Magnetic Particle Imaging - Anwendungen von magnetischen Nanopartikeln in Analytik und Bildgebung

Magnetic Particle Imaging (MPI) is a new imaging modality that delivers tracer-based volume images with high spatial and temporal resolution. The properties of the nanoparticular tracer, that needs to be present in the imaging volume for MPI to render image contrast, have direct impact on the MPI performance. The magnetization dynamics of the superparamagnetic nanoparticles are a critical factor in MPI system design. However, once understood and numerically modelled the particle's magnetization dynamics are key to enabling functional imaging with MPI based on potential particle functionalization. This thesis describes the development of a magnetic particle imaging scanner and its accompanying particle characterization technique, magnetic particle spectroscopy (MPS). The devices have been designed, built and tested to deliver insights into particle dynamics and to function as a prototype platform for MPI research. That includes the scanner hardware as well as the software for modelling the particle's magnetization response and image reconstruction. The main focus is on the development and evolution of the so called 'Mobility MPI' (mMPI) which promises to provide an estimate of the particle mobility, including the hydrodynamic diameter of the particles and the viscosity of the surrounding medium, in additional to the standard concentration-weighted MPI image. By allowing a discrimination between Néel and Brownian contributions, mMPI in conjunction with a suitable tracer enables binding detection in the imaging volume. The harmonic spectrum connected with the dynamic magnetization response of the tracer is studied in MPS. The ability for conducting bio-assays with MPS is explored and the results are evaluated in context of appropriate numerical models. Furthermore, the effect of viscosity on the MPI system matrix is studied and different approaches for deducing mobility information from an MPI experiment are investigated.Magnetic Particle Imaging (MPI) ist eine neue Bildgebungsmodalität, die Volumenbilder mit hoher räumlicher und zeitlicher Auflösung liefert. Die Eigenschaften des nanopartikulären Markers, der im Bildgebungsvolumen anwesend einen Bildkontrast generiert, haben dabei direkten Einfluss auf die MPI-Performance. Die Magnetisierungsdynamik der superparamagnetischen Nanopartikel ist auch ein entscheidender Faktor im MPI Systemdesign. Ein eingehendes Verständnis und die numerische Modellierung der Partikel-Magnetisierungsdynamik kann dabei ein Schlüssel zur Realisierung von funktionaler Bildgebung im MPI sein, die auf einer möglichen Funktionalisierung der Partikel beruht. Diese Arbeit beschreibt die Entwicklung eines Magnetic Particle Imaging Scanners und der dazugehörigen Charakterisierungstechnik, der Magnetic Particle Spektroscopy (MPS). Die Geräte wurden dabei entwickelt, gebaut und getestet, um Einblicke in die Partikeldynamik zu geben und um als Prototyp-Plattform für die MPI-Forschung zu dienen. Das schließt sowohl die Scanner-Hardware als auch die Software zur Modellierung der dynamischen Partikelantwort und zur Bildrekonstruktion ein. Der Fokus liegt hierbei auf der Entwicklung des sogenannten 'Mobility MPI' (mMPI), welches eine Bestimmung der Partikelbeweglichkeit zusätzlich zur konventionellen konzentrations-gewichteten MPI-Bildgebung ermöglicht. Die Partikelbeweglichkeit umfasst dabei den hydrodynamischen Durchmesser der Partikel und die Viskosität des sie umgebenden Mediums. Durch die Unterscheidung von Néel'schen und Brown'schen Beiträgen zur Magnetisierung ermöglicht mMPI in Verbindung mit einem geeigneten Marker die Bindungsdetektion im Bildgebungsvolumen. Das Harmonischen-Spektrum und die dynamische Magnetisierungsantwort des MPI-Markers werden im MPS untersucht. Außerdem wird die Durchführung von Bio-Assays auf der Basis von MPS erkundet, und die Ergebnisse werden mit entsprechenden numerischen Modellen verglichen. Darüber hinaus wird der Einfluss der Viskosität auf die MPI System-Matrix analysiert und verschiedene Ansätze zur Ableitung der Mobilitätsinformation der Partikel aus den MPI Messdaten untersucht

Biophysical Characterization of (Silica-coated) Cobalt Ferrite Nanoparticles for Hyperthermia Treatment

Magnetic hyperthermia is a technique that describes the heating of material through an external magnetic field. Classic hyperthermia is a medical condition where the human body overheats, being usually triggered by a heat stroke, which can lead to severe damage to organs and tissue due to the denaturation of cells. In modern medicine, hyperthermia can be deliberately induced to specified parts of the body to destroy malignant cells. Magnetic hyperthermia describes the way that this overheating is induced and it has the inherent advantage of being a minimal invasive method when compared to traditional surgery methods. This work presents a particle system that offers huge potential for hyperthermia treatments, given its good loss value, i.e., the particles dissipate a lot of heat to their surroundings when treated with an ac magnetic field. The measurements were performed in a low-cost custom hyperthermia setup. Additional toxicity assessments on Jurkat cells show a very low short-term toxicity on the particles and a moderate low toxicity after two days due to the prevalent health concerns towards nanoparticles in organisms

Diffusion-Controlled Synthesis of Magnetic Nanoparticles

Technological advancements of theMagnetic Particle Imaging (MPI) scanner and image reconstruction are important steps in the process of bringing MPI to preclinical and clinical applications. The future of this promising imaging modality, however, also crucially relies on the development of MPI tracers with high performance. An interesting material, not only for MPI, encompasses biogenic iron oxide nanoparticles due to their superior magnetic properties. It is a fact, however, that the production of such particles is extremely challenging. A promising approach for their manufacture is through the application of biomimetic synthesis routes. In the present study, a diffusion-controlled synthesis of magnetic nanoparticles, mimicking certain aspects of biomineralization in vitro is presented. The particles’ structural as well as static and dynamic magnetic properties are characterized and their potential as an MPI tracer is investigated

Initial imaging experiments with a direct-driven relaxation Magnetic Particle Imaging setup

This contribution presents initial imaging experiments with a newly designed imaging setup that facilitates Magnetic Particle Imaging (MPI) by recording the step response of the tracer in contrast to its higher harmonic spectrum. Such a concept promises a greatly reduced complexity in hardware and enables a much simpler time-domain evaluation of the receive signals. The concept borrows from magnetorelaxometry (MRX) subjecting the tracer to a step change in excitation field to affect a relaxation of the particles’ magnetization. For that reason, all experience from MRX data evaluation and modeling of the magnetization response apply to the imaging variant as well. The hardware design of the system opens a great deal of flexibility regarding excitation patterns and signal evaluation for future experiments.   Int. J. Mag. Part. Imag. 6(2), Suppl. 1, 2020, Article ID: 2009060, DOI: 10.18416/IJMPI.2020.200906

Modeling the impedance of water-cooled core-less multi-layered solenoid coils for MPI drive field generation

A complete lumped component model representing the wideband impedance of water-cooled multi-layered core-less solenoid coils is presented and analytical and numerical calculation methods for model elements are reviewed and extended. The model includes stray capacitances, mutual inductances and frequency-dependent resistive losses. Contrary to previous treatments of this topic, the model is not simplified further and is evaluated in its complete form, allowing accurate prediction of the coil impedance beyond the first resonant frequency. This aspect is especially important if the coil is part of a passive filter circuit, where higher resonances limit the filter bandwidth. Also, a liquid coolant is included in the calculations.Additionally, figures of merit for the evaluation of field homogeneity inside the coil are given.The model is applied to a MPI drive coil and is compared to measured data. It shows good agreement up to 4 MHz, including the second series resonance of the coil. Additionally, the influence of water-cooling on the coil impedance is investigated. Comparison of model results to measured data shows additional losses.Int. J. Mag. Part. Imag. 4(1), 2018, Article ID: 1804001, DOI: 10.18416/IJMPI.2018.180400

Temperature-dependent MPS measurements

The non-linear signal generation in Magnetic Particle Imaging (MPI) using magnetic nanoparticles as tracer materials is still not fully explained and a far-reaching research area. Magnetic Particle Spectroscopy (MPS) was developed to investigate the particle behavior in high externally applied magnetic field strengths and to derive mathematical models which describe the physical processes in MPI in detail. A new MPS setup was built which allows measurements between -13 °C and +114 °C in order to investigate the temperature dependence of the harmonics spectra. Temperature-dependent MPS measurements of diluted FeraSpinTM XL, either as suspension or freeze-dried in a mannitol matrix, using the new setup are shown and exemplarily discussed