Kerstin Lüdtke-Buzug

Magnetization response spectroscopy of superparamagnetic nanoparticles for magnetic particle imaging

Magnetic particle imaging (MPI) is a tomographic imaging modality sensitive to the spatial distribution of magnetic particles. The spectrometer, described in this paper, is capable of measuring the remagnetization spectrum of superparamagnetic nanoparticles. With this spectrometer the suitability of particles, for MPI, can be characterized. Furthermore, the spectrometer can be used to estimate the particle size distribution, which allows for more accurate simulations in MPI.

Magnetic particle imaging: current developments and future directions

Magnetic particle imaging (MPI) is a novel imaging method that was first proposed by Gleich and Weizenecker in 2005. Applying static and dynamic magnetic fields, MPI exploits the unique characteristics of superparamagnetic iron oxide nanoparticles (SPIONs). The SPIONs’ response allows a three-dimensional visualization of their distribution in space with a superb contrast, a very high temporal and good spatial resolution. Essentially, it is the SPIONs’ superparamagnetic characteristics, the fact that they are magnetically saturable, and the harmonic composition of the SPIONs’ response that make MPI possible at all. As SPIONs are the essential element of MPI, the development of customized nanoparticles is pursued with the greatest effort by many groups. Their objective is the creation of a SPION or a conglomerate of particles that will feature a much higher MPI performance than nanoparticles currently available commercially. A particle’s MPI performance and suitability is characterized by parameters such as the strength of its MPI signal, its biocompatibility, or its pharmacokinetics. Some of the most important adjuster bolts to tune them are the particles’ iron core and hydrodynamic diameter, their anisotropy, the composition of the particles’ suspension, and their coating. As a three-dimensional, real-time imaging modality that is free of ionizing radiation, MPI appears ideally suited for applications such as vascular imaging and interventions as well as cellular and targeted imaging. A number of different theories and technical approaches on the way to the actual implementation of the basic concept of MPI have been seen in the last few years. Research groups around the world are working on different scanner geometries, from closed bore systems to single-sided scanners, and use reconstruction methods that are either based on actual calibration measurements or on theoretical models. This review aims at giving an overview of current developments and future directions in MPI about a decade after its first appearance.

Magnetic particle imaging: Introduction to imaging and hardware realization

Magnetic Particle Imaging (MPI) is a recently invented tomographic imaging method that quantitatively measures the spatial distribution of a tracer based on magnetic nanoparticles. The new modality promises a high sensitivity and high spatial as well as temporal resolution. There is a high potential of MPI to improve interventional and image-guided surgical procedures because, today, established medical imaging modalities typically excel in only one or two of these important imaging properties. MPI makes use of the non-linear magnetization characteristics of the magnetic nanoparticles. For this purpose, two magnetic fields are created and superimposed, a static selection field and an oscillatory drive field. If superparamagnetic iron-oxide nanoparticles (SPIOs) are subjected to the oscillatory magnetic field, the particles will react with a non-linear magnetization response, which can be measured with an appropriate pick-up coil arrangement. Due to the non-linearity of the particle magnetization, the received signal consists of the fundamental excitation frequency as well as of harmonics. After separation of the fundamental signal, the nanoparticle concentration can be reconstructed quantitatively based on the harmonics. The spatial coding is realized with the static selection field that produces a field-free point, which is moved through the field of view by the drive fields. This article focuses on the frequency-based image reconstruction approach and the corresponding imaging devices while alternative concepts like x-space MPI and field-free line imaging are described as well. The status quo in hardware realization is summarized in an overview of MPI scanners.

A Spectrometer for Magnetic Particle Imaging

Recently, a new tomographic imaging technique called magnetic particle imaging was proposed. It allows for the high resolution measurement of the spatial distribution of magnetic nanoparticles. The method is based on the non-linear response of magnetic nanoparticles (e.g. superparamagnetic iron oxide particles, SPIOs).

Comparison of commercial iron oxide-based MRI contrast agents with synthesized high-performance MPI tracers.

Abstract Magnetic particle imaging (MPI) recently emerged as a new tomographic imaging method directly visualizing the amount and location of superparamagnetic iron oxide particles (SPIOs) with high spatial resolution. To fully exploit the imaging performance of MPI, specific requirements are demanded on the SPIOs. Most important, a sufficiently high number of detectable harmonics of the receive signal spectrum is required. In this study, an assessment of commercial iron oxide-based MRI contrast agents is carried out, and the result is compared with that of a new self-synthesized high-performance MPI tracer. The decay of the harmonics is measured with a magnetic particle spectrometer (MPS). For the self-synthesized carboxymethyldextran-coated SPIO, it can be demonstrated that despite a small iron core diameter, the particle performance is as good as in Resovist, the best-performing commercial SPIO today. However, the self-synthesized particles show the lowest iron concentration compared with Resovist, Sinerem, and Endorem. As the iron dose will be an important issue in human MPI, the synthesis technique and the separation chain for self-synthesis will be pursued for further improvements. In evaluations carried out with MPS, it can be shown in this work that the quality of the self-synthesized nanoparticles outperforms the three commercial tracer materials when the decay of harmonics is normalized by the iron concentration. The results of this work emphasize the importance of producing highly uniform and monodisperse superparamagnetic particles contributing to lower application of tracer concentration, better sensitivity, or a higher spatial resolution.

Magnetic particle imaging: kinetics of the intravascular signal in vivo.

The highest spectral MPI signal was measured directly after Resovist^® administration (3,21*10^-9 Am2Hz^-1). After application of Resovist^® the signal decreased to 39.7 % within 5 minutes and to 20.5 % and 12.1 % within 10 and 15 minutes, respectively (see Fig. 1). Within 30 minutes, the measured signal was below the background noise level.

Biological impact of superparamagnetic iron oxide nanoparticles for magnetic particle imaging of head and neck cancer cells

Background As a tomographic imaging technology, magnetic particle imaging (MPI) allows high spatial resolution and sensitivity, and the possibility to create real-time images by determining the spatial distribution of magnetic particles. To ensure a prospective biosafe application of UL-D (University of Luebeck-Dextran coated superparamagnetic nanoparticles), we evaluated the biocompatibility of superparamagnetic iron oxide nanoparticles (SPIONs), their impact on biological properties, and their cellular uptake using head and neck squamous cancer cells (HNSCCs). Methods SPIONs that met specific MPI requirements were synthesized as tracers. Labeling and uptake efficiency were analyzed by hematoxylin and eosin staining and magnetic particle spectrometry. Flow cytometry, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays, and real-time cell analyzer assays were used to investigate apoptosis, proliferation, and the cytokine response of SPION-labeled cells. The production of reactive oxygen species (ROS) was determined using a fluorescent dye. Experimental results were compared to the contrast agent Resovist®, a standard agent used in MPI. Results UL-D nanoparticles and Resovist particles were taken up in vitro by HNSCCs via unspecific phagocytosis followed by cytosolic accumulation. To evaluate toxicity, flow cytometry analysis was performed; results showed that dose- and time-dependent administration of Resovist induced apoptosis whereas cell viability of UL-D-labeled cells was not altered. We observed decreased cell proliferation in response to increased SPION concentrations. An intracellular production of ROS could not be detected, suggesting that the particles did not cause oxidative stress. Tumor necrosis factor alpha (TNF-α) and interleukins IL-6, IL-8, and IL-1β were measured to distinguish inflammatory responses. Only the primary tumor cell line labeled with >0.5 mM Resovist showed a significant increase in IL-1β secretion. Conclusion Our data suggest that UL-D SPIONs are a promising tracer material for use in innovative tumor cell analysis in MPI.

Simulation of the magnetization dynamics of diluted ferrofluids in medical applications

Abstract Ferrofluids, which are stable, colloidal suspensions of single-domain magnetic nanoparticles, have a large impact on medical technologies like magnetic particle imaging (MPI), magnetic resonance imaging (MRI) and hyperthermia. Here, computer simulations promise to improve our understanding of the versatile magnetization dynamics of diluted ferrofluids. A detailed algorithmic introduction into the simulation of diluted ferrofluids will be presented. The algorithm is based on Langevin equations and resolves the internal and the external rotation of the magnetic moment of the nanoparticles, i.e., the Néel and Brown diffusion. The derived set of stochastic differential equations are solved by a combination of an Euler and a Heun integrator and tested with respect to Boltzmann statistics.

Magnetic, Structural, and Particle Size Analysis of Single- and Multi-Core Magnetic Nanoparticles

We have measured and analyzed three different commercial magnetic nanoparticle systems, both multi-core and single-core in nature, with the particle (core) size ranging from 20 to 100 nm. Complementary analysis methods and same characterization techniques were carried out in different labs and the results are compared with each other. The presented results primarily focus on determining the particle size-both the hydrodynamic size and the individual magnetic core size-as well as magnetic and structural properties. The used analysis methods include transmission electron microscopy, static and dynamic magnetization measurements, and Mössbauer spectroscopy. We show that particle (hydrodynamic and core) size parameters can be determined from different analysis techniques and the individual analysis results agree reasonably well. However, in order to compare size parameters precisely determined from different methods and models, it is crucial to establish standardized analysis methods and models to extract reliable parameters from the data.

Preparation and Characterization of Dextran-Covered Fe3O4 Nanoparticles for Magnetic Particle Imaging

Magnetic particle imaging (MPI) is a recently proposed method for the visualization of the spatial distribution of iron-oxide nanoparticles. The principle is based on the superparamagnetic nature of Fe3O4 particles (SPIOs). Iron-oxide particles covered with dextran and derivates are widely used as contrast agents in MRI imaging. However, besides the spatial bio-distribution the image quality of the magnetic-particle imaging concept is determined by the particle diameter as well. Moreover, it is the particle size distribution that affects the measured magnetization response within MPI. Therefore, the spectral analysis of the synthesized nanoparticles is an essential assay step for particle validation.