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(a) Magnetic flux density perpendicular to the face of a neodymium magnet along the central axis. Closed circles and solid line represent the magnetic flux density measured using a Gauss meter and that calculated using a software program based on the finite element method (COMSOL Multiphysics ® , COMSOL Inc., Stockholm, Sweden), respectively; (b) Contour plot of the magnetic flux density around the neodymium magnet, computed by COMSOL Multiphysics ®. The numbers in the figure represent the magnetic flux density in Tesla. Scale bar = 10 mm.
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... magnetic targeting, a neodymium magnet (10 mm in diameter and 30 mm in length) (Sangyo Supply Co., Miyagi, Japan) was used. Figure 1(a) shows the magnetic flux density perpendicular to the face of the neodymium magnet along the central axis. The closed circles and solid line represent the magnetic flux density measured using a Gauss meter (GM-301, Denshijiki Industry Co., Ltd., Tokyo, Japan) and that calculated using a software program based on the finite element method (COMSOL Multiphysics ® , COMSOL Inc., Stockholm, Sweden), respectively. The magnetic field strength on the surface of the neodymium magnet was 0.55 T. Figure 1(b) shows the contour plot of the magnetic flux density around the neodymium magnet, which was computed using COMSOL Multiphys- ics ® (COMSOL Inc., Stockholm, ...
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... magnetic targeting, a neodymium magnet (10 mm in diameter and 30 mm in length) (Sangyo Supply Co., Miyagi, Japan) was used. Figure 1(a) shows the magnetic flux density perpendicular to the face of the neodymium magnet along the central axis. The closed circles and solid line represent the magnetic flux density measured using a Gauss meter (GM-301, Denshijiki Industry Co., Ltd., Tokyo, Japan) and that calculated using a software program based on the finite element method (COMSOL Multiphysics ® , COMSOL Inc., Stockholm, Sweden), respectively. The magnetic field strength on the surface of the neodymium magnet was 0.55 T. Figure 1(b) shows the contour plot of the magnetic flux density around the neodymium magnet, which was computed using COMSOL Multiphys- ics ® (COMSOL Inc., Stockholm, ...
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... animal experiments were approved by the animal ethics committee at Osaka University School of Medicine. Seven-week-old male BALB/c mice weighing 23.9 ± 2.2 g (mean ± standard deviation (SD)) were used. They were purchased from Charles River Laboratories Japan, Inc. (Yokohama, Japan), and were habituated to rearing envi- ronment for 1 week before the experiment. The animals had free access to food and water, and were kept under standard laboratory conditions of 22 -23 degree room temperatures, around 50% humidity, and a 12:12 hour light/dark cycle. Colon-26 cells (1 × 10 6 cells) were implanted subcutaneously into the mice under anesthesia by pentobarbital sodium (Somnopentyl, Kyoritsu Seiyaku Co., Tokyo, Japan) (0.012 mL/g body weight). Tumor vo- lumes in all mice were measured by a caliper every day. The mice were divided into two groups and were used for experiments 7 to 10 days after implantation when the tumor volume reached approximately 100 mm 3 . The tumors in one group (treated group, n = 8) were directly injected with Resovist ® with a concentration of 250 mM (0.2 mL) under anesthesia by pentobarbital sodium (Somnopentyl, Kyoritsu Seiyaku Co., Tokyo, Japan) (0.012 mL/g body weight) and the neodymium magnet (Figure 1(b)) was attached. The tumors in the other group (untreated group, n = 8) were also directly injected with Resovist ® in the same manner as in the treated group but the neodymium magnet was not attached. Figure 2 shows a photograph of our experimental setup for magnetic targeting. In the treated group, the neodymium magnet (Figure 1(b)) was attached to the tumor surface as shown in Figure 2. Figure 3 shows the time schedule for data acquisition in this study. Each tumor-bearing mouse was scanned 5 times using our MPI scanner [9] [10]; 2 min, 37 min, 1 day, 3 days, and 7 days after the injection of Resovist ® (Figure 3). After the MPI studies, X-ray CT images were obtained using a 4-row multi-slice CT scanner (As- teion, Toshiba Medical Systems Co., Tochigi, Japan) with a tube voltage of 120 kV, a tube current of 210 mA, and a slice thickness of 0.5 mm. The MPI image was co-registered with the X-ray CT image using the parame- ters for magnification and rotation, which were obtained using a phantom with 3 point sources with a diameter of 0.5 mm and filled with 100 mM MNPs [13]. It should be noted that the neodymium magnet (Figure 1(b)) was attached to the tumor surface for 20 min per event in the treated group and that the X-ray CT image after the first MPI study was substituted by that obtained after the second MPI ...
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... animal experiments were approved by the animal ethics committee at Osaka University School of Medicine. Seven-week-old male BALB/c mice weighing 23.9 ± 2.2 g (mean ± standard deviation (SD)) were used. They were purchased from Charles River Laboratories Japan, Inc. (Yokohama, Japan), and were habituated to rearing envi- ronment for 1 week before the experiment. The animals had free access to food and water, and were kept under standard laboratory conditions of 22 -23 degree room temperatures, around 50% humidity, and a 12:12 hour light/dark cycle. Colon-26 cells (1 × 10 6 cells) were implanted subcutaneously into the mice under anesthesia by pentobarbital sodium (Somnopentyl, Kyoritsu Seiyaku Co., Tokyo, Japan) (0.012 mL/g body weight). Tumor vo- lumes in all mice were measured by a caliper every day. The mice were divided into two groups and were used for experiments 7 to 10 days after implantation when the tumor volume reached approximately 100 mm 3 . The tumors in one group (treated group, n = 8) were directly injected with Resovist ® with a concentration of 250 mM (0.2 mL) under anesthesia by pentobarbital sodium (Somnopentyl, Kyoritsu Seiyaku Co., Tokyo, Japan) (0.012 mL/g body weight) and the neodymium magnet (Figure 1(b)) was attached. The tumors in the other group (untreated group, n = 8) were also directly injected with Resovist ® in the same manner as in the treated group but the neodymium magnet was not attached. Figure 2 shows a photograph of our experimental setup for magnetic targeting. In the treated group, the neodymium magnet (Figure 1(b)) was attached to the tumor surface as shown in Figure 2. Figure 3 shows the time schedule for data acquisition in this study. Each tumor-bearing mouse was scanned 5 times using our MPI scanner [9] [10]; 2 min, 37 min, 1 day, 3 days, and 7 days after the injection of Resovist ® (Figure 3). After the MPI studies, X-ray CT images were obtained using a 4-row multi-slice CT scanner (As- teion, Toshiba Medical Systems Co., Tochigi, Japan) with a tube voltage of 120 kV, a tube current of 210 mA, and a slice thickness of 0.5 mm. The MPI image was co-registered with the X-ray CT image using the parame- ters for magnification and rotation, which were obtained using a phantom with 3 point sources with a diameter of 0.5 mm and filled with 100 mM MNPs [13]. It should be noted that the neodymium magnet (Figure 1(b)) was attached to the tumor surface for 20 min per event in the treated group and that the X-ray CT image after the first MPI study was substituted by that obtained after the second MPI ...
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... animal experiments were approved by the animal ethics committee at Osaka University School of Medicine. Seven-week-old male BALB/c mice weighing 23.9 ± 2.2 g (mean ± standard deviation (SD)) were used. They were purchased from Charles River Laboratories Japan, Inc. (Yokohama, Japan), and were habituated to rearing envi- ronment for 1 week before the experiment. The animals had free access to food and water, and were kept under standard laboratory conditions of 22 -23 degree room temperatures, around 50% humidity, and a 12:12 hour light/dark cycle. Colon-26 cells (1 × 10 6 cells) were implanted subcutaneously into the mice under anesthesia by pentobarbital sodium (Somnopentyl, Kyoritsu Seiyaku Co., Tokyo, Japan) (0.012 mL/g body weight). Tumor vo- lumes in all mice were measured by a caliper every day. The mice were divided into two groups and were used for experiments 7 to 10 days after implantation when the tumor volume reached approximately 100 mm 3 . The tumors in one group (treated group, n = 8) were directly injected with Resovist ® with a concentration of 250 mM (0.2 mL) under anesthesia by pentobarbital sodium (Somnopentyl, Kyoritsu Seiyaku Co., Tokyo, Japan) (0.012 mL/g body weight) and the neodymium magnet (Figure 1(b)) was attached. The tumors in the other group (untreated group, n = 8) were also directly injected with Resovist ® in the same manner as in the treated group but the neodymium magnet was not attached. Figure 2 shows a photograph of our experimental setup for magnetic targeting. In the treated group, the neodymium magnet (Figure 1(b)) was attached to the tumor surface as shown in Figure 2. Figure 3 shows the time schedule for data acquisition in this study. Each tumor-bearing mouse was scanned 5 times using our MPI scanner [9] [10]; 2 min, 37 min, 1 day, 3 days, and 7 days after the injection of Resovist ® (Figure 3). After the MPI studies, X-ray CT images were obtained using a 4-row multi-slice CT scanner (As- teion, Toshiba Medical Systems Co., Tochigi, Japan) with a tube voltage of 120 kV, a tube current of 210 mA, and a slice thickness of 0.5 mm. The MPI image was co-registered with the X-ray CT image using the parame- ters for magnification and rotation, which were obtained using a phantom with 3 point sources with a diameter of 0.5 mm and filled with 100 mM MNPs [13]. It should be noted that the neodymium magnet (Figure 1(b)) was attached to the tumor surface for 20 min per event in the treated group and that the X-ray CT image after the first MPI study was substituted by that obtained after the second MPI ...
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... MPI is particularly useful because of the linear quantitation and lack of background signal, providing spatial information which allows the accurate monitoring of therapeutic agent delivery. 306 This information illustrates the quantity of drug delivered to the target site, as well as the drug dosage distribution within the body. The ability to track drug delivery also allows for real-time adjustment of ensuing doses, ensuring that the dosage at the target site remains within the patient's therapeutic window (Fig. 19), and that there are subcritical drug concentrations at off-target sites within the patient (e.g., organs). ...
Magnetic particle imaging (MPI) is an emerging tracer-based modality that enables real-time three-dimensional imaging of the non-linear magnetisation produced by superparamagnetic iron oxide nanoparticles (SPIONs), in the presence of an external oscillating magnetic field. As a technique, it produces highly sensitive radiation-free tomographic images with absolute quantitation. Coupled with a high contrast, as well as zero signal attenuation at-depth, there are essentially no limitations to where that can be imaged within the body. These characteristics enable various biomedical applications of clinical interest. In the opening sections of this review, the principles of image generation are introduced, along with a detailed comparison of the fundamental properties of this technique with other common imaging modalities. The main feature is a presentation on the up-to-date literature for the development of SPIONs tailored for improved imaging performance, and developments in the current and promising biomedical applications of this emerging technique, with a specific focus on theranostics, cell tracking and perfusion imaging. Finally, we will discuss recent progress in the clinical translation of MPI. As signal detection in MPI is almost entirely dependent on the properties of the SPION employed, this work emphasises the importance of tailoring the synthetic process to produce SPIONs demonstrating specific properties and how this impacts imaging in particular applications and MPI's overall performance.
... The ability to move particles with MPI for targeted drug delivery has also been presented. [13][14][15][16][17] Griese et al. 18 have demonstrated how to simultaneously move and image micron-sized magnetic particles with the Magnetic Particle Imaging/Navigation (MPIN) method with a temporal resolution of 2.9 Hz. Micron-sized particles have been used to target endothelial cells of the central nervous system to identify over-expressed surface proteins such as ICAM-1. ...
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... Here, MPI has great potential to offer this missing information. As a first step, in Ref. [90], an accumulation of particles at a certain position could be imaged with MPI. First setups are being investigated in which an MPI scanner is integrated into a coil setup for steering the MNPs, where steering and imaging is alternately operated [91]. ...
Magnetic particle imaging (MPI) is a new medical imaging technique that enables three-dimensional real-time imaging of a magnetic tracer material. Although it is not yet in clinical use, it is highly promising, especially for vascular and interventional imaging. The advantages of MPI are that no ionizing radiation is necessary, its high sensitivity enables the detection of very small amounts of the tracer material, and its high temporal resolution enables real-time imaging, which makes MPI suitable as an interventional imaging technique. As MPI is a tracer-based imaging technique, functional imaging is possible by attaching specific molecules to the tracer material. In the first part of this article, the basic principle of MPI will be explained and a short overview of the principles of the generation and spatial encoding of the tracer signal will be given. After this, the used tracer materials as well as their behavior in MPI will be introduced. A subsequent presentation of selected scanner topologies will show the current state of research and the limitations researchers are facing on the way from preclinical toward human-sized scanners. Furthermore, it will be briefly shown how to reconstruct an image from the tracer materials’ signal. In the last part, a variety of possible future clinical applications will be presented with an emphasis on vascular imaging, such as the use of MPI during cardiovascular interventions by visualizing the instruments. Investigations will be discussed, which show the feasibility to quantify the degree of stenosis and diagnose strokes and traumatic brain injuries as well as cerebral or gastrointestinal bleeding with MPI. As MPI is not only suitable for vascular medicine but also offers a broad range of other possible applications, a selection of those will be briefly presented at the end of the article.
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... 7) The magnetic targeting of therapeutic agents results in the concentration of the agents at the targeted site, consequently reducing or eliminating systemic unwanted side effects. 7) Recently, a new magnetic targeting strategy called "aerosol-based magnetic targeting" has been introduced for lung diseases. 8) Aerosol-based magnetic targeting uses magnetic aerosol droplets comprising nebulized MNPs and therapeutic agents. ...
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Magnetic targeting is a strategy for improving the efficacy of therapeutic agents and minimizing the unwanted side effects by attaching the therapeutic agents to magnetic nanoparticles (MNPs) and concentrating them to the targeted region such as solid tumors and regions of infection using external magnetic fields. This study was undertaken to investigate the usefulness of magnetic particle imaging (MPI) for monitoring the effect of aerosol-based magnetic targeting by phantom experiments using a simple flow model and nebulized MNPs. Our results suggest that MPI is useful for monitoring the effect of aerosol-based magnetic targeting.
... Recently, we also developed an MPI scanner with an FFL-encoding scheme for small animal studies [3] [4]. To date, we have used our MPI system to image the spatial distribution of MNPs and to quantify the amount of MNPs and their temporal changes in various tissues and organs such as the tumor and lung in mice, and reported that MPI is a useful tool for preclinical studies [5] [6] [7] [8]. ...
... In the saturated regions, the particles are effectively locked in place and neither an appreciable MPI signal nor heating occur in response to an AC excitation field. We and other groups have been actively exploring the ramifications of MPI and gradient fields in MFH (Tasci et al 2009, Khandhar et al 2012, Murase et al 2013, Bauer et al 2016, Behrends et al 2016, Kuboyabu et al 2016, Maruyama et al 2016. ...
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Magnetic nanoparticles (MNPs) exhibiting certain superparamagnetic properties are optimal in terms of drug delivery because they facilitate imaging and targeting of biological interactions at the cellular and molecular levels. In terms of monitoring, magnetic particle imaging (MPI) yields real-time MNPs position and concentration data, and guides MNPs to desired positions if an actuation function is available. Here, we describe a new, user-driven steering scheme for MNPs based on a virtual field free point (FFP). The scheme utilizes our current MPI system, with no need for additional hardware. The scheme facilitates interactive user manipulation with real-time imaging and MNPs actuation within the body. An FFP with four coils was used to model the resultant magnetic force and a virtual FFP to linearize that force with respect to the relative positions of the MNPs and the real FFP. Simulations and experiments confirmed that the direction and magnitude of the forces exerted on MNPs via manipulation of the virtual FFP were controllable. An intuitive guidance system featuring real-time MPI at 2 Hz and user-driven virtual FFP manipulation (via a mouse) was employed to show that MNPs trajectories can be controlled. Our MPI-based navigation platform allows the user to effectively guide MNPs using real-time visual feedback, facilitating targeted drug delivery.
Magnetic Particle Imaging (MPI) has been successfully used to visualize the distribution of superparamagnetic nanoparticles within 3D volumes with high sensitivity in real time. Since the magnetic field topology of MPI scanners is well suited for applying magnetic forces on particles and micron-sized ferromagnetic devices, MPI has been recently used to navigate micron-sized particles and micron-sized swimmers. In this work, we analyze the magnetophoretic mobility and the imaging performance of two different particle types for Magnetic Particle Imaging/Navigation (MPIN). MPIN constantly switches between imaging and magnetic modes, enabling quasi-simultaneous navigation and imaging of particles. We determine the limiting flow velocity to be 8.18 mL s⁻¹ using a flow bifurcation experiment, that allows all particles to flow only through one branch of the bifurcation. Furthermore, we have succeeded in navigating the particles through the branch of a bifurcation phantom narrowed by either 60% or 100% stenosis, while imaging their accumulation on the stenosis. The particles in combination with therapeutic substances have a high potential for targeted drug delivery and could help to reduce the dose and improve the efficacy of the drug, e.g. for specific tumor therapy and ischemic stroke therapy.
The untethered actuation of milli- and microdevices is of great interest for a variety of medical applications. A millimeter sized swimmer is shown, which is 3D-printed and coated with magnetic nanoparticles. The coating has to fulfill two requirements: First, it must have a high magnetic moment in order to show a strong reaction to a magnetic field for good actuation performance. Second, it has to be suitable for magnetic particle imaging (MPI). MPI is an emerging medical imaging technique, based on the nonlinear response of superparamagnetic nanoparticles to oscillating magnetic fields. It is aimed at dual use of an MPI scanner: for both actuation and visualization. When applying rotating homogeneous magnetic fields, the swimmer performs an axial movement due to its shape and the viscosity of the surrounding medium. These fields can be generated with an MPI scanner. The swimmer dynamics have been observed and a maximum swimming velocity of 6 mm/s at a rotation frequency of the magnetic field of 10 Hz was found. The experiments are performed with a commercially available preclinical MPI scanner. It is shown, that the swimmer is suitable to be imaged with MPI. Furthermore, sequentially acquired images of a moving swimmer are shown. For this, the MPI scanner was alternately driven in imaging and actuation mode.
