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Title page for ETD etd-07242015-131619


Type of Document Dissertation
Author Tucker-Schwartz, Jason Michael
URN etd-07242015-131619
Title Development of Photothermal Optical Coherence Tomography for In Vivo Imaging of Contrast Agents
Degree PhD
Department Biomedical Engineering
Advisory Committee
Advisor Name Title
Melissa Skala Committee Chair
Craig Duvall Committee Member
Duco Jansen Committee Member
Sharon Weiss Committee Member
Tom Yankeelov Committee Member
Keywords
  • imaging
  • optical coherence tomography
Date of Defense 2015-07-13
Availability unrestricted
Abstract
Sensitive and specific noninvasive in vivo imaging of contrast agents and endogenous molecules can supply molecular and functional information in animal models, providing essential insight into mechanisms of disease formation and progression, drug delivery, and treatment response. In cancer in particular, high resolution imaging is essential for capturing spatial heterogeneities in molecular expression and the tumor microenvironment that cause significant barriers to treatment efficacy and drug delivery. Optical coherence tomography (OCT) fills the niche of cellular-level resolution and penetration depths in tissue that exceed those obtained with microscopy, an attractive regime for imaging mouse models of cancer. In this dissertation, photothermal OCT (PTOCT), a functional extension of OCT, was developed for in vivo imaging of a variety of contrast agents and drug delivery vectors in live animals. The PTOCT signal was thoroughly characterized in phantoms and compared to theory, followed by a demonstration of picomolar sensitivity to gold nanorod contrast agents. Gold nanorods at physiologically relevant concentrations were then identified from within a live mouse at depths exceeding the standard limits of high resolution optical microscopy. Then, heterogeneities in gold nanorod delivery to tumors were imaged in the context of tissue and vessel morphology, demonstrating the utility of PTOCT as part of a powerful multimodality imaging platform for the development of nanomedicines and drug delivery technologies. The uptake of gold nanorods into mouse mammary tumors were tracked in three dimensions over 24 hours, and the specificity of the PTOCT signal was verified using multiphoton microscopy. Finally, photothermal optical lock-in optical coherence tomography (poli-OCT) was used to increase system throughput and allow for real time photothermal imaging. In vivo poli-OCT of indocyanine green identified lymphatic vessels in a mouse ear, and also identified picomolar concentrations of gold nanorods in subcutaneous injections at frame rates ten times faster than previously reported. Overall, the development of in vivo PTOCT combined with existing morphological and hemodynamic imaging capabilities of OCT will enable more comprehensive studies of drug delivery and molecular expression in mouse models of disease, particularly cancer.
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