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Development of a method to monitor glycine dynamics in the brain using Chemical Exchange Saturation Transfer Magnetic Resonance Imaging (CEST-MRI)

Research Project

Project/Area Number 20K16774
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52040:Radiological sciences-related
Research InstitutionNiigata University of Health and Welfare

Principal Investigator

Ohno Ken  新潟医療福祉大学, 医療技術学部, 助教 (40826153)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsMRI / CEST / Glycine / サロゲートマーカー / 化学交換飽和移動法(CEST) / グリシン(Glycine) / アルツハイマー病(AD) / 磁気共鳴画像法(MRI) / 統合失調症(Schizophrenia) / 化学交換飽和移動法 / グリシン
Outline of Research at the Start

本研究は、統合失調症やアルツハイマー病における認知障害の一因とされる脳内グリシン動態の変化を、化学交換飽和移動MRI(CEST MRI)を用いて無侵襲にモニタリングする新たな手法を開発することを目的とする。高用量グリシン投与は、統合失調症の症状を改善することが報告されている。しかし、脳内グリシン動態の調節機構は不明な点が多く、症状改善におけるグリシンの作用機序の詳細は分かっていない。脳内グリシン濃度分布を無侵襲かつ経時的に測定する脳内グリシン動態モニタリング法を確立することにより、統合失調症を初めとした中枢神経疾患の個々の病態評価および薬剤治療法の最適化の実現が期待できる。

Outline of Final Research Achievements

We developed a non-invasive method to monitor changes in brain glycine dynamics (GlyCEST method) using chemical exchange saturation transfer MRI (CEST-MRI), which is thought to contribute to cognitive impairment in schizophrenia and Alzheimer's disease. The GlyCEST effect increased with increasing glycine concentration. In normal mice, the GlyCEST effect was greater in the thalamus than in the cortex. This result was in good agreement with biochemical measurements. In 5xFAD mice, a mouse model of Alzheimer's disease, we observed a decrease in glycine concentration in the cortex and thalamus of 5xFAD mice. The GlyCEST method allowed us to measure the glycine concentration distribution in the mouse brain.

Academic Significance and Societal Importance of the Research Achievements

本開発手法により、生体における脳内グリシン濃度分布を無侵襲かつ経時的に測定する事が可能となり、客観的なサロゲートマーカーが無い統合失調症を初めとした中枢神経疾患の個々の病態評価および薬剤治療法の最適化の実現が期待できる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (15 results)

All 2023 2022 2021 2020

All Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 8 results,  Open Access: 8 results) Presentation (7 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Association between somatosensory sensitivity and regional gray matter volume in healthy young volunteers: a voxel-based morphometry study2023

    • Author(s)
      Onishi H, Nagasaka K, Yokota H, Kojima S, Ohno K, Sakurai N, Kodama N, Sato D, Otsuru N.
    • Journal Title

      Cereb Cortex

      Volume: 33 Issue: 5 Pages: 2001-2010

    • DOI

      10.1093/cercor/bhac188

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cortical signature related to psychometric properties of pain vigilance in healthy individuals: A voxel-based morphometric study2022

    • Author(s)
      Nagasaka Kazuaki、Otsuru Naofumi、Sato Rui、Watanabe Hiraku、Sakurai Noriko、Ohno Ken、Kodama Naoki、Onishi Hideaki
    • Journal Title

      Neuroscience Letters

      Volume: 772 Pages: 136445-136445

    • DOI

      10.1016/j.neulet.2022.136445

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] GlyCEST: Magnetic Resonance Imaging of Glycine - Distribution in the Normal Murine Brain and Alterations in 5xFAD Mice2021

    • Author(s)
      Ken Ohno,Masaki Ohkubo, Bingwen Zheng, Masaki Watanabe, Tsuyoshi Matsuda, Ingrid L. Kwee, Hironaka Igarashi
    • Journal Title

      Contrast Media & Molecular Imaging

      Volume: eCollection Pages: 8988762-8988762

    • DOI

      10.1155/2021/8988762

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Induction of Relaxation by Autonomous Sensory Meridian Response2021

    • Author(s)
      Noriko Sakurai, Ken Ohno, Satoshi Kasai, Kazuaki Nagasaka, Hideaki Onishi and Naoki Kodama
    • Journal Title

      Front. Behav. Neurosci.

      Volume: 15 Pages: 761621-761621

    • DOI

      10.3389/fnbeh.2021.761621

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gray Matter Volume Variability in Young Healthy Adults: Influence of Gender Difference and Brain-Derived Neurotrophic Factor Genotype2021

    • Author(s)
      Watanabe Hiraku、Kojima Sho、Nagasaka Kazuaki、Ohno Ken、Sakurai Noriko、Kodama Naoki、Otsuru Naofumi、Onishi Hideaki
    • Journal Title

      Cerebral Cortex

      Volume: bhab370 Issue: 12 Pages: 1-9

    • DOI

      10.1093/cercor/bhab370

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Contribution of the brain-derived neurotrophic factor and neurometabolites to the motor performance2021

    • Author(s)
      Sasaki Ryoki、Watanabe Hiraku、Miyaguchi Shota、Otsuru Naofumi、Ohno Ken、Sakurai Noriko、Kodama Naoki、Onishi Hideaki
    • Journal Title

      Behavioural Brain Research

      Volume: 412 Pages: 113433-113433

    • DOI

      10.1016/j.bbr.2021.113433

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Influence of Brain-Derived Neurotrophic Factor Genotype on Short-Latency Afferent Inhibition and Motor Cortex Metabolites2021

    • Author(s)
      Sasaki Ryoki、Otsuru Naofumi、Miyaguchi Shota、Kojima Sho、Watanabe Hiraku、Ohno Ken、Sakurai Noriko、Kodama Naoki、Sato Daisuke、Onishi Hideaki
    • Journal Title

      Brain Sciences

      Volume: 11 Issue: 3 Pages: 395-395

    • DOI

      10.3390/brainsci11030395

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Longitudinal GluCEST MRI Changes and Cerebral Blood Flow in 5xFAD Mice2020

    • Author(s)
      Igarashi Hironaka、Ueki Satoshi、Kitaura Hiroki、Kera Tae、Ohno Ken、Ohkubo Masaki、Terumitsu-Tsujita Mika、Kakita Akiyoshi、Kwee Ingrid L
    • Journal Title

      Contrast Media & Molecular Imaging

      Volume: 2020 Pages: 1-12

    • DOI

      10.1155/2020/8831936

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] グリシンCEST-MRイメージング法の開発とアルツハイマー病モデルマウスへの応用2022

    • Author(s)
      大野 健、計良 妙、大久保 真樹、渡辺 将樹、松田 豪、五十嵐 博中
    • Organizer
      第50回日本磁気共鳴医学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] GlyCEST: Magnetic Resonance Imaging of Glycine;Normal Distribution in the Brain and Alterations in 5xFAD Mice2022

    • Author(s)
      Ken Ohno, Tae Kera, Masaki Ohkubo, Masaki Watanabe, Tsuyoshi Matsuda, Hironaka Igarashi
    • Organizer
      The 11th NIPS-PRI-BRINU Joint Symposium
    • Related Report
      2021 Research-status Report
  • [Presentation] グリシン CEST-MR イメージング法の開発とアルツハイマー病モデルマウスへの応用2021

    • Author(s)
      大野 健、計良 妙、大久保 真樹、渡辺 将樹、松田 豪、五十嵐 博中
    • Organizer
      第64回日本脳循環代謝学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Brain metabolic alterations in anxiety disorder: 1H MRS study2021

    • Author(s)
      Ken Ohno, Noriko Sakurai, Naoki Kodama
    • Organizer
      The 23rd Asia-Australasia Conference of Radiological Technologists
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Elucidation of brain function in the relaxation effect of ASMR2021

    • Author(s)
      Noriko Sakurai, Ken Ohno, Satoshi Kasai, Naoki Kodama
    • Organizer
      The 23rd Asia-Australasia Conference of Radiological Technologists
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 1H-MRSを用いた不安症状を反映した脳代謝物質変化の検出2021

    • Author(s)
      大野健, 櫻井典子, 児玉直樹
    • Organizer
      第21回新潟医療福祉学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] 甘味と苦味の刺激に対する若者の脳機能の解明2021

    • Author(s)
      櫻井典子, 田中桃花, 大野健, 笠井聡, 児玉直樹
    • Organizer
      第21回新潟医療福祉学会学術集会
    • Related Report
      2021 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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