Optically Sensitive and Magnetically Identifiable Supraparticles as Indicators of Surface Abrasion.

Identifying and ensuring the integrity of products plays an important role in today's globalized world. Miniaturized information taggants in the packaging surface are therefore required to monitor the product itself instead of applying external labels. Ideally, multiple types of information are stored in such additives. In this work, micrometer-sized core-shell particles (supraparticles) were developed to provide material surfaces with both an identifier and a surface abrasion indication functionality. The core of the supraparticles contains iron oxide nanoparticles that allow identification of the surface with a spectral magnetic code resolved by magnetic particle spectroscopy. The fluorescent silica nanoparticles in the supraparticle shell can be abraded by mechanical stress and resolved by fluorescence spectroscopy. This provides information about the mechanical integrity of the system. The application as surfaces, that contain several types of information in one supraparticle, was demonstrated here by incorporating such bifunctional supraparticles as additives in a surface coating.

Design of a mobile, homogeneous, and efficient electromagnet with a large field of view for neonatal low-field MRI.

OBJECTIVE: In this work, a prototype of an effective electromagnet with a field-of-view (FoV) of 140 mm for neonatal head imaging is presented. The efficient implementation succeeded by exploiting the use of steel plates as a housing system. We achieved a compromise between large sample volumes, high homogeneity, high B0 field, low power consumption, light weight, simple fabrication, and conserved mobility without the necessity of a dedicated water cooling system. MATERIALS AND METHODS: The entire magnetic resonance imaging (MRI) system (electromagnet, gradient system, transmit/receive coil, control system) is introduced and its unique features discussed. Furthermore, simulations using a numerical optimization algorithm for magnet and gradient system are presented. RESULTS: Functionality and quality of this low-field scanner operating at 23 mT (generated with 500 W) is illustrated using spin-echo imaging (in-plane resolution 1.6 mm × 1.6 mm, slice thickness 5 mm, and signal-to-noise ratio (SNR) of 23 with a acquisition time of 29 min). B0 field-mapping measurements are presented to characterize the homogeneity of the magnet, and the B0 field limitations of 80 mT of the system are fully discussed. CONCLUSION: The cryogen-free system presented here demonstrates that this electromagnet with a ferromagnetic housing can be optimized for MRI with an enhanced and homogeneous magnetic field. It offers an alternative to prepolarized MRI designs in both readout field strength and power use. There are multiple indications for the clinical medical application of such low-field devices.

Myocardial T1: quantification by using an ECG-triggered radial single-shot inversion-recovery MR imaging sequence.

PURPOSE: To develop and validate a fast cardiac magnetic resonance imaging T1 mapping technique with high spatial resolution based on a radial inversion-recovery (IR) spoiled gradient-echo acquisition. MATERIALS AND METHODS: Approval for the study was granted by the local institutional review board, and all subjects gave written informed consent. An electrocardiographically triggered radial single-shot IR (TRASSI) sequence was developed in conjunction with a custom-written fitting algorithm. The proposed imaging technique was validated in phantom measurements and then used for cardiac T1 mapping in 62 subjects with or without cardiac disease. The study population included 51 healthy subjects, three patients with arrhythmia, and eight patients with myocardial infarction. The potential heart rate dependency of the TRASSI method was tested by using linear regression analysis. Statistically significant differences between the sexes and various section orientations were analyzed with a Student t test for independent groups and a repeated-measures analysis of variance for dependent groups. RESULTS: High-spatial-resolution T1 maps (1.17 × 1.17 mm) without motion artifacts and without heart rate dependency (slope = -0.0303, R(2) = 0.0000887, P = .899) were acquired with an acquisition time of less than 6 seconds in all subjects. The mean T1 of healthy left ventricular myocardium across all examined subjects was 1031 msec ± 33 (standard deviation). Testing for reproducibility in three individuals with 34 repetitive measurements revealed a mean standard deviation of 4.1 msec (0.412%). Subacute and chronic myocardial infarction could be detected in all eight patients. T1 disturbances due to arrhythmia proved to be minimal in three patients (standard deviation, <1.2%). CONCLUSION: Fast and accurate cardiac T1 mapping is feasible within a single-shot IR experiment.

Spatial phase encoding exploiting the Bloch-Siegert shift effect.

OBJECTIVE: The present work introduces an alternative to the conventional B0-gradient spatial phase encoding technique. By applying far off-resonant radiofrequency (RF) pulses, a spatially dependent phase shift is introduced to the on-resonant transverse magnetization. This so-called Bloch-Siegert (BS) phase shift has been recently used for B1(+)-mapping. The current work presents the theoretical background for the BS spatial encoding technique (BS-SET) using RF-gradients. MATERIALS AND METHODS: Since the BS-gradient leads to nonlinear encoding, an adapted reconstruction method was developed to obtain undistorted images. To replace conventional phase encoding gradients, BS-SET was implemented in a two-dimensional (2D) spin echo sequence on a 0.5 T portable MR scanner. RESULTS: A 2D spin echo (SE) measurement imaged along a single dimension using the BS-SET was compared to a conventional SE 2D measurement. The proposed reconstruction method yielded undistorted images. CONCLUSIONS: BS-gradients were demonstrated as a feasible option for spatial phase encoding. Furthermore, undistorted BS-SET images could be obtained using the proposed reconstruction method.

3D gradient system for two B0 field directions in earth's field MRI.

OBJECT: A new gradient system for earth's field magnetic resonance imaging (EFMRI) is presented that can be rotated relatively to the earth's field direction while maintaining the ability to encode images. Orthogonal components of the gradient field are exploited to reduce the number of gradient coils. MATERIALS AND METHODS: Two favorable orientations of the gradient system relative to the earth's magnetic field (parallel and perpendicular) are discussed. We introduce the theory for the magnetic fields of the new gradient system and illustrate the design of the coil geometries which were worked out with the help of simulations and a numerical optimization algorithm. Field mapping measurements and imaging experiments in the two different orientations of the gradient system were carried out. RESULTS: Orthogonal components of the gradient field take over the role of the additionally needed gradient fields when the gradient system is rotated relative to the earth's magnetic field. The results from the field mapping and imaging experiments verify the presented theory and show the functionality of the new gradient system. CONCLUSION: The presented system demonstrates that gradient coils can be used for image encoding in multiple directions. This fact can be exploited to realize an EFMRI setup for parallel and perpendicular prepolarization with a single set of gradient coils.

A system for in vivo on-demand ultra-low field Overhauser-enhanced 3D-Magnetic resonance imaging.

Development of very-low field MRI is an active area of research. It aims at reducing operating costs and improve portability. However, the signal-to-noise issue becomes prominent at ultra-low field (<1 mT), especially for molecular imaging purposes that addresses specific biochemical events. In the context of preclinical molecular MRI of abnormal proteolysis the paper describes a MRI system able to produce Overhauser-enhanced MR images in living rats through in situ Dynamic Nuclear Polarization at 206 µT using stable and non-toxic nitroxides. In parallel conventional images are generated at 206 µT following pre-polarization at 20 mT. Results show that nitroxides are visualized in 3D within a few minutes in the lungs, kidneys and bladder post-administration. This system will be used for molecular imaging of inflammation using protease-specific nitroxide probes.

Reducing RF-related heating of cardiac pacemaker leads in MRI: implementation and experimental verification of practical design changes.

There are serious concerns regarding safety when performing magnetic resonance imaging in patients with implanted conductive medical devices, such as cardiac pacemakers, and associated leads, as severe incidents have occurred in the past. In this study, several approaches for altering an implant's lead design were systematically developed and evaluated to enhance the safety of implanted medical devices in a magnetic resonance imaging environment. The individual impact of each design change on radiofrequency heating was then systematically investigated in functional lead prototypes at 1.5 T. Radiofrequency-induced heating could be successfully reduced by three basic changes in conventional pacemaker lead design: (1) increasing the lead tip area, (2) increasing the lead conductor resistance, and (3) increasing outer lead insulation conductivity. The findings show that radiofrequency energy pickup in magnetic resonance imaging can be reduced and, therefore, patient safety can be improved with dedicated construction changes according to a "safe by design" strategy. Incorporation of the described alterations into implantable medical devices such as pacemaker leads can be used to help achieve favorable risk-benefit-ratios when performing magnetic resonance imaging in the respective patient group.

Quantification and localization of contrast agents using delta relaxation enhanced magnetic resonance at 1.5 T.

OBJECT: Delta relaxation enhanced magnetic resonance (dreMR) is a new imaging technique based on the idea of cycling the magnetic field B (0) during an imaging sequence. The method determines the field dependency of the relaxation rate (relaxation dispersion dR (1)/dB). This quantity is of particular interest in contrast agent imaging because the parameter can be used to determine contrast agent concentrations and increases the ability to localize the contrast agent. MATERIALS AND METHODS: In this paper dreMR imaging was implemented on a clinical 1.5 T MR scanner combining conventional MR imaging with fast field-cycling. Two improvements to dreMR theory are presented describing the quantification of contrast agent concentrations from dreMR data and a correction for field-cycling with finite ramp times. RESULTS: Experiments demonstrate the use of the extended theory and show the measurement of contrast agent concentrations with the dreMR method. A second experiment performs localization of a contrast agent with a significant improvement in comparison to conventional imaging. CONCLUSION: dreMR imaging has been extended by a method to quantify contrast agent concentrations and improved for field-cycling with finite ramp times. Robust localization of contrast agents using dreMR imaging has been performed in a sample where conventional imaging delivers inconclusive results.

Contrast agent derived determination of the total circulating blood volume using magnetic resonance.

OBJECT: Knowledge of the total circulating blood volume (TCBV) is essential for the treatment of a variety of medical conditions and blood disorders. To date, blood volume analysis is rarely carried out due to the disadvantages of available methods. Our aim was to develop a widely available, simple, fast, yet accurate method for the determination of the total circulating blood volume. MATERIALS AND METHODS: Magnetic resonance (MR) is a well-established, non-invasive technique. In this article, we present a method that uses MR contrast agents for the determination of the blood volume. The dependence of MR relaxation times on the concentration of MR contrast agents allows the calculation of the volume the contrast agent has been diluted in. RESULTS: In phantom and in vivo experiments we could demonstrate that TCBV can be determined with high accuracy and precision. CONCLUSION: This work introduces a novel method for the determination of the total circulating blood volume using magnetic resonance contrast agents as tracers.

Reversible magnetism switching of iron oxide nanoparticle dispersions by controlled agglomeration.

The controlled agglomeration of superparamagnetic iron oxide nanoparticles (SPIONs) was used to rapidly switch their magnetic properties. Small-angle X-ray scattering (SAXS) and dynamic light scattering showed that tailored iron oxide nanoparticles with phase-changing organic ligand shells agglomerate at temperatures between 5 °C and 20 °C. We observed the concurrent change in magnetic properties using magnetic particle spectroscopy (MPS) with a temporal resolution on the order of seconds and found reversible switching of magnetic properties of SPIONs by changing their agglomeration state. The non-linear correlation between magnetization amplitude from MPS and agglomeration degree from SAXS data indicated that the agglomerates' size distribution affected magnetic properties.

Measuring RF-induced currents inside implants: Impact of device configuration on MRI safety of cardiac pacemaker leads.

Radiofrequency (RF)-related heating of cardiac pacemaker leads is a serious concern in magnetic resonance imaging (MRI). Recent investigations suggest such heating to be strongly dependent on an implant's position within the surrounding medium, but this issue is currently poorly understood. In this study, phantom measurements of the RF-induced electric currents inside a pacemaker lead were performed to investigate the impact of the device position and lead configuration on the amount of MRI-related heating at the lead tip. Seven hundred twenty device position/lead path configurations were investigated. The results show that certain configurations are associated with a highly increased risk to develop MRI-induced heating, whereas various configurations do not show any significant heating. It was possible to precisely infer implant heating on the basis of current intensity values measured inside a pacemaker lead. Device position and lead configuration relative to the surrounding medium are crucial to the amount of RF-induced heating in MRI. This indicates that a considerable number of implanted devices may incidentally not develop severe heating in MRI because of their specific configuration in the body. Small variations in configuration can, however, strongly increase the risk for such heating effects, meaning that hazardous situations might appear during MRI.

MRI thermometry: Fast mapping of RF-induced heating along conductive wires.

Conductive implants are in most cases a strict contraindication for MRI examinations, as RF pulses applied during the MRI measurement can lead to severe heating of the surrounding tissue. Understanding and mapping of these heating effects is therefore crucial for determining the circumstances under which patient examinations are safe. The use of fluoroptic probes is the standard procedure for monitoring these heating effects. However, the observed temperature increase is highly dependent on the positioning of such a probe, as it can only determine the temperature locally. Temperature mapping with MRI after RF heating can be used, but cooling effects during imaging lead to a significant underestimation of the heating effect. In this work, an MRI thermometry method was combined with an MRI heating sequence, allowing for temperature mapping during RF heating. This technique may provide new opportunities for implant safety investigations.

Spatial distribution of RF-induced E-fields and implant heating in MRI.

The purpose of this study was to assess the distribution of RF-induced E-fields inside a gel-filled phantom of the human head and torso and compare the results with the RF-induced temperature rise at the tip of a straight conductive implant, specifically examining the dependence of the temperature rise on the position of the implant inside the gel. MRI experiments were performed in two different 1.5T MR systems of the same manufacturer. E-field distribution inside the liquid was assessed using a custom measurement system. The temperature rise at the implant tip was measured in various implant positions and orientations using fluoroptic thermometry. The results show that local E-field strength in the direction of the implant is a critical factor in RF-related tissue heating. The actual E-field distribution, which is dependent on phantom/body properties and the MR-system employed, must be considered when assessing the effects of RF power deposition in implant safety investigations.

Stem cell labeling with iron oxide nanoparticles: impact of 3D culture on cell labeling maintenance.

AIM: We aimed to analyze the suitability of nanoparticles (M4E) for safe human mesenchymal stem cell (hMSC) labeling and determined cell labeling maintenance in 2D and 3D culture. MATERIALS & METHODS: We investigated cell-particle interaction and the particles' impact on cell viability, growth and proliferation. We analyzed cell labeling maintenance in 2D and 3D culture invasively and noninvasively. RESULTS: M4E do not affect cell viability, growth and proliferation and do not cause chromosomal aberrations. Cell labeling maintenance is up to five-times higher in 3D conditions compared with 2D culture. CONCLUSION: M4E allow safe hMSC labeling and noninvasive identification. Our hMSC-loaded, 3D tissue-engineered construct could serve as a graft for regenerative therapies, in which M4E-labeled hMSCs can migrate to their target.

Optimization of the AC-gradient method for velocity profile measurement and application to slow flow.

This work presents a spectroscopic method to measure slow flow. Within a single shot the velocity distribution is acquired. This allows distinguishing rapidly between single velocities within the sampled volume with a high sensitivity. The technique is based on signal acquisition in the presence of a periodic gradient and a train of refocussing RF pulses. The theoretical model for trapezoidal bipolar pulse shaped gradients under consideration of diffusion and the outflow effect is introduced. A phase correction technique is presented that improves the spectral accuracy. Therefore, flow phantom measurements are used to validate the new sequence and the simulation based on the theoretical model. It was demonstrated that accurate parabolic flow profiles can be acquired and flow variations below 200 µm/s can be detected. Three post-processing methods that eliminate static background signal are also presented for applications in which static background signal dominates. Finally, this technique is applied to flow measurement of a small alder tree demonstrating a typical application of in vivo plant measurements.

MRI Meets MPI: a bimodal MPI-MRI tomograph.

While magnetic particle imaging (MPI) constitutes a novel biomedical imaging technique for tracking superparamagnetic nanoparticles in vivo, unlike magnetic resonance imaging (MRI), it cannot provide anatomical background information. Until now these two modalities have been performed in separate scanners and image co-registration has been hampered by the need to reposition the sample in both systems as similarly as possible. This paper presents a bimodal MPI-MRI-tomograph that combines both modalities in a single system.MPI and MRI images can thus be acquired without moving the sample or replacing any parts in the setup. The images acquired with the presented setup show excellent agreement between the localization of the nanoparticles in MPI and the MRI background data. A combination of two highly complementary imaging modalities has been achieved.

Rapid spectroscopic velocity quantification using periodically oscillating gradients.

In this work two spectroscopic methods are described which allow rapid flow velocity quantification in the presence of a parabolic velocity distribution. This method requires only a single excitation and is based on flow encoding by periodically oscillating gradients. In the shown spin echo variant additional refocusing pulses correct for field inhomogeneities. A theoretical model is introduced, which describes the course of the derived spectra even in high flow region, where a significant part of the encoded spins leaves the sensitive area of the coil during data acquisition (outflow-effect). It was demonstrated that both methods can quantify flow velocities within the velocity range of 1mm/s up to 36 cm/s in the presence of a parabolic flow velocity distribution. The maximum velocity of the parabolic distribution is indicated in this method by a peak in the acquired spectrum from which the velocity could be quantified. Flow velocity quantification by periodically oscillating gradients seems a reasonable and fast alternative to established imaging techniques.

Feasibility of contrast-enhanced and nonenhanced MRI for intraprocedural and postprocedural lesion visualization in interventional electrophysiology: animal studies and early delineation of isthmus ablation lesions in patients with typical atrial flutter.

BACKGROUND: Imaging of myocardial ablation lesions during electrophysiology procedures would enable superior guidance of interventions and immediate identification of potential complications. The aim of this study was to establish clinically suitable MRI-based imaging techniques for intraprocedural lesion visualization in interventional electrophysiology. METHODS AND RESULTS: Interventional electrophysiology was performed under magnetic resonance guidance in an animal model, using a custom setup including magnetic resonance-conditional catheters. Various pulse sequences were explored for intraprocedural lesion visualization after radiofrequency ablation. The developed visualization techniques were then used to investigate lesion formation in patients immediately after ablation of atrial flutter. The animal studies in 9 minipigs showed that gadolinium-DTPA-enhanced T1-weighted and nonenhanced T2-weighted pulse sequences are particularly suitable for lesion visualization immediately after radiofrequency ablation. MRI-derived lesion size correlated well with autopsy (R(2)=0.799/0.709 for contrast-enhanced/nonenhanced imaging). Non-contrast agent-enhanced techniques were suitable for repetitive lesion visualization during electrophysiological interventions, thus allowing for intraprocedural monitoring of ablation success. The patient studies in 24 patients with typical atrial flutter several minutes to hours after cavotricuspid isthmus ablation confirmed the results from the animal experiments. Therapeutic lesions could be visualized in all patients using contrast-enhanced and also nonenhanced MRI with high contrast-to-noise ratio (94.6±35.2/111.1±32.6 versus 48.0±29.0/68.0±37.3 for ventricular/atrial lesions and contrast-enhanced versus nonenhanced imaging). CONCLUSIONS: MRI allows for precise lesion visualization in electrophysiological interventions just minutes after radiofrequency ablation. Nonenhanced T2-weighted MRI is particularly feasible for intraprocedural delineation of lesion formation as lesions are detectable within minutes after radiofrequency delivery and imaging can be repeated during interventions.

Feasibility of real-time MRI with a novel carbon catheter for interventional electrophysiology.

BACKGROUND: Cardiac MRI offers 3D real-time imaging with unsurpassed soft tissue contrast without x-ray exposure. To minimize safety concerns and imaging artifacts in MR-guided interventional electrophysiology (EP), we aimed at developing a setup including catheters for ablation therapy based on carbon technology. METHODS AND RESULTS: The setup, including a steerable carbon catheter, was tested for safety, image distortion, and feasibility of diagnostic EP studies and radiofrequency ablation at 1.5 T. MRI was performed in 3 different 1.5-T whole-body scanners using various receive coils and pulse sequences. To assess unintentional heating of the catheters by radiofrequency pulses of the MR scanner in vitro, a fluoroptic thermometry system was used to record heating at the catheter tip. Programmed stimulation and ablation therapy was performed in 8 pigs. There was no significant heating of the carbon catheters while using short, repetitive radiofrequency pulses from the MR system. Because there was no image distortion when using the carbon catheters, exact targeting of the lesion sites was possible. Both atrial and ventricular radiofrequency ablation procedures including atrioventricular node modulation were performed successfully in the scanner. Potential complications such as pericardial effusion after intentional perforation of the right ventricular free wall during ablation could be monitored in real time as well. CONCLUSIONS: We describe a newly developed EP technology for interventional electrophysiology based on carbon catheters. The feasibility of this approach was demonstrated by safety testing and performing EP studies and ablation therapy with carbon catheters in the MRI environment.

Investigating the locomotion of the sandfish in desert sand using NMR-imaging.

The sandfish (Scincus scincus) is a lizard having the remarkable ability to move through desert sand for significant distances. It is well adapted to living in loose sand by virtue of a combination of morphological and behavioural specializations. We investigated the bodyform of the sandfish using 3D-laserscanning and explored its locomotion in loose desert sand using fast nuclear magnetic resonance (NMR) imaging. The sandfish exhibits an in-plane meandering motion with a frequency of about 3 Hz and an amplitude of about half its body length accompanied by swimming-like (or trotting) movements of its limbs. No torsion of the body was observed, a movement required for a digging-behaviour. Simple calculations based on the Janssen model for granular material related to our findings on bodyform and locomotor behaviour render a local decompaction of the sand surrounding the moving sandfish very likely. Thus the sand locally behaves as a viscous fluid and not as a solid material. In this fluidised sand the sandfish is able to "swim" using its limbs.