Grant: Discovery Grants Program - Individual

My research program is focused on developing technologies to advance cellular and molecular imaging (CMI) with an emphasis on imaging cells. CMI enables the visualization and quantitation of cellular and molecular events in living subjects. CMI research includes multiple imaging modalities, cell labeling agents and labeling techniques. Our lab has been developing cellular magnetic resonance imaging (MRI) tools for more than a decade using both superparamagnetic iron oxide- (SPIO) and fluorine-19 (19F)-based contrast agents for numerous important applications. We have shown that SPIO-based MRI cell tracking has very high sensitivity (we were first in the world to demonstrate single cell detection), but low specificity. Contrastingly, our work has demonstrated that 19F-MRI cell tracking has high specificity, but low sensitivity. Magnetic Particle Imaging (MPI) is a new imaging modality that directly detects SPIO. SPIO-MPI cell tracking could overcome the challenges of MRI-based cell tracking allowing for both high sensitivity and high specificity cell detection. Like 19F cell tracking, MPI addresses the specificity and quantitation issues of iron-based MRI cell tracking. With MPI we "see" only the tracer, anywhere in the body, independent of depth, and with no signal from background tissue or air, and it is quantitative since image intensity is linear with the tracer concentration. Furthermore, MPI also addresses the sensitivity issue of 19F based cell tracking. The current detection limit for MPI is unknown but it has been estimated at approximately 200 labeled cells in vitro and 500 cells in vivo. In July 2019, Canada's first MPI system, a Momentum MPI scanner, was installed at the Robarts Research Institute. The overarching theme of my research program is to innovate and advance cellular imaging technologies. My long term goal is to discover, develop and validate cell tracking technologies that will improve and expand capabilities for monitoring and quantifying the fate of cells in vivo. This includes: (i) optimization and implementation of novel MRI cell tracking methods for improved cell detection, (ii) implementing complementary, multi-modality approaches for cell tracking, (iii) characterization of cellular imaging probes and (iv) to train a new generation of interdisciplinary HQP known as "Cellular and Molecular Imaging Scientists." who have expertise in a range of imaging modalities. My short-term goals revolve around the development of MPI as a sensitive, quantitative cell tracking technique to complement our suite of advanced cellular imaging approaches. Our specific goal is to improve MPI sensitivity and resolution. To achieve this goal, we have the following aims: Aim 1: To investigate and optimize MPI imaging parameters and cell labeling methods for improving cell detection by MPI. Aim 2: To develop, characterize and test different SPIOs for MPI.