First Advisor

Mark Woods

Date of Publication

Spring 9-29-2017

Document Type

Thesis

Degree Name

Master of Science (M.S.) in Chemistry

Department

Chemistry

Language

English

Subjects

Magnetic resonance imaging, Contrast media (Diagnostic imaging)

DOI

10.15760/etd.5829

Physical Description

1 online resource (xv, 156 pages)

Abstract

Generating MR image contrast from exogenous contrast media through chemical exchange saturation transfer (CEST) offers several exciting new possibilities, such as multicolored imaging, the interleaving of pre- and post-contrast images, and the potential to perform ratiometric metabolic imaging. The major limitation of the deployment of CEST imaging is the comparatively high detection limits of exogenous agents and particularly at the low B1 power levels required to meet SAR requirements. The large chemical shifts afforded by paramagnetic (paraCEST) agents permit more rapid exchange kinetics and therefore potentially more effective contrast agents. Despite comparatively large chemical shifts, many Ln3+ DOTA-tetraamide (DOTAM) chelates traditionally investigated as CEST agents are predicted to have exchange kinetics that are considerably faster than optimal at very low B1 powers. This work explores two methodologies for slowing water exchange kinetics in Ln3+ DOTAM chelates and improving CEST imaging: structural manipulation and encapsulation. In the first method, rigid Ln3+ NB-DOTAM chelates with hydrophobic amide substituents was thoroughly studied using NMR spectroscopy techniques in order to assess their ability to produce CEST contrast at low B1 power levels.

NMR techniques utilized included 1H NMR, variable temperature, COSY, and CEST experiments. The phenyl amide substituent in the pseudo-axial position afforded chelates with considerably slow water proton exchange rates and appreciably more CEST contrast than isomeric chelates with the amide substituent in the pseudo-equatorial position. The second method involved characterizing a vesicle system to be used for encapsulating a Ln3+ DOTAM chelate. The vesicles prepared were analyzed using the following NMR techniques: 1H NMR, T1, shift reagent, and CEST experiments. The vesicle system chosen for study did not afford slow water exchange kinetics to enhance CEST contrast. A second vesicle system was attempted but the vesicle synthesis was difficult, parameters studied were not optimized, and the second system did not exhibit slow water exchange with the limited amount of experiments run and data collected.

Rights

In Copyright. URI: http://rightsstatements.org/vocab/InC/1.0/ This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).

Persistent Identifier

http://archives.pdx.edu/ds/psu/22146

Download

Share

COinS