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.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-07242015-131619 |
| Date | 28 July 2015 |
| Creators | Tucker-Schwartz, Jason Michael |
| Contributors | Melissa Skala, Craig Duvall, Duco Jansen, Sharon Weiss, Tom Yankeelov |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-07242015-131619/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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