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Quantitative diagnosis of non-alcoholic steatohepatitis by ultrasound and elucidation of the mechanism of occurrence by ultratrace mass spectrometry

Research Project

Project/Area Number 18K12119
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 90130:Medical systems-related
Research InstitutionDoshisha University

Principal Investigator

WATANABE Yoshiaki  同志社大学, 研究開発推進機構, 嘱託研究員 (60148377)

Co-Investigator(Kenkyū-buntansha) 秋山 いわき  同志社大学, 生命医科学部, 教授 (80192912)
池川 雅哉  同志社大学, 生命医科学部, 教授 (60381943)
飯島 尋子  兵庫医科大学, 医学部, 教授 (80289066)
吉田 憲司  千葉大学, フロンティア医工学センター, 准教授 (10572985)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsNASH / 胆汁酸 / メダカ / 腸肝循環 / イメージング質量分析 / 超音波 / 消化器系 / 超微量質量分析 / イメージング / 多変量解析 / 非アルコール性脂肪肝炎 / 超音波診断 / 温度変化 / 遺伝因子 / 非アルコール性脂肪性肝炎(NASH) / 生体組織音速 / 鑑別診断 / るメタボローム解析
Outline of Final Research Achievements

A new system to elucidate the pathogenic basis of non-alcoholic hepatitis from the metabolic aspect in detail using a medaka model is developed. Specifically, the main bile acid of medaka, which is rare for fish, is C24 (TCA) and C27 (THCA), and succeeded in visualizing the distribution of these two bile acids within one medaka individual. In addition, the main component analysis revealed the site and metabolism of each digestive organ. Regarding the relationship It was suggested that these two bile acids are functioning. Using this research method, it will be possible to comprehensively analyze the enterohepatic circulation of bile including bile acids, which will lead to the elucidation of the molecular basis from fatty liver to carcinogenesis in the model of one individual medaka.

Academic Significance and Societal Importance of the Research Achievements

肝がん(HCC)への進行性が注目されている非アルコール性脂肪性肝(NASH)の発生機序の解明を胆汁酸の分布に着目し,メダカを対象種として実験的な検討を行った.メダカ成魚の一個体全体に対して12μm厚の全身凍結切片を作製し,消化器系における顕微質量計を用いてイメージング質量分析を行い,肝臓・胆嚢・上部~下部腸官領域で得られたスペクトラムの特徴を多変量解析や機械学習法を応用した画像統計ソフトを用いて特定した.この結果,胆汁酸の腸肝循環の解明がNASHの発生機序解明に繋がる可能性が示唆された.

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (25 results)

All 2020 2019 2018

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 5 results) Presentation (15 results) (of which Int'l Joint Research: 6 results) Book (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Attenuation imaging based on ultrasound technology for assessment of hepatic steatosis: A comparison with magnetic resonance imaging‐determined proton density fat fraction2020

    • Author(s)
      Tada Toshifumi、Kumada Takashi、Toyoda Hidenori、Nakamura Shinichiro、Shibata Yusuke、Yasuda Satoshi、Watanuki Yutaka、Tsujii Kazuyuki、Fukuda Naoya、Fujioka Mamoru、Takeshima Kenji、Niwa Fumihiko、Ogawa Sadanobu、Hashinokuchi Shinichi、Kataoka Saki、Ichikawa Hironori、Iijima Hiroko
    • Journal Title

      Hepatology Research

      Volume: 50 Issue: 12 Pages: 1319-1327

    • DOI

      10.1111/hepr.13563

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: new trends and role of ultrasonography2020

    • Author(s)
      Tada Toshifumi、Nishimura Takashi、Yoshida Masahiro、Iijima Hiroko
    • Journal Title

      Journal of Medical Ultrasonics

      Volume: 47 Issue: 4 Pages: 511-520

    • DOI

      10.1007/s10396-020-01058-y

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Usefulness of Attenuation Imaging with an Ultrasound Scanner for the Evaluation of Hepatic Steatosis.2019

    • Author(s)
      Tada T, Iijima H, Kobayashi N, Yoshida M, Nishimura T, Kumada T, Kondo R, Yano H, Kage M, Nakano C, Aoki T, Aizawa N, Ikeda N, Takashima T, Yuri Y, Ishii N, Hasegawa K, Takata R, Yoh K, Sakai Y, Nishikawa H, Iwata Y, Enomoto H, Hirota S, Fujimoto J, Nishiguchi S.
    • Journal Title

      Ultrasound Med Biol.

      Volume: 45(10) Issue: 10 Pages: 2679-2687

    • DOI

      10.1016/j.ultrasmedbio.2019.05.033

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Elevated levels of circulating ITIH4 are associated with hepatocellular carcinoma with nonalcoholic fatty liver disease: from pig model to human study.2019

    • Author(s)
      Nakamura N, Hatano E, Iguchi K, Sato M, Kawaguchi H, Ohtsu I, Sakurai T, Aizawa N, Iijima H, Nishiguchi S, Tomono T, Okuda Y, Wada S, Seo S, Taura K, Uemoto S, Ikegawa M.
    • Journal Title

      BMC Cancer.

      Volume: 19(1) Issue: 1 Pages: 621-621

    • DOI

      10.1186/s12885-019-5825-8

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Liver Fibrosis Markers as Assessed by Ultrasound Elastography and Serum Samples: A Large Comparative Study in Hepatitis Virus B and C Liver Diseases2019

    • Author(s)
      Nishimura T, Iijima H, Nishikawa H, Kondo R, Yano H, Kage M, Aoki T, Nakano C, Yuri Y, Ishii N, Hasegawa K, Takata R, Yoh K, Sakai Y, Takashima T, Aizawa N, Ikeda N, Iwata Y, Enomoto H, Hirota S, Fujimoto J, Nishiguchi S.
    • Journal Title

      Hepatol Res .

      Volume: 49(7) Issue: 7 Pages: 721-730

    • DOI

      10.1111/hepr.13332

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ultrasonic measurement of sound velocity fluctuations in biological tissue due to ultrasonic heating and estimation of thermo-physical properties2019

    • Author(s)
      Yukako Tsujimoto Mai Morimoto Naotaka Nitta Iwaki Akiyama
    • Journal Title

      Journal of Medical Ultrasonics

      Volume: 46 Issue: 1 Pages: 35-43

    • DOI

      10.1007/s10396-018-0916-8

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Changes in liver stiffness and steatosis among patients with hepatitis C virus infection who received direct-acting antiviral therapy and achieved sustained virological response2018

    • Author(s)
      Kobayashi N, Iijima H, Tada T, Kumada T, Yoshida M, Aoki T, Nishimura T, Nakano C, Takata R, Yoh K, Ishii A, Takashima T, Sakai Y, Aizawa N, Nishikawa H, Ikeda N, Iwata Y, Enomoto H, Hirota S, Fujimoto J, Nishiguchi S.
    • Journal Title

      Eur J Gastroenterol Hepatol

      Volume: 30 Pages: 546-551

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pathological findings that contribute to tissue stiffness in the spleen of liver cirrhosis patients2018

    • Author(s)
      Kondo R, Kage M, Iijima H, Fujimoto J, Nishimura T, Aizawa N, Akiba J, Naito Y, Kusano H, Nakayama M, Mihara Y, Tanigawa M, Yano H.
    • Journal Title

      Hepatol Res.

      Volume: 48 Pages: 1000-1007

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Effect of attenuation correction on backscattering coefficient evaluation of lymphedema,2020

    • Author(s)
      Wakana Saito, Masaaki Omura, Shinsuke Akita, Kenji Yoshida, Tadashi Yamaguchi
    • Organizer
      The 41th Symposium on UltraSonic Electronics
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Backscattering Analysis for Characterization of lymphedema Dermis and Hypodermis2020

    • Author(s)
      Wakana Saito, Masaaki Omura, Shinsuke Akita, Kenji Yoshida, Tadashi Yamaguchi
    • Organizer
      IEEE International, Ultrasonics Symposium
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 肝脂肪の評価における超音波減衰法"Attenuation imaging"とMRI-PDFFとの比較・検討.(一般)2020

    • Author(s)
      多田 俊史, 中村 進一郎, 森井 和彦, 豊田 秀徳, 安田 諭, 飯島 尋子, 熊田 卓
    • Organizer
      第93回学術集会 2020.11 WEB開催
    • Related Report
      2020 Annual Research Report
  • [Presentation] C型慢性肝炎SVR後のVFMAP scoreによる肝発癌予測と肝硬度の推移2020

    • Author(s)
      西村 貴士, 榎本 平之, 飯島 尋子
    • Organizer
      第24回日本肝臓学会大会 2020.11 大阪
    • Related Report
      2020 Annual Research Report
  • [Presentation] Clinically Significant Portal Hypertension C型肝硬変に対するDAA治療による肝硬度変化の意義.(一般)2020

    • Author(s)
      池田 直人, 西川 浩樹, 岩田 恵典, 榎本 平之, 飯島 尋子
    • Organizer
      第27回日本門脈圧亢進症学会総会 2020.10 WEB開催
    • Related Report
      2020 Annual Research Report
  • [Presentation] 食道胃静脈瘤の評価における超音波エラストグラフィーの有用性.(シンポジウム・ワークショップ パネル(その他))2020

    • Author(s)
      會澤 信弘, 飯島 尋子, 西口 修平
    • Organizer
      第56回日本肝臓学会総会 2020.8 大阪
    • Related Report
      2020 Annual Research Report
  • [Presentation] イメージング質量分析法を用いたメダカ消化器官の胆汁酸の網羅的解析2019

    • Author(s)
      野島嵩文,辻 雄大,上野智弘,山口真一,中邨智之, 池川雅哉,森脇弘規,渡辺好章
    • Organizer
      第25回 Hindgut Club Japanシンポジウム
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] イメージング質量分析法を用いたメダカ胆汁酸の可視化2019

    • Author(s)
      野島嵩文、辻 雄大、西野嘉晃、上野智弘、廣瀬まゆみ、 吉田憲司、中邨智之、秋山いわき、池川雅哉、渡辺好章
    • Organizer
      第3回 京都生体質量分析研究会シンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] イメージング質量分析法を用いたメダカ胆汁酸の網羅的解析2019

    • Author(s)
      野島嵩文,辻 雄大,上野智弘,山口真一,中邨智之, 池川雅哉,森脇弘規,渡辺好章
    • Organizer
      第44回日本医用マススペクトル学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] イメージング質量分析法を用いたメダカ胆汁酸の可視化2019

    • Author(s)
      野島嵩文、辻 雄大、西野嘉晃、上野智弘、廣瀬まゆみ、 吉田憲司、中邨智之、秋山いわき、池川雅哉、渡辺好章
    • Organizer
      京都生体質量分析研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] Measurement of temperature dependance of sound velocity in biological tissues2018

    • Author(s)
      Yukako Tsujimoto, Daiki Mtsuda, Kiyoyuki Minamiguchi, Toshiro Tanaka, Toshiko Hirai, Iwaki Akiyama
    • Organizer
      Symposium on Ultrasonic Electronics
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Estimation of the thermo-physical property of biological tissues from temperature rise due to ultrasound exposure2018

    • Author(s)
      Yukako Tsujimoto , Iwaki Akiyama
    • Organizer
      176th Meeting Acoustical Society of America
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 高周波超音波の照射に伴う DNA 分子の二重鎖切断2018

    • Author(s)
      吉田憲司,石原和也,秋山いわき,吉川研一,渡辺好章
    • Organizer
      日本超音波医学会第91回学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 超音波照射によるメダカ胚のプロテオーム解析2018

    • Author(s)
      池川雅哉,松本恵李那,吉田憲司,秋山いわき,廣瀬まゆみ,渡辺好章
    • Organizer
      日本超音波医学会第91回学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Usefulness of Superb Micro Vascular Imaging in the Diagnosis of Focal NodularHyperplasia2018

    • Author(s)
      Takashi Nishimura1, Mariko Hashimoto, Chikage Nakano, Nobuhiro Aizawa, Naoto Ikeda, TomoyukiTakashima, Hiroki Nishikawa, Yoshinori Iwata, Hirayuki Enomoto, Jiro Fujimoto, Shuhei Nishiguchi Hiroko Iijima.
    • Organizer
      The 69th Annual Meeting of the American Association for the Study of Liver Diseases
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Book] 肝臓領域の超音波overview.これ一冊ですべてわかる消化器超音波検査.(35)2020

    • Author(s)
      飯島尋子 西村貴士
    • Total Pages
      292
    • Publisher
      日本メディカルセンター
    • Related Report
      2020 Annual Research Report
  • [Patent(Industrial Property Rights)] 超音波診断装置2018

    • Inventor(s)
      秋山いわき
    • Industrial Property Rights Holder
      学校法人同志社
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-201075
    • Filing Date
      2018
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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