BME PhD Prospectus Defense - Kavon Karrobi

  • Starts: 10:00 am on Wednesday, October 25, 2017
Title: "Monitoring of Chemotherapy Resistance with Multiscale Diffuse and Nonlinear Imaging" Committee: Prof. Darren Roblyer, BME (Advisor, Chair) Prof. Muhammad Zaman, BME Prof. Thomas Bifano, ME Prof. David Waxman, Biology Abstract: Diffuse Optical Imaging (DOI) provides endogenous hemodynamic information of biological tissue on the macroscopic scale. This is accomplished by using near-infrared light to non-invasively probe deep tissue and quantify the absorption and scattering properties of biological tissue. Over the last decade, DOI techniques have been shown to successfully predict early response to chemotherapy through distinct hemodynamic changes in breast cancer patients during pre-surgical treatment in the neoadjuvant setting. However, it is currently unknown if DOI is sensitive to chemo-resistance, let alone able to differentiate chemo-response from chemo-resistance based on tissue-level hemodynamics, as chemo-resistance is biologically distinct from initial chemo-response. Conversely, there is a growing body of evidence linking key chemo-induced microvascular dynamics with resistance to treatment. Notably, intravital microscopy methods have played an important role in characterizing these unique microvascular metrics of chemo-resistance in the preclinical setting. Thus, the overall objective of this thesis is to assess whether wide-field label-free diffuse imaging can identify treatment resistance by establishing robust correlations between tissue-level hemodynamics and key microvascular metrics of chemo-resistance. This will be accomplished through the development of a multiscale preclinical imaging technique called Diffuse and Nonlinear Imaging (DNI) that uses Spatial Frequency Domain Imaging (SFDI) for wide-field mapping of tumor hemodynamics, and Multiphoton Microscopy (MPM) to image tumor microvascular architecture with cellular resolution. DNI will then be used to monitor a resistant mammary tumor model in mice. Wide-field imaging metrics of chemo-resistance will be verified through multiscale correlations with important microvascular metrics of treatment resistance. Importantly, SFDI measures the same parameters as clinical Diffuse Optical Spectroscopy, providing a pathway to the clinic.
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