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Objective. The availability of magnetic nanoparticles with medical approval for human intervention is fundamental to the clinical translation of magnetic particle imaging (MPI). In this work, we thoroughly evaluate and compare the magnetic properties of an magnetic resonance imaging (MRI) approved tracer to validate its performance for MPI in future human trials. Approach. We analyze whether the recently approved MRI tracer Resotran is suitable for MPI. In addition, we compare Resotran with the previously approved and extensively studied tracer Resovist, with Ferrotran, which is currently in a clinical phase III study, and with the tailored MPI tracer Perimag. Main results. Initial magnetic particle spectroscopy measurements indicate that Resotran exhibits performance characteristics akin to Resovist, but below Perimag. We provide data on four different tracers using dynamic light scattering, transmission electron microscopy, vibrating sample magnetometry measurements, magnetic particle spectroscopy to derive hysteresis, point spread functions, and a serial dilution, as well as system matrix based MPI measurements on a preclinical scanner (Bruker 25/20 FF), including reconstructed images. Significance. Numerous approved magnetic nanoparticles used as tracers in MRI lack the necessary magnetic properties essential for robust signal generation in MPI. The process of obtaining medical approval for dedicated MPI tracers optimized for signal performance is an arduous and costly endeavor, often only justifiable for companies with a well-defined clinical business case. Resotran is an approved tracer that has become available in Europe for MRI. In this work, we study the eligibility of Resotran for MPI in an effort to pave the way for human MPI trials.

In Magnetic Particle Imaging, a field-free region is maneuvered throughout the field of view using a time-varying magnetic field known as the drive-field. Human-sized systems operate the drive-field in the kHz range and generate it by utilizing strong currents that can rise to the kA range within a coil called the drive field generator. Matching and tuning between a power amplifier, a band-pass filter and the drive-field generator is required. Here, for reasons of safety in future human scanners, a symmetrical topology and a transformer, called inductive coupling network is used. Our primary objectives are to achieve floating potentials to ensure patient safety, attaining high linearity and high gain for the resonant transformer. We present a novel systematic approach to the design of a loss-optimized resonant toroid with a D-shaped cross section, employing segmentation to adjust the inductance-to-resistance ratio while maintaining a constant quality factor. Simultaneously, we derive a specific matching condition of a symmetric transmit-receive circuit for magnetic particle imaging. The chosen setup filters the fundamental frequency and allows simultaneous signal transmission and reception. In addition, the decoupling of multiple drive field channels is discussed and the primary side of the transformer is evaluated for maximum coupling and minimum stray field. Two prototypes were constructed, measured, decoupled, and compared to the derived theory and to method-of-moment based simulations.

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

Objective. Magnetic Particle Imaging (MPI) is capable of high temporal resolution measurements of the spatial distribution of magnetic nanoparticles and therefore well suited for perfusion imaging, which is an important tool in medical diagnosis. Perfusion imaging in MPI usually requires a fresh bolus of tracer material to capture the key signal dynamics. Here, we propose a method to decouple the imaging sequence from the injection of additional tracer material, without further increasing the administered iron dose in the body with each image. Approach. A bolus of physiological saline solution without any particles (negative contrast) diminishes the steady-state concentration of a long-circulating tracer during passage. This depression in the measured concentration contributes to the required contrast dynamics. The presence of a long-circulating tracer is therefore a prerequisite to obtain the negative contrast. As a quantitative tracer based imaging method, the signal is linear in the tracer concentration for any location that contains nanoparticles and zero in the surrounding tissue which does not provide any intrinsic signal. After tracer injection, the concentration over time (positive contrast) can be utilized to calculate dynamic diagnostic parameters like perfusion parameters in vessels and organs. Every acquired perfusion image thus requires a new bolus of tracer with a sufficiently large iron dose to be visible above the background. Main results. Perfusion parameters are calculated based on the time response of the proposed negative bolus and compared to a positive bolus. Results from phantom experiments show that normalized signals from positive and negative boli are concurrent and deviations of calculated perfusion maps are low. Significance. Our method opens up the possibility to increase the total monitoring time, while minimizing the iron dose per acquired image., Comment: 19 pages, 6 figures

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