Establishment of new UK/Canada Collaboration towards the Advancement of Magnetic Particle Imaging (MPI)

The intention for this research exchange is to provide unique knowledge exchange and expertise around Magnetic Particle Imaging (MPI). MPI is a new, emerging imaging modality which detects nanomolar concentrations of Superparamagnetic Iron Oxide Nanoparticle (SPION) tracers in vivo. The University of Liverpool (UoL) recently installed the Momentum MPI Scanner from Magnetic Insight inc. (August 2023) following successful EPSRC Strategic Award funding; the first in the UK and one of only 12 worldwide. This includes the lab at the University of Western Ontario (UWO), who installed the equivalent system in 2019. The laboratory at UWO is world renowned for pioneering research in in vivo cell tracking studies and is an early contributor to the advancement and implementation of MPI for regenerative medicine investigation.

The fundamental methodology of MPI is to detect the non-linear response of SPIONs under application of a sinusoidal drive magnetic field. The technique employs a non-uniform field distribution to define an image voxel, known as the Field-Free Point (FFP). SPION tracers are imaged directly, which allows for highly sensitive, quantitative detection with no background signal. Thus, MPI is a powerful, innovative technology for cell tracking studies enabling quantitative assessment of transplanted labelled cell therapies, providing real-time biodistribution and safety information in areas of the body where other imaging modalities fail.
Importantly, the optimal SPION tracer for MPI is still unknown; to date, expensive commercial materials that were developed for use in MRI are the main tracers employed for MPI use across all in vitro and in vivo studies. Furthermore, as global access to MPI equipment to date has been rare, there is no defined analytical protocol for measurement employed across all research groups. This will become of increasing importance as global access to equipment grows and research output accelerates.

The aim for this exchange is to develop research synergies between material science and physics groups at UoL with biological application research at UWO towards:

- Optimal SPION tracer development
- Standardised data analysis and quantification
- Cross-disciplinary knowledge exchange

The UoL group comprises materials chemistry focused on SPION synthesis specifically designed for MPI. The UWO group is the reverse and is composed of biophysicists using commercial materials for MPI predominantly for cell tracking studies. Universal standardised data analysis and quantification through co-operative development and demonstration between the two research groups will allow for MPI as an emerging technology to accelerate through common analytical practice. Likewise, co-operative SPION synthesis will develop optimal SPIONs specific for MPI in and regenerative medicine applications.

MPI detects the non-linear magnetisation response of SPIONs under application of a sinusoidal drive magnetic field. Signal intensity and resolution derives from SPION Relaxation, which is a combination of Brownian (whole particle) and Néel (magnetic moment) relaxation. Broadly speaking, Brownian relaxation dominates for larger particles and Néel relaxation dominates for smaller particles, with theory estimating a SPION core size of 25-30 nm for optimal MPI signal. SPION nanostructures with various shapes and surface chemistry will be synthesised with high precision by thermal decomposition and co-precipitation methods. Synthesis will be facilitated by the Momentum MPI software modules Relax and MAGimage, which interrogate such Brownian and Néel relaxation processes to facilitate optimal SPION synthesis in terms of MPI signal generation. Optimisation towards biological application will arise through SPION surface modification. This will include silica shell growth and/or addition of functionalised surface stabilisers such as carbohydrates (dextran/carboxydextran) or amphiphilic block co-polymers. In addition to the MPI scanner, SPION synthetic analysis will include x-ray diffraction, transition electron microscopy and magnetometry. Biological evaluation will include cell accumulation assays for optimal cell uptake analysis.
Strategies for MPI data analysis and quantification will be developed so that data can be shared and compared across our institutes, and others. This will involve testing of novel SPIONs and SPION-labelled stem cell samples in both labs and will include methods for signal calibration and accurate quantification of cell number, measurements of image noise, standard sample preparation, analysis of ROI size and placement, image reconstruction and comparisons of the magnetic properties of newly synthesised SPIONs for MPI.