UC Berkeley

Magnetic particle imaging (MPI) is a sensitive, high contrast tracer modality that directly images superparamagnetic iron oxide nanoparticles (SPIOs), enabling radiation-free theranostic imaging. With zero tissue signal, persistent biosafe tracers, and no ionizing radiation, MPI has shown great promise for cell tracking, vascular imaging, and imaging applications. Indeed, its capability for multi-month studies and exquisite contrast position itself uniquely for immune-cell based diagnoses and extended monitoring of immunotherapies. However, MPI resolution is currently limited by scanner and particle constraints. Recent tracers have experimentally shown 10x resolution and signal improvements, with dramatically sharper M-H curves. Experiments suggest that this results from interparticle interactions, conforming to literature definitions of superferromagnetism. We thus call our tracers superferromagnetic iron oxide nanoparticles (SFMIOs). While SFMIOs provide excellent signal and resolution, they exhibit hysteresis, with non-negligible remanence and coercivity. In my dissertation I provide the first report on MPI scanning with remanence and coercivity, including the first quantitative measurements of SFMIO remanence decay and reformation using a novel multi-echo pulse sequence. We also describe an SNR-optimized pulse sequence for SFMIOs under human electromagnetic safety limitations. I separately investigate ex vivo and in situ labeling neutrophils and macrophages and tracking to inflammation and immune activity with XY Zhou and P Chandrasekharan. I demonstrate the first antibody MPI (Ab-MPI) images using antibody-conjugated SPIOs (Ab-SPIOs), showing bone marrow and sites of lipopolysaccharide-induced myositis. Through bioluminescent imaging, electron microscopy, flow cytometry and histopathology, I confirm labeling and tracking of neutrophils and macrophages. Excitingly, our images are able to differentiate between the acute inflammation response from neutrophils, and the chronic response from macrophages. With the resolution improvements from SFMIOs, which could be used to reduce hardware costs by 100x, and the demonstrated applications of Ab-SPIOs, MPI demonstrates incredible potential for clinical diagnosis and immunotherapy monitoring.