Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Doctor of Philosophy

Program

Medical Biophysics

Collaborative Specialization

Molecular Imaging

Supervisor

Foster, Paula J.

Abstract

The Foster lab has been developing cellular MRI tools for well over a decade using superparamagnetic iron oxide (SPIO)-based contrast agents for numerous applications cell tracking applications. SPIO are used to label cells which are indirectly detected as regions of signal loss. The main challenge with this technique is quantification of cell number, which is important for applications such as dendritic cell (DC)-based immunotherapies where cell number is used as a predictor of immunotherapeutic response.

Magnetic particle imaging (MPI) is a novel pre-clinical modality that shows promise for cell tracking. MPI directly detects the nonlinear magnetization response of superparamagnetic iron oxide nanoparticles (SPIO), without background signal or attenuation from tissues. This allows for high cellular sensitivity, specificity, and quantification of iron. With these advantages, MPI overcomes the challenges of cellular magnetic resonance imaging (MRI).

This thesis describes our three goals for implementing MPI as a sensitive and quantitative technique for cell tracking: (i) test commercially available SPIO for MPI, (ii) quantify DC migration in vivo and (iii) test and validate novel image parameters. We contributed to the advancement of this technology by detecting as few as 1000 DC (4.4 ng) in vivo. With clinical MPI systems currently being developed, this work contributed significantly towards the development, validation, and implementation of MPI as an advanced therapeutic cell tracking modality.

Summary for Lay Audience

Imaging is one of the best ways to understand the way cells move and interact throughout the body. This can be done using different imaging systems, such as Magnetic Resonance Imaging (MRI). This technique uses a special type of iron to label cells which makes them appear as dark or black areas on images. However, MRI images are already shades of black and white; this makes seeing the cells difficult in certain areas of the body which naturally show as dark, such as long or bone. As well, it is difficult to accurately measure the number of cells from dark areas. Measuring cell number is very important in cellular imaging, especially for applications such as cancer immunotherapy. The more cells that reach their targeted areas, the better the immune response. It is important for us to have a way to measure how many cells are there so we can better understand the immunotherapeutic response. In 2019, a brand-new imaging modality was installed at the Robarts Research Institute called Magnetic Particle Imaging (MPI). MPI also detects iron labeled cells, but instead they are directly detected as a bright spot on images. This direct detection allows us to more easily determine exactly how many cells are within a certain area. This thesis describes the tools we developed for labeling cells with iron, imaging them using pre-clinical animal models, and quantifying the number of cells in images. This work helps us understand cell tracking techniques which ultimately leads to the improvement of cancer treatments.

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