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Time- and space-super-resolution holographic microscope for label-free tissue dyanmics imaging

Research Project

Project/Area Number 23KF0186
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeMulti-year Fund
Section外国
Review Section Basic Section 90110:Biomedical engineering-related
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) ZHU YUE  筑波大学, 医学医療系, 外国人特別研究員
Project Period (FY) 2023-11-15 – 2026-03-31
Project Status Granted (Fiscal Year 2023)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2025: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2024: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2023: ¥300,000 (Direct Cost: ¥300,000)
Keywords4D Microscope. / Imaging formation theory / Aberration. / Computational refocusing
Outline of Research at the Start

本研究は細胞・培養組織の活動性を外部からのコントラスト源の導入なく、三次元的に、かつ、光分解にイメージングする新規のホログラフィック顕微鏡を開発する研究プロジェクトである。この新しい顕微鏡は、波長領域干渉断層計、ホログラフィック信号処理、時間統計解析といおう3つの技術の組み合わせによって実現される。更に本研究では、この新規顕微鏡を用いた培養がん細胞の評価プロトコルを確立する。

Outline of Annual Research Achievements

To establish a new microscopy that visualizes tissue viability and metabolic activity, we first proposed an imaging formation theory and built the basement of hardware based on this theory.
Optical coherence tomography is expected to have a high-resolution and extended imaging depth. Cellular-level resolution is essential in recent applications of non-invasive tissue imaging. Hence higher lateral resolution and deep imaging depth are required due to thick tissue in organs. However, the trade-off between lateral resolution and depth-of-focus is problematic especially for high-resolution OCT microscope. The defocus can be holographically corrected. but the maximum correctable defocus was only empirically known. Therefore, the theoretical framework for OCT imaging formation is required.
First, we employed two-dimensional pupil-based function to model the lateral imaging process of optical coherence microscope. Then discuss the defocus issue in complex signal. Finally derive the maximum correctable defocus (MCD) to theoretically evaluate the effect of computational refocusing.
For the hardware, we designed the optical system by Zemax and balance the lateral resolution and depth-of-focus. To address this issue, the defocus was investigated. Then, our colleague took responsibility to make a mechanical design and assemble the parts together. Currently, the optimization about signal processing, and high-speed signal acquisition mechanism are still ongoing.
This OCT microscope was found to have virtually infinitly large MCD and is particularly suitable for microscopy

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

The plan for first working package is from Month-1 to 8, and the task is to establish a basement SS-FF-OCM theory and hardware. Currently, the theory has been produced to prepare for the manuscript. At the same time, the hardware is also ongoing and now can take images. More imaging processing steps will be further needed.
So, the progress is on the track smoothly.

Strategy for Future Research Activity

After establishing the imaging formation theory, we will build an optimal system of SS-FF-OCM (Swept-source full-field optical coherence microscope) based on this theory. Because the pupil-function of the full-field illumination is designed to be a delta function, and the delta-function is crucial to achieve an ideal holographic signal correction. Therefore, for the next step, a method of digital adaptive optics will be proposed.
The method is to evaluate the importance of pupil-aperture-function-based computational refocusing and aberration correction for microscopy. In the study of digital adaptive optics, we need to first model the point spread function of complex signal and derive how the aberration is intact with complex signal. By Zernike polynomial fitting, cancel the phase error in the spatial frequency domain.
Currently, there is no changes in the research plan. One of the possible challenges may be the holographic correction of high-order aberration, because these aberrations will be intact with defocus. To address this issue, we need to first consider the maximum correctable defocus, and conduct computational refocusing, and evaluate the pupil-aperture-function-based computational refocusing, which is our current study.

Report

(1 results)
  • 2023 Research-status Report
  • Research Products

    (2 results)

All 2024

All Presentation (2 results) (of which Int'l Joint Research: 2 results)

  • [Presentation] Theoretical consideration of maximum numerically correctable defocus of point-scanning and full-field optical coherence tomography2024

    • Author(s)
      Zhu Yue
    • Organizer
      SPIE Photonics West BiOS
    • Related Report
      2023 Research-status Report
    • Int'l Joint Research
  • [Presentation] Fractal-based contrast correction for defocus in full-field optical coherence tomography2024

    • Author(s)
      Zhu Yue
    • Organizer
      SPIE Photonics Europe
    • Related Report
      2023 Research-status Report
    • Int'l Joint Research

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Published: 2023-11-17   Modified: 2024-12-25  

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