UC Berkeley

Magnetic particle imaging (MPI) is an emerging tracer imaging modality with high sensitivity and ideal image contrast. MPI uses low-frequency magnetic fields to image the spatial distribution of superparamagnetic iron oxide (SPIO) tracers. There is ideal image contrast because background tissue (bone, muscle, blood, fat) produces no MPI signal. Moreover, there is zero depth attenuation of low-frequency magnetic fields in tissue, allowing for quantitative imaging. In this dissertation, I describe several new preclinical imaging applications which take advantage of the unique physics of MPI: lung perfusion imaging, white blood cell tracking, and enzyme-responsive nanocarriers.

Pulmonary embolism (PE), a blood clot in the lung, is usually diagnosed with CT pulmonary angiography. However, patients with poor renal function are not able to tolerate the high iodine dose. The MPI tracer is kidney-safe because it clears through the liver and spleen instead of the kidneys. Moreover, imaging around air-tissue interfaces such as those in the lung do not result in imaging artifacts (unlike in magnetic resonance imaging) because of the comparably low gradient homogeneity needed. Hence, MPI has ideal properties for a kidney-safe alternative lung perfusion imaging method. In Chapter 2, I show fabrication and optimization of the first MPI lung perfusion imaging agent, MAA-SPIO, and \textit{in vivo} lung perfusion images in a rat. I quantitatively track the biodistribution and clearance of the tracer over time. Additionally, I show that the lung perfusion imaging method can be paired with a method for lung ventilation imaging using aerosolized SPIOs. This allows for imaging of both the lung capillaries and lung airways.

In Chapter 3, I discuss MPI white blood cell imaging. This technique is of particular interest for tracking autologous cell-based immunotherapies, such as chimeric antigen receptor T cells (CAR-T). Moreover, the natural homing abilities of the WBCs can localize difficult-to-find infections, such as osteomyelitis, and a similar technique is used in nuclear medicine. However, MPI allows for effective long-term cell tracking because no radionuclide tag is used. I demonstrate dynamic imaging of MPI tracer-tagged white blood cells (WBC) administered to \textit{in vivo} mice, and initial work on tracking these WBCs in a mouse model of inflammation.

In Chapter 4, I demonstrate proof-of-concept work on a concept for enzyme-responsive nanocarriers. Tracers that can visualize and respond to the function of biological and cellular processes would allow for more specific disease diagnoses. I show that aggregated SPIOs have a quenched MPI signal as compared to stably-dispersed SPIOs, and that SPIOs can be encapsulated in a liposomal formulation. In the platform described, the enzyme hydrolyzes the SPIO-containing liposomes, and MPI signal quenching is observed. These projects represent novel work in diverse categories of MPI applications research, showcasing the strengths of the unique physics of MPI.