Nonlinear Magnetic Response Research Articles

Modeling Magnetic Particle Imaging for Dynamic Tracer Distributions

Magnetic Particle Imaging (MPI) is a promising tracer-based, functional medical imaging technique which measures the non-linear magnetization response of magnetic nanoparticles to a dynamic magnetic field. For image reconstruction, system matrices from time-consuming calibration scans are used predominantly. Finding modeled forward operators for magnetic particle imaging, which are able to compete with measured matrices in practice, is an ongoing topic of research. The existing models for magnetic particle imaging are by design not suitable for arbitrary dynamic tracer concentrations. Neither modeled nor measured system matrices account for changes in the concentration during a single scanning cycle. In this paper we present a new MPI forward model for dynamic concentrations. A static model will be introduced briefly, followed by the changes due to the dynamic behavior of the tracer concentration. Furthermore, the relevance of this new extended model is examined by investigating the influence of the extension and example reconstructions with the new and the standard model.

Targeting Brain Tumors with Mesenchymal Stem Cells in the Experimental Model of the Orthotopic Glioblastoma in Rats.

Despite multimodal approaches for the treatment of multiforme glioblastoma (GBM) advances in outcome have been very modest indicating the necessity of novel diagnostic and therapeutic strategies. Currently, mesenchymal stem cells (MSCs) represent a promising platform for cell-based cancer therapies because of their tumor-tropism, low immunogenicity, easy accessibility, isolation procedure, and culturing. In the present study, we assessed the tumor-tropism and biodistribution of the superparamagnetic iron oxide nanoparticle (SPION)-labeled MSCs in the orthotopic model of C6 glioblastoma in Wistar rats. As shown in in vitro studies employing confocal microscopy, high-content quantitative image cytometer, and xCelligence system MSCs exhibit a high migratory capacity towards C6 glioblastoma cells. Intravenous administration of SPION-labeled MSCs in vivo resulted in intratumoral accumulation of the tagged cells in the tumor tissues that in turn significantly enhanced the contrast of the tumor when high-field magnetic resonance imaging was performed. Subsequent biodistribution studies employing highly sensitive nonlinear magnetic response measurements (NLR-M2) supported by histological analysis confirm the retention of MSCs in the glioblastoma. In conclusion, MSCs due to their tumor-tropism could be employed as a drug-delivery platform for future theranostic approaches.

Modeling the magnetization dynamics for large ensembles of immobilized magnetic nanoparticles in multi-dimensional magnetic particle imaging

Magnetic nanoparticles (MNPs) play an important role in biomedical applications including imaging modalities such as magnetic resonance imaging (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. The image-to-voltage mapping is linear and described by a system matrix. 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. As an immediate consequence, the system matrix 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 magnetic easy axis during immobilization one can encode the angle of the particle’s magnetic easy axis into the magnetization response providing a relevant benchmark system for model-based approaches. In this work we address the modeling problem for immobilized and oriented MNPs in the context of MPI. We investigate a model-based approach where the magnetization response is simulated by a Néel 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 different 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.

Effective Néel relaxation time constant and intrinsic dipolar magnetism in a multicore magnetic nanoparticle system

The coexisting Néel and Brownian relaxation behaviors of magnetic nanoclusters in a viscous medium lead to a highly nonlinear field-dependent magnetization response, which can benefit magnetic particle imaging and hyperthermia. To empirically correlate the moment and particle dynamics with the core and cluster sizes, we performed spectroscopic susceptometry to assess frequency-dependent complex magnetic susceptibility of water-dispersed magnetic nanoclusters at very low field amplitude. The superparamagnetic core particles of nanoclusters should undergo fast moment dynamics. However, for the nanoclusters experiencing the field-driven Brownian relaxation, their constituent core particles appear to collectively behave as a large effective core with a long Néel relaxation time constant. We later numerically interpolated the phase-delay spectra of the immobilized nanoclusters to estimate the Néel relaxation time constant attributed to the intrinsic dipolar interparticle magnetism. From additional static magnetometry, the overlapping bimodal magnetic moment distribution predicts the secondary core sizes larger than the actual sizes from the electron microscopy images. The different estimates of the effective Néel relaxation time constant obtained from the (nearly field-free) frequency-dependent and (static) field-dependent magnetization responses further indicate the activation energies limiting the relaxation behavior of magnetic nanoclusters. This finding highlights the number of effective cores affecting the intracluster interaction energy.

Anomalous and anisotropic nonlinear susceptibility in the proximate Kitaev magnet \u03b1-RuCl3

The leading order nonlinear (NL) susceptibility, χ3, in a paramagnet is negative and diverges as T → 0. This divergence is destroyed when spins correlate and the NL response provides unique insights into magnetic order. Dimensionality, exchange interaction, and preponderance of quantum effects all imprint their signatures in the NL magnetic response. Here, we study the NL susceptibilities in the proximate Kitaev magnet α-RuCl3, which differs from the expected antiferromagnetic behavior. For T < Tc = 7.5 K and field B in the ab-plane, we obtain contrasting NL responses in low (<2 T) and high field regions. For low fields, the NL behavior is dominated by a quadratic response (positive χ2), which shows a rapid rise below Tc. This large χ2 > 0 implies a broken sublattice symmetry of magnetic order at low temperatures. Classical Monte Carlo (CMC) simulations in the standard K − H − Γ model secure such a quadratic B dependence of M, only for T ≈ Tc with χ2 being zero as T → 0. It is also zero for all temperatures in exact diagonalization calculations. On the other hand, we find an exclusive cubic term (χ3) that describes the high field NL behavior well. χ3 is large and positive both below and above Tc crossing zero only for T > 50 K. In contrast, for B ∥ c-axis, no separate low/high field behaviors are measured and only a much smaller χ3 is apparent.

Evaluation of the Biodistribution of Mesenchymal Stem Cells in a Pre-clinical Renal Tuberculosis Model by Non-linear Magnetic Response Measurements

Bone-marrow derived mesenchymal stem cells (MSCs) exert anti-tuberculosis effects due to their potential to repair damaged tissues and modulate inflammatory immune responses. MSCs were reported to be recruited to the Mycobacterium tuberculosis (Mtb) affected sites in the organism. However, due to limitations of presently applied in vivo imaging techniques the trafficking and biodistribution of MSCs in Mtb-infected organisms is not possible. In the current study MSCs were labeled with superparamagnetic iron oxide nanoparticles (SPIONs) as a negative MR contrast agent for imaging the biodistribution of MSCs in vivo. Trafficking of SPIONs-labeled MSCs was analyzed in a preclinical model of renal tuberculosis in male Chinchilla rabbits (n = 18) following intravenous administration on the days 0, 2, 3, and 7 employing a highly sensitive method of non-linear longitudinal magnetic response (NLR-M2) measurements. Within 48 h after injection, nanoparticle-labeled MSCs accumulated predominantly in lung, spleen, liver tissues, and paratracheal lymph nodes with subsequent decrease over the observation period of 7 days. The recruitment of MSCs to Mtb-affected organs was further proven by immunohistological analysis. NLR-M2 allowed the detection of SPIONs-labeled cells at low concentrations in different organs and tissues giving insights of in vivo mesenchymal stem cells trafficking in organism after TB infection.

Detection method of nonlinear magnetized harmonic signal of medical magnetic nanoparticles

Medical magnetic nanoparticles are nano-medical materials with superparamagnetism, which can be collected in the tumor tissue through blood circulation, and magnetic particle imaging technology can be used to visualize the concentration of magnetic nanoparticles in the living body to achieve the purpose of tumor imaging. Based on the nonlinear magnetization characteristics of magnetic particles and the frequency characteristics of their magnetization, a differential detection method for the third harmonic of magnetic particle detection signals is proposed. It was modeled and analyzed, to study the nonlinear magnetization response characteristics of magnetic particles under alternating field, and the spectral characteristics of magnetic particle signals. At the same time, the relationship between each harmonic and the amount of medical magnetic nanoparticle samples was studied. On this basis, a signal detection experimental system was built to analyze the spectral characteristics and power spectral density of the detected signal, and to study the relationship between the signal and the excitation frequency. The signal detection experiment was carried out by the above method. The experimental results showed that under the alternating excitation field, the medical magnetic nanoparticles would generate a spike signal higher than the background sensing signal, and the magnetic particle signal existed in the odd harmonics of the detected signal spectrum. And the spectral energy was concentrated at the third harmonic, that is, the third harmonic magnetic particle signal detection that meets the medical detection requirement could be realized. In addition, the relationship between each harmonic and the particle sample volume had a positive growth relationship, and the detected medical magnetic nanoparticle sample volume could be determined according to the relationship. At the same time, the selection of the excitation frequency was limited by the sensitivity of the system, and the detection peak of the third harmonic of the detection signal was reached at the excitation frequency of 1 kHz. It provides theoretical and technical support for the detection of medical magnetic nanoparticle imaging signals in magnetic particle imaging research.

Theoretical Study of the Frequency Multiplier Based on Irregular Quarter-Wavelength Microstrip Resonator with Thin Magnetic Film

The characteristics of a frequency doubler on a resonant microstrip structure with a thin magnetic film were studied theoretically. The electrodynamic calculation of the structure was performed within the quasi-static approximation. Nonlinear response of film magnetization was calculated taking into account the second-order terms in the Landau-Lifshitz equation. The frequency response of the microstrip resonator was calculated. It was shown that due to the use of the resonant circuit, high efficiency of the input signal energy conversion into the output signal at a doubled frequency was achieved. The optimal values of the magnitude and direction of an external static magnetic field, which ensure the maximum output power at a doubled frequency, were determined.

Application of mesenchymal stem cells in kidney and urinary tract diseases: literature review and own experience

SummaryIn recent years, cell therapy of diseases of various or-gans and tissues is gaining popularity, including the use of mesenchymal stem cells (MSCs). Many studies have confirmed the presence of pronounced immunoregula-tory properties in this type of cells, which are mediated both by direct action on target cells and by signaling mo-lecules and cytokines. This review is devoted to the pos-sibilities of using MSCs in urological pathology, including a description of the mechanisms of action on the human immune system and the prospects for using this type of cells in experimental and clinical practice. The article presents our own experience in studying the distribution of mesenchymal stem cells in various tissues and organs on a model of kidney tuberculosis in rabbits. Material and methods. The study involved 18 rabbits with kid-ney tuberculosis, which were injected intravenously with mesenchymal stem cells labeled with superparamagnetic iron oxide nanoparticles (SPION), followed by highly sen-sitive nonlinear longitudinal magnetic response imaging (NLR-M2). Results. 48 hours after the injection, MSCs ac-cumulated in the lungs, spleen, liver, paratracheal lymph nodes, and kidneys. Conclusion. The NLR-M2 method allows detecting SPION-labeled cells in various organs and tissues, giving an idea of the mesenchymal stem cells movement in the body.

Nonlinear Magnetic Response of a Viscoelastic Ferrocolloid: Effective Field Approximation

A viscoelastic ferrocolloid has been probed with the use of a weak alternating magnetic field, which causes rotational oscillations of nanoparticles. The rheology of the dispersion medium has been described using Jeffry’s phenomenological scheme, according to which, colloidal particles are assumed to be magnetically rigid. The Langevin equations that describe the Brownian rotational motion have been used to derive a set of equations for the dynamic magnetization and orientation kinetics of a colloidal ensemble. The solution of the problem has been obtained by the effective field method. The linear and cubic dynamic magnetic susceptibilities, as well as the orientational response of the system, have been found. It has been shown that, in the spectra of the responses of all orders, from linear to cubic ones, the effects of mechanical retardation (stress relaxation) lead to the appearance of specific features, namely, an increase in the medium elasticity is accompanied by variations in the position and height of the main maximum. Expressions have been proposed to relate the rheological parameters of the used Jeffry’s model with the structural characteristics of a polymer solution, i.e., the number of monomers in a macromolecule, the blob size, and the concentration of the physical network nodes.

Experimental comparison of four nonlinear magnetic detection methods and considerations on clinical usability

Superparamagnetic iron oxide nanoparticles (SPIONs) are promising for clinical applications, because they have a characteristic nonlinear magnetic response when an external magnetic field is applied. This nonlinearity enables the distinct detection of SPIONs and makes measurements less sensitive to the human body and surgical steel instruments. In clinical applications, only a limited field strength for the magnetic detection is allowed. The signal to noise ratios (SNRs) of four nonlinear magnetic detection methods are compared. These methods include differential magnetometry and three variations of magnetic particle spectroscopy: frequency mixing, second harmonic detection and third harmonic detection. All methods were implemented on the same hardware and experimentally compared for various field strengths. To make the comparison fair, the same power was supplied to the excitation coil each time. In general, the SNR increases with increasing field strength. The SNR per drive field of all methods stabilizes or even decreases for field strengths above 6 mT. The second harmonic detection has the best SNR and the most room for improvement.

AC magnetometry with active stabilization and harmonic suppression for magnetic nanoparticle spectroscopy and thermometry.

Magnetic nanoparticle (MNP) thermometry based on magnetic particle spectroscopy (MPS) is explored as a potential approach for realizing in-situ temperature measurement of 3D objects. MNP thermometry relies on the nonlinear magnetization response to an AC drive field. This nonlinear response has functional dependence on frequency and temperature, governed by the complex magnetization dynamics of MNPs suspended in solution. In this work, we introduce our approach for accurate and precise AC magnetization measurements using actively stabilized drive fields ranging from DC to 10 kHz. To isolate the harmonic response of MNPs from the drive field, we also perform active cancellation to reach drive field suppression up to 120 dB. Active stabilization and cancellation are utilized for real-time, sensitive measurements of AC magnetization of commercial samples, with stability on the timescale of hours. Initial results for MNP thermometry are demonstrated using this technique, and we achieved a total temperature uncertainty of 410 mK and 170 mK at 100 ms and 10 s integration time, respectively.

Spin Symmetry Breaking: Superparamagnetic and Spin Glass-Like Behavior Observed in Rod-Like Liquid Crystalline Organic Compounds Contacting Nitroxide Radical Spins

Liquid crystalline (LC) organic radicals were expected to show a novel non-linear magnetic response to external magnetic and electric fields due to their coherent collective molecular motion. We have found that a series of chiral and achiral all-organic LC radicals having one or two five-membered cyclic nitroxide radical (PROXYL) units in the core position and, thereby, with a negative dielectric anisotropy exhibit spin glass (SG)-like superparamagnetic features, such as a magnetic hysteresis (referred to as ‘positive magneto-LC effect’), and thermal and impurity effects during a heating and cooling cycle in weak magnetic fields. Furthermore, for the first time, a nonlinear magneto-electric (ME) effect has been detected with respect to one of the LC radicals showing a ferroelectric (chiral Smectic C) phase. The mechanism of the positive magneto-LC effect is proposed and discussed by comparison of our experimental results with the well-known magnetic properties of SG materials and on the basis of the experimental results of a nonlinear ME effect. A recent theoretical study by means of molecular dynamic simulation and density functional theory calculations suggesting the high possibility of conservation of the memory of spin-spin interactions between magnetic moments owing to the ceaseless molecular contacts in the LC and isotropic states is briefly mentioned as well.

Novel Benchtop Magnetic Particle Spectrometer for Process Monitoring of Magnetic Nanoparticle Synthesis.

Magnetic nanoparticles combine unique magnetic properties that can be used in a variety of biomedical applications for therapy and diagnostics. These applications place high demands on the magnetic properties of nanoparticles. Thus, research, development, and quality assurance of magnetic nanoparticles requires powerful analytical methods that are capable of detecting relevant structural and, above all, magnetic parameters. By directly coupling nanoparticle synthesis with magnetic detectors, relevant nanoparticle properties can be obtained and evaluated, and adjustments can be made to the manufacturing process in real time. This work presents a sensitive and fast magnetic detector for online characterization of magnetic nanoparticles during their continuous micromixer synthesis. The detector is based on the measurement of the nonlinear dynamic magnetic response of magnetic nanoparticles exposed to an oscillating excitation at a frequency of 25 kHz, a technique also known as magnetic particle spectroscopy. Our results underline the excellent suitability of the developed magnetic online detection for coupling with magnetic nanoparticle synthesis based on the micromixer approach. The proven practicability and reliability of the detector for process monitoring forms the basis for further application fields, e.g., as a monitoring tool for chromatographic separation processes.

Magnetic Nanoparticle Detection by Utilizing Nonlinear Magnetization for Sentinel Lymph Nodes of Breast Cancer Patients

To minimize the invasiveness and improve the patient's quality of life, sentinel lymph node (SLN) biopsy with magnetic nanoparticles (MNPs) containing superparamagnetic iron oxide is performed on breast cancer patients. Identifying the first SLN by quantification of the amount of MNPs can help to investigate the cancer metastasis. We developed the device for performing iron quantification during surgery. The compact desktop-size device can be easily introduced into operation rooms, and simple system of the device enables identification of the first SLN. We investigated the optimum nonlinear magnetic responses that are attributed to magnetic relaxations under moderate small ac and dc magnetic fields (~1 mT) and found that ac magnetic fields with <; 5 kHz are effective in the detection of MNPs. In addition, our clinical trials revealed more iron (40 μg) in the first lymph node than in the second lymph node (10 μg), clearly indicating intraoperative quantification in the first node.

Magnetic response of a highly nonlinear soliton lattice in a monoaxial chiral helimagnet

We present the theory of nonlinear ac magnetic response for the highly nonlinear regime of the chiral soliton lattice. Increasing of the dc magnetic field perpendicularly to the chiral axis results in crossover inside the phase, when nearly isolated $2\pi$-kinks are partitioned by vast ferromagnetic domains. Assuming that each of the kink reacts independently from the other ones to the external ac field, we demonstrate that internal deformations of such a kink give rise to the nonlinear response.

Vibrating reed magnetometer studies of superconducting and magnetic materials

ABSTRACTApplications of sensitive vibrating reed magnetometry to a variety of superconducting and magnetic materials are reviewed. The advantages of conducting vibrating reed studies of small single crystals, ceramics, thin films and multilayers with high anisotropy, composition gradients, strain and nonlinear magnetic response are documented. The equilibrium and dynamic properties of magnetic flux in superconductors, and coexistence of magnetic and superconducting states are emphasised. Vibrating reed experiments on Nb, NbSe2, (Ba0.6K0.4)BiO3, HoNi2B2C, {Nb(x)/Ni(y)}Z multilayer films, and κ-(ET)2Cu{N(CN)2}Br have revealed subtle, exotic superconducting behaviours that remain unexplained. Future prospects for vibrating reed measurements of ferromagnetic thin films with patterned nanostructures are considered.

Robust cycloid crossover driven by anisotropy in the skyrmion host GaV4S8

We report on the anomalous magnetization dynamics of the cycloidally-modulated spin textures under the influence of uniaxial anisotropy in multiferroic $\mathrm{GaV_4S_8}$. The temperature and field dependence of the linear ac susceptibility [$\chi_{1\omega}^{\prime}(T,H)$], ac magnetic loss [$\chi_{1\omega}^{\prime\prime}(T,H)$], and nonlinear ac magnetic response [$M_{3\omega}(T,H)$] are examined across the magnetic phase diagram in the frequency range $f = 10-10000$ Hz. According to recent theory, skyrmion vortices under axial crystal symmetry are confined along specific orientations, resulting in enhanced robustness against oblique magnetic fields and altered spin dynamics. We characterize the magnetic response of each spin texture and find that the dynamic rigidity of the N\'eel skyrmion lattice appears enhanced compared to Bloch-type skyrmions in cubic systems, even in the multidomain state. Anomalous $M_{3\omega}$ and strong dissipation emerge over the same phase regime where strong variations in the cycloid pitch were observed on lowering temperature in recent small-angle neutron scattering experiments [White et al., Phys. Rev. B 97, 020401(R) (2018)]. Here, we show that strong anisotropy also drives an extended crossover of the zero-field cycloid texture in $\mathrm{GaV_4S_8}$. The frequency dependence of these dynamic signatures is consistent with that of a robust anharmonic spin texture exhibiting a correlated domain arrangement. The results underpin the essential role of magnetic anisotropy in enhancing the rigidity of topological spin textures for diverse applications.

Magnetic particle imaging performance of liposomes encapsulating iron oxide nanoparticles

Magnetic Particle Imaging (MPI) is a new imaging modality that quantifies spatial distribution of superparamagnetic iron oxide nanoparticles in a field of view through their non-linear magnetization response to an applied magnetic field. Liposomes loaded with magnetic nanoparticles (magnetoliposomes) are potential theranostic drug carriers that can combine magnetic properties with drug carrier ability. Prior work suggests that MPI signal can be affected by dipolar interactions between magnetic nanoparticles in close proximity – for instance, in a polymer matrix. Here we evaluate if encapsulating magnetic nanoparticles in liposomes has an impact in their MPI performance. For this purpose, magnetoliposomes were prepared using charge-stabilized iron oxide nanoparticles (IONPs) and their physical, magnetic and MPI properties were characterized. Interestingly, encapsulation of IONPs in magnetoliposomes led to an increase in MPI signal per unit mass.

Теоретическое исследование умножителя частоты на основе нерегулярного четвертьволнового микрополоскового резонатора с тонкой магнитной пленкой

The characteristics of a frequency doubler on a resonance microstrip structure with a thin magnetic film have been studied theoretically. The electrodynamic calculation of the structure was performed in the framework of the quasistatic approximation. Nonlinear response of the film magnetization was calculated by taking into account second-order terms in the Landau-Lifshitz equation. The amplitude-frequency characteristic of the microstrip resonator was calculated. It was shown that due to the use of the resonant design, high conversion efficiency of the input signal energy to the output signal at a double frequency was achieved. The optimum values of the external constant magnetic field magnitude and orientation, at which generation of the second harmonic peaked, were determined.