Optimized Receive Frontend Hardware for Magnetic Particle Imaging, Characterization Tools, and Biosensors

Magnetic Particle Imaging (MPI) is an emerging medical imaging modality that detects the strong magnetization of superparamagnetic iron oxide nanoparticle tracers. MPI has proven applications in angiography, stroke, stem cell tracking, white blood cell tracking, lung perfusion, traumatic brain injury, and gastrointestinal bleed imaging among many other highly critical medical imaging applications. However, MPI receive frontend hardware suffers from direct feedthrough interference as a result of simultaneous transmit and receive and is currently not optimized for higher resolution tracers that require a ten-fold wider bandwidth. In this dissertation I will discuss my PhD work that introduces methods to optimize for signal-to-noise ratio and suppress feedthrough interference for inductive sensors used in MPI, specifically for benchtop magnetic particle sensing systems.The first part will discuss design methodologies for the preamplifier and receive coil. The preamplifier can be designed for another ten-fold lower noise over a five-fold wider bandwidth despite the challenge of broadband noise matching for inductive sensors. The receive coil can be designed for a ten-fold higher sensitivity per volume and lower inductance with microcoils. The second part will discuss methods to suppress feedthrough interference with passive and active cancellation. Passive cancellation is done using gradiometric coils designed with linear programming to achieve better mechanical shimming tolerance, cancelling feedthrough by three orders of magnitude. Active cancellation using an adaptive feedforward scheme reduces feedthrough by another two orders of magnitude

Design of a more easily shimmable gradiometric coil using linear programming

Magnetic particle imaging (MPI) is a tracer imaging modality that detects superparamagnetic iron oxide nanoparticles (SPIOs), enabling sensitive, radiation-free imaging of cells and disease pathologies. The arbitrary waveform relaxometer (AWR) is an indispensable platform for developing magnetic nanoparticle tracers and evaluating tracer performace for magnetic particle imaging applications. One of the biggest challenges in arbitrary waveform excitation is direct feedthrough interference, which is usually six orders of magnitude larger than the signal from magnetic nanoparticles. Direct feedthrough is often mitigated with a gradiometric cancellation coil which requires extremely precise placement in order to achieve adequate decoupling from the transmit excitation coil. This work will showcase a coil design of a transmit coil that meets excitation capability requirements with an order of magnitude more forgiving mechanical tolerance

Brownian superparamagnetic nanoparticles for cell viability assessment in Magnetic Particle Imaging

Molecular imaging tools can noninvasively track cells in vivo. However, no techniques today can rapidly monitor cell therapies to allow for nimble treatment optimization for each patient, the epitome of Personalized Medicine. Magnetic Particle Imaging (MPI) is a new tracer imaging technology that could soon provide MDs unequivocal therapy treatment feedback in just three days. MPI with Brownian superparamagnetic iron oxide nanoparticles shows promise towards noninvasive sensing of cell viability via viscosity changes in apoptotic cells. This unique ability could greatly improve the efficacy of cell therapies by enabling rapid personalization of the treatment

Computational modeling of superferromagnetism in finite-length chains of superparamagnetic Iron Oxide tracers for use in super-resolution Magnetic Particle Imaging

Magnetic Particle Imaging (MPI) is a novel tracer imaging modality that images the spatial distribution of super- paramagnetic iron oxide nanoparticles (SPIOs), allowing for the sensitive and radiation-free imaging of labeled cells and targeted disease. Recent works have shown that at high concentrations, SPIOs display extremely sharp magnetic responses, resulting in 10-fold resolution and signal improvements. Dubbed superferromagnetic iron oxide particles (SFMIOs), these particles appear to interact with neighbours, effectively amplifying applied fields. This work performs a simulation of ensembles of linear chains of interacting SPIOs to elucidate SFMIO behavior and guide practical constraints in SFMIO synthesis. We show that working within certain physical constraints (chain length distributions and SPIO separation) preserves the improvements observed from SFMIOs

Non-radioactive imaging of bone marrow using antibody-conjugated nanoparticles in magnetic particle imaging

Bone marrowserves a crucial role in the body, producing hematopoietic stem cells and blood products. Imaging bone marrow could help doctors determine bone marrow disorders and have an early understanding of the metastatic distribution of tumors in the bone. Colloidal tracers that target the reticuloendothelial system (RES) such as the liver, spleen and bone marrow are commonly used to image bone marrow. Alternatively, antibodies specific to granulocytes, especially neutrophils, can be used to image the myeloid distribution of bone marrow. Using antibody functionalized superparamagnetic iron oxide (SPIO) nanoparticles as tracers, magnetic particle imaging (MPI) could image bone marrow in vivo. In this work, we imaged bone marrow in vivo using anti-Ly6G antibody functionalized nanoparticles that are specific towards surface antigens expressed on granulocytes

Magnetic Particle Imaging in Vascular Imaging, Immunotherapy, Cell Tracking, and Noninvasive Diagnosis

Magnetic particle imaging (MPI) is a new tracer-based imaging modality that is useful in diagnosing various pathophysiology related to the vascular system and for sensitive tracking of cytotherapies. MPI uses nonradioactive and easily assimilated nanometer-sized iron oxide particles as tracers. MPI images the nonlinear Langevin behavior of the iron oxide particles and has allowed for the sensitive detection of iron oxide-labeled therapeutic cells in the body. This review will provide an overview of MPI technology, the tracer, and its use in vascular imaging and cytotherapies using molecular targets

Self-collecting a cervico-vaginal specimen for cervical cancer screening: An exploratory study of acceptability among medically underserved women in rural Appalachia

OBJECTIVE: Innovative screening methods such as self-testing for human papillomavirus (HPV) may alleviate barriers to cervical cancer screening. The purpose of this exploratory study was to determine whether Appalachian Kentucky women would be amenable to self-collecting a cervico-vaginal specimen for HPV testing. METHODS: Women aged 30–64 who were overdue for guideline-recommended cervical cancer screening were recruited from a primary care clinic in southeastern Kentucky. The women were asked to self-collect a specimen, using a cervico-vaginal brush, based on verbal and printed directions provided by a research nurse. All study participants, regardless of laboratory-confirmed HPV status, received the same counseling on the importance of cervical cancer screening and offered navigation to follow-up Pap testing at the local health department. RESULTS: Thirty-one women were approached and recruited to participate in the study, indicating a 100% acceptance rate of HPV self-testing. Of the 31 women, 26 tested negative for high-risk HPV and five tested positive. All of the women with negative results declined nurse navigation to Pap testing, whereas four of the five women with positive results accepted nurse navigation and received subsequent Pap smear screenings (all results were normal). CONCLUSIONS: Among this sample of Appalachian Kentucky women, self-collecting a cervico-vaginal specimen for HPV testing was highly acceptable. This exploratory study provides impetus for larger studies among high-risk, medically underserved women in rural communities. Tailoring alternative cancer screening strategies to meet the complex needs of rural women is likely to lead to reductions in cervical cancer incidence and mortality among this vulnerable population