Distribution Of Magnetic Nanoparticles Research Articles

Design of the distribution of iron oxide (Fe3O4) nano-particle drug in realistic cholangiocarcinoma model and the simulation of temperature increase during magnetic induction hyperthermia

The prognosis for Cholangiocarcinoma (CCA) is unfavorable, necessitating the development of new therapeutic approach such as magnetic hyperthermia therapy (MHT) which is induced by magnetic nano-particle (MNPs) drug to bridge the treatment gap. Given the deep location of CCA within the abdominal cavity and proximity to vital organs, accurately predict the individualized treatment effects and safety brought by the distribution of MNPs in tumor will be crucial for the advancement of MHT in CCA. The Mimics software was used in this study to conduct three-dimensional reconstruction of abdominal computed tomography (CT) and magnetic reso-nance imaging images from clinical patients, resulting in the generation of a realistic digital geometric model representing the human biliary tract and its adjacent structures. Subsequently, The COMSOL Multiphysics software was utilized for modeling CCA and calculating the heat transfer law resulting from the multi-regional distribution of MNPs in CCA. The temperature within the central region of irregular CCA measured approximately 46°C, and most areas within the tumor displayed temperatures surpassing 41°C. The temperature of the inner edge of CCA is only 39 ~ 41℃, however, it can be ameliorated by adjusting the local drug concentration through simulation system. For CCA with diverse morphologies and anatomical locations, the multi-regional distribution patterns of intratumoral MNPs and a slight overlap of drug distribution areas synergistically enhance intratumoral temperature while ensuring treatment safety. The present study highlights the practicality and imperative of incorporating personalized intratumoral MNPs distribution strategy into clinical practice for MHT, which can be achieved through the development of an integrated simulation system which incorporates medical image data and numerical calculations.

Human head sized magnetorelaxometry imaging of magnetic nanoparticles with optically pumped magnetometers — A feasibility study

Magnetic nanoparticles (MNP) offer exciting biomedical applications, e.g. magnetic hyperthermia for tumor treatment. The knowledge of the quantitative spatial distribution of MNP in the human body is a key for treatment safety and efficiency. Here we experimentally demonstrate the reconstruction of the quantitative MNP distribution of a human head phantom by magnetorelaxometry imaging (MRXI). The MRXI setup is composed of a 50 channel optically pumped magnetometer (OPM) system and 72 excitation coils, which are operated inside a magnetically shielded room. With our setup, we were able to reconstruct a glioblastoma phantom with a clinically relevant iron amount. A simulation study reveals, that currently the main limitations in terms of reconstruction quality arise from geometrical uncertainties of the setup. Summing up, we demonstrate the feasibility of OPM-MRXI for large regions of interest, potentially advancing the monitoring of MNP in related treatments.

Treatment Temperature and Magnetic Field Distribution for Magnetic Hyperthermia Using Magnetic Nanoparticles

A minimally invasive cancer treatment method utilizing magnetic nanoparticles (MNPs) and magnetic coils, magnetic hyperthermia, generates heat locally inside the body to degenerate cancer cells. The uniformity of the coil's magnetic field is a crucial factor in enhancing the therapeutic effect. In this study, we evaluated the temperature distribution of MNPs on induction heating experiments at various distances using two types of coils. We found that the 2‐turn coil with a larger outer diameter and higher magnetic field uniformity resulted in a treatment temperature region approximately twice as wide as the 4‐turn coil, indicating the enhancement of the treatment effect under the uniform magnetic field distributions. © 2024 Institute of Electrical Engineer of Japan and Wiley Periodicals LLC.

External magnet-guided targeted delivery and tissue distribution analysis of anti-cluster of differentiation 3 conjugated magnetic nanoparticles of Fe3O4 using in vivo imaging system

Drug distribution is a vital parameter for depicting the pharmacokinetic properties of therapeutic agents. Magnetic nanoparticles (MNPs) conjugated with anti-cluster of differentiation 3 (anti-CD3) monoclonal antibody (MNPs-Ab) is a promising immunotherapeutic agent. Magnet-guided targeted delivery of MNPs has been studied exclusively in oncology. The distribution of MNPs is routinely analyzed by measuring Fe levels using inductively coupled mass spectrometry (ICP-MS). However, the ICP-based methods measure the total iron content, including endogenous iron. We used an efficient approach that measured MNPs-Ab distribution after intravenous administration using an in vivo imaging system. The fluorescent-labeled anti-CD3s are conjugated with dextran-coated magnetic nanoparticles (50 nm diameter) by the glutaraldehyde conjugation method. MNPs-Ab was intravenously administered to BALB/c mice. The fluorescence intensity in live animal and organs were analyzed after 0, 1, and 24 h. The conjugation of fluorescently labeled antibodies with MNPs was validated. The attachment of a permanent magnet on the dorsal skin area successfully guided the intravenously injected Ab-MNPs within 24 h. However, after 1 h, no observable fluorescence was seen at the target site. The in vitro organ distribution study confirms nanoparticles’ predominant distribution in the liver and kidneys-the intensities of the fluorescence increase after 24 h than 1 h. Our in vivo imaging studies confirmed the external magnet-driven targeted distribution of the antibody-conjugated nanoparticle. Besides, the in vivo imaging system enables rapidly identifying the distributed nanoparticles.

Nitrogen-vacancy center magnetic imaging of Fe3O4 nanoparticles inside the gastrointestinal tract of Drosophila melanogaster.

Widefield magnetometry based on nitrogen-vacancy centers enables high spatial resolution imaging of magnetic field distributions without a need for spatial scanning. In this work, we show nitrogen-vacancy center magnetic imaging of Fe3O4 nanoparticles within the gastrointestinal tract of Drosophila melanogaster larvae. Vector magnetic field imaging based on optically detected magnetic resonance is carried out on dissected larvae intestine organs containing accumulations of externally loaded magnetic nanoparticles. The distribution of the magnetic nanoparticles within the tissue can be clearly deduced from the magnetic stray field measurements. Spatially resolved magnetic imaging requires the nitrogen-vacancy centers to be very close to the sample making the technique particularly interesting for thin tissue samples. This study is a proof of principle showing the capability of nitrogen-vacancy center magnetometry as a technique to detect magnetic nanoparticle distributions in Drosophila melanogaster larvae that can be extended to other biological systems.

Use of magnetic nanoparticles in an Ionic liquid (BMIM-PF6) based vortex‐assisted dispersive liquid–liquid microextraction (VSLLME) for measuring the traces amounts of cadmium in environmental, biological and nutritional samples

In the present project, the magnetic nanoparticles were used in a type of an ionic liquid based micro-extraction to measure trace amounts of cadmium in different real samples containing environmental water samples, saliva and human hair. In the optimum condition, the recovery percentages for the real sample were about 94.5% to 101.3%, showing the designed method is suitable to be used for analyzing the real environmental and biological samples. The main parameters were evaluated and optimized as follows: pH was 2.5, the volume of ionic liquid was 150 µl, the amount of Fe3O4 magnetic nanoparticles was 50mg, the volume of the complexing agent was 12 µl, and the vortex time was 1 min and 2 min for ionic liquid, and magnetic nanoparticle distribution steps, respectively. Also, the volume of the medium was 10 to 20 ml.

Magnetic particle image scanner based on asymmetric core-filled electromagnetic actuator

Monitoring the distribution of magnetic nanoparticles (MNPs) in the vascular system is an important task for the advancement of precision therapeutics and drug delivery. Despite active targeting using active motilities, it is required to visualize the position and concentration of carriers that reach the target, to promote the development of this technology. In this work, a feasibility study is presented on a tomographic scanner that allows monitoring of the injected carriers quantitatively in a relatively short interval. The device is based on a small-animal-scale asymmetric magnetic platform integrated with magnetic particle imaging technology. An optimized isotropic field-free region (FFR) generation method using a magnetic manipulation system (MMS) is derived and numerically investigated. The in-vitro and in-vivo tracking performances are demonstrated with a high position accuracy of approximately 1 mm. A newly proposed tracking method was developed, specialized in vascular system, with quick scanning time (about 1s). In this paper, the primary function of the proposed system is to track magnetic particles using a magnetic manipulation system. Through this, proposed method enables the conventional magnetic actuation systems to upgrade the functionalities of both manipulation and localization of magnetic objects.

Progressive Pretraining Network for 3D System Matrix Calibration in Magnetic Particle Imaging.

Magnetic particle imaging (MPI) is an emerging technique for determining magnetic nanoparticle distributions in biological tissues. Although system-matrix (SM)-based image reconstruction offers higher image quality than the X-space-based approach, the SM calibration measurement is time-consuming. Additionally, the SM should be recalibrated if the tracer's characteristics or the magnetic field environment change, and repeated SM measurement further increase the required labor and time. Therefore, fast SM calibration is essential for MPI. Existing calibration methods commonly treat each row of the SM as independent of the others, but the rows are inherently related through the coil channel and frequency index. As these two elements can be regarded as additional multimodal information, we leverage the transformer architecture with a self-attention mechanism to encode them. Although the transformer has shown superiority in multimodal fusion learning across several fields, its high complexity may lead to overfitting when labeled data are scarce. Compared with labeled SM (i.e., full size), low-resolution SM data can be easily obtained, and fully using such data may alleviate overfitting. Accordingly, we propose a pseudo-label-based progressive pretraining strategy to leverage unlabeled data. Our method outperforms existing calibration methods on a public real-world OpenMPI dataset and simulation dataset. Moreover, our method improves the resolution of two in-house MPI scanners without requiring full-size SM measurements. Ablation studies confirm the contributions of modeling SM inter-row relations and the proposed pretraining strategy.

Bayesian design of measurements for magnetorelaxometry imaging *

The aim of magnetorelaxometry imaging is to determine the distribution of magnetic nanoparticles inside a subject by measuring the relaxation of the superposition magnetic field generated by the nanoparticles after they have first been aligned using an external activation magnetic field that has subsequently been switched off. This work applies techniques of Bayesian optimal experimental design to (sequentially) selecting the positions for the activation coil in order to increase the value of data and enable more accurate reconstructions in a simplified measurement setup. Both Gaussian and total variation (TV) prior models are considered for the distribution of the nanoparticles. The former allows simultaneous offline computation of optimized designs for multiple consecutive activations, while the latter introduces adaptability into the algorithm by using previously measured data in choosing the position of the next activation. The TV prior has a desirable edge-enhancing characteristic, but with the downside that the computationally attractive Gaussian form of the posterior density is lost. To overcome this challenge, the lagged diffusivity iteration is used to provide an approximate Gaussian posterior model and allow the use of the standard Bayesian A- and D-optimality criteria for the TV prior as well. Two-dimensional numerical experiments are performed on a few sample targets, with the conclusion that the optimized activation positions lead, in general, to better reconstructions than symmetric reference setups when the target distribution or region of interest are nonsymmetric in shape.

Magnetic-field induced asymmetric hydrogel fibers for tough actuators with programmable deformation

Ingenious design of soft actuators with high mechanical performance, rapid actuation, and programmable deformation is necessary for their practical applications in the fields of artificial muscles, smart textiles, and soft robotics. Here we used a facile magnetic-field induction strategy to fabricate programmable actuators composed of tough hydrogel fibers. The anisotropic hydrogel fibers that consisted of dual physically cross-linked networks showed high tensile strength (28.9 MPa), while the asymmetric distribution of magnetic nanoparticles in hydrogel networks endowed the actuators with rapid bending velocity (3.2°·min−1·mm−1) in response to solvents. The pick-and-place manipulation of objects from ethanol to water were demonstrated by using the soft grippers composed of asymmetric hydrogel fibers. Furthermore, smart curtains that were woven by hydrogel fibers automatically rolled up or spread out in response to the change of ambient humidity. This work proved that tough hydrogel fibers fabricated by our magnetic-field induction strategy provided more possibilities in the field of soft actuators.

Estimation of biomolecule amount by analyzing magnetic nanoparticle cluster distributions from alternating current magnetization spectra for magnetic biosensing

The hydrodynamic size distribution of magnetic nanoparticle (MNP) clusters is crucial for determining the amounts of biomolecules by analyzing the distributions of the Brownian relaxation time in the corresponding alternating current (AC) magnetization spectra. This study proposes a method for estimating the distribution of MNP clusters from recorded AC magnetization spectra using an experimental-based model. The proposed model is used to form a matrix equation that comprises the distribution and AC magnetization spectra of MNP clusters, and the MNP–biomolecule cluster distribution is obtained by solving an inverse problem. The results show that the variations in the MNP clusters distribution estimated from the model correspond to those measured by dynamic light scattering. The MNP cluster distributions estimated using the experimental model were used to estimate streptavidin concentrations in the range of 0.19–3.38 μM. The estimated values agree accurately with the true values, demonstrating the feasibility of the proposed method for biosensing.

Studies on Re-188 Labeling and In Vivo Distribution of Magnetic Nanoparticles with Different Morphologies and Sizes

Studies on Re-188 Labeling and In Vivo Distribution of Magnetic Nanoparticles with Different Morphologies and Sizes

Saline bolus for negative contrast perfusion imaging in magnetic particle imaging.

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 of a future patient by utilizing a positive-negative contrast sequence, while minimizing the iron dose per acquired image.

Preparation and PET/CT imaging of implant directed 68Ga-labeled magnetic nanoporous silica nanoparticles

BackgroundImplant infections caused by biofilm forming bacteria are a major threat in orthopedic surgery. Delivering antibiotics directly to an implant affected by a bacterial biofilm via superparamagnetic nanoporous silica nanoparticles could present a promising approach. Nevertheless, short blood circulation half-life because of rapid interactions of nanoparticles with the host’s immune system hinder them from being clinically used. The aim of this study was to determine the temporal in vivo resolution of magnetic nanoporous silica nanoparticle (MNPSNP) distribution and the effect of PEGylation and clodronate application using PET/CT imaging and gamma counting in an implant mouse model.MethodsPEGylated and non-PEGylated MNPSNPs were radiolabeled with gallium-68 (68Ga), implementing the chelator tris(hydroxypyridinone). 36 mice were included in the study, 24 mice received a magnetic implant subcutaneously on the left and a titanium implant on the right hind leg. MNPSNP pharmacokinetics and implant accumulation was analyzed in dependence on PEGylation and additional clodronate application. Subsequently gamma counting was performed for further final analysis.ResultsThe pharmacokinetics and biodistribution of all radiolabeled nanoparticles could clearly be visualized and followed by dynamic PET/CT imaging. Both variants of 68Ga-labeled MNPSNP accumulated mainly in liver and spleen. PEGylation of the nanoparticles already resulted in lower liver uptakes. Combination with macrophage depletion led to a highly significant effect whereas macrophage depletion alone could not reveal significant differences. Although MNPSNP accumulation around implants was low in comparison to the inner organs in PET/CT imaging, gamma counting displayed a significantly higher %I.D./g for the tissue surrounding the magnetic implants compared to the titanium control. Additional PEGylation and/or macrophage depletion revealed no significant differences regarding nanoparticle accumulation at the implantation site.ConclusionTracking of 68Ga-labeled nanoparticles in a mouse model in the first critical hours post-injection by PET/CT imaging provided a better understanding of MNPSNP distribution, elimination and accumulation. Although PEGylation increases circulation time, nanoparticle accumulation at the implantation site was still insufficient for infection treatment and additional efforts are needed to increase local accumulation.

Content-Noise Feature Fusion Neural Network for Image Denoising in Magnetic Particle Imaging∗.

Magnetic particle imaging (MPI) is a tomographic imaging method that quantitatively determines the distribution of magnetic nanoparticles (MNPs). However, the performance of MPI is primarily limited by the noise in the receive coil and electronic devices, which causes quantification errors for MPI images. Existing methods cannot efficiently eliminate noise while preserve structural details in MPI images. To address this problem, we propose a Content-Noise Feature Fusion Neural Network equipped with tailored modules of noise learning and content learning. It can simultaneously learn content and noise features of raw MPI images. Experimental results show that the proposed method outperforms the state-of-the-art methods on structural details preservation and image noise reduction of different levels.

Human-sized quantitative imaging of magnetic nanoparticles with nonlinear magnetorelaxometry

Objective. Magnetorelaxomety imaging (MRXI) is a noninvasive imaging technique for quantitative detection of magnetic nanoparticles (MNPs). The qualitative and quantitative knowledge of the MNP distribution inside the body is a prerequisite for a number of arising biomedical applications, such as magnetic drug targeting and magnetic hyperthermia therapy. It was shown throughout numerous studies that MRXI is able to successfully localize and quantify MNP ensembles in volumes up to the size of a human head. However, deeper regions that lie far from the excitation coils and the magnetic sensors are harder to reconstruct due to the weaker signals from the MNPs in these areas. On the one hand, stronger magnetic fields need to be applied to produce measurable signals from such MNP distributions to further upscale MRXI, on the other hand, this invalidates the assumption of a linear relation between applied magnetic field and particle magnetization in the current MRXI forward model which is required for the imaging procedure. Approach. We tackle this problem by introducing a nonlinear MRXI forward model that is also valid for strong magnetic excitation fields. Main results. We demonstrate in our experimental feasibility study that scaling up the imaging region to the size of a human torso using nonlinear MRXI is possible. Despite the extreme simplicity of the imaging setup applied in this study, an immobilized MNP sample with 6.3 cm3 and 12 mg Fe could be localized and quantified with an acceptable quality. Significance. A well-engineered MRXI setup could provide much better imaging qualities in shorter data acquisition times, making nonlinear MRXI a viable option for the supervision of MNP related therapies in all regions of the human body, specifically magnetic hyperthermia.

Extraction method of nanoparticles concentration distribution from magnetic particle image and its application in thermal damage of magnetic hyperthermia

Magnetic particle imaging (MPI) technology can generate a real-time magnetic nanoparticle (MNP) distribution image for biological tissues, and its use can overcome the limitations imposed in magnetic hyperthermia treatments by the unpredictable MNP distribution after the intratumoral injection of nanofluid. However, the MNP concentration distribution is generally difficult to be extracted from MPI images. This study proposes an approach to extract the corresponding concentration value of each pixel from an MPI image by a least squares method (LSM), which is then translated as MNP concentration distribution by an interpolation function. The resulting MPI-based concentration distribution is used to evaluate the treatment effect and the results are compared with the ones of two baseline cases under the same dose: uniform distribution and MPI-based distribution considering diffusion. Additionally, the treatment effect for all these cases is affected by the blood perfusion rate, which is also investigated deeply in this study. The results demonstrate that the proposed method can be used to effectively reconstruct the concentration distribution from MPI images, and that the weighted LSM considering a quartic polynomial for interpolation provides the best results with respect to other cases considered. Furthermore, the results show that the uniformity of MNP distribution has a positive correlation with both therapeutic temperature distribution and thermal damage degree for the same dose and a critical power dissipation value in the MNPs. The MNPs uniformity inside biological tissue can be improved by the diffusion behavior after the nanofluid injection, which can ultimately reflect as an improvement of treatment effect. In addition, the blood perfusion rate considering local temperature can have a positive effect on the treatment compared to the case which considers a constant value during magnetic hyperthermia.

Magnetically Stimulable Graphene Oxide/Polypropylene Nanocomposites.

Core-shell magnetic air-stable nanoparticles have attracted increasing interest in recent years. Attaining a satisfactory distribution of magnetic nanoparticles (MNPs) in polymeric matrices is difficult due to magnetically induced aggregation, and supporting the MNPs on a nonmagnetic core-shell is a well-established strategy. In order to obtain magnetically active polypropylene (PP) nanocomposites by melt mixing, the thermal reduction of graphene oxides (TrGO) at two different temperatures (600 and 1000 °C) was carried out, and, subsequently, metallic nanoparticles (Co or Ni) were dispersed on them. The XRD patterns of the nanoparticles show the characteristic peaks of the graphene, Co, and Ni nanoparticles, where the estimated sizes of Ni and Co were 3.59 and 4.25 nm, respectively. The Raman spectroscopy presents typical D and G bands of graphene materials as well as the corresponding peaks of Ni and Co nanoparticles. Elemental and surface area studies show that the carbon content and surface area increase with thermal reduction, as expected, following a reduction in the surface area by the support of MNPs. Atomic absorption spectroscopy demonstrates about 9-12 wt % metallic nanoparticles supported on the TrGO surface, showing that the reduction of GO at two different temperatures has no significant effect on the support of metallic nanoparticles. Fourier transform infrared (FT-IR) spectroscopy shows that the addition of a filler does not alter the chemical structure of the polymer. Scanning electron microscopy of the fracture interface of the samples demonstrates consistent dispersion of the filler in the polymer. The TGA analysis shows that, with the incorporation of the filler, the initial (Tonset) and maximum (Tmax) degradation temperatures of the PP nanocomposites increase up to 34 and 19 °C, respectively. The DSC results present an improvement in the crystallization temperature and percent crystallinity. The filler addition slightly enhances the elastic modulus of the nanocomposites. The results of the water contact angle confirm that the prepared nanocomposites are hydrophilic. Importantly, the diamagnetic matrix is transformed into a ferromagnetic one with the addition of the magnetic filler.

Magnetomotive Ultrasound Shear Wave Elastography (MMUS-SWE): A Validation Study From Simulations to Experiments.

Ultrasound elastography is a functional imaging method that enables the measurement of soft tissue elasticity, which is associated with the pathological process of many diseases. However, the measurement area of the conventional elastography method is subjectively selected. Inspired by the targeted imaging technology, we propose a method of magnetomotive ultrasound shear wave elastography (MMUS-SWE). This method utilizes the magnetic force between the magnetic nanoparticles (MNPs) and the external magnetic field to generate shear waves. Then, it can detect the distribution of MNPs and the elasticity of the tissue around the MNPs. As MNPs have been widely used for targeted labeling, the strategy to induce local vibration by MNPs will be more specific than that of the conventional SWE. In this study, the theoretical feasibility was verified by the finite element simulation model. Then, an experimental system was built, and the experimental feasibility of the method was demonstrated through phantom experiments, in vitro tissue experiments, and in vivo experiments. The results show that the distribution of the MNPs and the elastic information of tissues surrounding the MNPs can be detected simultaneously. This technology is expected to realize targeted elasticity measurement based on the MNPs and has potential applications for disease diagnosis.

System Matrix Reconstruction Algorithm for Thermoacoustic Imaging With Magnetic Nanoparticles Based on Acoustic Reciprocity Theorem.

According to the acoustic reciprocity theorem (ART), we propose a system matrix reconstruction algorithm of thermoacoustic imaging for magnetic nanoparticles (MNPs) by a single-pulse magnetic field. In both cases of inhomogeneous and homogeneous acoustic velocity, we respectively derive the linear equation between the sound pressure detection value and the distribution of MNPs. The image reconstruction problem is converted to an inverse matrix solution by using the truncated singular value decomposition (TSVD) method. In forward problem, the calculated forward results are consistent with the simulated thermoacoustic signal signals. In inverse problem, we build the two-dimensional breast cancer model. The TSVD method based on the ART faithfully reflects the distribution of abnormal tissue labeled by the MNPs. In the experiment, the biological sample injected with the MNPs is used as the imaging target. The reconstructed image well reflects the cross-sectional images of the MNPs area. The TSVD method based on the ART takes into account energy attenuation and inhomogeneous acoustic velocity, and use a non-focused broadband ultrasonic transducer as the receiver to obtain a larger imaging field-of-view (FOV). By comparing the image metrics, we prove that the algorithm is superior to the traditional time reversal method. The TSVD method based on the ART can better suppress noise, which is expected to reduce the cost by reducing the number of detectors. It is of great significance for future clinical applications.