The design, evaluation, and application of ultrasensitive nanoparticle contrast agents for high resolution functional in vivo imaging studies and preclinical diagnostics
- 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.
|Type of resource
|electronic; electronic resource; remote
|1 online resource.
|SoRelle, Elliott Daniel
|Stanford University, Biophysics Program.
|De la Zerda, Adam
|De la Zerda, Adam
|Statement of responsibility
|Elliott Daniel SoRelle.
|Submitted to the Program in Biophysics.
|Thesis (Ph.D.)--Stanford University, 2017.
- © 2017 by Elliott Daniel SoRelle
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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