Miniature magneto-mechanical resonators for wireless tracking and sensing.

Sensor miniaturization enables applications such as minimally invasive medical procedures or patient monitoring by providing process feedback in situ. Ideally, miniature sensors should be wireless, inexpensive, and allow for remote detection over sufficient distance by an affordable detection system. We analyze the signal strength of wireless sensors theoretically and derive a simple design of high-signal resonant magneto-mechanical sensors featuring volumes below 1 cubic millimeter. As examples, we demonstrate real-time tracking of position and attitude of a flying bee, navigation of a biopsy needle, tracking of a free-flowing marker, and sensing of pressure and temperature, all in unshielded environments. The achieved sensor size, measurement accuracy, and workspace of ~25 centimeters show the potential for a low-cost wireless tracking and sensing platform for medical and nonmedical applications.

Non-Cartesian k-space trajectory calculation based on concurrent reading of the gradient amplifiers' output currents.

PURPOSE: Non-Cartesian imaging sequences involve sampling during rapid variation of the encoding field gradients. The quality of the reconstructed images often suffers from insufficient knowledge of the exact dynamics of the actual fields applied during sampling. METHODS: We propose determination of the accurate field dynamics by measuring the currents at the gradient amplifier outputs using the amplifiers' internal sensors concurrently with imaging. The actual dynamic field evolution is then determined by convolution with the measured current-to-field impulse response function of the gradient coil. Integration of the gradient field evolution allows derivation of the k-space trajectory for reconstruction. RESULTS: The current-based approach is investigated in spiral and ultrashort TE phantom imaging. In comparison with the model-based product reconstruction as well as a correction approach based on the conventional input waveform-to-field impulse response function, it provides slightly improved image quality. The improvement is ascribed to a better representation of eddy current and amplifier nonlinearity effects. CONCLUSION: Trajectory calculation based on measured amplifier output currents offers a robust, purely measurement-based alternative to conventional model-based approaches. The implementation can mitigate gradient amplifier imperfections with no or little additional hardware effort.

Trajectory correction based on the gradient impulse response function improves high-resolution UTE imaging of the musculoskeletal system.

PURPOSE: UTE sequences typically acquire data during the ramping up of the gradient fields, which makes UTE imaging prone to eddy current and system delay effects. The purpose of this work was to use a simple gradient impulse response function (GIRF) measurement to estimate the real readout gradient waveform and to demonstrate that precise knowledge of the gradient waveform is important in the context of high-resolution UTE musculoskeletal imaging. METHODS: The GIRF was measured using the standard hardware of a 3 Tesla scanner and applied on 3D radial UTE data (TE: 0.14 ms). Experiments were performed on a phantom, in vivo on a healthy knee, and in vivo on patients with spine fractures. UTE images were reconstructed twice, first using the GIRF-corrected gradient waveforms and second using nominal-corrected waveforms, correcting for the low-pass filter characteristic of the gradient chain. RESULTS: Images reconstructed with the nominal-corrected gradient waveforms exhibited blurring and showed edge artifacts. The blurring and the edge artifacts were reduced when the GIRF-corrected gradient waveforms were used, as shown in single-UTE phantom scans and in vivo dual-UTE gradient-echo scans in the knee. Further, the importance of the GIRF-based correction was indicated in UTE images of the lumbar spine, where thin bone structures disappeared when the nominal correction was employed. CONCLUSION: The presented GIRF-based trajectory correction method using standard scanner hardware can improve the quality of high-resolution UTE musculoskeletal imaging.

Rapid acquisition of the 3D MRI gradient impulse response function using a simple phantom measurement.

PURPOSE: To provide a simple tool for rapid measurement of the 3D gradient modulation transfer function (GMTF) of clinical MRI systems using a phantom. Knowledge of the transfer function is useful for gradient chain characterization, system calibration, and improvement of image reconstruction results. METHODS: Starting from the well-established thin slice method used for phantom-based measurement of the 1D GMTF, we add phase encoding to partition the thin slices into voxels that act as localized field probes. From the signal phase evolution measured at the 3D voxel positions, the GMTF can be derived for cross and higher order spatial terms represented by spherical harmonics up to 3rd order. RESULTS: Using spherical phantoms, 16 GMTFs representing all terms up to 3rd order harmonics can be determined in a scan time of <2 min. A large voxel volume of >1 mL yields high SNR, enabling signal acquisition using the system's body coil. The method is applied for improving system calibration and for characterizing the effect of additional hardware in the bore. CONCLUSION: The presented method seems well-suited for rapid measurement of the GMTF of a clinical system, as it delivers high-quality results in a short scan time.

Noninvasive monitoring of blood flow using a single magnetic microsphere.

Noninvasive medical imaging of blood flow relies on mapping the transit of a contrast medium bolus injected intravenously. This has the draw-back that the front of the bolus widens until the tissue of interest is reached and quantitative flow parameters are not easy to obtain. Here, we introduce high resolution (millimeter/millisecond) 3D magnetic tracking of a single microsphere locally probing the flow while passing through a vessel. With this, we successfully localize and evaluate diameter constrictions in an arteria phantom after a single passage of a microsphere. We further demonstrate the potential for clinical application by tracking a microsphere smaller than a red blood cell.

Remote magnetic actuation using a clinical scale system.

Remote magnetic manipulation is a powerful technique for controlling devices inside the human body. It enables actuation and locomotion of tethered and untethered objects without the need for a local power supply. In clinical applications, it is used for active steering of catheters in medical interventions such as cardiac ablation for arrhythmia treatment and for steering of camera pills in the gastro-intestinal tract for diagnostic video acquisition. For these applications, specialized clinical-scale field applicators have been developed, which are rather limited in terms of field strength and flexibility of field application. For a general-purpose field applicator, flexible field generation is required at high field strengths as well as high field gradients to enable the generation of both torques and forces on magnetic devices. To date, this requirement has only been met by small-scale experimental systems. We have built a highly versatile clinical-scale field applicator that enables the generation of strong magnetic fields as well as strong field gradients over a large workspace. We demonstrate the capabilities of this coil-based system by remote steering of magnetic drills through gel and tissue samples with high torques on well-defined curved trajectories. We also give initial proof that, when equipped with high frequency transmit-receive coils, the machine is capable of real-time magnetic particle imaging while retaining a clinical-scale bore size. Our findings open the door for image-guided radiation-free remote magnetic control of devices at the clinical scale, which may be useful in minimally invasive diagnostic and therapeutic medical interventions.

Interactive Magnetic Catheter Steering With 3-D Real-Time Feedback Using Multi-Color Magnetic Particle Imaging.

Magnetic particle imaging (MPI) is an emerging tomographic method that enables sensitive and fast imaging. It does not require ionizing radiation and thus may be a safe alternative for tracking of devices in the catheterization laboratory. The 3-D real-time imaging capabilities of MPI have been demonstrated in vivo and recent improvements in fast online image reconstruction enable almost real-time data reconstruction and visualization. Moreover, based on the use of different magnetic particle types for catheter visualization and blood pool imaging, multi-color MPI enables reconstruction of separate images for the catheter and the vessels from simultaneously measured data. While these are important assets for interventional imaging, MPI field generators can furthermore apply strong forces on a magnetic catheter tip. It is the aim of this paper to give a first demonstration of the combination of real-time multi-color MPI with online reconstruction and interactive field control for the application of forces on a magnetic catheter model in a phantom experiment.

Magnetic Particle Imaging (MPI): Experimental Quantification of Vascular Stenosis Using Stationary Stenosis Phantoms.

Magnetic Particle Imaging (MPI) is able to provide high temporal and good spatial resolution, high signal-to-noise ratio and sensitivity. Furthermore, it is a truly quantitative method as its signal strength is proportional to the concentration of its tracer, superparamagnetic iron oxide nanoparticles (SPIOs). Because of that, MPI is proposed to be a promising future method for cardiovascular imaging. Here, an interesting application may be the quantification of vascular pathologies like stenosis by utilizing the proportionality of the SPIO concentration and the MPI signal strength. In this study, the feasibility of MPI based stenosis quantification is evaluated based on this application scenario. Nine different stenosis phantoms with a normal diameter of 10 mm each and different stenoses of 1-9 mm and ten reference phantoms with a straight diameter of 1-10 mm were filled with a 1% Resovist dilution and measured in a preclinical MPI-demonstrator. The MPI signal intensities of the reference phantoms were compared to each other and the change of signal intensity within each stenosis phantom was used to calculate the degree of stenosis. These values were then compared to the known diameters of each phantom. As a second measurement, the 5 mm stenosis phantom was used for a serial dilution measurement down to a Resovist dilution of 1:3200 (0.031%), which is lower than a first pass blood concentration of a Resovist bolus in the peripheral arteries of an average adult human of at least about 1:1000. The correlation of the stenosis values based on MPI signal intensity measurements and based on the known diameters showed a very good agreement, proving the high precision of quantitative MPI in this regard.

Spatially selective remote magnetic actuation of identical helical micromachines.

Magnetic micromachines can be controlled remotely inside the human body by application of external magnetic fields, making them promising candidates for minimally invasive local therapy delivery. For many therapeutic scenarios, a large team of micromachines is required, but a convincing approach for controlling individual team members is currently missing. We present a method for selective control of identical helical micromachines based on their spatial position. The micromachines are operated by uniform rotating fields, whereas spatial selection is achieved by application of a strong field gradient that locks all machines except those located inside a small movable volume. We deliver experimental evidence of three-dimensional selective actuation with a spatial selectivity on the order of millimeters over a workspace large enough for clinical applications. Selective control of teams of helical micromachines may improve minimally invasive therapeutic approaches and may lead to more flexible local drug delivery systems or adaptive medical implants. As an example, we propose a concept for adaptive radiation treatment in cancer therapy based on selective switching of radioactive sources distributed inside a tumor.

Multi-color magnetic particle imaging for cardiovascular interventions.

Magnetic particle imaging (MPI) uses magnetic fields to visualize the spatial distribution of superparamagnetic iron oxide nanoparticles (SPIOs). Guidance of cardiovascular interventions is seen as one possible application of MPI. To safely guide interventions, the vessel lumen as well as all required interventional devices have to be visualized and be discernible from each other. Until now, different tracer concentrations were used for discerning devices from blood in MPI, because only one type of SPIO could be imaged at a time. Recently, it was shown for 3D MPI that it is possible to separate different signal sources in one volume of interest, i.e. to visualize and discern different SPIOs or different binding states of the same SPIO. The approach was termed multi-color MPI. In this work, the use of multi-color MPI for differentiation of a SPIO coated guide wire (Terumo Radifocus 0.035″) from the lumen of a vessel phantom filled with diluted Resovist is demonstrated. This is achieved by recording dedicated system functions of the coating material containing solid Resovist and of liquid Resovist, which allows separation of their respective signal in the image reconstruction process. Assigning a color to the different signal sources results in a differentiation of guide wire and vessel phantom lumen into colored images.

Magnetic Particle Imaging: A Resovist Based Marking Technology for Guide Wires and Catheters for Vascular Interventions.

Magnetic particle imaging (MPI) is able to provide high temporal and good spatial resolution, high signal to noise ratio and sensitivity. Furthermore, it is a truly quantitative method as its signal strength is proportional to the concentration of its tracer, superparamagnetic iron oxide nanoparticles (SPIOs), over a wide range practically relevant concentrations. Thus, MPI is proposed as a promising future method for guidance of vascular interventions. To implement this, devices such as guide wires and catheters have to be discernible in MPI, which can be achieved by coating already commercially available devices with SPIOs. In this proof of principle study the feasibility of that approach is demonstrated. First, a Ferucarbotran-based SPIO-varnish was developed by embedding Ferucarbotran into an organic based solvent. Subsequently, the biocompatible varnish was applied to a commercially available guidewire and diagnostic catheter for vascular interventional purposes. In an interventional setting using a vessel phantom, the coating proved to be mechanically and chemically stable and thin enough to ensure normal handling as with uncoated devices. The devices were visualized in 3D on a preclinical MPI demonstrator using a system function based image reconstruction process. The system function was acquired with a probe of the dried varnish prior to the measurements. The devices were visualized with a very high temporal resolution and a simple catheter/guide wire maneuver was demonstrated.

Steering of Magnetic Devices With a Magnetic Particle Imaging System.

Small magnetic devices have been steered in arbitrary direction and with variable force using a preclinical demonstrator system for magnetic particle imaging (MPI). Fast localization due to the high imaging rate of over 40 volumes/s and strong forces due to the high field gradient of more than 1 T/m render an MPI system, a good platform for image-guided steering of magnetic devices. In this paper, these capabilities are demonstrated in phantom experiments, where a closed feedback loop has been realized to exert translational forces in horizontal and vertical direction on a magnetic device moving in a viscous medium. The MPI system allows for the controlled application of those forces by combining variable homogeneous fields with strong field gradients.

Balanced UTE-SSFP for 19F MR imaging of complex spectra.

PURPOSE: A novel technique for highly sensitive detection of multiresonant fluorine imaging agents was designed and tested with the use of dual-frequency 19F/1H ultrashort echo times (UTE) sampled with a balanced steady-state free precession (SSFP) pulse sequence and three-dimensional (3D) radial readout. METHODS: Feasibility of 3D radial balanced UTE-SSFP imaging was demonstrated for a phantom comprising liquid perfluorooctyl bromide (PFOB). Sensitivity of the pulse sequence was measured and compared with other sequences imaging the PFOB (CF2 )6 line group including UTE radial gradient-echo (GRE) at α = 30°, as well as Cartesian GRE, balanced SSFP, and fast spin-echo (FSE). The PFOB CF3 peak was also sampled with FSE. RESULTS: The proposed balanced UTE-SSFP technique exhibited a relative detection sensitivity of 51 µmolPFOB(-1) min(-1/2) (α = 30°), at least twice that of other sequence types with either 3D radial (UTE GRE: 20 µmolPFOB(-1) min(-1/2) ) or Cartesian k-space filling (GRE: 12 µmolPFOB(-1) min(-1/2) ; FSE: 16 µmolPFOB(-1) min(-1/2) ; balanced SSFP: 23 µmolPFOB(-1) min(-1/2) ). In vivo imaging of angiogenesis-targeted PFOB nanoparticles was demonstrated in a rabbit model of cancer on a clinical 3 Tesla scanner. CONCLUSION: A new dual 19F/1H balanced UTE-SSFP sequence manifests high SNR, with detection sensitivity more than two-fold better than traditional techniques, and alleviates imaging problems caused by dephasing in complex spectra.

Magnetic particle imaging with tailored iron oxide nanoparticle tracers.

Magnetic particle imaging (MPI) shows promise for medical imaging, particularly in angiography of patients with chronic kidney disease. As the first biomedical imaging technique that truly depends on nanoscale materials properties, MPI requires highly optimized magnetic nanoparticle tracers to generate quality images. Until now, researchers have relied on tracers optimized for MRI T2(∗) -weighted imaging that are sub-optimal for MPI. Here, we describe new tracers tailored to MPI's unique physics, synthesized using an organic-phase process and functionalized to ensure biocompatibility and adequate in vivo circulation time. Tailored tracers showed up to 3 × greater signal-to-noise ratio and better spatial resolution than existing commercial tracers in MPI images of phantoms.

On the formulation of the image reconstruction problem in magnetic particle imaging.

In magnetic particle imaging (MPI), the spatial distribution of magnetic nanoparticles is determined by applying various static and dynamic magnetic fields. Due to the complex physical behavior of the nanoparticles, it is challenging to determine the MPI system matrix in practice. Since the first publication on MPI in 2005, different methods that rely on measurements or simulations for the determination of the MPI system matrix have been proposed. Some methods restrict the simulation to an idealized model to speed up data reconstruction by exploiting the structure of an idealized MPI system matrix. Recently, a method that processes the measurement data in x-space rather than frequency space has been proposed. In this work, we compare the different approaches for image reconstruction in MPI and show that the x-space and the frequency space reconstruction techniques are equivalent.

Perspectives on clinical magnetic particle imaging.

After realizing the worlds' first preclinical magnetic particle imaging (MPI) demonstrator, Philips is now realizing the worlds' first whole-body clinical prototype to prove the feasibility of MPI for clinical imaging. After a brief introduction of the basic MPI imaging process, this contribution presents an overview on the determining factors for key properties, i.e., spatial resolution, acquisition speed, sensitivity, and quantitativeness, and how these properties are influenced by scaling up from preclinical to clinical instrumentation. Furthermore, it is discussed how this scale up affects the physiological compatibility of the method as well as hardware parameters such as power requirements for drive field generation, selection and focus field generation, and the design of the receive chain of the MPI device.

Red blood cells as carriers in magnetic particle imaging.

Red blood cells (RBCs) represent intravascular carriers for drugs, biologics, and other therapeutic agents, characterized by their unique longevity in the bloodstream, availability, considerable surface and volume, high biocompatibility, and natural mechanisms for safe elimination. Recently, the potential of RBCs loaded with superparamagnetic iron oxide (SPIO) nanoparticles as a tracer material for magnetic particle imaging (MPI) to realize a blood-pool tracer agent with longer blood retention time for imaging of the circulatory system, has been investigated. MPI is a new tomographic imaging approach that can quantitatively map magnetic nanoparticle distributions in vivo. However, SPIO contrast agents, such as Resovist, have a short blood half-life due to rapid uptake by the reticuloendothelial system, which limits the applicability of such compounds for certain applications such as long-term monitoring. Here, we report the in vitro magnetic characterization study of human SPIO-loaded RBCs and the first MPI results obtained after intravenous injection of murine SPIO-loaded RBCs in an in vivo MPI experiment.

Micro-magnetic simulation study on the magnetic particle imaging performance of anisotropic mono-domain particles.

The performance of magnetic mono-domain particles is of crucial importance in magnetic particle imaging (MPI). So far, the behavior of mono-domain particles has been modeled within the framework of Langevin theory. This theory predicts the dependence of the MPI signal on the particle core size, but cannot account for the influence of the shape, i.e. the anisotropy of the particle core. In this study we present the first micro-magnetic ab initio simulation of spectra of anisotropic particles with different core diameters in an oscillating magnetic field at 25 and 100 kHz. We find that the MPI signal strongly depends on the anisotropy of the magnetic core. Thus, a difference of 3 nm between the principal axes of a prolate ellipsoid with the volume of a 30 nm sphere can result in a complete loss of the MPI signal. Smaller anisotropies, however, can increase the MPI performance of the particle. The simulations show that the effect of the anisotropy on the MPI signal depends on the frequency of the oscillating magnetic field. At 100 kHz, the optimal signal is found at smaller anisotropies than at 25 kHz. Furthermore, the simulations show that experimental spectroscopic results for Resovist® can only be explained quantitatively by particles with a magnetic core size of at least 25 nm.

Magnetic particle imaging: visualization of instruments for cardiovascular intervention.

PURPOSE: To evaluate the feasibility of different approaches of instrument visualization for cardiovascular interventions guided by using magnetic particle imaging (MPI). MATERIALS AND METHODS: Two balloon (percutaneous transluminal angioplasty) catheters were used. The balloon was filled either with diluted superparamagnetic iron oxide (SPIO) ferucarbotran (25 mmol of iron per liter) or with sodium chloride. Both catheters were inserted into a vessel phantom that was filled oppositional to the balloon content with sodium chloride or diluted SPIO (25 mmol of iron per liter). In addition, the administration of a 1.4-mL bolus of pure SPIO (500 mmol of iron per liter) followed by 5 mL of sodium chloride through a SPIO-labeled balloon catheter into the sodium chloride-filled vessel phantom was recorded. Images were recorded by using a preclinical MPI demonstrator. All images were acquired by using a field of view of 3.6 × 3.6 × 2.0 cm. RESULTS: By using MPI, both balloon catheters could be visualized with high temporal (21.54 msec per image) and sufficient spatial (≤ 3 mm) resolution without any motion artifacts. The movement through the field of view, the inflation and deflation of the balloon, and the application of the SPIO bolus were visualized at a rate of 46 three-dimensional data sets per second. CONCLUSION: Visualization of SPIO-labeled instruments for cardiovascular intervention at high temporal resolution as well as monitoring the application of a SPIO-based tracer by using labeled instruments is feasible. Further work is necessary to evaluate different labeling approaches for diagnostic catheters and guidewires and to demonstrate their navigation in the vascular system after administration of contrast material. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120424/-/DC1.

Fundamentals and applications of magnetic particle imaging.

Magnetic particle imaging (MPI) is a new medical imaging technique which performs a direct measurement of magnetic nanoparticles, also known as superparamagnetic iron oxide. MPI can acquire quantitative images of the local distribution of the magnetic material with high spatial and temporal resolution. Its sensitivity is well above that of other methods used for the detection and quantification of magnetic materials, for example, magnetic resonance imaging. On the basis of an intravenous injection of magnetic particles, MPI has the potential to play an important role in medical application areas such as cardiovascular, oncology, and also in exploratory fields such as cell labeling and tracking. Here, we present an introduction to the basic function principle of MPI, together with an estimation of the spatial resolution and the detection limit. Furthermore, the above-mentioned medical applications are discussed with respect to an applicability of MPI.