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2023 Fiscal Year Annual Research Report

Holographic optical coherence microscope for high-penetration and label free imaging of intracellular activities

Research Project

Project/Area Number 21H01836
Research InstitutionUniversity of Tsukuba

Principal Investigator

安野 嘉晃  筑波大学, 医学医療系, 教授 (10344871)

Co-Investigator(Kenkyū-buntansha) 松阪 諭  筑波大学, 医学医療系, 客員研究員 (00372665)
巻田 修一  筑波大学, 医学医療系, 准教授 (50533345)
三浦 雅博  東京医科大学, 医学部, 教授 (60199958)
福田 慎一  筑波大学, 医学医療系, 准教授 (80643246)
Project Period (FY) 2021-04-01 – 2024-03-31
Keywords光コヒーレンストモグラフィー / Dynamic OCT / In vitro imaging / drug testing / imaging theory
Outline of Annual Research Achievements

本課題では、生体の活動性を非侵襲・ラベルフリー・3次元的に可視化する新しい顕微的光イメージング手法 dynamic optical coherence tomography (dynamic OCT)を確立した。 Dynamic OCT は連続したOCTは信号計測と、その時系列信号の統計解析を組み合わせることで、外部からのコントラストエージェントの導入なく生体の活動性を可視化する手法である。
本研究では、新たにこの手法を開発し、それを用いた腫瘍スフェロイドの薬剤反応試験、肺胞オルガノイドの線維化過程の可視化、マウス肝臓のゾーン構造の可視化、マウス腎臓の腎障害モデルによる組織活動性の低下の評価に成功した。特に、腫瘍スフェロイドの薬剤反応試験では、三種類の抗がん剤を異なる濃度でスフェロイドに適用し、抗がん剤の作用機序に対応した異った細胞反応が発生することが、その空間パターンも含めて明瞭費可視化された。
さらに、dynamic OCTの理論的な基礎となるOCTのスペックル現象の数理的解明を試み、スペックルが加算的なノイズであること、OCT画像の中にはインコヒーレントなスペックルを伴わない成分が存在することを解明した。
また、この研究を通じで、今後の dynamic OCT 開発における課題も明確になった。一つはより直接的に生体内の組織ダイナミクスに関連した dynamic OCT手法の開発である。今後、今回開発されたスペックル現象の数理モデルを用いてこの問題に取り組むことに成る。もう一つの課題はdynamic OCTの長い計測時間音短縮である。これは、deep-learning 画像生成モデルを用いてより少ない量のデータ(OCT画像)から高品位な dynamic OCTを生成する手法を確立することで対応する予定である。

Research Progress Status

令和5年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和5年度が最終年度であるため、記入しない。

  • Research Products

    (38 results)

All 2024 2023

All Journal Article (13 results) (of which Int'l Joint Research: 11 results,  Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (25 results) (of which Int'l Joint Research: 22 results,  Invited: 1 results)

  • [Journal Article] Label-free visualization and quantification of the drug-type-dependent response of tumor spheroids by dynamic optical coherence tomography2024

    • Author(s)
      Abd El-Sadek Ibrahim、Morishita Rion、Mori Tomoko、Makita Shuichi、Mukherjee Pradipta、Matsusaka Satoshi、Yasuno Yoshiaki
    • Journal Title

      Scientific Reports

      Volume: 14 Pages: -

    • DOI

      10.1038/s41598-024-53171-4

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Quantitative dynamic optical coherence tomography by multi-time-window signal intensity variance2024

    • Author(s)
      Morishita Rion、El-Sadek Ibrahim A.、Mukherjee Pradipta、Seesan Tanatchaya、Lim Yiheng、Mori Tomoko、Furukawa Atsuko、Matsusaka Satoshi、Makita Shuichi、Yasuno Yoshiaki
    • Journal Title

      Proc. SPIE

      Volume: 12830 Pages: -

    • DOI

      10.1117/12.3003694

    • Int'l Joint Research
  • [Journal Article] Investigating the dependency of dynamic optical coherence tomography signals on resolution and wavelength by experimental and simulation approaches2024

    • Author(s)
      Fujimura Shumpei、Abd El-Sadek Ibrahim、Mukherjee Pradipta、Lim Yiheng、Zhu Lida、Morishita Rion、Feng Yuanke、Yasuno Yoshiaki
    • Journal Title

      Proc. SPIE

      Volume: PC12830 Pages: -

    • DOI

      10.1117/12.3005612

    • Int'l Joint Research
  • [Journal Article] Mathematical modeling of intracellular and intratissue activities for understanding dynamic optical coherence tomography signals2024

    • Author(s)
      Feng Yuanke、Fujimura Shumpei、Lim Yiheng、Seesan Thitiya、Morishita Rion、Abd El-Sadek Ibrahim、Mukherjee Pradipta、Yasuno Yoshiaki
    • Journal Title

      Proc. SPIE

      Volume: 12830 Pages: -

    • DOI

      10.1117/12.3005637

    • Int'l Joint Research
  • [Journal Article] In vivo dynamic optical coherence tomography with hardware- and software-based motion correction2024

    • Author(s)
      Guo Yu、Morishita Rion、Abd El-Sadek Ibrahim、Mukherjee Pradipta、Zhu Yiqiang、Yasuno Yoshiaki
    • Journal Title

      Proc. SPIE

      Volume: 12830 Pages: -

    • DOI

      10.1117/12.3005623

    • Int'l Joint Research
  • [Journal Article] Theoretical consideration of maximum numerically correctable defocus of point-scanning and full-field optical coherence tomography2024

    • Author(s)
      Zhu Yue、Shuichi Makita、Yasuno Yoshiaki
    • Journal Title

      Proc. SPIE

      Volume: 12830 Pages: -

    • DOI

      10.1117/12.2692849

    • Int'l Joint Research
  • [Journal Article] Four-dimensional image formation theory for all optical microscopy including optical coherence tomography2024

    • Author(s)
      Fukutake Naoki、Makita Shuichi、Yasuno Yoshiaki
    • Journal Title

      Proc. SPIE

      Volume: 12847 Pages: -

    • DOI

      10.1117/12.3002194

  • [Journal Article] Label-free intratissue activity imaging of alveolar organoids with dynamic optical coherence tomography2023

    • Author(s)
      Morishita Rion、Suzuki Toshio、Mukherjee Pradipta、Abd El-Sadek Ibrahim、Lim Yiheng、Lichtenegger Antonia、Makita Shuichi、Tomita Kiriko、Yamamoto Yuki、Nagamoto Tetsuharu、Yasuno Yoshiaki
    • Journal Title

      Biomedical Optics Express

      Volume: 14 Pages: 2333-2351

    • DOI

      10.1364/BOE.488097

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Theoretical model for en face optical coherence tomography imaging and its application to volumetric differential contrast imaging2023

    • Author(s)
      Tomita Kiriko、Makita Shuichi、Fukutake Naoki、Morishita Rion、Abd El-Sadek Ibrahim、Mukherjee Pradipta、Lichtenegger Antonia、Tamaoki Junya、Bian Lixuan、Kobayashi Makoto、Mori Tomoko、Matsusaka Satoshi、Yasuno Yoshiaki
    • Journal Title

      Biomedical Optics Express

      Volume: 14 Pages: 3100-3124

    • DOI

      10.1364/BOE.491510

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Multi-focus averaging for multiple scattering suppression in optical coherence tomography2023

    • Author(s)
      Zhu Lida、Makita Shuichi、Tamaoki Junya、Lichtenegger Antonia、Lim Yiheng、Zhu Yiqiang、Kobayashi Makoto、Yasuno Yoshiaki
    • Journal Title

      Biomedical Optics Express

      Volume: 14 Pages: 4828-4844

    • DOI

      10.1364/BOE.493706

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Renal tubular function and morphology revealed in kidney without labeling using three-dimensional dynamic optical coherence tomography2023

    • Author(s)
      Mukherjee Pradipta、Fukuda Shinichi、Lukmanto Donny、Tran Thi Hang、Okada Kosuke、Makita Shuichi、El-Sadek Ibrahim Abd、Lim Yiheng、Yasuno Yoshiaki
    • Journal Title

      Scientific Reports

      Volume: 13 Pages: -

    • DOI

      10.1038/s41598-023-42559-3

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Label-free drug response evaluation of human derived tumor spheroids using three-dimensional dynamic optical coherence tomography2023

    • Author(s)
      Abd El-Sadek Ibrahim、Shen Larina Tzu-Wei、Mori Tomoko、Makita Shuichi、Mukherjee Pradipta、Lichtenegger Antonia、Matsusaka Satoshi、Yasuno Yoshiaki
    • Journal Title

      Scientific Reports

      Volume: 13 Pages: -

    • DOI

      10.1038/s41598-023-41846-3

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Polarization-artifact reduction and accuracy improvement of Jones-matrix polarization-sensitive optical coherence tomography by multi-focus-averaging based multiple scattering reduction2023

    • Author(s)
      Zhu Lida、Makita Shuichi、Tamaoki Junya、Zhu Yiqiang、Mukherjee Pradipta、Lim Yiheng、Kobayashi Makoto、Yasuno Yoshiaki
    • Journal Title

      Biomedical Optics Express

      Volume: 15 Pages: 256-276

    • DOI

      10.1364/BOE.509763

    • Peer Reviewed / Open Access
  • [Presentation] Quantitative dynamic optical coherence tomography by multi-time-window signal intensity variance2024

    • Author(s)
      Rion Morishita, Ibrahim A. El-Sadek, Pradipta Mukherjee, Tanatchaya Seesan, Yiheng Lim, Tomoko Mori, Atsuko Furukawa, Satoshi Matsusaka, Shuichi Makita, Yoshiaki Yasuno
    • Organizer
      Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXVIII, BiOS 2024/Photonics west
    • Int'l Joint Research
  • [Presentation] Longitudinal drug response imaging of tumor spheroids using dynamic optical coherence tomography in conjunction with cell cultivation2024

    • Author(s)
      Ibrahim Abd El-Sadek, Rion Morishita, Masato Iwatsuki, Atsuko Furukawa, Shuichi Makita, Pradipta Mukherjee, Satoshi Matsusaka, Yoshiaki Yasuno
    • Organizer
      SPIE BiOS 2024, Dynamics and Fluctuations in Biomedical Photonics XXI2024
    • Int'l Joint Research
  • [Presentation] In vivo dynamic and multi-contrast imaging of human skin by motion-suppressed dynamic optical coherence tomography2024

    • Author(s)
      Yu Guo, Rion Morishita, Ibrahim Abd El-Sadek, Pradipta Mukherjee, Yiqiang Zhu, Yoshiaki Yasuno
    • Organizer
      SPIE BiOS 2024, Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXVIII;
    • Int'l Joint Research
  • [Presentation] Investigating the dependency of dynamic optical coherence tomography signals on resolution and wavelength by experimental and simulation approaches2024

    • Author(s)
      Shumpei Fujimura, Ibrahim Abd El-Sadek, Pradipta Mukherjee, Yiheng Lim, Lida Zhu, Rion Morishita, Yuanke Feng, Yoshiaki Yasuno
    • Organizer
      SPIE BiOS 2024, Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXVIII
    • Int'l Joint Research
  • [Presentation] Wavelength and resolution dependency of dynamic optical coherence tomography2024

    • Author(s)
      Shumpei Fujimura, Ibrahim Abd El-Sadek, Pradipta Mukherjee, Yiheng Lim, Lida Zhu, Rion Morishita, Yuanke Feng, Yoshiaki Yasuno
    • Organizer
      SPIE BiOS 2024, Wavelength and resolution dependency of dynamic optical coherence tomography
    • Int'l Joint Research
  • [Presentation] In vivo dynamic optical coherence tomography with hardware- and software-based motion correction2024

    • Author(s)
      Yu Guo, Rion Morishita, Ibrahim Abd El-Sadek, Pradipta Mukerjee, Yiqiang Zhu, Yasuno Yoshiaki
    • Organizer
      SPIE BiOS 2024, Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXVIII
    • Int'l Joint Research
  • [Presentation] Mathematical modeling of intracellular and intratissue activities for understanding dynamic optical coherence tomography signals2024

    • Author(s)
      Yuanke Feng, Shumpei Fujimura, Yiheng Lim, Thitiya Seesan, Rion Morishita, Ibrahim G. Abd El-Sadek, Pradipta Mukerjee, Yoshiaki Yasuno
    • Organizer
      SPIE BiOS 2024, Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXVIII
    • Int'l Joint Research
  • [Presentation] Characterizing intracellular activities of dynamic optical coherence tomography: A mathematical modeling approach2024

    • Author(s)
      Yuanke Feng, Shumpei Fujimura, Yiheng Lim, Thitiya Seesan, Rion Morishita, Ibrahim Abd El-Sadek, Pradipta Mukherjee, Yoshiaki Yasuno
    • Organizer
      SPIE BiOS 2024, Label-free Biomedical Imaging and Sensing (LBIS) 2024
    • Int'l Joint Research
  • [Presentation] Optic axis imaging of biological samples by Jones matrix optical coherence tomography2024

    • Author(s)
      Yiheng Lim, Pradipta Mukherjee, Shuichi Makita, Yoshiaki Yasuno
    • Organizer
      Polarized Light and Optical Angular Momentum for Biomedical Diagnostics 2025
    • Int'l Joint Research
  • [Presentation] Computational method for improving the lateral resolution of retinal OCT images with Lissajous scan OCT2024

    • Author(s)
      Shuichi Makita, Lida Zhu, Yoshiaki Yasuno
    • Organizer
      Ophthalmic Technologies XXXIV
    • Int'l Joint Research
  • [Presentation] Deep learning-based scatterer density estimation for the analysis of retinal tissue property2024

    • Author(s)
      Yusong Liu, Ibrahim Abd El-Sadek, Shuichi Makita, Tomoko Mori, Atsuko Furukawa, Satoshi Matsusaka, Yoshiaki Yasuno
    • Organizer
      Ophthalmic Technologies XXXV
    • Int'l Joint Research
  • [Presentation] Stokes analysis of optic axis orientation in single-mode fiber polarization-sensitive optical coherence tomography2024

    • Author(s)
      Yiheng Lim, Pradipta Mukherjee, Shuichi Makita, Yoshiaki Yasuno
    • Organizer
      SPIE BiOS 2024, Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXIX
    • Int'l Joint Research
  • [Presentation] Volumetric digital aberration correction of point-scanning optical coherence tomography by simulating aberrated system response function2024

    • Author(s)
      Shuichi Makita, Lida Zhu, Yiqiang Zhu, Pradipta Mukherjee, Yiheng Lim, Rion Morishita, Ibrahim Abd El-Sadek, Yoshiaki Yasuno
    • Organizer
      SPIE BiOS 2024, Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXVIII
    • Int'l Joint Research
  • [Presentation] Four-dimensional image formation theory for all optical microscopy including optical coherence tomography2024

    • Author(s)
      Naoki Fukutake, Shuichi Makita, Yoshiaki Yasuno
    • Organizer
      SPIE BiOS 2024, Multiphoton Microscopy in the Biomedical Sciences XXIV
    • Int'l Joint Research
  • [Presentation] Theoretical consideration of maximum numerically correctable defocus of point-scanning and full-field optical coherence tomography2024

    • Author(s)
      Yue Zhu, Makita Shuichi, Yoshiaki Yasuno
    • Organizer
      SPIE BiOS 2024, Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXVIII
    • Int'l Joint Research
  • [Presentation] Mathematical formulation of meaningful OCT image and speckle with dispersed scatterer modeling2024

    • Author(s)
      Yoshiaki Yasuno, Kiriko Tomita, Naoki Fukutake, Shuichi Makita
    • Organizer
      SPIE BiOS 2024, Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXVIII
    • Int'l Joint Research
  • [Presentation] Deep-learning-based high-speed volumetric dynamic optical coherence tomography2024

    • Author(s)
      Yusong Liu, Ibrahim Abd El-Sadek, Shuichi Makita, Tomoko Mori, Atsuko Furukawa, Satoshi Matsusaka, Yoshiaki Yasuno
    • Organizer
      SPIE BiOS 2024, Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXIX
    • Int'l Joint Research
  • [Presentation] Multiple scattering suppression for in vivo OCT measurement by B-scan-wise-multi-focus averaging method2024

    • Author(s)
      Yiqiang Zhu, Lida Zhu, Shuichi Makita, Yiheng Lim, Yu Guo, Yoshiaki Yasuno
    • Organizer
      SPIE BiOS 2024, Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXVIII
    • Int'l Joint Research
  • [Presentation] Studying the effect of gluconeogenesis inhibitor drug on liver functionality using dynamic optical coherence tomography2024

    • Author(s)
      Pradipta Mukherjee, Shinichi Fukuda, Donny Lukmanto, Kosuke Okada, Thi Hang Tran, Ibrahim Abd El-Sadek, Shuichi Makita, Yoshiaki Yasuno
    • Organizer
      SPIE BiOS 2024, Dynamics and Fluctuations in Biomedical Photonics XXI
    • Int'l Joint Research
  • [Presentation] New formulation of OCT for analytical signal-to-speckle separation and volumetric differential contrast imaging2023

    • Author(s)
      Kiriko Tomita, Shuichi Makita, Naoki Fukutake, Rion Morishita, Ibrahim Abd El-Sadek, Pradipta Mukherjee, Antonia Lichtenegger, Yoshiaki Yasuno
    • Organizer
      European Conference on Biomedical Optics
    • Int'l Joint Research / Invited
  • [Presentation] Label-free intra-tissue activity imaging of alveolar organoid with three-dimensional dynamic optical coherence tomography2023

    • Author(s)
      Rion Morishita, Pradipta Mukherjee, Ibrahim Abd El-Sadek, Toshio Suzuki, Antonia Lichtenegger, YiHeng Lim, Zhu Yiqiang, Shuichi Makita, Yuki Yamamoto, Tetsuharu Nagamoto, Yoshiaki Yasuno
    • Organizer
      European Conference on Biomedical Optics
    • Int'l Joint Research
  • [Presentation] Speculative/philosophical modeling of measurement for comprehending modern OCT imaging2023

    • Author(s)
      Yoshiaki Yasuno
    • Organizer
      European Conference on Biomedical Optics
    • Int'l Joint Research
  • [Presentation] Quantitative intra-tissue activity imaging technique for evaluating in vitro cell culture samples by optical coherence tomography2023

    • Author(s)
      Rion Morishita, Toshio Suzuki, Pradipta Mukherjee, Ibrahim Abd El-Sadek, Tanachaya Seesan, Yiheng Lim, Shuichi Makita, Yuki Yamamoto, Tetsuharu Nagamoto,
    • Organizer
      The Japan Society of Applied Physics 2024
  • [Presentation] Stokes analysis for single-mode fiber polarization-sensitive optical coherence tomography2023

    • Author(s)
      Yiheng Lim, Pradipta Mukherjee, Shuichi Makita, Yoshiaki Yasuno
    • Organizer
      Optics & Photonic Japan 2023
  • [Presentation] Deep learning-based multi-contrast optical coherence tomography for retinal tissue analysis2023

    • Author(s)
      Thitiya Seesan, Shuichi Makita, Masahiro Miura, Yoshiaki Yasuno
    • Organizer
      Optics & Photonic Japan 2023

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Published: 2024-12-25  

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