The design, evaluation, and application of ultrasensitive nanoparticle contrast agents for high resolution functional in vivo imaging studies and preclinical diagnostics

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Abstract/Contents

Abstract
In this dissertation, I explore the use of noble metal nanoparticles called large gold nanorods (LGNRs) as exogenous contrast agents in conjunction with optical coherence tomography (OCT), a high-resolution biomedical imaging modality. First, I study surface chemical properties and modifications of LGNRs to adapt them for in vivo use and demonstrate their optical enhancements relative to nanorods of conventional proportions. Along with colleagues, I proceed to characterize concentration-dependent trends in OCT contrast produced by LGNRs (and scattering media in general); demonstrate spectrally-encoded detection of LGNRs in vivo to improve visualization of microvasculature in tumor models and enable functional mapping of lymphatic capillary networks; and leverage the porosity of intratumoral blood vessels to deliver LGNRs to the tumor stroma, whereupon they accumulate in tumor-associated leukocytes, effectively enabling immune cell tracking studies in solid tumors. In addition to contrast agent development and applications for in vivo imaging, I and colleagues report a method based on hyperspectral microscopy to explore the interactions between nanoparticles and mammalian tissues in ex vivo settings. The method, called HSM-AD, is proposed as a new approach for characterizing nanoparticle biodistribution. The research component of this dissertation concludes with the use of HSM-AD in conjunction with traditional biodistribution methods to yield data that may compel preclinical exploration of nanoparticle contrast agents in judiciously selected diagnostic instances. I conclude with a brief perspective on future directions of the reported work and a small reflection.

Description

Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2017
Issuance monographic
Language English

Creators/Contributors

Associated with SoRelle, Elliott Daniel
Associated with Stanford University, Biophysics Program.
Primary advisor De la Zerda, Adam
Thesis advisor De la Zerda, Adam
Thesis advisor Brandman, Onn
Thesis advisor Chu, Steven
Thesis advisor Moerner, William
Advisor Brandman, Onn
Advisor Chu, Steven
Advisor Moerner, William

Subjects

Genre Theses

Bibliographic information

Statement of responsibility Elliott Daniel SoRelle.
Note Submitted to the Program in Biophysics.
Thesis Thesis (Ph.D.)--Stanford University, 2017.
Location electronic resource

Access conditions

Copyright
© 2017 by Elliott Daniel SoRelle
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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