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    Multimodal Imaging of Tumor Microenvironment in Murine Window Chamber Models Using Optical, Magnetic Resonance, and Nuclear Imaging Techniques

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    Author
    Leung, Hui Min
    Issue Date
    2015
    Keywords
    Hyperspectral imaging
    Magnetic resonance imaging
    Multimodal imaging
    Patient derived xenografts
    Response to treatment
    Optical Sciences
    Breast cancer
    Advisor
    Gmitro, Arthur F.
    
    Metadata
    Show full item record
    Publisher
    The University of Arizona.
    Rights
    Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
    Abstract
    Pre-clinical study of cancer often involves imaging different aspects of a tumor, ranging from visualizing sub-cellular detail to imaging of the tumor anatomy. Multimodal imaging seeks to combine imaging techniques with complementary strengths and use them to provide a more complete picture of the disease. In this dissertation work, the development of various optical, nuclear and magnetic resonance imaging (MRI) techniques applicable to the study of cancer xenografts in murine window chamber models was carried out. Two types of window chamber models were used in this work: the dorsal skinfold WC (DSFWC) model and the mammary WC (MWC) model. The MWC was specifically used to study breast cancer xenografts. In this work, optical pH imaging with a pH-sensitive fluorescent agent was used to evaluate methods to achieve tumor-specific pH modulation. Temporary tumor acidification was performed by administration of an agent that consists of glucose and meta-iodobenzylguanidine. On the other hand, re-normalization of pHₑ in acidic tumor tissue was achieved by administration of buffer solutions, such as sodium bicarbonate. A broadband reflectance spectral imaging system was developed to perform in vivo imaging of oxygen saturation in the MWC murine model. The imaging system was used to study tissue oxygenation changes in animals that receive chemotherapy. Preliminary results were obtained to evaluate the utility of the MWC murine model in imaging the spatiotemporal changes in oxygen saturation (SaO₂) as an early biomarker of response to neo-adjuvant chemotherapy. To study metabolic activity, nuclear imaging of radiolabeled fluorodeoxyglucose (18F-FDG) was carried out using a beta-imager, as well as a pre-clinical PET system. The 2D nuclear imaging capability of the beta-imager was cross-validated with the 3D PET imaging system. Anatomical and functional MRI was performed on the MWC murine model. Anatomical MRI was used to study tumor growth rates, which aid in the identification of animals that responded to chemotherapy. In addition, diffusion-weighted (DW) MRI, dynamic-contrast-enhancement (DCE) MRI, and perfusion MRI were performed to study various functional aspects of the tumor xenografts. Lastly, work was done to incorporate patient derived xenograft (PDX) tumors into the MWC murine model. As opposed to xenografts grown from cultured cancer cells, PDX tumors better recapitulate characteristics of human tumors. This new cancer model is aimed at improving the translational power of pre-clinical studies employing window chamber models.
    Type
    text
    Electronic Dissertation
    Degree Name
    Ph.D.
    Degree Level
    doctoral
    Degree Program
    Graduate College
    Optical Sciences
    Degree Grantor
    University of Arizona
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