Graduate Studies

 

First Advisor

Forrest Kievit

Degree Name

Doctor of Philosophy (Ph.D.)

Committee Members

Gregory Bashford, Rebecca Wachs, Ryan Pedrigi

Department

Biomedical Engineering

Date of this Version

8-2025

Document Type

Dissertation

Citation

A dissertation presented to the Graduate College of the University of Nebraska in partial fulfillment of requirements for the degree of Doctor of Philosophy

Major: Biomedical Engineering

Under the supervision of Professor Forrest M. Kievit

Lincoln, Nebraska, August 2025

Comments

Copyright 2025, Evan Timothy Curtis. Used by permission

Abstract

Advances in magnetic resonance imaging (MRI) provide the opportunity to investigate research questions that have been left unanswered. In the cases of traumatic brain injury (TBI) and carotid artery atherosclerosis, MRI is a resource for non-invasively viewing the phenomena taking place. Additionally, potential interventions and treatments can be observed without harm to the subject. This dissertation expands the understanding of two preclinical applications of MRI: traumatic brain injury and carotid artery atherosclerosis in mouse models.

TBI is a leading cause of death and disability for individuals between 15–45 years of age and effective pharmaceutical interventions for treating the secondary damage associated with TBI are limited. Here, we investigate using MRI a potential treatment’s effect in a TBI mouse model. In the study we observed the extent of vasogenic edema formation using T2-weighted images. Furthermore, advanced MRI techniques were explored for evaluating the microstructure and metabolite composition of the brain. The results suggest that a copolymer nanoparticle (NPC3) has the potential to mediate edema.

In carotid artery atherosclerosis, MRI was applied to measure the lumen area of the carotid artery in a mouse model. To better understand the environment conducive to plaque formation and regression a cuff was placed on the left carotid artery. Upstream and downstream lumen areas relative to cuff placement were determined with a gradient echo pulse sequence. The measurement revealed that lumen areas returned to baseline sizes after cuff removal, which is evidence that cuff removal after five-weeks restores carotid artery lumen patency.

This dissertation demonstrates how advanced MRI techniques can be used to gain insights into two major areas of preclinical research: traumatic brain injury and carotid artery atherosclerosis. By combining structural, diffusion-based, and spectroscopic imaging modalities, MRI reveals both microstructural damage and metabolic disruption following TBI, and that treatment with NPC3 may offer a neuroprotective effect. Similarly, in the carotid artery model, non-invasive MRI enabled precise, longitudinal assessment of vascular remodeling in response to mechanical injury and recovery. Together, using the power of MRI to non-invasively monitor pathophysiological processes and therapeutic responses in vivo, this work provides original imaging evidence of nanoparticle mediation of vasogenic edema in TBI and the tracking of lumen area in a plaque regression model of atherosclerosis.

Advisor: Forrest M. Kievit

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