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The Development of Field Dependent M...

Harrison, Victoria S. R.

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The Development of Field Dependent Multimodal Imaging Probes.

Record Type:	Electronic resources : Monograph/item
Title/Author:	The Development of Field Dependent Multimodal Imaging Probes./
Author:	Harrison, Victoria S. R.
Description:	241 p.
Notes:	Source: Dissertation Abstracts International, Volume: 76-10(E), Section: B.
Contained By:	Dissertation Abstracts International76-10B(E).
Subject:	Analytical chemistry. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3705262
ISBN:	9781321781502

The Development of Field Dependent Multimodal Imaging Probes.
Harrison, Victoria S. R.

The Development of Field Dependent Multimodal Imaging Probes. - 241 p.

Source: Dissertation Abstracts International, Volume: 76-10(E), Section: B.

Thesis (Ph.D.)--Northwestern University, 2015.

Magnetic Resonance Imaging (MRI) can be used to obtain high resolution, tomographic images of opaque organisms through the perturbation of water proton nuclear spins. Unlike other imaging modalities, it does not require the use of ionizing radiation or optically clear samples, making it well suited to non-invasive longitudinal studies. Because of this, MRI has become a major focus of translational imaging research, with the ultra-high resolution achievable with high-field magnets making it particularly well suited to applications such as the fate mapping transplanted stem cells, detecting cancer, and tracking of gene expression.

ISBN: 9781321781502Subjects--Topical Terms:

3168300
Analytical chemistry.

The Development of Field Dependent Multimodal Imaging Probes.
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100 1 $a Harrison, Victoria S. R. $3 3192981
245 1 4 $a The Development of Field Dependent Multimodal Imaging Probes.
300 $a 241 p.
500 $a Source: Dissertation Abstracts International, Volume: 76-10(E), Section: B.
500 $a Adviser: Thomas J. Meade.
502 $a Thesis (Ph.D.)--Northwestern University, 2015.
520 $a Magnetic Resonance Imaging (MRI) can be used to obtain high resolution, tomographic images of opaque organisms through the perturbation of water proton nuclear spins. Unlike other imaging modalities, it does not require the use of ionizing radiation or optically clear samples, making it well suited to non-invasive longitudinal studies. Because of this, MRI has become a major focus of translational imaging research, with the ultra-high resolution achievable with high-field magnets making it particularly well suited to applications such as the fate mapping transplanted stem cells, detecting cancer, and tracking of gene expression.
520 $a The need to differentiate regions of tissues or organs that are magnetically similar but histologically distinct has been a major impetus for the development of MR contrast enhancement agents (CAs). These agents selectively shorten the longitudinal (T1) or transverse ( T2) relaxation times of water in the region of interest, allowing the visualization of a wide range of otherwise undetectable biomarkers. The efficacy with which a CA shortens T1 is termed its relaxivity; agents with higher relaxivities are more sensitive and are detectable at lower concentrations.
520 $a Unfortunately the design strategies that lead to high relaxivities at low field strengths (slow rotational motion; protein binding; optimized water exchange) do not apply at higher fields. As MR imaging increasingly moves to higher fields due to improved resolution and faster acquisition time, it thus becomes important to design new agents that have excellent properties over a broader range of imaging field strengths.
520 $a Part I of this thesis describes the development of a new class of MR probes that have high relaxivities at increased magnetic field strengths. These probes are built off of a modular architecture which incorporates azide bearing Gd(III) chelates, alkyne modified scaffolds and a functional group for further modification. This system was designed so that optimal scaffolds, contrast agents, and secondary functionality can be selected independently of each other and combined using standardized methods. Chapter Two describes the development and synthesis of the original trialkyne scaffold and azide functionalized chelate. This design lead to a contrast agent which performed 450% better than clinical agents at high field strengths. Chapter Three details further optimization of the scaffold developed in Chapter Two. Additional contrast agents were clicked onto the central core in the hopes of lengthening tau R and boosting relaxivity. To further amplify relaxivity, a number of gadolinium chelates with reduced water residence lifetimes (taum) were developed.
520 $a Part II of this thesis details the development of a series of MR-optical probes that can co-register and validate imaging information from both MR and fluorescence data. Chapter Four details the development of a multimodal agent for cell labeling applications. The agent is based off of the scaffold developed in Chapter Two and consists of three macrocyclic Gd(III) chelates conjugated to a fluorophore. The modular synthesis developed here is amenable for the incorporation of a variety of fluorophores to generate molecular constructs for a number of applications. Chapter Five details the development of two NIR-conjugated MR contrast agent which can be used in vivo due to near-IR emission wavelengths and preferential accumulation in tumors. A detailed discussion of these agent's synthesis, photophysical properties, relaxivity, and unusual cell-labeling proficiency takes place in this chapter.
590 $a School code: 0163.
650 4 $a Analytical chemistry. $3 3168300
650 4 $a Organic chemistry. $3 523952
650 4 $a Inorganic chemistry. $3 3173556
690 $a 0486
690 $a 0490
690 $a 0488
710 2 $a Northwestern University. $b Chemistry. $3 1030729
773 0 $t Dissertation Abstracts International $g 76-10B(E).
790 $a 0163
791 $a Ph.D.
792 $a 2015
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3705262