimed to develop quantitative imaging techniques for the partial pressure of oxygen and extracellular pH for malignant tumors. In this study, electron spin resonance (ESR) spectroscopy was applied to the three-dimensional mapping of the partial pressure of oxygen and pH in solution samples. Using a molecular probe that can concurrently detect the partial pressure of oxygen and pH, we showed the feasibility of concurrent mapping the partial pressure of oxygen and pH in solution samples.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
    Date (from‐to) : 2018/10 -2022/03 
    Author : Hirata Hiroshi
     
    We aimed to develop multiple imaging techniques for the partial pressure of oxygen, extracellular pH, and reduction-oxidation (redox) status using magnetic resonance techniques. This program was conducted internationally with Prof. Valery V. Khramtsov at West Virginia University, WV, USA. In Japan, each imaging technique for electron spins and nuclear spins was developed to visualize malignant tumors’ physiological parameters. The developed imaging techniques were tested and demonstrated in their feasibility studies.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2018/06 -2021/03 
    Author : Inanami Osamu
     
    The aim of this study is to develop new metabolic analysis methods and imaging techniques for cancer metabolism and its novel radiation response, which will lead to the development of future therapies. In this study, we found cancer cells with dependence on mitochondrial electron transport chain (ETC), glutamine metabolism, and lipid metabolism, confirming the diversity of cancer cell metabolism. As a new cancer-specific metabolic evaluation system, ESR oximetry was established to evaluate mitochondrial ETC activity at the cellular level, and radiation response was clarified. In addition, we established a rapid ESR imaging method for tissue reduction state reflecting glutathione metabolism and an in vivo imaging method using pH-sensitive probes for extracellular pH changes reflecting glucose metabolism in an international collaboration.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2017/04 -2020/03 
    Author : Inanami Osamu
     
    In this study, in order to clarify a novel metabolic target of radiotherapy for cancer, we established a mitochondrial-dependent metabolic assay for cancer metabolism using electron spin resonance (ESR) with a new oxygen probe. Using this method, it was clarified that ATP production by not only glucose metabolism but also electron transport system (ETC) was increased by irradiation as a survival strategy of solid tumors. Furthermore, we have found that this radiation-induced energy response can induce strong radiosensitization by glutaminolysis involved in the TCA cycle and mitochondrial inhibitory drugs. In particular, it was demonstrated that glutamine synthase inhibitors and ETC inhibitors can cause a strong radiosensitizing effect.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2016/04 -2018/03 
    Author : Hirata Hiroshi, MATSUMOTO Shingo
     
    The purpose of this study was to clarify the outcomes of the model experiments of oxygen partial pressure-guided radiation therapy. A miniature multi-leaf collimator (MLC) was developed for the model experiments using tumor-bearing mice. This miniature MLC was planned to control the intensity and the distribution of X-ray irradiation to tumor model mice. Also, the computation method for obtaining the collimator opening from the three-dimensional data of oxygen partial pressure in mouse tumors was developed and implemented. Moreover, tumor-growth curves were obtained for non-treated and uniform X-ray irradiated mice. These data will be the control data of tumor growth. For preparing tumor-bearing mice, murine squamous cell carcinoma (SCC VII) cells were subcutaneously implanted in mouse hind legs.
  • Japan Society for the Promotion of Science：科学研究費補助金 (基盤研究(A))
    Date (from‐to) : 2014/04 -2018/03 
    Author : Hiroshi Hirata
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2014/04 -2017/03 
    Author : Miyake Minoru, HIRATA Hiroshi
     
    We conducted experiments regarding to the equipment for practical usage of EPR portable spectrometer, and also evaluated measurements with volunteers, and analyzed the detection limit of this device. 34 volunteers in Fukushima prefecture participated the practical measurements. As the results, ratio of EPR signal intensity versus standard signal intensity with PDT was 0.087±0.051. The intensity of the signals that were obtained were not significantly above those seen in volunteers. The detection limits for radiation exposures are calculated. The sensitivities are 77.0%, 99.9% and specificities are 78.0%, 99.8% with 1Gy, 2Gy exposures respectively under ex-vivo condition. We demonstrated that it is feasible to transport the dosimeter to the site and make valid measurements as a triage purposes with high dose (>2-4Gy).
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2014/04 -2016/03 
    Author : AKABA Hideo, HIRATA Hiroshi
     
    The purpose of the present work was developing a compact low field magnetic resonance imaging (MRI) system running on a same magnetic circuit used for a 750 MHz CW electron paramagnetic resonance imaging (EPRI) system. A current source to drive a high inductance gradient coil of ~ a few mH with the response time of ~ 50 us was developed. We demonstrated that nuclear magnetic resonance (NMR) signal acquisition was possible without the interference of an EPR probe by setting a NMR probe located outside the EPR probe. Low field EPR/NMR co-imaging of a test sample was succeeded using the same magnetic circuit without moving the sample.
  • キラリティー磁気共鳴分子イメージング
    内閣府：最先端・次世代研究開発支援プログラム
    Date (from‐to) : 2011/02 -2014/03 
    Author : 平田 拓
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2011 -2013 
    Author : MIYAKE Minoru, MATSUI Yoshiro, IWASAKI Akinori, YAMAGUCHI Ichiro, KUNUGIDA Naoki, HIRATA Hiroshi
     
    The measuring device for the radiation exposure dose in human teeth enamel using L-band in vivo Electron Paramagnetic Resonace (EPR) was newly developed. The loop-resonator designed for human upper central incisor were specially made, the S / N ratio with this new resonator, it was improved of 2.7 times that of the conventional apparatus. 95.0% sensitivity and 90.0% specificity in 1Gy irradiated specimen as the detection sensitivity were achieved. Further, the structure of the measuring setting was modified which can be measured in a sitting position, it can be reduced the measurement noise due to moving of the subjects. The measurement from 35 volunteers was performed, and the data of the background EPR signals in existing in enamel were obtained.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2010 -2012 
    Author : FUJII Hirotada, HIRATA Hiroshi, ITOH Kouichi, NAGASAKI Yukio
     
    Electron paramagnetic resonance (EPR) imaging using nitroxides is a powerful, noninvasive method for visualizing the redox status modulated by oxidative stress in vivo. However, to date, it has not always been possible to obtain three-dimensional (3D) images with a continuous wave (CW)-EPR imager in small rodents while using nitroxides. Due to improvements in imagers that enable rapid data-acquisition, the feasibility of 3D EPR imaging with good quality in mice was tested with nitroxides of different lipophilicities. The improved CW-EPR imager may be a useful noninvasive tool for assessing changes in the redox status of living subjects under oxidative stress.
  • 高速電子常磁性共鳴イメージング法の開発
    科学技術振興機構：先端計測分析技術・機器開発事業
    Date (from‐to) : 2008/10 -2011/03 
    Author : 平田 拓
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2009 -2011 
    Author : NAKAGAWA Kouichi, HIRATA Hitoshi
     
    Electron spin resonance (ESR) in conjunction with a slow-tumbling simulation was utilized for defining various stratum corneum (SC) lipid structures. The α-terpineol enhanced about three times permeation of the single chain 5-DSA than that of the control. We also studied psoriasis vulgaris SC (pv-SC). We found that the pv-SC is less ordering of the structure than that of the control SC, indicating abnormal architecture of the pv-sc. A 9 GHz ESR imager that is capable of the imaging surface area of thin materials has been built. More importantly, the TE111 cavity does not require inserting the sample into the cavity and placing samples into ESR tubes. In addition, the components of the 9 GHz imager and imaging data processing are developed.
  • 文部科学省：科学研究費補助金 (基盤研究(B))
    Date (from‐to) : 2009 -2011 
    Author : 平田 拓
     
    平成22年度は、計画通り電子スピン共鳴(ESR)スペクトルからpHおよび酸素分圧を可視化する実験を行った。pH感受性および酸素感受性のニトロキシルラジカル分子二種類を使用し、試験管による模擬試料を用いてpHおよび酸素分圧を可視化した。実験に先立ち取得したpHおよび酸素分圧の校正曲線を用いて、スペクトル空間ESRイメージング法により得られたスペクトル情報をpHおよび酸素感受性に変換した。実験の結果、pHの分解能0.1程度、酸素分圧の分解能5mmHgが得られた。しかしながら、酸素分圧の測定値の精度が十分ではないことが明らかとなったため、データ処理の方法等を再検討した。その結果、実験において次の課題が明らかとなり、データ処理により外乱の影響を取り除く補正を行った。すなわち、(1)マグネット温度のドリフトによる中心磁場の変化、(2)磁場掃引幅の誤差、(3)磁場掃引幅の変化に起因する中心磁場の変化、(4)水溶液試料中のうず電流によるスペクトルの歪み、が最終的に得られるスペクトル情報に対して外乱となることが分かった。pHの可視化については、ニトロキシルラジカルの超微細構造による3つのエネルギー吸収スペクトルの内、低磁場側のスペクトルと中間のスペクトルの間隔を測定することによりpHを測定した。それぞれのスペクトルを単独で測定したデータから二つのエネルギー吸収の間隔を求める方法においては、上...
  • 文部科学省：科学研究費補助金 (萌芽研究, 挑戦的萌芽研究)
    Date (from‐to) : 2008 -2010 
    Author : 平田 拓
     
    平成22年度は、電子常磁性共鳴(EPR)イメージング法の解像度改善を目指した。大学内において動物実験の計画が承認されるまでの時間を用いて、模擬試料による解像度改善の実験を行った。また、三次元画像再構成時に自動的に解像度と信号対雑音比を最適化するプログラムを開発した。加えて、分子イメージングの一種であるEPRイメージングの画像を動物の解剖学的画像に重ね合わせるために、EPR/NMRコレジストレーション・イメージングに利用するソフトウエアを開発した。その結果、三次元画像再構成の最適化と、EPRおよびプロトンNMR画像の半自動重ね合せが実現した。画像の重ね合せには、キャピラリー管による位置合わせのマーカーを用いた。EPR画像の解像度改善のためには、正確に点広がり関数を推定する必要があるが、実験に使用したデータセットでは、繰り返しデコンボリューションによる一定の解像度改善は見られたが、目標とする5倍の解像度改善には至らなかった。一方、EPR/NMRコレジストレーション・イメージングは、実用的に使用可能なソフトウエアをMatlab上に構成することができたため、今後の実験に供することが可能である。特に、画像の重ね合せを半自動で行う点は、訓練されていないオペレータが操作することを容易にするため、実用的な観点からも前進したといえる。EPRイメージングの解像度改善には、いまだ考慮されていない要...
  • Ministry of Education, Culture, Sports, Science and Technology：Grants-in-Aid for Scientific Research(基盤研究(B))
    Date (from‐to) : 2007 -2009 
    Author : Hirotada FUJII, 黄田 育宏, Kouichi ITOH, Hiroshi HIRATA, Ikuhiro KIDA
     
    Electron Spin Resonance Imaging is a versatile imaging method of visualizing free radicals that are so called reactive oxygen species generated in biological systems. In this project, we have developed the ESR・MRI combined system which is capable of visualizing both ESR image and MR image. With this newly developed system, we plan to do the diagnostic study to screen the metabolic syndrome.
  • Ministry of Education, Culture, Sports, Science and Technology：Grants-in-Aid for Scientific Research(基盤研究(B))
    Date (from‐to) : 2006 -2008 
    Author : Hiroshi HIRATA, 藤井 博匡, 伊藤 康一, Hirotada FUJII, Kouichi ITOH, Hideo AKABA
     
    実験小動物として用いられるマウスを対象として、電子スピン共鳴(ESR)イメージング法の研究を行った。マウス頭部を計測する650MHzのマイクロ波共振器を作製し、ESR分光装置を改良した。また、スライス選択ESR画像を取得するイメージング法を開発した。さらに、データ取得を高速化することにより、マウス頭部において、半減時が短い六員環のナイトロキシルラジカルを可視化することに成功した。
  • Ministry of Education, Culture, Sports, Science and Technology：Grants-in-Aid for Scientific Research(基盤研究(B))
    Date (from‐to) : 2005 -2006 
    Author : Hirotada FUJII, 伊藤 康一, 平田 拓
     
    For molecular imaging studies in the fields of biological and biomedical sciences, electron spin resonance (ESR)/magnetic resonance imaging (MRI) dual-imaging system was developed. This system, ESR/MRI dual-imaging system, was constructed using the permanent magnet (Nb-Fe-B material). The ESR and MRI part of the dual-imaging system was operated at 1.2 GHz (0.04 Tesla) and 22 MHz (0.5 Tesla), respectively. In order to obtain higher spatial resolution for ESR imaging of relatively-large line width, 2 mTesla/cm magnetic field gradient was used. We also developed ESR and MRI resonator for co-re...
  • Ministry of Education, Culture, Sports, Science and Technology：Grants-in-Aid for Scientific Research(基盤研究(C))
    Date (from‐to) : 2004 -2005 
    Author : Hiroshi HIRATA, 藤井 博匡
     
    The major goal of this project was to develop engineering technologies regarding EPR spectroscopy with small animals in brain/neuroscience studies. Major accomplishments in this project were as follows :(1) Developed a sensitive EPR resonator for a subject animal. We could detect EPR spectra from the head of a mouse (25 g body wt.). Spin probes we used were Oxo-63.(2) Developed a cw-EPR imaging system. We developed a systematic approach to automatically select a cutoff frequency of a window function for use in image reconstruction.(3) Improved stability of a cw-EPR spectrometer. Our spectro...
  • Ministry of Education, Culture, Sports, Science and Technology：Grants-in-Aid for Scientific Research(基盤研究(A))
    Date (from‐to) : 2002 -2004 
    Author : Hideo UTSUMI, 輿石 一郎, 門司 晃, 井口 登與志, 安井 久喬, 竹下 彰, 古賀 登, 平田 拓
     
    It is reported that reactive oxygen species (ROS) are involved in the initiation and/or progression of circulatory diseases. In order to analyze is vivo ROS generation non-invasively, we developed the In vivo spin electron resonance (ESP)/spin probe technique using a signal decay rate of a nitroxyl radical as an index of ROS generation and clarified the association of ROS generation with several diseases in experimental animals.In this study, we performed non-invasive measurement of ROS generation in the models of diabetes and obese as representative circulatory diseases. When carbamoyl-PRO...
  • 文部科学省：科学研究費補助金(若手研究(B))
    Date (from‐to) : 2002 -2003 
    Author : 平田 拓
     
    生命科学研究に用いることを目的、マイクロ波周波数1.1GHzの電子スピン共鳴分光装置の開発を行った。動物実験における深刻な問題は感度の不足と、動物の動きによる擾乱である。本研究では、電子スピン共鳴スペクトロスコピーの高感度化を目指し、以下の研究を行った。(1)自動マッチング制御と自動チューニング制御の相互干渉を無くすための非干渉化法を開発した。この技術は、2入力2出力のフィードバック制御系において、伝達関数行列を対角化することにより非干渉化を実現する物である。実際の回路実装では、反転増幅器の利得を調整し、二つのフィードバックループ間の干渉を補償した。マウスを用いた実験により、相互干渉がない場合に、より安定に計測がおこなえ、実験動物の動き(呼吸や心拍)に起因する雑音が抑圧できる事を実証した。その結果、信号対雑音比を改善する事ができ、高感度化に寄与することが示された。(2)連続波電子スピン共鳴スペクトロスピーでは、磁界変調と位相検波を用いて高感度計測を行っている。磁界変調により、制御回路の電位が影響を受け、ベースラインが変動するといった問題がある。そのため、磁界変調の影響が少ない、光デバイスを用いたマイクロ波共振器の共振周波数チューニング法を開発した。光ファイバーを介して、離れた場所にあるLEDの光強度により、共振器に結合されたループに接続された光導電セルのインピーダンスを制御し...
  • Ministry of Education, Culture, Sports, Science and Technology：Grants-in-Aid for Scientific Research(基盤研究(A))
    Date (from‐to) : 2002 -2003 
    Author : Mitsuhiro ONO, 平田 拓, 下山 雄平, 赤塚 孝雄, 鈴木 洋介
     
    The goal of this study was the development of an EPR imager for the cerebral function analysis. A key problem of the image reconstruction in EPR imaging was tacked. A systematic selection of filtering function to obtain the optimum image resolution was investigated. The direct Fourier transformation reconstitution(DFTR)method is suitable to understand the effect of the filter characteristics. We paid attention to the signal-to-noise ratio of the spectra to determine the cut-off frequency in the filter function. Although the usefulness of the image reconstruction by this technique should be ...
  • 文部科学省：科学研究費補助金(萌芽研究)
    Date (from‐to) : 2002 -2003 
    Author : 内海 英雄, 山田 健一, 輿石 一郎, 平田 拓
     
    フリーラジカルの生成と種々の疾患の成因・進展との関連性を視覚的に解明する上で、プロトン・電子スピン二重共鳴画像解析によって臓器・組織位置とフリーラジカル分布を重畳することは非常に重要であると考えられるが、未だ試みられていなかった。そこで今回、二重共鳴画像解析システムを開発するに当たり、ESRI用のサドル型磁場変調コイルの内側にMRIラジオパルス波のソレノイド型受信コイル、さらにその内側にESRマイクロ波のパラレルコイル型共振コイルを備えた共振デバイスを製作した。本デバイスのパラレルコイル内における磁場均一性に関して、磁束密度の標準偏差は軸長方向、動径方向ともに平均値の5%程度であった。また、最も内側のパラレルコイルを外して生理食塩水のMR画像を取得したところ、設置した状態と比べて画像の形状、信号雑音比ともにほぼ同じであった。次に、4本の試験管に各々濃度の異なるニトロキシルラジカルを封入した擬似試料を作成し、本デバイスを用いてESRI計測したところ、その画像輝度はラジカル濃度に比例して増加しており、このESR画像における各中心間距離はMR画像及び実際の試料における距離と一致した。以上より、MRI、ESRIともに計測可能な共振デバイスの開発に成功し、本デバイスを用いてフリーラジカル分布情報と解剖学的情報との重畳が可能であることを示した。本システムを動物計測に応用し、画像化システム...
  • Ministry of Education, Culture, Sports, Science and Technology：Grants-in-Aid for Scientific Research(基盤研究(B))
    Date (from‐to) : 2000 -2002 
    Author : Mitsuhiro ONO, 山本 哲也, 平田 拓, 下山 雄平, 鈴木 洋介
     
    A frequency modulation (FM) method was developed to measure electron paramagnetic resonance (EPR) absorption. The first-derivative spectrum of 1,1-diphenyl-2-picrylhydrazyl (DPPH) powder was measured with this FM method. Frequency modulation of up to 1.6 MHz (peak-to-peak) was achieved at a microwave carrier frequency of 1.1 GHz. By using a tunable microwave resonator and automatic control systems, we achieved a practical continuous-wave (CW) EPR spectrometer that incorporates the FM method. In the present experiments, the EPR signal intensity was proportional to the magnitude of frequency ...
  • 文部科学省：科学研究費補助金(奨励研究(A))
    Date (from‐to) : 2000 -2001 
    Author : 平田 拓
     
    本年度は二つのサブ・プロジェクトを実施した。【サブプロジェクト3】自動マッチング制御回路の開発:高周波検波回路と作動増幅器から構成される自動マッチング制御回路を開発した。共振器の入力インピーダンスが50オームよりも大きい場合には、反射波は入射波と同じ位相を有するが、インピーダンスが50オームより小さい場合には入射波と180度異なる位相を持つ反射波が観測される。この反射波の位相を検出する事によりインピーダンス整合の状態を検出する。インピーダンス制御のための帰還制御回路の応答は、実験動物の動きよりも速く、ESR信号を得るための磁界変調周波数よりも低くなければいけない。マウスの心拍数は最高で毎分600回程度(10Hz相当)、磁界変調周波数は通常100kHzである。帰還制御のカットオフ周波数は1kHz程度で十分動物の動きによる擾乱を補償できると考えられる。昨年度開発したサーフェイスコイルと帰還制御システムを現有する1.1GHzスペクトロメーターにおいてテストを行なった。スピーカーに取り付けたアームの振動により実験動物の擾乱を模擬し、インピーダンス不整合が補償されることを実験的に確認した。この実験では、信号対雑音比が約2倍に改善された。【サブプロジェクト4】自動マッチング制御回路の安定性解析:開発した自動マッチング制御システムのブロックダイアグラムと数学的モデルを定式化した。モデルは、...
  • 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 : Mitsuhiro ONO, 湯浅 哲也, 山本 哲也, 下山 雄平, 赤塚 孝雄, 平田 拓
     
    In order to develop a 0.2 Testar PEDRI (Proton Electron Double Resonance Imaging), microwave applicators have been studied.The frequencies are 8 MHz for NMR and 5.6 GHz for EPR.A NMR RF applicator is a solenoid or a birdcage coil. An EPR microwave applicator must be able to withstand 5 W CW and to generate homogeneous magnetic fields of about 10 mm X 20 mm. In this study, a basic applicator consists of a TE_<10> rectangular waveguide to obtain microwave magnetic fields mentioned above. We measured distribution of magnetic fields of (1) a waveguide without a flange, (2) a waveguide with a fl...
  • 文部科学省：科学研究費補助金(奨励研究(A))
    Date (from‐to) : 1998 -1999 
    Author : 平田 拓
     
    共振周波数と整合状態を電圧により制御可能なサーフェイスコイル型共振器を試作した(共振周波数は1.2GHz)。この共振器は、印加する電圧により約10MHzの範囲で共振周波数を制御することが可能である。通常のキャビティー共振器を使用した自動周波数制御では、搬送波周波数の0.1%程度の周波数調整しかできない。今回試作した共振器を使用すれば、搬送波周波数の約1%の範囲で共振周波数を制御することが可能である。共振周波数を電子的に制御するために、自動周波数制御回路を開発した。周波数の差を直流出力に変換する位相検波回路と可変容量ダイオードに印可する逆バイアスを制御する回路を製作した。実験的に共振器の共振周波数を擾乱し、それを安定化する性能試験を実施した。その結果、共振周波数可変範囲と同程度の周波数擾乱に対しては極めて安定的に自動周波数制御が行えることを確認した。実際のESRスペクトロメーターに共振器と制御システムを組み込み、従来のESRスペクトロメーターとの性能比較を行った。その結果、今回試作した電子同調サーフェイスコイル型共振器と自動周波数制御回路を組み合わせたシステムにおいて、従来システムに比べ信号対雑音比が約二倍改善された。今回の試作において、帰還制御回路の発振が観測された。制御性能を低下させず、発振を除去し制御回路の安定性を向上させることが今後の課題である。
  • Ministry of Education, Culture, Sports, Science and Technology：Grants-in-Aid for Scientific Research(国際学術研究)
    Date (from‐to) : 1997 -1998 
    Author : Shigetoshi OHSHIMA, Chaloupka He, 楠 正暢, 平田 拓, 沢谷 邦男, 小野 光弘, Heintz Chalo
     
    We could obtain some new results of HTS filters and antennas by the joint study between Yamagata University and Wuppertal University, The results are as follows.(1) 1997Dr.Kusunoki visited the laboratory of Prof.Chaloupka in Wuppertal University and researched about design of superconducting filters. Our group had investigated the formation process of YBCO thin films and measured its superconducting properties. We also designed superconducting antenna and filters.Prof.Chaloupka's group investigated superconducting filters.(2) 1998Prof.Chaloupka stayed our laboratory for about three weeks an...
  • Ministry of Education, Culture, Sports, Science and Technology：Grants-in-Aid for Scientific Research(基盤研究(C))
    Date (from‐to) : 1997 -1998 
    Author : Hisashi USUKI, 平田 拓, 小野 光弘, 合田 文則, 前田 肇
     
    In vivo ESR oximetry is being used to obtain measurements of partial oxygen tension in tissue of biological systems with an ease and accuracy that has not been possible previous other methods. It appears quite possible that the technique will become a widely used clinical tools. The developments of ESR oximetry needs following three parts of investigations to obtain ESR spectra in moving animals and human subjects.1) Improvements of ESR spectrometer. We investigated a flexible surface-coil type resonator for this purpuse.2) The discovery and developments of oxygen sensitive paramagnetic mat...
  • Ministry of Education, Culture, Sports, Science and Technology：Grants-in-Aid for Scientific Research(基盤研究(B))
    Date (from‐to) : 1996 -1998 
    Author : Mitsuhiro ONO, 塙 政利, 平田 拓, 下山 雄平
     
    The study of the behavior of free radicals in a living body has recently become very important in pathology, physiology and pharmacology, We have developed a 350MHz pulsed EPR(Electron paramagnetic resonance) spectrometer especially used for in situ measurement of a rat's whole body, and obtained the following results.(1) Optimum pulse width and quality factor Q of the resonator are 10-68ns and 10-60, respectively, for the relaxation time constant T_2=10-100ns of bio-radicals, and 68-158ns and 60-280, respectively, for T_2=100-800ns of radicals in solid materials.(2) Using this spectrometer...
  • Ministry of Education, Culture, Sports, Science and Technology：Grants-in-Aid for Scientific Research(一般研究(B), 基盤研究(B))
    Date (from‐to) : 1995 -1997 
    Author : Shigetoshi OHSHIMA, 神戸 士郎, 平田 拓, 楠 正暢
     
    We have investigated the super-gain superconducting antenna, design, fabrication and characterization. These experimental results are as follows ;(1) Establishment of the design method of patch antenna operated at microwave region.We designed the patch antenna with a resonance frequency of 5 GHz. We could obtain the Cu patch antenna with input impedance of approximately 50 ohms and the resonance frequency of 50 ohms.(2) Fabrication and characterization of superconducting patch antenna.We fabricated the superconducting patch antenna using YBCO thin films. The input impedance of these antenna...
  • 文部科学省：科学研究費補助金(奨励研究(A))
    Date (from‐to) : 1994 -1994 
    Author : 平田 拓
     
    1.電子スピン共鳴計測用-フェイスコイル型共振器の共振尖鋭度と充填率(試料内にある磁気エネルギーと共振器の蓄えるエネルギーの比)の評価を可能にするためにそれらの定式化を行った。その際、生体試料内で生じる電磁波の損失を表す等価的な抵抗の値を求めることを可能にした。2.1でおこなった定式化に基づいて数値計算を行えるようにし、電子スピン共鳴計測の際に得られる信号強度の推定を可能にした。3.数値計算と定式化の妥当性を検証するために、計算モデルと同様の共振器を試作し、実際の電子スピン共鳴計測を行った。その結果、実験結果と数値計算の結果が一致することを確認した。4.信号強度の評価法が妥当であることが確認できたので、その評価法を用いたサーフェイスコイル型共振器の設計指針を明らかにした。その結果、試料の寸法と媒質の物理定数が与えられたとき、サーフェイスコイル型共振器の全長が短いものほど大きな信号が得られること、並びに信号強度が最大となるようなサーフェイスコイルの寸法が存在することが明らかになった。この研究により、当初の予定通り信号強度を最大とするようにサーフェイスコイル型共振器を設計することが可能になった。

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