Medicine and Health Sciences Commons^™

Advancing Non-Invasive Imaging Techniques For Tracking Cellular Therapeutics In Vivo, Olivia C. Sehl

Electronic Thesis and Dissertation Repository

Cell therapies, including mesenchymal stem cells (MSC) and regulatory T cells (Tregs) have shown potent and long-lasting therapeutic benefit in several disease applications. Unfortunately, the effectiveness of these therapies is variable and following administration, it is largely unknown where therapeutic cells traffic and how many persist over time. This thesis aims to advance and compare iron- and fluorine-19 (¹⁹F)-based magnetic resonance imaging (MRI) and magnetic particle imaging (MPI) for therapeutic cell tracking.

First, we developed a trimodal imaging approach to study MSC fate in vivo. In a mouse model, iron-labeled MSC were detected by MRI and MPI, …

Investigating The Mechanisms Of Breast Cancer Metastasis Using Multimodality Molecular Imaging, Katie Parkins

Electronic Thesis and Dissertation Repository

Introduction: Breast cancer recurrence continues to be a significant challenge in the clinic. Despite successful removal and/or treatment of the original tumour, many patients experience relapse in the breast or at distant sites. Furthermore, the diagnosis of metastatic disease often occurs too late for effective treatment. Methods: In this thesis, we combine iron-based cellular MRI and longitudinal BLI to noninvasively track the fate of cancer cells into overt tumours in the mouse brain. We then apply this imaging model to study the effect of a primary breast tumour on the growth of secondary metastases in an immune competent …

Hepcidin-Mediated Iron Regulation In P19 Cells Is Detectable By Mri, Kobra Alizadeh Pourbouyeh

Electronic Thesis and Dissertation Repository

Magnetic resonance imaging (MRI) can be used to track cellular activities in the body using iron-based contrast agents. However, intrinsic cellular iron handling mechanisms may also influence the detection of magnetic resonance (MR) contrast. For instance, inflammation involves downregulation of iron export in macrophages by the hormone hepcidin, due to degradation of the iron export protein, ferroportin (Fpn). We examined the effect of hepcidin on iron regulation and MR transverse relaxation rates in multi-potent P19 cells, which display high iron export activity, similar to macrophages. In response to varying conditions of iron supplementation, our results showed similar Fpn expression in …

Development And Optimization Of 19f-Mri For Tracking Cellular Therapeutics, Jeffrey M. Gaudet

Electronic Thesis and Dissertation Repository

Introduction: This thesis aims to advance magnetic resonance imaging (MRI) for imaging cellular therapeutics. Traditional, proton-based, MRI provides detailed anatomical images, particularly of soft tissue. However, in order to obtain information at a cellular level specialized imaging agents are required to detect the cells of interest. Perfluorocarbons containing non-radioactive fluorine-19 (¹⁹F) are both biologically safe and MR sensitive. Methods: Pre-clinical ¹⁹F-MRI was implemented on a Varian 9.4T MRI scanner, using a dual ¹⁹F/¹H-tuned birdcage volume coil. Mesenchymal stromal cells (MSC) were pre-labeled with a commercial, FDA approved ¹⁹F-perfluorocarbon emulsion, then implanted intramuscularly into …

Magnetic Resonance Imaging Of Breast Cancer Brain Metastasis Progression And Responses To Radiotherapy, Donna H. Murrell

Electronic Thesis and Dissertation Repository

Introduction: The incidence of brain metastasis due to breast cancer is increasing and prognosis is poor. Treatment is challenging for this disease because systemic therapy has limited efficacy due to the presence of the blood-brain barrier. In addition, it is thought that disseminated dormant cancer cells persist in metastatic organs and may evade treatment, thereby facilitating a mechanism for later recurrence. Methods: In this thesis, we use contrast-enhanced MRI and high resolution anatomical MRI to characterize blood-brain barrier integrity associated with the development of brain metastases due to HER2+ breast cancer in the SUM-190-BR3, JIMT-1-BR3, and MDA-MB-231-BR-HER2 experimental models. We …

Magnetic Resonance Imaging Of A Natural Killer Cell Therapy In A Mouse Model Of Prostate Cancer, Christiane L. Mallett

Electronic Thesis and Dissertation Repository

Purpose: This thesis uses magnetic resonance imaging (MRI) techniques to study natural killer (NK) cell therapy in a nude mouse model of prostate cancer. Cellular MRI, anatomical MRI and hyperpolarized ¹³C spectroscopy were used to study various aspects of the model. Methods: The cells used were KHYG-1 NK cells and PC-3M prostate cancer cells. Imaging was performed on a clinical 3T GE MR 750 scanner, using a high-performance gradient insert for acquisition with the balanced steady state free precession (bSSFP) sequence, and using the built-in gradients for ¹³C pyruvate spectroscopy. Pyruvate was hyperpolarized by dynamic nuclear polarization. Results: …