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Development and testing of multi-modal, multi-scale imaging systems for rare-earth-doped contrast agents

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TitleInfo
Title
Development and testing of multi-modal, multi-scale imaging systems for rare-earth-doped contrast agents
Name (type = personal)
NamePart (type = family)
Higgins
NamePart (type = given)
Laura
NamePart (type = date)
1989-
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Laura Higgins
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Pierce
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Mark C
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Mark C Pierce
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Advisory Committee
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chair
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Moghe
NamePart (type = given)
Prabhas V
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Prabhas V Moghe
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Advisory Committee
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internal member
Name (type = personal)
NamePart (type = family)
Boustany
NamePart (type = given)
Nada
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Nada Boustany
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Advisory Committee
Role
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internal member
Name (type = personal)
NamePart (type = family)
Davidov
NamePart (type = given)
Tomer
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Tomer Davidov
Affiliation
Advisory Committee
Role
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outside member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
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theses
OriginInfo
DateCreated (qualifier = exact)
2016
DateOther (qualifier = exact); (type = degree)
2016-10
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2016
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
Rare-earth based nanoparticles have appealing properties for use as contrast agents in biomedical imaging. With unique luminescent properties and a refractive index that is higher than that of tissue, these versatile materials have a wide range of potential applications spanning basic science research to preclinical testing and clinical translation. The goal of this dissertation was to exploit the unique optical properties of these materials to develop new multi-modal, multi-scale imaging platforms and expand the applicability of these materials in biomedicine. Under near-infrared excitation, these particles emit conventional Stokes-shifted fluorescence in the short wave infrared region (SWIR), as well as a higher-energy upconversion signal in the visible spectrum. Previous work, focused on wide-field imaging of the SWIR fluorescence, has shown the ability to detect the accumulation of biofunctionalized rare-earth albumin nanocomposites (fREANCs) in preclinical models of cancer metastasis. This dissertation builds upon previous studies, exploring high- resolution imaging of these particles to serve as an “optical biopsy” through the combination of confocal microscopy and optical coherence tomography (OCT). Confocal microscopy provides subcellular resolution imaging from near the tissue surface while OCT is capable of imaging tissue microstructure up to 1-2 mm below the surface, both important factors in the evaluation of disease progression. High-resolution imaging of these materials in thick tissues has been limited by the long emission lifetimes of the rare-earth elements. This work demonstrates that line- scanning confocal microscopy (LSC) can overcome these challenges by extending the excitation and emission time while maintaining frame rate, providing a method for real- time, high-resolution imaging of rare-earth doped contrast agents in ex vivo tissue samples. Although the refractive index mismatch did not increase OCT backscattering in tissue, motivating the development of fREANCs as a molecularly-targeted OCT contrast agent, OCT can still provide valuable insight into tissue disease state based on native optical properties. From this work, a multi-modal imaging platform was developed combining OCT with line-scanning confocal microscopy of fREANCs. A first-generation proof-of-concept system, combining OCT with full-field fluorescence microscopy allowed for the identification of potential technical challenges, before integrating OCT within the line- scanning microscope. Through the combination of LSC and OCT, the second-generation system achieved an en face lateral resolution of 2.8 μm (LSC) with an imaging depth of 1.4 mm (OCT). Finally, this multi-modal imaging platform was evaluated within a preclinical study, designed to explore multi-scale imaging of fREANCs to identify tumors in the lungs. Through this work, signature features of healthy and malignant tissue were identified within the multi-modal image sets, with the potential to serve as a basis for future high-resolution in vivo imaging as a method of “optical biopsy” in the presence of fREANCs. More generally, the technical development of multi-scale, multi-modal imaging presented here, ranging from the macroscopic to microscopic scale, may be beneficial across a broad range of emerging applications for rare-earth based nanoscale contrast agents.
Subject (authority = RUETD)
Topic
Biomedical Engineering
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Title
Rutgers University Electronic Theses and Dissertations
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ETD
Identifier
ETD_7569
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electronic resource
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application/pdf
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text/xml
Extent
1 online resource (xv, 107 p. : ill.)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Laura M. Higgins
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
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NjNbRU
Identifier (type = doi)
doi:10.7282/T3ZP48FB
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Higgins
GivenName
Laura
MiddleName
M.
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2016-09-13 20:00:12
AssociatedEntity
Name
Laura Higgins
Role
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Affiliation
Rutgers University. Graduate School - New Brunswick
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Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
RightsEvent
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2016-10-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2018-10-31
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after October 31st, 2018.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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2016-09-15T20:34:19
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2016-09-15T20:34:19
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