Characterization of the clinically approved MRI tracer resotran for magnetic particle imaging in a comparison study.

Objective.The availability of magnetic nanoparticles (MNPs) 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 (MPS) 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, MPS 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 MNPs 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.

Resonant inductive coupling network for human-sized magnetic particle imaging.

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 an inductive coupling network are used. Our primary objectives are to achieve floating potentials to ensure patient safety while 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 for 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 method-of-moment based simulations.

Particle interactions and their effect on magnetic particle spectroscopy and imaging.

Signal stability is crucial for an accurate diagnosis via magnetic particle imaging (MPI). However, MPI-tracer nanoparticles frequently agglomerate during their in vivo applications leading to particle interactions altering the signal. Here, we investigate the influence of such magnetic coupling phenomena on the MPI signal. We prepared Zn0.4Fe2.6O4 nanoparticles by flame spray synthesis and controlled their inter-particle distance by varying SiO2 coating thickness. The silica shell affected the magnetic properties indicating stronger particle interactions for a smaller inter-particle distance. The SiO2-coated Zn0.4Fe2.6O4 outperformed the bare sample in magnetic particle spectroscopy (MPS) in terms of signal/noise, however, the shell thickness itself only weakly influenced the MPS signal. To investigate the importance of magnetic coupling effects in more detail, we benchmarked the MPS signal of the bare and SiO2-coated Zn-ferrites against commercially available PVP-coated Fe3O4 nanoparticles in water and PBS. PBS is known to destabilize nanoparticle colloids mimicking in vivo-like agglomeration. The bare and coated Zn-ferrites showed excellent signal stability, despite their agglomeration in PBS. We attribute this to their process-intrinsic aggregated morphology formed during their flame-synthesis, which generates an MPS signal only little affected by PBS. On the other hand, the MPS signal of commercial PVP-coated Fe3O4 strongly decreased in PBS compared to water, indicating strongly changed particle interactions. The relevance of this effect was further investigated in a human cell model. For PVP-coated Fe3O4, we detected a strong discrepancy between the particle concentration obtained from the MPS signal and the actual concentration determined via ICP-MS. The same trend was observed during their MPI analysis; while SiO2-coated Zn-ferrites could be precisely located in water and PBS, PVP-coated Fe3O4 could not be detected in PBS at all. This drastically limits the sensitivity and also general applicability of these commercial tracers for MPI and illustrates the advantages of our flame-made Zn-ferrites concerning signal stability and ultimately diagnostic accuracy.

System Matrix Based Reconstruction for Pulsed Sequences in Magnetic Particle Imaging.

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) Tm-1) in x- and y-direction was achieved and a superior sensitivity for pulsed sequences was detected on the basis of reference phantoms.

Magnetic particle imaging for assessment of cerebral perfusion and ischemia.

Stroke is one of the leading worldwide causes of death and sustained disability. Rapid and accurate assessment of cerebral perfusion is essential to diagnose and successfully treat stroke patients. Magnetic particle imaging (MPI) is a new technology with the potential to overcome some limitations of established imaging modalities. It is an innovative and radiation-free imaging technique with high sensitivity, specificity, and superior temporal resolution. MPI enables imaging and diagnosis of stroke and other neurological pathologies such as hemorrhage, tumors, and inflammatory processes. MPI scanners also offer the potential for targeted therapies of these diseases. Due to lower field requirements, MPI scanners can be designed as resistive magnets and employed as mobile devices for bedside imaging. With these advantages, MPI could accelerate and improve the diagnosis and treatment of neurological disorders. This review provides a basic introduction to MPI, discusses its current use for stroke imaging, and addresses future applications, including the potential for clinical implementation. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease.

Design of a head coil for high resolution mouse brain perfusion imaging using magnetic particle imaging.

Magnetic particle imaging (MPI) is a novel and versatile imaging modality developing toward human application. When up-scaling to human size, the sensitivity of the systems naturally drops as the coil sensitivity depends on the bore diameter. Thus, new methods to push the sensitivity limit further have to be investigated to cope for this loss. In this paper a dedicated surface coil for mice is developed, improving the sensitivity in cerebral imaging applications. Similar to magnetic resonance imaging the developed surface coil improves the sensitivity due to the closer vicinity to the region of interest. With the developed surface coil presented in this work, it is possible to image tracer samples containing only 896 pg[Formula: see text] and detect even small vessels and anatomical structures within a wild type mouse model. As current sensitivity measures require a tracer system a new method for determining a sensitivity measure without this requirement is presented and verified to enable comparison between MPI receiver systems.

Monitoring Intracranial Cerebral Hemorrhage Using Multicontrast Real-Time Magnetic Particle Imaging.

Magnetic particle imaging (MPI) is an innovative radiation-free tomographic imaging method providing excellent temporal resolution, contrast, sensitivity, and safety. Mobile human MPI prototypes suitable for continuous bedside monitoring of whole-brain perfusion have been developed. However, for the clinical translation of MPI, a crucial gap in knowledge still remains: while MPI can visualize the reduction in blood flow and tissue perfusion in cerebral ischemia, it is unclear whether MPI works in intracranial hemorrhage. Our objective was to investigate the capability of MPI to detect intracranial hemorrhage in a murine model. Intracranial hemorrhage was induced through the injection of collagenase into the striatum of C57BL/6 mice. After the intravenous infusion of a long-circulating MPI-tailored tracer consisting of superparamagnetic iron oxides, we detected the intracranial hemorrhage in less than 3 min and could monitor hematoma expansion in real time. Multicontrast MPI can distinguish tracers based on their physical characteristics, core size, temperature, and viscosity. By employing in vivo multicontrast MPI, we were able to differentiate areas of liquid and coagulated blood within the hematoma, which could provide valuable information in surgical decision making. Multicontrast MPI also enabled simultaneous imaging of hemorrhage and cerebral perfusion, which is essential in the care of critically ill patients with increased intracranial pressure. We conclude that MPI can be used for real-time diagnosis of intracranial hemorrhage. This work is an essential step toward achieving the clinical translation of MPI for point-of-care monitoring of different stroke subtypes.

Development of long circulating magnetic particle imaging tracers: use of novel magnetic nanoparticles and entrapment into human erythrocytes.

Aim: Magnetic particle imaging (MPI) is highly promising for biomedical applications, but optimal tracers for MPI, namely superparamagnetic iron oxide-based contrast agents, are still lacking. Materials & methods: The encapsulation of commercially available nanoparticles, specifically synomag®-D and perimag®, into human red blood cells (RBCs) was performed by a hypotonic dialysis and isotonic resealing procedure. The amounts of superparamagnetic iron oxide incorporated into RBCs were determined by Fe quantification using nuclear magnetic resonance and magnetic particle spectroscopy. Results: Perimag-COOH nanoparticles were identified as the best nanomaterial for encapsulation in RBCs. Perimag-COOH-loaded RBCs proved to be viable cells showing a good magnetic particle spectroscopy performance, while the magnetic signal of synomag-D-COOH-loaded RBCs dropped sharply. Conclusion: Perimag-COOH-loaded RBCs could be a potential tool for MPI diagnostic applications.