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Analysis of cellular functions in fibrosis using nonlinear light scattering

Research Project

Project/Area Number 21K18038
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 90110:Biomedical engineering-related
Research InstitutionThe University of Tokushima

Principal Investigator

HASE Eiji  徳島大学, ポストLEDフォトニクス研究所, 特任助教 (50805512)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2023: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords線維化 / SHG / ブリルアン散乱 / 第2高調波発生 / 線維症 / 脂肪滴 / 弾性率 / コラーゲン / SHG顕微鏡 / ブリルアン散乱顕微鏡 / イメージング / 非線形光学顕微鏡 / 第2高調波発生 / パルス誘導ブリルアン散乱
Outline of Research at the Start

線維症では,細胞により産生されるコラーゲンを始めとする細胞外マトリックスが過剰に沈着した結果,組織が硬化し,臓器機能不全をもたらす.本研究では,線維化過程において線維芽細胞と筋線維芽細胞,およびコラーゲンという3者をターゲットとし,新しい光プローブとして非線形光散乱を駆使することによって,これまで評価することが困難であったこれら3者の時空間的関係を計測し,線維化における細胞の機能を解析する.具体的には,非線形散乱光としてパルス誘導ブリルアン散乱光と第2高調波発生光を用いて,両細胞の線維化における機能をコラーゲン線維形成能の観点から考察し,線維症の病態の理解と治療に向けた知見を得る.

Outline of Final Research Achievements

In this study, we aimed to develop optical methods for the detailed evaluation of fibrosis. First, we constructed polarization-resolved second-harmonic-generation (PR-SHG) microscopy and demonstrated that the collagen orientation degree obtained from PR-SHG analysis could reflect the stages of fibrosis. Next, we developed a Brillouin scattering microscope and applied it to the observation of lipid droplets in the liver tissues of MASH model mice, demonstrating the feasibility of evaluating MASLD progression from the perspective of the mechanical properties of lipid droplets. Finally, we developed a multimodal microscope combining SHG microscopy and Brillouin scattering microscopy, aiming to visualize collagen distribution and local elasticity variations due to fibrosis progression.

Academic Significance and Societal Importance of the Research Achievements

本研究の学術的意義として,1.病理学分野の観点から,新たな光学診断法の可能性を示し,2.医用分光学分野の観点から,脂肪の硬さ(粘弾性)から病態を判別しうることを示し,最後に3.光工学分野の観点から新たなイメージ・コントラストを提供する可視化手法の開発を行った.これらの成果は,社会的には医療現場での診断精度向上や患者への迅速な治療提供に貢献することが期待される.

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (9 results)

All 2024 2023 2022

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (7 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results)

  • [Journal Article] Quantification of collagen fiber properties in alcoholic liver fibrosis using polarization-resolved second harmonic generation microscopy2023

    • Author(s)
      Matsuzaki Saya、Hase Eiji、Takanari Hiroki、Hayashi Yuri、Hayashi Yusaku、Oshikata Haruto、Minamikawa Takeo、Kimura Satoko、Ichimura-Shimizu Mayuko、Yasui Takeshi、Harada Masafumi、Tsuneyama Koichi
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 22100-22100

    • DOI

      10.1038/s41598-023-48887-8

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Assessment of ultra-early-stage liver fibrosis in human non-alcoholic fatty liver disease by second-harmonic generation microscopy2022

    • Author(s)
      Takeo Minamikawa, Eiji Hase, Mayuko Ichimura-Shimizu, Yuki Morimoto, Akihiro Suzuki, Takeshi Yasui, Satoko Nakamura, Akemi Tsutsui, Koichi Takaguchi, and Koichi Tsuneyama
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 6 Pages: 3357-3357

    • DOI

      10.3390/ijms23063357

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Molecular imaging analysis of lipid droplets in nonalcoholic fatty liver disease by use of Brillouin scattering microscopy2024

    • Author(s)
      Eiji Hase, Naoya Okubo, Kazuki Yasumaru, Yu Tokizane, Takeo Minamikawa, and Takeshi Yasui
    • Organizer
      SPIE Photonics West 2024 (BiOS2024)
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ブリルアン散乱顕微鏡を用いたヒト皮膚の力学的特性解析2024

    • Author(s)
      大久保 直哉、長谷 栄治、時実 悠、南川 丈夫、安井 武史
    • Organizer
      第71回応用物理学会春季学術講演会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Development of second-harmonic-generation microscopy and its application to human skin diagnostics2023

    • Author(s)
      Eiji Hase and Takeshi Yasui
    • Organizer
      OPIC2023 (LDC2023)
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Analysis of Accumulated Lipid Molecular Properties in Nonalcoholic Fatty Liver Disease by Use of Brillouin Scattering Microscopy2023

    • Author(s)
      Naoya Okubo, Eiji Hase, Kazuki Yasumaru, Yu Tokizane, Takeo Minamikawa, and Takeshi Yasui
    • Organizer
      33rd International Symposium on Imaging, Sensing, and Optical Memory (ISOM23)
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ブリルアン・ラマン散乱顕微鏡を用いた非アルコール性脂肪性疾患における脂質の分子物性解析(2)  ー蓄積脂肪滴のブリルアンイメージングー2023

    • Author(s)
      大久保 直哉、長谷 栄治、安丸 和樹、時実 悠、南川 丈夫、安井 武史
    • Organizer
      第84回応用物理学会秋季学術講演会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ブリルアン・ラマン散乱顕微鏡を用いた非アルコール性脂肪性肝疾患における脂質の分子物性解析(1) -ブリルアン散乱顕微鏡の構築と肝組織のブリルアンイメージング-2022

    • Author(s)
      長谷 栄治,南川 丈夫,時実 悠,安井 武史
    • Organizer
      第83回応用物理学会秋季学術講演会
    • Related Report
      2022 Research-status Report
  • [Presentation] Analysis of lipid molecular properties in nonalcoholic fatty liver disease by use of Brillouin microspectroscopy2022

    • Author(s)
      E. Hase, T. Minamikawa, Y. Tokizane, and T. Yasui
    • Organizer
      SPIE Biomedical Imaging and Sensing Conference 2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research

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Published: 2021-04-28   Modified: 2025-01-30  

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