Visualization of spatial and temporal temperature distributions with magnetic particle imaging for liver tumor ablation therapy.

Temperature-resolved magnetic particle imaging (MPI) represents a promising tool for medical imaging applications. In this study an approach based on a single calibration measurement was applied for highlighting the potential of MPI for monitoring of temperatures during thermal ablation of liver tumors. For this purpose, liver tissue and liver tumor phantoms embedding different superparamagnetic iron oxide nanoparticles (SPION) were prepared, locally heated up to 70 °C and recorded with MPI. Optimal temperature MPI SPIONs and a corresponding linear model for temperature calculation were determined. The temporal and spatial temperature distributions were compared with infrared (IR) camera results yielding quantitative agreements with a mean absolute deviation of 1 °C despite mismatches in boundary areas.

First magnetic particle imaging angiography in human-sized organs by employing a multimodal ex vivo pig kidney perfusion system.

OBJECTIVE: Magnetic particle imaging (MPI) is a new, fast 3D imaging technique, which is considered promising for angiographies. As available MPI scanners suffer from restricted spatial resolution and are mostly constructed for small animal imaging, no vessels within one organ have been depicted by MPI, yet. The purpose of this study was to develop an ex vivo organ perfusion system to display vessels within one organ of human size by MPI and to compare the results to an established 3D imaging technique. APPROACH: An ex vivo porcine kidney perfusion system compatible with digital subtraction angiography (DSA), magnetic resonance tomography and MPI was developed. DSA was used to exemplarily prove intact vessel structures under ex vivo perfusion in two organs. Perfusion in nine organs was displayed by the 3D imaging techniques magnetic resonance angiography (MRA) and MPI angiography. All visible vessels in MRA and MPI were counted and their number compared between both techniques. MAIN RESULTS: The ex vivo organ perfusion system allowed us to perform angiographies by DSA, MRA and MPI. With it, organs of human size could be imaged in small animal scanners, which permitted us to depict vessels within one organ by MPI for the first time. In comparison to MRA, 33% of all vessels were visible in MPI, a difference probably caused by restricted spatial resolution in MPI. SIGNIFICANCE: The presented ex vivo organ perfusion system can serve to practically evaluate MPI's potential for angiography in human-sized organs. This is especially relevant as long as available, for angiography-suited MPI scanners still suffer from size and spatial resolution restrictions.

Correction of linear system drifts in magnetic particle imaging.

Magnetic particle imaging (MPI) is a tracer-based imaging technique that can be used for imaging vessels and organ perfusion with high temporal resolution. Background signals are a major source for image artifacts and in turn restrict the sensitivity of the method in practice. While static background signals can be removed from the measured signal by taking a dedicated background scan and performing subtraction, this simple procedure is not applicable in case of non-stationary background signals that occur in practice due to e.g. temperature drifts in the electromagnetic coils of the MPI scanner. Within this work we will investigate a dynamic background subtraction method that is based on two background measurements taken before and after the object measurement. Using first-order interpolation it is possible to remove linear background changes and in turn significantly suppress artifacts. The method is evaluated using static and dynamic phantom measurements and it is shown that dynamic background subtraction is capable of reducing the artifact level approximately by a factor of four.

Human-sized magnetic particle imaging for brain applications.

Determining the brain perfusion is an important task for diagnosis of vascular diseases such as occlusions and intracerebral haemorrhage. Even after successful diagnosis, there is a high risk of restenosis or rebleeding such that patients need intense attention in the days after treatment. Within this work, we present a diagnostic tomographic imager that allows access to brain perfusion quantitatively in short intervals. The device is based on the magnetic particle imaging technology and is designed for human scale. It is highly sensitive and allows the detection of an iron concentration of 263 pmolFe ml-1, which is one of the lowest iron concentrations imaged by MPI so far. The imager is self-shielded and can be used in unshielded environments such as intensive care units. In combination with the low technical requirements this opens up a variety of medical applications and would allow monitoring of stroke on intensive care units.

Hybrid system calibration for multidimensional magnetic particle imaging.

Magnetic particle imaging visualizes the spatial distribution of superparamagnetic nanoparticles. Because of its key features of excellent sensitivity, high temporal and spatial resolution and biocompatibility of the tracer material it can be used in multiple medical imaging applications. The common reconstruction technique for Lissajous-type trajectories uses a system matrix that has to be previously acquired in a time-consuming calibration scan, leading to long downtimes of the scanning device. In this work, the system matrix is determined by a hybrid approach. Using the hybrid system matrix for reconstruction, the calibration downtime of the scanning device can be neglected. Furthermore, the signal to noise ratio of the hybrid system matrix is much higher, since the size of the required nanoparticle sample can be chosen independently of the desired voxel size. As the signal to noise ratio influences the reconstruction process, the resulting images have better resolution and are less affected by artefacts. Additionally, a new approach is introduced to address the background signal in image reconstruction. The common technique of subtraction of the background signal is replaced by extending the system matrix with an entry that represents the background. It is shown that this approach reduces artefacts in the reconstructed images.

Magnetic particle imaging: from proof of principle to preclinical applications.

Tomographic imaging has become a mandatory tool for the diagnosis of a majority of diseases in clinical routine. Since each method has its pros and cons, a variety of them is regularly used in clinics to satisfy all application needs. Magnetic particle imaging (MPI) is a relatively new tomographic imaging technique that images magnetic nanoparticles with a high spatiotemporal resolution in a quantitative way, and in turn is highly suited for vascular and targeted imaging. MPI was introduced in 2005 and now enters the preclinical research phase, where medical researchers get access to this new technology and exploit its potential under physiological conditions. Within this paper, we review the development of MPI since its introduction in 2005. Besides an in-depth description of the basic principles, we provide detailed discussions on imaging sequences, reconstruction algorithms, scanner instrumentation and potential medical applications.

First experimental comparison between the Cartesian and the Lissajous trajectory for magnetic particle imaging.

Magnetic particle imaging (MPI) is a quantitative imaging modality that allows us to determine the distribution of superparamagnetic nanoparticles. Sampling is achieved by moving a field-free point (FFP) along a specific trajectory through the volume of interest. The magnetic material that lies along the path or in the close vicinity of the FFP changes its magnetization and induces a voltage in the surrounding receiver coils. Various trajectories for the FFP are conceivable, but most experimental MPI scanners either use a Cartesian or a Lissajous sampling trajectory. For the first time, this study compares both sampling methods experimentally using an MPI scanner that allows us to implement both sampling patterns. By default, the scanner is capable of scanning 2D and 3D field of views using a Lissajous trajectory. But since it also has a 1D mode, it is possible to perform Cartesian measurements by shifting the 1D scan line in a perpendicular direction to the FFP movement using the focus field. These line scans are jointly reconstructed to obtain a 2D image. In a further step, the unidirectional Cartesian trajectory is improved by interchanging the excitation and the focus-field direction leading to a bidirectional Cartesian trajectory. Our findings reveal similar results for the bidirectional Cartesian and Lissajous trajectory concerning the overall image quality and sensitivity. In a more detailed view, the bidirectional Cartesian trajectory achieves a slightly higher spatial center resolution, whereas the Lissajous trajectory is more efficient regarding the temporal resolution since less acquisition time is needed to reach an adequate image quality.

Detection and Compensation of Periodic Motion in Magnetic Particle Imaging.

The temporal resolution of the tomographic imaging method magnetic particle imaging (MPI) is remarkably high. The spatial resolution is degraded for measured voltage signal with low signal-to-noise ratio, because the regularization in the image reconstruction step needs to be increased for system-matrix approaches and for deconvolution steps in x -space approaches. To improve the signal-to-noise ratio, blockwise averaging of the signal over time can be advantageous. However, since block-wise averaging decreases the temporal resolution, it prevents resolving the motion. In this paper, a framework for averaging motion-corrupted MPI raw data is proposed. The motion is considered to be periodic as it is the case for respiration and/or the heartbeat. The same state of motion is thus reached repeatedly in a time series exceeding the repetition time of the motion and can be used for averaging. As the motion process and the acquisition process are, in general, not synchronized, averaging of the captured MPI raw data corresponding to the same state of motion requires to shift the starting point of the individual frames. For high-frequency motion, a higher frame rate is potentially required. To address this issue, a binning method for using only parts of complete frames from a motion cycle is proposed that further reduces the motion artifacts in the final images. The frequency of motion is derived directly from the MPI raw data signal without the need to capture an additional navigator signal. Using a motion phantom, it is shown that the proposed method is capable of averaging experimental data with reduced motion artifacts. The methods are further validated on in-vivo data from mouse experiments to compensate the heartbeat.

In vivo liver visualizations with magnetic particle imaging based on the calibration measurement approach.

Magnetic particle imaging (MPI) facilitates the rapid determination of 3D in vivo magnetic nanoparticle distributions. In this work, liver MPI following intravenous injections of ferucarbotran (Resovist®) was studied. The image reconstruction was based on a calibration measurement, the so called system function. The application of an enhanced system function sample reflecting the particle mobility and aggregation status of ferucarbotran resulted in significantly improved image reconstructions. The finding was supported by characterizations of different ferucarbotran compositions with the magnetorelaxometry and magnetic particle spectroscopy technique. For instance, similar results were obtained between ferucarbotran embedded in freeze-dried mannitol sugar and liver tissue harvested after a ferucarbotran injection. In addition, the combination of multiple shifted measurement patches for a joint reconstruction of the MPI data enlarged the field of view and increased the covering of liver MPI on magnetic resonance images noticeably.

Geometry planning and image registration in magnetic particle imaging using bimodal fiducial markers.

PURPOSE: Magnetic particle imaging (MPI) is a quantitative imaging modality that allows the distribution of superparamagnetic nanoparticles to be visualized. Compared to other imaging techniques like x-ray radiography, computed tomography (CT), and magnetic resonance imaging (MRI), MPI only provides a signal from the administered tracer, but no additional morphological information, which complicates geometry planning and the interpretation of MP images. The purpose of the authors' study was to develop bimodal fiducial markers that can be visualized by MPI and MRI in order to create MP-MR fusion images. METHODS: A certain arrangement of three bimodal fiducial markers was developed and used in a combined MRI/MPI phantom and also during in vivo experiments in order to investigate its suitability for geometry planning and image fusion. An algorithm for automated marker extraction in both MR and MP images and rigid registration was established. RESULTS: The developed bimodal fiducial markers can be visualized by MRI and MPI and allow for geometry planning as well as automated registration and fusion of MR-MP images. CONCLUSIONS: To date, exact positioning of the object to be imaged within the field of view (FOV) and the assignment of reconstructed MPI signals to corresponding morphological regions has been difficult. The developed bimodal fiducial markers and the automated image registration algorithm help to overcome these difficulties.

Using data redundancy gained by patch overlaps to reduce truncation artifacts in magnetic particle imaging.

The imaging technology magnetic particle imaging allows the detection of magnetic material, in particular superparamagnetic nanoparticles, by remagnetization of the material via magnetic fields. The application is aimed at medical imaging where the particles are applied as tracer directly into the blood stream. Medical safety considerations such as peripheral nerve stimulation limit the maximal amplitude of the magnetic fields and in turn the field of view size. To handle this constraint the concept of patches was introduced, which allows a shift of a field of view to different positions in order to enlarge the imaging area. If this is done statically an overlap of patches can be used to reduce truncation artifacts occurring at the adjacent edges. In this contribution, a differentiation of two different kinds of patch overlaps, i.e. a trajectory and a system matrix overlap, is made. Further, different concepts to combine the resulting redundant information are investigated with respect to the reduction of truncation artifacts. The methods are analyzed in detail in a simulation study and validated on experimental data.

Online reconstruction of 3D magnetic particle imaging data.

Magnetic particle imaging is a quantitative functional imaging technique that allows imaging of the spatial distribution of super-paramagnetic iron oxide particles at high temporal resolution. The raw data acquisition can be performed at frame rates of more than 40 volumes s(-1). However, to date image reconstruction is performed in an offline step and thus no direct feedback is available during the experiment. Considering potential interventional applications such direct feedback would be mandatory. In this work, an online reconstruction framework is implemented that allows direct visualization of the particle distribution on the screen of the acquisition computer with a latency of about 2 s. The reconstruction process is adaptive and performs block-averaging in order to optimize the signal quality for a given amount of reconstruction time.

Artifact free reconstruction with the system matrix approach by overscanning the field-free-point trajectory in magnetic particle imaging.

Magnetic particle imaging is a tracer-based imaging method that utilizes the non-linear magnetization response of iron-oxide for determining their spatial distribution. The method is based on a sampling scheme where a sensitive spot is moved along a trajectory that captured a predefined field-of-view (FOV). However, particles outside the FOV also contribute to the measurement signal due to their rotation and the non-sharpness of the sensitive spot. In the present work we investigate artifacts that are induced by particles not covered by the FOV and show that the artifacts can be mitigated by using a system matrix that covers not only the region of interest but also a certain area around the FOV. The findings are especially relevant when using a multi-patch acquisition scheme where the boundaries of neighboring patches have to be handled.

Combined Preclinical Magnetic Particle Imaging and Magnetic Resonance Imaging: Initial Results in Mice.

PURPOSE: Magnetic particle imaging (MPI) is a new radiologic imaging modality. For the first time, a commercial preclinical scanner is installed. The goal of this study was to establish a workflow between MPI and magnetic resonance imaging (MRI) scanners for a complete in vivo examination of a mouse and to generate the first co-registered in vivo MR-MP images. MATERIALS AND METHODS: The in vivo examination of five mice were performed on a preclinical MPI scanner and a 7 Tesla preclinical MRI system. MRI measurements were used for anatomical referencing and validation of the injection of superparamagnetic iron oxide (SPIO) particles during a dynamic MPI scan. We extracted MPI data of the injection phase and co-registered it with MRI data. RESULTS: A workflow process for a combined in vivo MRI and MPI examination was established. A successful injection of ferucarbotran was proven in MPI and MRI. MR-MPI co-registration allocated the SPIOs in the inferior vena cava and the heart during and shortly after the injection. CONCLUSION: The acquisition of preclinical MPI and MRI data is feasible and allows the combined analysis of MR-MPI information.

Symmetries of the 2D magnetic particle imaging system matrix.

In magnetic particle imaging (MPI), the relation between the particle distribution and the measurement signal can be described by a linear system of equations. For 1D imaging, it can be shown that the system matrix can be expressed as a product of a convolution matrix and a Chebyshev transformation matrix. For multidimensional imaging, the structure of the MPI system matrix is not yet fully explored as the sampling trajectory complicates the physical model. It has been experimentally found that the MPI system matrix rows have symmetries and look similar to the tensor products of Chebyshev polynomials. In this work we will mathematically prove that the 2D MPI system matrix has symmetries that can be used for matrix compression.

Joint reconstruction of non-overlapping magnetic particle imaging focus-field data.

The focus field is a key component to enable clinical applications in magnetic particle imaging (MPI). Due to physiological constraints, the method of choice is to place the focus of a small acquisition volume at various static positions in space and acquire the full field-of-view using a multi-station approach. In the first experiments, overlapping drive-field patches were used and boundary artifacts between drive-field patches were reduced using image processing. In this work we show that artifact-free reconstruction of non-overlapping focus-field data is feasible by using a joint reconstruction algorithm. This enables maximum scanning efficiency in multi-station focus-field experiments, which is key for reaching sufficiently short acquisition times to image the human heart.

Weighted iterative reconstruction for magnetic particle imaging.

Magnetic particle imaging (MPI) is a new imaging technique capable of imaging the distribution of superparamagnetic particles at high spatial and temporal resolution. For the reconstruction of the particle distribution, a system of linear equations has to be solved. The mathematical solution to this linear system can be obtained using a least-squares approach. In this paper, it is shown that the quality of the least-squares solution can be improved by incorporating a weighting matrix using the reciprocal of the matrix-row energy as weights. A further benefit of this weighting is that iterative algorithms, such as the conjugate gradient method, converge rapidly yielding the same image quality as obtained by singular value decomposition in only a few iterations. Thus, the weighting strategy in combination with the conjugate gradient method improves the image quality and substantially shortens the reconstruction time. The performance of weighting strategy and reconstruction algorithms is assessed with experimental data of a 2D MPI scanner.

The postglacial recolonization of Northern Europe by Rana arvalis as revealed by microsatellite and mitochondrial DNA analyses.

The postglacial history of the moor frog (Rana arvalis) in Northern Europe was investigated with the aid of eight variable microsatellite loci and a 661 bp sequence of the mitochondrial cytochrome b gene. A division between eastern and western mitochondrial lineages was discovered, supporting two recolonization routes to Fennoscandia since the last glacial maximum. This result was corroborated by the microsatellite data, which revealed a contact zone between the two lineages in Northern Sweden. These findings add to the increasing evidence that an intraspecific genetic biodiversity founded on the existence of eastern and western clades is a common element in Fennoscandian fauna and flora.

Trajectory analysis for magnetic particle imaging.

Recently a new imaging technique called magnetic particle imaging was proposed. The method uses the nonlinear response of magnetic nanoparticles when a time varying magnetic field is applied. Spatial encoding is achieved by moving a field-free point through an object of interest while the field strength in the vicinity of the point is high. A resolution in the submillimeter range is provided even for fast data acquisition sequences. In this paper, a simulation study is performed on different trajectories moving the field-free point through the field of view. The purpose is to provide mandatory information for the design of a magnetic particle imaging scanner. Trajectories are compared with respect to density, speed and image quality when applied in data acquisition. Since simulation of the involved physics is a time demanding task, moreover, an efficient implementation is presented utilizing caching techniques.