Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Medical Biophysics

Supervisor

Dr. Neil Gelman

2nd Supervisor

Dr. Donna Goldhawk

Joint Supervisor

Abstract

Reporter gene-based methods of labeling cells with iron is an emerging method of providing magnetic resonance imaging (MRI) contrast for long-term cell tracking and monitoring of cellular activities. This thesis investigates 9.4 T NMR properties of mammalian cells over-expressing a magnetotactic bacterial putative iron transport gene, MagA, and the associated untransfected parental cells. Cells were cultured in medium alone or supplemented with 250 μM ferric nitrate. Using the Carr-Purcell-Meiboom-Gill sequence, the relationship between R2 and interecho time was analyzed for each of the cell types using a model based on water diffusion in weak magnetic field inhomogeneities (Jensen and Chandra, 2000) as well as a fast-exchange model (Luz and Meiboom, 1963). Iron levels were assessed with inductively-coupled plasma mass spectrometry. As expected from previous work, the iron content in iron-supplemented, MagA-expressing cells was higher than the unsupplemented or parental cell lines. With regard to NMR, increases in R2 with increasing interecho time were typically greatest in the cells containing higher iron content. The dependence of R2 on interecho time in iron-supplemented, MagA-expressing cells was better represented by the Jensen-Chandra model compared to the Luz-Meiboom model, which is consistent with comparisons of these models in iron-containing tissues. On the other hand, the Luz-Meiboom model performed better than the Jensen-Chandra model for the remaining cell types. These findings provide insight into the high field relaxation mechanisms present in cells expressing a candidate MR reporter gene, which should be valuable for optimizing MRI contrast for long-term cell tracking and monitoring of cellular activities.

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