Ksenija Gräfe

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.

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.

2D Images Recorded With a Single-Sided Magnetic Particle Imaging Scanner

Magnetic Particle Imaging is a new medical imaging modality, which detects superparamagnetic iron oxide nanoparticles. The particles are excited by magnetic fields. Most scanners have a tube-like measurement field and therefore, both the field of view and the object size are limited. A single-sided scanner has the advantage that the object is not limited in size, only the penetration depth is limited. A single-sided scanner prototype for 1D imaging has been presented in 2009. Simulations have been published for a 2D single-sided scanner and first 1D measurements have been carried out. In this paper, the first 2D single-sided scanner prototype is presented and the first calibration-based reconstruction results of measured 2D phantoms are shown. The field free point is moved on a Lissajous trajectory inside a 30 ×30 mm2 area. Images of phantoms with a maximal distance of 10 mm perpendicular to the scanner surface have been reconstructed. Different cylindrically shaped holes of phantoms have been filled with 6.28 μl undiluted Resovist. After the measurement and image reconstruction of the phantoms, particle volumes could be distinguished with a distance of 2 mm and 6 mm in vertical and horizontal direction, respectively.

System Matrix Recording and Phantom Measurements with a Single-Sided Magnetic Particle Imaging Device

Magnetic particle imaging (MPI) is a new imaging method, which uses superparamagnetic iron oxide nanoparticles as tracer material. Due to their tube-like design, most MPI devices have limited patient access. In this paper, an improved oil-cooled single-sided MPI device is presented that has the advantage that all coils, which are generating the magnetic fields or receiving the particle signal, are coplanar and on one side of the patient only. In consequence, the object, which will be scanned, is not limited in size. In this paper, a first 1-D image recorded with the new device is presented.

Magnetic-Particle-Imaging for Sentinel Lymph Node Biopsy in Breast Cancer

Magnetic Particle Imaging (MPI) is a very recent medical imaging technique providing tomographic data avoiding use of ionizing radiation. The first MPI scanner presented by Gleich and Weizenecker has a closed geometry which has to fit the object of interest [1]. In order to be able to examine larger objects, Sattel et al. developed a new coil configuration, the single-sided MPI scanner geometry [2]. The detection of axillary sentinel lymph nodes is one medical application scenario. MPI improves the surgical procedure by real-time 3D image guidance and may contribute towards reducing cost and the time needs per patient. This contribution presents improvements of various coil topologies. Furthermore, the cooling system is optimized and the send and receive chain will be improved.

Single-sided magnetic particle imaging: magnetic field and gradient

Magnetic Particle Imaging (MPI) has been presented by Gleich and Weizenecker in 2005. Since then, a number of innovations have been introduced by many di erent research groups. In 2009, for instance, Sattel et al. presented a novel single-sided MPI scanner geometry. The major advantage of this particular scanner geometry is the unlimited measurement eld. For the imaging process in MPI, super-paramagnetic iron oxide nanoparticles (SPIONs) are applied as tracer material. The tracer is excited by sinusoidally varying magnetic elds. In this contribution, simulated magnetic elds were evaluated based on the measured eld distribution of a single-sided scanner realization. It is of particular importance to know the quality of the gradient elds, since image resolution in MPI is directly linked to the gradient strength.

Detection and distribution of superparamagnetic nanoparticles in lymphatic tissue in a breast cancer model for magnetic particle imaging

Introduction The axillary lymph node extraction (ALNE) is part of the surgical staging in breast cancer. Radical ALNE was associated with high morbidity and significant loss of QoL. The adverse effects decreased since the introduction of the sentinel lymph node biopsy (SNLB), with dyes and radio nuclides as tracer substances. They could be replaced by super paramagnetic iron oxide nano particles (SPIOs). Through the magnetic particle imaging (MPI), a 3D-imaging and distinct localization of SPIOs can be achieved in SNLB. Qualitative and quantitative enrichment of SPIOs in the axillary lymphatic tissue is unexplored until now. Methods We aim to prove the principle of SNLB by MPI within a healthy mouse model and than in a tumor bearing mouse model with metastatic axillary lymph nodes. Axillary and environmental tissues are analyzed with different techniques: histology, Prussian blue staining, electron microscopy, atomic absorption spectrometry and MPI spectrometry. Results The SPIOs are moving from the injection site through the lymph-fat tissue to the axillary region and finally into the axillary lymph nodes. They are following the traces of lymphatic vessels, respecting the borders and spaces between different tissues e.g. muscle fibers. SPIOs were found in the neighborhood of collagen fibers. They accumulate in the cortex region of lymph nodes. We present first results of the approach of SNLB by MPI. Conclusion The use of SPIOs and the MPI technique as SNLB tracer and finder as a new SNLB technique will be less complex and incriminating for patient and staff and makes it more precise. A MPI hand probe for use in the operating theatre is under construction. Therewith the SNL detection can be easily performed and by the avoidance of intensive surgical exploration the morbidity is dramatically reduced. The tracer for MPI is easy to obtain. This makes the method accessible to all patients. The concept of SNLB by MPI can be applied in principle in all solid tumors.

Asymmetric Scanner Design for Interventional Scenarios in Magnetic Particle Imaging

Magnetic particle imaging is an imaging modality that acquires quantitative information about the spatial distribution of magnetic nanoparticles. In combination with an excellent spatial and temporal resolution and due to the fact that no harmful radiation is used, the imaging technique offers possibilities with respect to medical application. As such, interventional scenarios, where it is mandatory to visualize the used instruments, are a perfectly suitable area of application. This paper describes the results of a feasibility study where a novel single-sided coil arrangement based on approximated elliptical coils is designed to be integrated into a patient table. Using such coils perfectly matches the requirements of good patient access, large field of view (FOV), and available space in the table. A small change in the aspect ratio leads to an enlarged FOV with sufficient gradient strength in all directions.

Approximated elliptical coils in magnetic particle imaging

The paper presented results of simulated and measured magnetic fields of an approximated elliptical coil. The simulation values are coincided with the measurement values. Using the relative error as difference metric, the difference between simulation and measurement is presented as well. The visual comparison between the images as well as the resulting values of the relative error show only a minimal difference in the inner zone of the coils. The gradient values for the prototype coil arrangement for x, y and z direction were also shown. With an increasing side length the gradients in x and y direction decrease, while the gradient in z direction slightly increases.

Phantom simulation based on measured gradient fields of a single-sided MPI scanner

Figure 2 shows the reconstruction result using a simulated selection field and a simulated drive field. The resolution of the reconstruction decreases with the distance to the coil assembly of the single-sided scanner. This result will be used to verify later results.