Date of Award

2006

Degree Type

Thesis

Degree Name

Master of Science

Program

Medical Biophysics

Supervisor

Dr. Paula Foster

Second Advisor

Dr. Greg Dekaban

Third Advisor

Dr. Steve Karlik

Abstract

The thesis herein addresses an important, yet unresolved, problem in the field of cellular MRI. The natural ability of macrophages to engulf foreign particles has made them ideal candidates for taking up cellular MR labels in vivo. In multiple sclerosis, macrophage populations in the circulation increase substantially as they home to the CNS where they cause a massive and destructive inflammatory response. Labeling macrophages in the circulation and being able detect and track them in the CNS can significantly improve the prognosis of MS and thus aid in the correct identification of a treatment plan. However, it remains unknown whether it is indeed labeled macrophages from the circulation that are detected on MR images or whether they are different cell populations actively involved in MS. In the present thesis, two novel methods are used to determine the source of the MR label in the CNS. One study utilizes a transgenic mouse where peripheral macrophages express the green fluorescent protein while other cell populations do not. Another study utilizes clodronate liposomes to deplete the’ macrophage population in the circulation prior to injection of the MR label. By using the mentioned two approaches it was determined that the source of label on MR images is largely attributed to peripheral macrophages from the circulation. The findings illustrated in this thesis will have a major impact on our understanding of neuroinflammation in multiple sclerosis and on the development of diseasemodifying therapies.

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