2022 Fiscal Year Annual Research Report
Label-free volumetric microscopy for visualizing intracellular motility of tumor cell culture
| Project/Area Number |
22F22355
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| Allocation Type | Single-year Grants |
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| Research Institution | University of Tsukuba |
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Principal Investigator |
安野 嘉晃 筑波大学, 医学医療系, 教授 (10344871)
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| Co-Investigator(Kenkyū-buntansha) |
HOSSEIN IBRAHIM 筑波大学, 医学医療系, 外国人特別研究員
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| Project Period (FY) |
2022-11-16 – 2025-03-31
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| Keywords | Dynamic OCT / Tumor spheroid / Anti-cancer drug test / Label-free oncology / Cancer diagnosis |
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| Outline of Annual Research Achievements |
In FY 2022, the proposed OCT microscope has been successfully used for the anti-cancer drug investigations of the tumor spheroid. Three anti-cancer drugs were applied to human breast cancer (MCF-7) spheroids and the dynamic OCT microscopic images revealed totally different response patterns among the applied drugs. In addition, the dynamic OCT patterns were consistent with the standard fluorescence microscopic images. The results may proof the feasibility of our proposed to perform anti-cancer drug investigations.
The above mentioned results have been published as an oral and poster presentations in an international conference (Photonics West 2023, BiOS conference) and a journal paper is now under writing. Several co-authored work were published in the same conference. In addition, a co-authored paper about dynamic optical coherence tomography based evaluation of human derived alveolar organoids has been published in Biomedical Optics Express journal.
Further development of our proposed microscope has been also performed during FY 2022. It includes allowing the longitudinal imaging ability of our microscope. This has been performed by integrating a cultivation chamber with the microscope to allow the simulations tissue activity imaging during cultivation. The cultivation chamber integration was successful so far. And we successfully obtained the D-OCT images though the cultivation chamber window and the cap of the well plate containing the samples. It will allow future longitudinal drug response evaluation of tumor spheroids and fresh ex-vivo tissue.
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| 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 purpose of this research was to establish a multifunctional optical coherence microscope (OCM) for anti-cancer drug development and cancer diagnosis. This project includes two major points; (1) extension of University of Tsukuba OCT microscope (OCM) and (2) its pre-clinical translation. One of the important extensions to the OCT microscope is the tissue activity imaging using the so-called dynamic optical coherence tomography (D OCT) method. This method has been successfully established.
To make our OCM as a standard tool for anti-cancer drug investigation, several preclinical are required. One of the important studies we performed during FY2022 is the anti-cancer drugs response evaluation of human derived tumor cell cultures (tumor spheroids). Such a study was successfully performed and the results were promising and agreed with the fluorescence microscopic findings.
In addition, one of the planned developments was enable longitudinal evaluation of the tissue activity using our proposed OCM. To do this, we need to keep the cells in cell cultivation conditions during the OCT measurements. In FY2022, we successfully integrated cultivation chamber to our proposed microscope and obtained the D-OCT images of tumor spheroids during cultivation over 12 hours.
Due to the above mentioned achievements, we think that the progress of our multifunctional OCT microscope goes smoothly and we are reaching to our goal to establish such a label-free microscope for anti-cancer drug investigations and cancer diagnosis without using any external contrast agents.
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| Strategy for Future Research Activity |
In future, we are going to extend our OCT microscope to increase its tissue specificity. The new extensions include (1) more quantitative evaluation of tissue activity, (2) sub-resolution tissue microstructural evaluation via scattering and polarization analysis, (3) achieving high imaging depth, and (4) allowing in-vivo dynamic OCT imaging. These extensions enable evaluating the abnormalities in cell metabolism by (1), extra-cellular matrix by (2), fine and deep structural abnormality imaging by (3), and in vivo cancer diagnosis and anti-cancer drug testing by (4).
For (1) we are going to develop new algorithms to obtain a quantitative tissue activity fingerprints. For (2), birefringence (collagen-sensitive), and degree of polarization uniformity (melanin-sensitive), and optic axis orientation (will be newly developed in Tsukuba Univ. to be sensitive to the fibrous orientation) will be adapted to our OCM. For (3), multi-focus averaging developed in Univ. Tsukuba will be adapted to our OCM. For (4) hardware for sample fixation and software for tissue motion correction, will be developed to allow in vivo tissue activity imaging.
We are going to perform several pre-clinical studies as follows. First, a longitudinal tumor spheroid-based anti-cancer drug testing using different drugs and tumor cell lines will be performed. Second study involves diagnostic evaluation of the metabolic activity, polarization, scattering properties of ex-vivo human cancer biopsies. Third, in-vivo cancer diagnosis and drug response of the mouse and zebrafish tumor models will be performed.
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[Presentation] Volumetric differential contrast imaging by computationally augmented optical coherence tomography microscopy2023
Author(s)
Kiriko Tomita, Shuichi Makita, Naoki Fukutake, Rion Morishita, Ibrahim Abd El-Sadek, Pradipta Mukherjee, Antonia Lichtengger, Junya Tamaoki, Lixuan Bian, Makoto Kobayashi, Tomoko Mori, Satoshi Matsusaka, Yoshiaki Yasuno
Organizer
Label-free Biomedical Imaging and Sensing (LBIS) 2023
Int'l Joint Research
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[Presentation] Low- and high-resolution volumetric dynamic optical coherence tomography of in vitro cell cultures2023
Author(s)
Rion Morishita, Ibrahim Abd El-Sadek, Pradipta Mukherjee, Tomoko Mori, Suzuki Toshio, Antonia Lichtengger, Lim Yi Heng, Zhu Yiqiang, Shuichi Makita, Yuki Yamamoto, Tetsuharu Nagamoto, Satoshi Matsusaka, Yoshiaki Yasuno
Organizer
Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXVII
Int'l Joint Research
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[Presentation] Disperse scatterer model of OCT and its application to design volumetric differential contrast imaging2023
Author(s)
Kiriko Tomita, Shuichi Makita, Naoki Fukutake, Rion Morishita, Ibrahim Abd El-Sadek, Pradipta Mukherjee, Antonia Lichtenegger, Junya Tamaoki, Lixuan Bian, Makoto Kobayashi, Tmoko Mori, Satoshi Matsusaka, Yoshiaki Yasuno
Organizer
Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXVII
Int'l Joint Research
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[Presentation] Non-invasive and label-free zebrafish investigations using polarization-sensitive optical coherence tomography2023
Author(s)
Antonia Lichtenegger, Junya Tamaoki, Pradipta Mukherjee, Roxane Licandro, Lida Zhu, Tomoko Mori, Rion Morishita, Lixuan Bian, Ibrahim Abd El-Sadek, Shuichi Makita, Konrad Leskovar, Satoshi Matsusaka, Martin Distel, Makoto Kobayashi, Bernhard Baumann, Yoshiaki Yasuno
Organizer
Label-free Biomedical Imaging and Sensing (LBIS) 2023
Int'l Joint Research
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