Biological Systems Engineering
ASSESSMENT OF NANOPARTICLE ACCUMULATION WITH DYNAMIC CONTRAST-ENHANCED MAGNETIC RESONANCE IMAGING
Dr. Forrest Kievit
Dr. Greg Bashford
Dr. Yufeng Ge
Date of this Version
Miller, Hunter A., "ASSESSMENT OF NANOPARTICLE ACCUMULATION WITH DYNAMIC CONTRAST-ENHANCED MAGNETIC RESONANCE IMAGING" (2020). Biological Systems Engineering--Dissertations, Theses, and Student Research.
Nanoparticle (NP)-based therapeutics promise to improve medicine in multiple areas by increasing target engagement. To date, most research has focused on cancer, aiming to increase uptake using the enhanced permeability and retention (EPR) effect. Despite pre-clinical success in proof-of-concept studies, understanding of the fundamental interactions between NP and biological systems that govern outcomes remains incomplete. To realize the potential of NPs for cancer therapeutics, and to expand their application into other diseases, the roles physicochemical properties play in NP uptake must be better understood. Some investigations have been performed into the effects of size and surface charge on uptake into specific tissues and cells, but optimal properties vary by application. To investigate the role of NP properties on biological outcomes, assessment must be performed that can meaningfully compare NPs. Toward that end, a dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and kinetic modeling protocol was developed and applied to compare uptake of contrast-enhancing NPs in two animal models, traumatic brain injury (TBI) and atherosclerosis. DCE-MRI compares pre- and post-contrast images to quantify contrast agent (CA) uptake. In TBI, significantly greater accumulation was seen in focal injury than in contralateral brain. Uptake was affected by post-injury administration time in one NP, suggesting properties affect optimal administration time. In a mouse model of atherosclerosis, significantly greater NP uptake was detected in plaque regions than in control artery. Plaque phenotype did not affect uptake, but past studies and NP behavior in other applications suggest modifying NP properties may result in differential uptake between phenotype.
Advisor: Forrest M. Kievit
A thesis Presented to the Faculty of The Graduate College of the University of Nebraska In Partial Fulfillment of Requirements For the Degree of Master of Science, Major: Agricultural and Biological Systems Engineering, Under the Supervision of Professor Forrest M. Kievit. Lincoln, Nebraska: April, 2020
Copyright 2020 Hunter A. Miller