Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Medical Biophysics

Supervisor

Paula J. Foster, Ph.D.

Abstract

Spinal cord injury (SCI) remains one of the most devastating conditions in medicine; it is a complex medical condition with no cure currently available. Inflammation plays an important role in SCI as it can have both beneficial and detrimental effects. Cell therapy has emerged as a promising treatment for SCI due to the potential for stem cells, including multipotent mesenchymal stromal cells (MSC), for tissue regeneration and immunomodulation of the inflammatory cascade after the initial trauma. However, there are still important, unresolved questions regarding cell therapy that magnetic resonance imaging (MRI) can help to address by producing high-resolution images with exquisite soft tissue contrast in a non-invasive, non-destructive and three-dimensional (3D) manner, allowing a dynamic view of changing pathology and cellular events in vivo.

In this thesis in vivo longitudinal imaging of SCI in mouse and rat models is presented using MRI. A resolution of 200μm in all three planes was achieved using a balanced steady state free precession (bSSFP) pulse sequence in a 3T whole-body clinical scanner. Using iron oxide particles as a contrast agent, cellular MRI was used to assess direct MSC transplantation in a mouse model and acute inflammation in a rat model. This was the first study to use cellular MRI for cell tracking in a mouse SCI model. We report on the use of cellular MRI to locate transplanted cells and monitor their overall distribution as well as to evaluate the delivery of transplanted cells to the target tissue in the early phase. Limitations of long-term cell tracking using iron oxide are also discussed. This is also the first study using cellular MRI to image in vivo cells associated with the inflammatory response within the lesion in a rat SCI model and the first demonstration of the use of bSSFP at 3T for rat body imaging.

Having the tools for longitudinal in vivo cell monitoring in SCI will help gain a better understanding of both inflammation and response to cell therapy. As these tools are refined, they can be used to test different potential treatments for SCI and optimize them.


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