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Non-invasive ex-vivo/in-vivo tissue analysis platform

Non-invasive ex-vivo/in-vivo tissue analysis platform

Antonia Lichtenegger (ORCID: 0000-0002-6422-9547)
  • Grant DOI 10.55776/J4460
  • Funding program Erwin Schrödinger
  • Status ended
  • Start December 1, 2020
  • End November 30, 2022
  • Funding amount € 99,178
  • Project website

Disciplines

Biology (20%); Medical-Theoretical Sciences, Pharmacy (10%); Physics, Astronomy (70%)

Keywords

    Optical Coherence Tomography, Tissue Analysis, Ex-Vivo, In-Vivo, Image Processing, Artifical Intelligence

Abstract Final report

Cancer usually has a devastating diagnosis and is going to remain a major cause of mortality and morbidity in the upcoming decades worldwide. Research is needed for a deeper understanding of the mechanisms involved in cancer-related pathologies to find better treatment possibilities. The gold-standard for cancer diagnosis and to investigate related pathologies is ex-vivo tissue analysis, so called histology. The procedure involves multiple steps and still takes up to couple of minutes. Here it would be beneficial to have a real-time ex-vivo tissue analysis and diagnosis tool. Also for pre-clinical cancer studies using animal models or cellular structures a new, inexpensive, multi-modal 3D imaging approach would be beneficial. Optical coherence tomography (OCT) or microscopy based OCT (OCM) is an optical imaging technique which provides axial resolutions in the micrometer range over 1-2 millimeters in depth. OCM data is 3D, and these morphological data sets are recorded in real time based only on the intrinsic contrast of the various tissue types. The project will be conducted by Lichtenegger, PhD. She recently finished her PhD in Medical Physics at the Center for Medical Physics and Biomedical Engineering at the Medical University of Vienna under the supervision of Prof. Baumann. In the first 14 months of the project, she will be working in the lab of Prof. Yasuno in the Computational Optics Group at the University of Tsukuba in Japan. In this research project a multimodal OCM platform will be established and will enable multi-contrast measurements of both ex-vivo tissue samples and in-vivo cell cultures and animal models. OCM offers a rather inexpensive method to retrieve the tissue morphology in cellular resolution. The technique is non-destructive; no slicing or labeling is needed to gain tissue specific contrast in comparison to conventional histology. The proposed platform aims to unite and expand existing OCM technologies. The goal is to find a sensitive method to differentiate tumorous and healthy tissue in pre-clinical cancer related research. The project is divided into six work-packages, which include the data acquisition, the post-processing, the data visualization and analysis, data validation and the establishment of new imaging protocols. During her PhD in Austria she developed a multimodal OCM setup operating in the visible wavelength region. In her returning phase to Austria she will improve this setup based on the knowledge gained at the University of Tsukuba. This project will improve and advance ex-vivo and in-vivo pre-clinical tissue analysis. The platform will offer a novel, fast, relatively inexpensive and highly advanced method for real-time, non-destructive tissue imaging.

Cancer usually has a devastating diagnosis and will remain a major cause of mortality and morbidity worldwide in the coming decades. To find better treatment options, research is needed for a deeper understanding of the mechanisms involved in tumor-related pathologies. The gold standard for cancer diagnosis and the study of related pathologies is ex vivo tissue analysis, known as histology. The procedure involves multiple steps and takes several minutes. Here, it would be beneficial to have a real-time ex vivo tissue analysis and diagnostic tool. Also, for preclinical cancer studies using animal models or cellular structures, a new, low-cost, multimodal three-dimensional (3D) imaging approach would be beneficial. Optical coherence tomography (OCT) or microscopy-based OCT (OCM) is an optical imaging technique that provides micron-scale axial resolutions over an imaging range of 1-2 millimeters. OCM datasets are 3D, and these morphological representations are recorded in real time based only on the inherent contrast of the different tissue types. The project has been conducted by Dr. Lichtenegger. She recently completed her PhD in Medical Physics at the Center for Medical Physics and Biomedical Engineering at the Medical University of Vienna under the supervision of Prof. Baumann. For 17 months of the project, she has been working in Prof. Yasuno's lab in the Computational Optics Group at the University of Tsukuba in Japan. In her research project, a multimodal OCM platform has been developed to measure ex vivo tissue samples as well as in vivo cell cultures and in vivo animal models. OCM provides a fairly inexpensive method to determine tissue morphology at a cellular resolution. The technique is non-destructive; compared to conventional histology, no additional steps are required to obtain tissue-specific contrasts. The imaging setup offers a sensitive method to differentiate tumorous and healthy tissue areas in preclinical cancer research. A focus of her project was set on zebrafish-based studies. The zebrafish is an established animal model in the pre-clinical research field because of several advantages compared to commonly used rodent models. The small size, the fast maturation time and the large number of offspring enables cost-effective and high-throughput studies. Even though it is not a mammal, humans and zebrafish share a high degree of genome structure, as around 70% of human genes have at least one obvious ortholog in zebrafish. During her PhD in Austria, she has developed a multimodal OCM setup; in her return phase to Austria, she upgraded this setup based on the knowledge gained at the University of Tsukuba. In this project a novel, fast, relatively inexpensive, and highly sophisticated method for real-time nondestructive tissue imaging has been introduced to improve and advance preclinical ex vivo, in vitro and in vivo tissue analysis.

Research institution(s)
  • The University of Tsukuba - 100%
  • Medizinische Universität Wien - 100%
International project participants
  • Masahiro Miura, The University of Tokyo - Japan
  • Hideaki Kano, The University of Tsukuba - Japan
  • Satoshi Matsusaka, University of Tsukuba - Japan
  • Shinichi Fukuda, University of Tsukuba - Japan

Research Output

  • 143 Citations
  • 19 Publications
  • 2 Disseminations
  • 4 Scientific Awards
  • 1 Fundings
Publications
  • 2022
    Title Computational refocusing of Jones matrix polarization-sensitive optical coherence tomography and investigation of defocus-induced polarization artifacts
    DOI 10.1364/boe.454975
    Type Journal Article
    Author Zhu L
    Journal Biomedical Optics Express
    Pages 2975-2994
    Link Publication
  • 2022
    Title Label-free metabolic imaging of non-alcoholic-fatty-liver-disease (NAFLD) liver by volumetric dynamic optical coherence tomography
    DOI 10.48550/arxiv.2204.08249
    Type Preprint
    Author Mukherjee P
  • 2022
    Title Longitudinal investigation of a xenograft tumor zebrafish model using polarization-sensitive optical coherence tomography.
    DOI 10.1038/s41598-022-19483-z
    Type Journal Article
    Author Lichtenegger A
    Journal Scientific reports
    Pages 15381
  • 2022
    Title Optical Coherence Tomography Is a Promising Tool for Zebrafish-Based Research—A Review
    DOI 10.3390/bioengineering10010005
    Type Journal Article
    Author Lichtenegger A
    Journal Bioengineering
    Pages 5
    Link Publication
  • 2022
    Title Label-free drug response evaluation of human derived tumor spheroids using three-dimensional dynamic optical coherence tomography
    DOI 10.48550/arxiv.2211.06148
    Type Preprint
    Author El-Sadek I
  • 2022
    Title Non-destructive characterization of adult zebrafish models using Jones matrix optical coherence tomography
    DOI 10.1364/boe.455876
    Type Journal Article
    Author Lichtenegger A
    Journal Biomedical Optics Express
    Pages 2202-2223
    Link Publication
  • 2022
    Title Multicontrast investigation of in vivo wildtype zebrafish in three development stages using polarization-sensitive optical coherence tomography
    DOI 10.1117/1.jbo.27.1.016001
    Type Journal Article
    Author Lichtenegger A
    Journal Journal of Biomedical Optics
    Pages 016001-016001
    Link Publication
  • 2022
    Title Label-free metabolic imaging of non-alcoholic-fatty-liver-disease (NAFLD) liver by volumetric dynamic optical coherence tomography
    DOI 10.1364/boe.461433
    Type Journal Article
    Author Mukherjee P
    Journal Biomedical Optics Express
    Pages 4071-4086
    Link Publication
  • 2022
    Title Longitudinal investigation of a xenograft tumor zebrafish model using polarization-sensitive optical coherence tomography
    DOI 10.21203/rs.3.rs-1686888/v1
    Type Preprint
    Author Lichtenegger A
    Link Publication
  • 2023
    Title Multi-focus averaging for multiple scattering suppression in optical coherence tomography
    DOI 10.1364/boe.493706
    Type Journal Article
    Author Makita S
    Journal Biomedical Optics Express
  • 2023
    Title Label-free intratissue activity imaging of alveolar organoids with dynamic optical coherence tomography.
    DOI 10.1364/boe.488097
    Type Journal Article
    Author Morishita R
    Journal Biomedical optics express
    Pages 2333-2351
  • 2023
    Title Theoretical model for en face optical coherence tomography imaging and its application to volumetric differential contrast imaging.
    DOI 10.1364/boe.491510
    Type Journal Article
    Author Makita S
    Journal Biomedical optics express
    Pages 3100-3124
  • 2023
    Title Label-free intratissue activity imaging of alveolar organoids with dynamic optical coherence tomography
    DOI 10.48550/arxiv.2301.13114
    Type Other
    Author Morishita R
    Link Publication
  • 2021
    Title Investigation of the scattering and attenuation properties of cataracts formed in mouse eyes with 1060-nm and 1310-nm swept-source optical coherence tomography
    DOI 10.1364/boe.433927
    Type Journal Article
    Author Eugui P
    Journal Biomedical Optics Express
    Pages 6391-6406
    Link Publication
  • 2021
    Title Three-dimensional dynamics optical coherence tomography for tumor spheroid evaluation
    DOI 10.1364/boe.440444
    Type Journal Article
    Author El-Sadek I
    Journal Biomedical Optics Express
    Pages 6844-6863
    Link Publication
  • 2021
    Title Reconstruction of visible light optical coherence tomography images retrieved from discontinuous spectral data using a conditional generative adversarial network
    DOI 10.1364/boe.435124
    Type Journal Article
    Author Lichtenegger A
    Journal Biomedical Optics Express
    Pages 6780-6795
    Link Publication
  • 2023
    Title Label-free drug response evaluation of human derived tumor spheroids using three-dimensional dynamic optical coherence tomography.
    DOI 10.1038/s41598-023-41846-3
    Type Journal Article
    Author Abd El-Sadek I
    Journal Scientific reports
    Pages 15377
  • 2023
    Title Multi-focus averaging for multiple scattering suppression in optical coherence tomography
    DOI 10.48550/arxiv.2304.11309
    Type Other
    Author Makita S
    Link Publication
  • 2023
    Title Theoretical model for en face optical coherence tomography imaging and its application to volumetric differential contrast imaging
    DOI 10.48550/arxiv.2303.13139
    Type Other
    Author Makita S
    Link Publication
Disseminations
  • 2021 Link
    Title Organization and realization of the "Kinderuni" (childerns university)
    Type Participation in an activity, workshop or similar
    Link Link
  • 2022 Link
    Title Participation at the research festival in Vienna
    Type Participation in an activity, workshop or similar
    Link Link
Scientific Awards
  • 2022
    Title Reviewer of the 2022 Siegman School
    Type Appointed as the editor/advisor to a journal or book series
    Level of Recognition Continental/International
  • 2022
    Title Guest Editor in Bioengineering
    Type Appointed as the editor/advisor to a journal or book series
    Level of Recognition Continental/International
  • 2022
    Title Subcommittee chair CLEO 2022/2023
    Type Appointed as the editor/advisor to a journal or book series
    Level of Recognition Continental/International
  • 2021
    Title Award of Excellence
    Type Poster/abstract prize
    Level of Recognition Regional (any country)
Fundings
  • 2021
    Title ÖFG Travel Grant
    Type Travel/small personal
    Start of Funding 2021
    Funder Medical University of Vienna

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