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Since the initial patent in 2001, the Magnetic Particle Imaging (MPI) community has been striving to develop an MPI scanner suitable for human applications. Numerous contributions from different research fields, regarding tracer development, reconstruction methods, hardware engineering, and sequence design have been employed in pursuit of this objective. In this work, we introduce and thoroughly characterize an improved head-sized MPI scanner with an emphasis on human safety. The scanner is operated by open-source software that enables scanning, monitoring, analysis, and reconstruction, designed to be handled by end users. Our primary focus is to present all technical components of the scanner, with the ultimate objective to investigate brain perfusion imaging in phantom experiments. We have successfully achieved full 3D single- and multi-contrast imaging capabilities at a frame rate of 4 Hz with sufficient sensitivity and resolution for brain applications. To assess system characterization, we devised sensitivity, resolution, perfusion, and multi-contrast experiments, as well as field measurements and sequence analysis. The acquired images were captured using a clinically approved tracer and suitable magnetic field strengths, while adhering to the established human peripheral nerve stimulation thresholds. This advanced scanner holds potential as a tomographic imager for diagnosing conditions such as ischemic stroke or intracranial hemorrhage in environments lacking electromagnetic shielding. Furthermore, due to its low power consumption it may have the potential to facilitate long-term monitoring within intensive care units for various applications., Comment: 22 pages, 9 figures

Precise knowledge of magnetic fields is crucial in many medical imaging applications like magnetic resonance imaging or magnetic particle imaging (MPI) as they are the foundation of these imaging systems. For the investigation of the influence of field imperfections on imaging, a compact and unique representation of the magnetic fields using real solid spherical harmonics, which can be obtained by measuring a few points of the magnetic field only, is of great assistance. In this manuscript, we review real solid harmonic expansions as a general solution of Laplace's equation including an efficient calculation of their coefficients using spherical t-designs. We also provide a method to shift the reference point of an expansion by calculating the coefficients of the shifted expansion from the initial ones. These methods are used to obtain the magnetic fields of an MPI system. Here, the field-free-point of the spatial encoding field serves as unique expansion point. Lastly, we quantify the severity of the distortions of the static and dynamic fields in MPI by analyzing the expansion coefficients., Comment: 25 pages

The non-equidistant fast Fourier transform (NFFT) is an extension of the famous fast Fourier transform (FFT), which can be applied to non-equidistantly sampled data in time/space or frequency domain. It is an approximative algorithm that allows to control the approximation error in such a way that machine precision is reached while keeping the algorithmic complexity in the same order as a regular FFT. The NFFT plays a major role in many signal processing applications and has been intensively studied from a theoretical and computational perspective. The fastest CPU implementations of the NFFT are implemented in the low-level programming languages C and C++ and require a compromise between code generalizability, code readability, and code efficiency. The programming language Julia promises new opportunities in optimizing these three conflicting goals. In this work we show that Julia indeed allows to develop an NFFT implementation, which is completely generic, dimension-agnostic and requires about 2-3 times less code than other famous libraries while still being one of the fastest NFFT implementations developed to date., Comment: 26 pages

Magnetic Particle Imaging (MPI) is a tomographic imaging technique for determining the spatial distribution of superparamagnetic nanoparticles. Current MPI systems are capable of imaging iron masses over a wide dynamic range of more than four orders of magnitude. In theory, this range could be further increased using adaptive amplifiers, which prevent signal clipping. While this applies to a single sample, the dynamic range is severely limited if several samples with different concentrations or strongly inhomogeneous particle distributions are considered. One scenario that occurs quite frequently in pre-clinical applications is that a highly concentrated tracer bolus in the vascular system "shadows" nearby organs with lower effective tracer concentrations. The root cause of the problem is the ill-posedness of the MPI imaging operator, which requires regularization for stable reconstruction. In this work, we introduce a simple two-step algorithm that increases the dynamic range by a factor of four. Furthermore, the algorithm enables spatially adaptive regularization, i.e. highly concentrated signals can be reconstructed with maximum spatial resolution, while low concentrated signals are strongly regularized to prevent noise amplification.

Magnetic particle imaging is a tracer based imaging technique to determine the spatial distribution of superparamagnetic iron oxide nanoparticles with a high spatial and temporal resolution. Due to physiological constraints, the imaging volume is restricted in size and larger volumes are covered by shifting object and imaging volume relative to each other. This results in reduced temporal resolution, which can lead to motion artifacts when imaging dynamic tracer distributions. A common source of such dynamic distributions are cardiac and respiratory motion in in-vivo experiments, which are in good approximation periodic. We present a raw data processing technique that combines data snippets into virtual frames corresponding to a specific state of the dynamic motion. The technique is evaluated on the basis of measurement data obtained from a rotational phantom at two different rotational frequencies. These frequencies are determined from the raw data without reconstruction and without an additional navigator signal. The reconstructed images give reasonable representations of the rotational phantom frozen in several different states of motion while motion artifacts are suppressed.

The tomographic imaging method magnetic particle imaging (MPI) requires a multi-patch approach for capturing large field of views. This approach consists of a continuous or stepwise spatial shift of a small sub-volume of only few cubic centimeters size, which is scanned using one or multiple excitation fields in the kHz range. Under the assumption of ideal magnetic fields, the MPI system matrix is shift invariant and in turn a single matrix suffices for image reconstruction significantly reducing the calibration time and reconstruction effort. For large field imperfections, however, the method can lead to severe image artifacts. In the present work we generalize the efficient multi-patch reconstruction to work under non-ideal field conditions, where shift invariance holds only approximately for small shifts of the sub-volume. Patches are clustered based on a magnetic-field-based metric such that in each cluster the shift invariance holds in good approximation. The total number of clusters is the main parameter of our method and allows to trade off calibration time and image artifacts. The magnetic-field-based metric allows to perform the clustering without prior knowledge of the system matrices. The developed reconstruction algorithm is evaluated on a multi-patch measurement sequence with 15 patches, where efficient multi-patch reconstruction with a single calibration measurement leads to strong image artifacts. Analysis reveals that calibration measurements can be decreased from 15 to 11 with no visible image artifacts. A further reduction to 9 is possible with only slight degradation in image quality.

Improving resolution and sensitivity will widen possible medical applications of magnetic particle imaging. Pulsed excitation promises such benefits, at the cost of more complex hardware solutions and restrictions on drive field amplitude and frequency. State-of-the-art systems utilize a sinusoidal excitation to drive superparamagnetic nanoparticles into the non-linear part of their magnetization curve, which creates a spectrum with a clear separation of direct feed-through and higher harmonics caused by the particles response. One challenge for rectangular excitation is the discrimination of particle and excitation signals, both broad-band. Another is the drive-field sequence itself, as particles that are not placed at the same spatial position, may react simultaneously and are not separable by their signal phase or shape. To overcome this potential loss of information in spatial encoding for high amplitudes, a superposition of shifting fields and drive-field rotations is proposed in this work. Upon close view, a system matrix approach is capable to maintain resolution, independent of the sequence, if the response to pulsed sequences still encodes information within the phase. Data from an Arbitrary Waveform Magnetic Particle Spectrometer with offsets in two spatial dimensions is measured and calibrated to guarantee device independence. Multiple sequence types and waveforms are compared, based on frequency space image reconstruction from emulated signals, that are derived from measured particle responses. A resolution of 1.0 mT (0.8 mm for a gradient of (-1.25,\,-1.25,\,2.5) T/m) in x- and y-direction was achieved and a superior sensitivity for pulsed sequences was detected on the basis of reference phantoms., Comment: 15 pages, 12 figures

Magnetic nanoparticles (MNPs) play an important role in biomedical applications including imaging modalities such as MRI and magnetic particle imaging (MPI). The latter one exploits the non-linear magnetization response of a large ensemble of magnetic nanoparticles to magnetic fields which allows determining the spatial distribution of the MNP concentration from measured voltage signals. Currently, modeling the voltage signals of large ensembles of MNPs in an MPI environment is not yet accurately possible, especially for liquid tracers in multi-dimensional magnetic excitation fields. Thus, the voltage-to-image mapping is still obtained in a time consuming calibration procedure. While the ferrofluidic case can be seen as the typical setting, more recently immobilized and potentially oriented MNPs have received considerable attention. By aligning the particles during immobilization, one can encode the angle of the easy axis into the magnetization response providing a sophisticated benchmark system for model-based approaches. In this work, we address the modeling problem for immobilized, oriented MNPs in the context of MPI. We investigate a model-based approach where the magnetization response is simulated by a N\'eel rotation model for the particle's magnetic moments and the ensemble magnetization is obtained by solving a Fokker-Planck equation approach. Since the parameters of the model are a-priori unknown, we investigate different methods for performing a parameter identification and discuss two models: One where a single function vector is used from the space spanned by the model parameters and another where a superposition of function vectors is considered. We show that our model can much more accurately reproduce the orientation dependent signal response when compared to the equilibrium model, which marks the current state-of-the-art for model-based system matrix simulations in MPI.