Hardware Innovations and Biomedical Applications of Magnetic Particle Imaging

Magnetic particle imaging (MPI) shows extraordinary promise for biomedical applications: it is highly sensitive, linearly quantitative anywhere in the body, has zero signal from biological tissue, and is safe for patients. One of the major challenges in MPI is spatial resolution, which is fundamentally governed by selection field gradient strength and nanoparticle properties. In Chapter 3 of this dissertation, I describe the design and construction of a high gradient field-free line (FFL) scanner for improved spatial resolution. This is the world's first iron return MPI scanner, and the highest resolution FFL imager in the world. Armed with MPI-tailored nanoparticles created by our collaborators at the University of Washington and Lodespin Labs, we were able to achieve 700 micron resolution in vivo. We also successfully demonstrated dynamic projection MPI as well as 3D projection reconstruction MPI with this scanner. In addition to hardware innovations, I have also demonstrated the use of MPI in two very important applications, namely cancer imaging and gastrointestinal (GI) bleed detection. In Chapter 2 of this dissertation, I demonstrated the first use of MPI for in vivo cancer imaging with systemic tracer administration. Due to the enhanced permeability and retention (EPR) effect, the tumor was highlighted with tumor-to-background ratio of up to 50. The nanoparticle dynamics in the tumor was also well appreciated, with initial wash-in on the tumor rim, peak uptake at 6 hours, and eventual clearance beyond 48 hours. In Chapter 4 of this dissertation, I demonstrated the first use of MPI along with long-circulating, PEG-stabilized SPIOs for rapid in vivo detection and quantification of GI bleed. MPI-tailored, long-circulating SPIOs were systemically administered into a disease model of GI bleed. The tracer biodistribution was then tracked over time using our custom-built high resolution FFL MPI scanner which was described in Chapter 3. Dynamic MPI projection images captured tracer accumulation in the lower GI tract with excellent contrast. The robust contrast, sensitivity, safety, ability to image anywhere in the body, along with our MPI-tailored long-circulating SPIOs, demonstrates the outstanding promise of MPI as a clinical diagnostic tool