Imaging Of Magnetic Nanoparticles Research Articles

Recent Developments in Magnetic Hyperthermia Therapy (MHT) and Magnetic Particle Imaging (MPI) in the Brain Tumor Field: A Scoping Review and Meta-Analysis.

Magnetic hyperthermia therapy (MHT) is a promising treatment modality for brain tumors using magnetic nanoparticles (MNPs) locally delivered to the tumor and activated with an external alternating magnetic field (AMF) to generate antitumor effects through localized heating. Magnetic particle imaging (MPI) is an emerging technology offering strong signal-to-noise for nanoparticle localization. A scoping review was performed by systematically querying Pubmed, Scopus, and Embase. In total, 251 articles were returned, 12 included. Articles were analyzed for nanoparticle type used, MHT parameters, and MPI applications. Preliminary results show that MHT is an exciting treatment modality with unique advantages over current heat-based therapies for brain cancer. Effective application relies on the further development of unique magnetic nanoparticle constructs and imaging modalities, such as MPI, that can enable real-time MNP imaging for improved therapeutic outcomes.

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.

Imaging of Magnetic Nanoparticles with Permeability Tomography.

Magnetic nanoparticles are being increasingly used in numerous biomedical applications for diagnosis and therapy. During the course of these applications nanoparticle biodegradation and body clearance may occur. In this context, a portable, non-invasive, non-destructive and contactless imaging device can be relevant to trace the nanoparticle distribution before and after the medical procedure. We present a method for in vivo imaging the nanoparticles based on the magnetic induction technique, and we show how to properly tune it for magnetic permeability tomography, maximizing the permeability selectivity. A tomograph prototype was designed and built to demonstrate the feasibility of the proposed method. It includes data collection, signal processing and image reconstruction. Useful selectivity and resolution are achieved on phantoms and animals, proving that the device can be used to monitor the presence of magnetic nanoparticles without requiring any particular sample preparation. By this way, we show that magnetic permeability tomography may become a powerful technique to assist medical procedures.

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.

Specific absorption rate of randomly oriented magnetic nanoparticles in a static magnetic field.

Numerical simulations using the stochastic Landau-Lifshitz equation are performed to study magnetization dynamics of dilute assemblies of iron oxide nanoparticles exposed to an alternating (ac) magnetic field with an amplitude H ac = 200 Oe and a frequency f = 300 kHz and a static (dc) magnetic field in the range H dc = 0-800 Oe. The specific absorption rate (SAR) of the assemblies is calculated depending on the angle between the directions of the ac and dc magnetic fields. For the case of an inhomogeneous dc magnetic field created by two opposite magnetic fluxes, the spatial distribution of the SAR in the vicinity of the field-free point is obtained for assemblies with different nanoparticle size distributions. The results obtained seem to be helpful for the development of a promising joint application of magnetic nanoparticle imaging and magnetic hyperthermia.

Magneto-thermal-acoustic imaging of magnetic nanoparticles with tissue structure imaging function

Magneto-thermal-acoustic imaging with magnetic nanoparticles (MNPs) is a novel medical imaging modality based on the thermoacoustic (TA) effect of MNPs. We proposed a new dual-modality imaging strategy that combines the TA and echo signals. Based on the synthetic aperture method, we used TA signals to image cancer tissues labeled with MNPs and applied echo signals to achieve tissue structure imaging. In the simulation, we constructed a breast cancer model and assumed that cancer tissue was labeled with MNPs. Under a limited field of view, the TA and echo signals were collected using a multi-element transducer array. By fusing the imaging results of the TA and echo signals, we obtained a boundary distribution map of the breast cancer model, and accurately located the tumor tissue. In this experiment, we built a multi-channel acquisition system. Pork tissue labeled with MNPs was used as the breast cancer phantom. We collected a total of 120 TA and echo signals at 1 mm intervals using a multi-element transducer array and faithfully imaged the boundary distribution map of the phantom. Compared with the traditional linear back projection method based on focused transducers, we demonstrated that the proposed method not only improves the lateral resolution of the image, but also makes accurate cancer identification easier. This provides a promising medical imaging technology for clinical applications.

Numerical and Experimental Study of Colored Magnetic Particle Mapping via Magnetoelectric Sensors

Colored imaging of magnetic nanoparticles (MNP) is a promising noninvasive method for medical applications such as therapy and diagnosis. This study investigates the capability of the magnetoelectric sensor and projected gradient descent (PGD) algorithm for colored particle detection. In the first step, the required circumstances for image reconstruction are studied via a simulation approach for different signal-to-noise ratios (SNR). The spatial accuracy of the reconstructed image is evaluated based on the correlation coefficient (CC) factor. The inverse problem is solved using the PGD method, which is adapted according to a nonnegativity constraint in the complex domain. The MNP characterizations are assessed through a magnetic particle spectrometer (MPS) for different types. In the experimental investigation, the real and imaginary parts of the MNP's response are used to detect the spatial distribution and particle type, respectively. The experimental results indicate that the average phase difference for CT100 and ARA100 particles is 14 degrees, which is consistent with the MPS results and could satisfy the system requirements for colored imaging. The experimental evaluation showed that the magnetoelectric sensor and the proposed approach could be potential candidates for color bio-imaging applications.

Developing magnetorelaxometry imaging for human applications

Objective. Magnetic nanoparticles (MNPs) are a promising tool in biomedical applications such as cancer therapy and diagnosis, where localization and quantification of MNP distributions are often mandatory. This can be obtained by magnetorelaxometry imaging (MRXI). Approach. In this work, the capability of MRXI for quantitative imaging of MNP inside larger volumes such as a human head is investigated. We developed a human head phantom simulating a glioblastoma multiforme (GBM) tumor containing MNP for magnetic hyperthermia treatment. The sensitivity of our MRXI setup for detection of MNP concentrations in the range of 3–19 mg cm−3 was studied. Main result. The results show the high capability of MRXI to detect MNPs in a human head sized volume. Superficial sources with a concentration larger than 12 mg cm-3 could be reconstructed with a resulotion of about 1 cm-3. Significance. The reconstruction of the MNP distribution, mimicking a GBM tumor of 7 cm3 volume with clinically relevant iron concentration, demonstrates the in vivo feasibility of MRXI in humans.

Thermoacoustic concentration imaging of magnetic nanoparticles under single-pulse magnetic fields

Under a single-pulse magnetic field (SMF), we proposed a thermoacoustic (TA) concentration imaging method of magnetic nanoparticles (MNPs). This method derived the relationship between the concentration of MNPs and TA signals based on the mechanism of the TA effect. In the simulation, we ideally reconstructed the concentration map of the MNPs from the simulated TA signals. It proves the feasibility of the proposed method. In the experiment, a multi-channel acquisition system was built, and the MNP suspension with the iron concentration of 1 mg/ml was injected into two gaps of the phantom. Then, 128 TA signals were obtained by a multi-channel acquisition system. Finally, the imaging results faithfully reconstructed the cross-sectional image of the MNP area in the phantom. It is demonstrated that the TA concentration imaging of the MNPs under the SMF has the potential to achieve low-concentration MNP imaging in vivo, which provides a promising molecular imaging method for imaging MNP-labeled cancer tissues.

Quantitative imaging of magnetic nanoparticles in an unshielded environment using a large AC susceptibility array

BackgroundNon-invasive magnetic imaging techniques are necessary to assist magnetic nanoparticles in biomedical applications, mainly detecting their distribution inside the body. In Alternating Current Biosusceptometry (ACB), the magnetic nanoparticle's magnetization response under an oscillating magnetic field, which is applied through an excitation coil, is detected with a balanced detection coil system.ResultsWe built a Multi-Channel ACB system (MC-ACB) containing nineteen pick-up coils and obtained 2D quantitative images of magnetic nanoparticle distributions by solving an inverse problem. We reconstructed the magnetic nanoparticles spatial distributions in a field of view of 14 × 14 cm2 with a spatial resolution of 2.0 cm and sensitivity in the milligram scale. A correlation coefficient between quantitative reconstructed and nominal magnetic nanoparticle distributions above 0.6 was found for all measurements.ConclusionBesides other interesting features such as sufficient large field of view dimension for mice and rat studies, portability, and the ability to assess the quantitative magnetic nanoparticles distributions in real-time, the MC-ACB system is a promising tool for quantitative imaging of magnetic nanoparticles distributions in real-time, offering an affordable setup for easy access in clinical or laboratory environments.

Numerical study on imaging of magnetic nanoparticles with ultrasound based on saturation magnetization

Imaging of magnetic nanoparticles with ultrasound utilizes ultrasound excitation and electromagnetic receiving. At present, the size of magnetic nanoparticles (MNPs) for the imaging method is required to be no less than 100 nm, which limits its application in human bodies. To overcome the limitation of particle size, imaging of MNPs with ultrasound based on saturation magnetization is proposed. The relationship between the concentration of superparamagnetic pear-shaped MNPs and the induced voltage under saturation magnetization is derived based on the classical Langevin theory of paramagnetism. A 3D simulation model is constructed and numerical research is carried out under the saturated magnetic field provided by the Helmholtz coil. The concentration image is reconstructed by point-by-point scanning. Numerical studies show that the induced voltage is rich in the concentration information of superparamagnetic pear-shaped MNPs, proving the feasibility of the method. The maximum induced voltage, which enhances the imaging effect, occurs under the minimum radius of the detection coil containing the region of interest. MNPs under 20 nm still meet the imaging requirements in the proposed method. This research pushes the imaging of MNPs with ultrasound based on saturation magnetization a further step forward to practical applications in the biomedical field.

Brain Tumor Imaging and Delivery of Sub-5 nm Magnetic Iron Oxide Nanoparticles in an Orthotopic Murine Model of Glioblastoma

Brain Tumor Imaging and Delivery of Sub-5 nm Magnetic Iron Oxide Nanoparticles in an Orthotopic Murine Model of Glioblastoma

Magnetic nanoparticles in theranostic applications

Nanomedicine research recently started exploring the combination of therapy and diagnostics, so-called theranostics, as an approach to offer a more flexible, personal, and precise care with improved patient outcomes. As magnetic nanoparticles show great potential in a variety of diagnostic and therapeutic applications, they are prime candidates to be used in a theranostic platform to realize this vision. This Perspective gives an overview of state-of-the-art magnetic imaging techniques and theranostic applications based on magnetic nanoparticles and discusses their opportunities and associated challenges. In order to address these challenges and to exploit these opportunities to the fullest, we discuss three promising research directions. The first considers the use of novel magnetic field sequences to utilize the rich magnetic dynamics of the particles, allowing a more accurate diagnosis and boosting the performance of many nanoparticle-based applications. Second, we introduce the innovative concept of smart theranostics based on feedback mechanisms between the particle applications and their supporting imaging procedure to enhance the performance of both and to allow real-time monitoring of treatment efficiency. Finally, we show the twofold advantage of applying data-driven models to enhance therapy and diagnostics on the one hand and for handling the platform’s large amount of data and associated decision support algorithms on the other. The latter research track is extended to include hybrid models in which physics-based and data-driven models are combined to overcome challenges of applications with limited data, making the data-driven part understandable, as well as in uncovering unknown nanoparticle dynamics. Contrasting other literature works, which mainly focus on developing magnetic nanoparticles with the right characteristics, we put forward advances in magnetic nanoparticle imaging techniques and applications to enable the use of a broader range of magnetic nanoparticles in theranostics. We seek to emphasize the importance of these building blocks as many research opportunities with a very high potential are still left open. Therefore, we encourage researchers to also take these aspects into account to advance theranostic applications of magnetic nanoparticles to real clinical environments.

Magnetic Nanoparticle Imaging: Insight on the Effects of Magnetic Interactions and Hysteresis of Tracers

Magnetic Nanoparticle Imaging: Insight on the Effects of Magnetic Interactions and Hysteresis of Tracers

Analysis of the Relationship Between Periampullary Diverticulum and Recurrent Bile Duct Stones After Endoscopy on Magnetic Resonance Imaging of Magnetic Nanoparticles

The objective of this work was to investigate the effect of magnetic resonance cholangiopancreatography (MRCP) based on super-paramagnetic iron oxide nanoparticles (SPIONs) on the recurrence diagnosis of periampullary diverticulum (PAD) and bile duct stone (BDS), so as to provide a scientific research basis for the recidivation factors of bile duct stones in clinic. Patients with PAD diagnosed in hospital from July 2019 to March 2021 (who had undergone endoscopic gallstone surgery) were selected for study in this work. They were rolled into two groups, the parapapillary group (123 cases) and the cholangiopancreatic duct directly opening in the diverticulum group (97 cases), according to the clinical classification. Then, 100 patients without PAD who had undergone bile duct node therapy were selected as the control group. The recidivation of BDS, serological index, and biliary pressure index before and after treatment were compared. The relationship between PAD and recidivation of bile duct stones was analyzed. The results showed that the average particle size, hydration kinetic particle size, effective time, and duration of polyethylene glycol (PEG)/polyethyleneimine (PEI)/poly aspartic acid-super-paramagnetic iron oxide nanoparticles(PASP-SPIONs) were better than PEG/PEI-SPIONs and SPIONs. The recidivation rate of BDS in Groups R and X was remarkably higher than the rate in control group (P < 0.05). Before treatment, common bile duct pressure in the control group was lower obviously than that in Groups R and X (P < 0.05). After treatment, the indexes including total bilirubin, direct bilirubin, and alkaline phosphatase in control group were lower than those in Groups R and X (P < 0.05). The incidence of complications in Groups R and X was much higher than in contrast to the control group (P < 0.05). Therefore, PEG/PEI/PASP-SPIONs had good contrast effect and could be used as magnetic resonance imaging contrast agent. Complications such as common bile duct pressure and infection were increased by PAD, which may be the main factor for the recidivation of BDS.

Adaptive Model for Magnetic Particle Mapping Using Magnetoelectric Sensors.

Imaging of magnetic nanoparticles (MNPs) is of great interest in the medical sciences. By using resonant magnetoelectric sensors, higher harmonic excitations of MNPs can be measured and mapped in space. The proper reconstruction of particle distribution via solving the inverse problem is paramount for any imaging technique. For this, the forward model needs to be modeled accurately. However, depending on the state of the magnetoelectric sensors, the projection axis for the magnetic field may vary and may not be known accurately beforehand. As a result, the projection axis used in the model may be inaccurate, which can result in inaccurate reconstructions and artifact formation. Here, we show an approach for mapping MNPs that includes sources of uncertainty to both select the correct particle distribution and the correct model simultaneously.

Evaluating selection criteria for optimized excitation coils in magnetorelaxometry imaging

Objective. Magnetorelaxometry imaging (MRXI) is an experimental imaging technique applicable for noninvasive, qualitative and quantitative imaging of magnetic nanoparticles (MNPs). Accurate reconstructions of nanoparticle distributions are crucial for several novel treatment methods employing MNPs such as magnetic drug targeting or magnetic hyperthermia therapy. Hence, it is desirable to design MRXI setups such that the reconstruction accuracy is maximized for a given set of design parameters. Several attempts exist in literature that focus on the improvement of MRXI and other related linear inverse problems with respect to various figures of merit. However, to date it remains unclear, which approach leads to the largest benefit for the reconstruction accuracy. Thus, the aim of this study is to compare the different figures of merit, thereby determining the most reliable and effective optimization approach for magnetorelaxometry setups. Approach. In the present simulation study, we translate these figures of merit to various cost functions, allowing us to optimize the electromagnetic coil positions and radii of two distinct MRXI setups with an adapted tabu search algorithm. Multiple artificial MNP phantoms are reconstructed employing the optimized setups and the resulting imaging qualities are subsequently compared. Main results. The extensive amount of generated synthetic data unprecedented in previous MRXI studies identifies the condition number as the most reliable indicator for good imaging results. This is the case for both the qualitative as well as the quantitative reconstruction accuracies. Significance. The results of this study show that optimized coil configurations increase the reconstruction quality compared to the state-of-the-art. The insights obtained here can also be extended to other design parameters of MRXI setups, thus enabling more reliable reconstructions of MNP ensembles which will ultimately render the aforementioned treatment methods safer and more efficient.

The Imaging of Magnetic Nanoparticles with Low-power Magnetoacoustic Tomography.

The magnetic nanoparticles have been widely explored as an important kind of biomaterial for the treatment and diagnosis of cancer. Imaging of magnetic nanoparticles can greatly facilitate treatment and diagnosis in both preclinical and clinical applications. The magnetoacoustic tomography is a non-invasive imaging modality for the distribution of the magnetic nanoparticles. However, the traditional magnetoacoustic imaging system requires higher power and the large instantaneous current that suffers cost and safety issues. In this paper, we propose a low-power magnetoacoustic tomography system, whose power amplifier only has 30 W peak power. The system used a pulse train of excitation to gain energy accumulation by resonance. The reconstructed algorithm, i.e. universal back-projection, was applied for imaging. To prove the feasibility and potential of the proposed system, we performed the imaging experiments with the gelatin phantom containing the magnetic nanoparticles.

Deep Learned Super Resolution of System Matrices for Magnetic Particle Imaging.

Magnetic Particle Imaging (MPI) is a new imaging technique that allows high resolution & high frame-rate imaging of magnetic nanoparticles (MNP). It relies on the nonlinear response of MNPs under a magnetic field. The imaging process can be modeled linearly, and then image reconstruction can be case as an inverse problem using a measured system matrix (SM). However, this calibration measurement is time consuming so it reduces practicality. In this study, we proposed a novel method for accelerating the SM calibration based on joint super-resolution (SR) and denoising of sensitivty maps (i.e., rows of SM). The proposed method is based on a deep convolutional neural network (CNN) architecture with residual-dense blocks. Model training was performed using noisy SM measurements simulated for varying MNP size and gradient strengths. Comparisons were performed against conventional low-resolution SM calibration, noisy high-resolution SM calibration, and bicubic upsampling of low-resolution SM. We show that the proposed method improves high-resolution SM recovery, and in turn leads to improved resolution and quality in subsequently reconstructed MPI images.

2D Quantitative Imaging of Magnetic Nanoparticles by an AC Biosusceptometry Based Scanning Approach and Inverse Problem.

The use of magnetic nanoparticles (MNPs) in biomedical applications requires the quantitative knowledge of their quantitative distribution within the body. AC Biosusceptometry (ACB) is a biomagnetic technique recently employed to detect MNPs in vivo by measuring the MNPs response when exposed to an alternate magnetic field. The ACB technique presents some interesting characteristics: non-invasiveness, low operational cost, high portability, and no need for magnetic shielding. ACB conventional methods until now provided only qualitative information about the MNPs’ mapping in small animals. We present a theoretical model and experimentally demonstrate the feasibility of ACB reconstructing 2D quantitative images of MNPs’ distributions. We employed an ACB single-channel scanning approach, measuring at 361 sensor positions, to reconstruct MNPs’ spatial distributions. For this, we established a discrete forward problem and solved the ACB system’s inverse problem. Thus, we were able to determine the positions and quantities of MNPs in a field of view of with good precision and accuracy. The results show the ACB system’s capabilities to reconstruct the quantitative spatial distribution of MNPs with a spatial resolution better than , and a sensitivity of of MNPs fixed in gypsum. These results show the system’s potential for biomedical application of MNPs in several studies, for example, electrochemical-functionalized MNPs for cancer cell targeting, quantitative sensing, and possibly in vivo imaging.