| 研究実績の概要 |
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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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
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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| 今後の研究の推進方策 |
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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