Radon-based Image Reconstruction for MPI using a continuously rotating FFL

Magnetic particle imaging is a relatively new tracer-based medical imaging technique exploiting the non-linear magnetization response of magnetic nanoparticles to changing magnetic fields. If the data are generated by using a field-free line, the sampling geometry resembles the one in computerized tomography. Indeed, for an ideal field-free line rotating only in between measurements it was shown that the signal equation can be written as a convolution with the Radon transform of the particle concentration. In this work, we regard a continuously rotating field-free line and extend the forward operator accordingly. We obtain a similar result for the relation to the Radon data but with two additive terms resulting from the additional time-dependencies in the forward model. We jointly reconstruct particle concentration and corresponding Radon data by means of total variation regularization yielding promising results for synthetic data.Comment: YRM & CSE Workshop on Modeling, Simulation & Optimization of Fluid Dynamic Applications 202

Single Harmonic-based Narrowband Magnetic Particle Imaging

Visualization of the in vivo spatial distribution of superparamagnetic iron oxide nanoparticles (SPIONs) is crucial to biomedicine. Magnetic particle imaging (MPI) is one of the most promising approaches for direct measurements of the SPION distribution. In this paper, we systematically investigate a single-harmonic-based narrowband MPI approach. Herein, only the 3rd harmonic at 15 kHz of the SPION signal induced in an excitation magnetic field of 5 kHz is measured via a narrowband detection system for imaging during scanning a field-free-point in a field of view. Experiments on spot and line phantoms are performed to evaluate the spatial distribution by the assessment of the full width at half maximum and modulation transfer function at different excitation magnetic fields from 4 to 10 mT. Experimental results demonstrate that reconstructed images have a spatial resolution of 1.6 and 1.5 mm for a gradient field of 2.2 T/m and 4.4 T/m in x- and z-direction, respectively, at an excitation magnetic field of 4 mT. In terms of line gap, two lines with a gap of 0.5 mm are resolved. With increasing the excitation magnetic field to 10 mT, the spatial resolution gets worse to 2.4 and 2.0 mm in x- and z-direction, respectively. Moreover, the custom-built MPI scanner allows a limit of detection of 53 microgram (Fe)/mL (500 ng Fe weight) using perimag SPIONs. In addition, the excellent performance is demonstrated by imaging experiments on an "emg" logo phantom. We believe that the proposed narrowband MPI approach is a promising approach for SPION imaging

Low drive field amplitude for improved image resolution in magnetic particle imaging

Purpose: Magnetic particle imaging (MPI) is a new imaging technology that directly detects superparamagnetic iron oxide nanoparticles. The technique has potential medical applications in angiography, cell tracking, and cancer detection. In this paper, the authors explore how nanoparticle relaxation affects image resolution. Historically, researchers have analyzed nanoparticle behavior by studying the time constant of the nanoparticle physical rotation. In contrast, in this paper, the authors focus instead on how the time constant of nanoparticle rotation affects the final image resolution, and this reveals nonobvious conclusions for tailoring MPI imaging parameters for optimal spatial resolution. Methods: The authors first extend x-space systems theory to include nanoparticle relaxation. The authors then measure the spatial resolution and relative signal levels in an MPI relaxometer and a 3D MPI imager at multiple drive field amplitudes and frequencies. Finally, these image measurements are used to estimate relaxation times and nanoparticle phase lags. Results: The authors demonstrate that spatial resolution, as measured by full-width at half-maximum, improves at lower drive field amplitudes. The authors further determine that relaxation in MPI can be approximated as a frequency-independent phase lag. These results enable the authors to accurately predict MPI resolution and sensitivity across a wide range of drive field amplitudes and frequencies. Conclusions: To balance resolution, signal-to-noise ratio, specific absorption rate, and magnetostimulation requirements, the drive field can be a low amplitude and high frequency. Continued research into how the MPI drive field affects relaxation and its adverse effects will be crucial for developing new nanoparticles tailored to the unique physics of MPI. Moreover, this theory informs researchers how to design scanning sequences to minimize relaxation-induced blurring for better spatial resolution or to exploit relaxation-induced blurring for MPI with molecular contrast. © 2016 American Association of Physicists in Medicine

X-Band Rapid-Scan EPR

The advantages of rapid-scan EPR relative to CW and pulse techniques for samples with long longitudinal relaxation time T1 (Ns0 defects in diamond, N@C60, and amorphous hydrogenated silicon), heterogeneous samples (crystalline 1:1 α,γ-bisdiphenylene-β-phenylallyl (BDPA):benzene), lossy samples (aqueous nitroxyl radicals), and transient radicals (5-tert-butoxycarbonyl-5-methyl-1-pyrroline-N-oxide (BMPO)-superoxide adduct) were studied. For samples with long relaxation times, CW (continuous wave) EPR is challenging due to power saturation and distortions from passage effects. In rapid-scan EPR, the field is swept through resonance in a time that is short relative to T2. In rapid-scan EPR, the magnetic field is on resonance for a short time relative to CW EPR. Because of this, the energy absorbed by the spins, for the same microwave B1, is less than in conventional CW spectra, and the signal does not saturate as readily. For samples with long electron relaxation times, pulse techniques can also be challenging, particularly if T2 is long and T2* is short. Rapid-scan EPR is a powerful alternative to CW and pulse EPR because it is a straight-forward technique that does not require the high power of pulse EPR. For the samples studied, improvements in signal-to-noise ranging from factors of 10 to 250 were observed. Rapid-scan can also be used to extract relaxation information from a sample. The rapid-scan spectra for lithium phthalocyanine (LiPc) and 15N-PDT (4-oxo-2,2,6,6-tetra-perdeuteromethyl-piperidinyl-15N-oxyl-d16) were simulated to determine T2. The extraction of T2 from the rapid-scan spectra of BDPA was also attempted. Through our difficulty in simulating the rapid-scan spectra of BDPA, we realized that commercial BDPA was not a homogeneous sample. The experiments studying BDPA demonstrated that rapid-scan experiments can give insight into the relaxation of a sample that might not otherwise be evident with conventional CW EPR. Finally, rapid-scan EPR at X-band was applied to spin trapping experiments. Superoxide was generated by the reaction of xanthine oxidase and hypoxanthine and trapped with BMPO. Spin trapping with 5-tert-butoxycarbonyl-5-methyl-1-pyrroline N-oxide (BMPO) to form BMPO-OOH adduct converts the short-lived superoxide into a more stable spin adduct. The detection limit for spin-trapped superoxide was compared between CW and rapid-scan EPR. The signal-to-noise ratio was more than 40 times greater for rapid-scan than for CW EPR. We also demonstrated detection of superoxide produced by Enterococcus faecalis at rates that are too low for detection by CW EPR

Synthesis of Fe-oxide nanoparticles using microreactors

The work described in this thesis focuses upon the development of a novel adaptable continuous flow technique for the synthesis of iron oxide nanoparticles using commercially available microreactor system, to allow for easy scaling up towards a larger industrial scale. The development of the technique focussed around the conversion of commonly used research techniques, which require the use of specifically designed microreactors, for use upon commercially available microreactors in which the design is fixed. A 2D continuous flow focussed technique was developed based upon the attempted conversion of the droplet coalescence and co-axial flow technique which has been previously used for nanoparticle synthesis by other research groups.The nanoparticles produced using this technique were extensively characterised, in terms of physical and magnetic properties, and seen to be comparable, to those produced by other groups and those currently used as magnetic cores for MRI contrast applications. A critical evaluation of the effect of reaction parameters, e.g. reagent concentration, flow rate, and temperature upon nanoparticle size was made, however little quantifiable conclusions could be drawn. The structure of the nanoparticles was further investigated using a previously developed powder X-ray diffraction calibration technique which relied upon the asymmetry of peaks relating to specific reflections in the γ-Fe₂O₃ and Fe₃O₄ phases present in the nanoparticles. The structures were determined to contain higher quantities of γ-Fe₂O₃ which is more chemically stable but less magnetically favourable of the two phases. Further analysis using Mössbauer and solid state Infra-red analysis confirmed these findings, and as such attempts were made to control the amount of these phases within the nanoparticles. The synthesis technique was therefore adapted to allow for control of the amount of these phases within the nanoparticles by addition of oxidation and reducing agents into the synthesis. By doing this it proved able to synthesise nanoparticles which using the above powder X-ray diffraction technique were seen to be almost completely formed of γ-Fe₂O₃, synthesis of nanoparticles with higher weight percentages of Fe₃O₄, however proved not to be possible.Further work upon attempting to alter the magnetic properties of the nanoparticles has involved developing cation substitution reactions performed using microreactors. In batch these reactions are common place, however to the best of the author’s knowledge however no attempt has yet been made at cation substitution using microreactors. Partial replacement of Fe with another metal cation in the spinel structure was attempted to create a series of MxFe₃₋ₓO₄ compounds, this has been seen to alter the cation distribution and magnetic properties of the nanoparticles by other research groups. Several attempts at substituting Co, Mn, Zn, V, and Sn into the structure in batch. Zn substitution appeared the most successful in batch, and the synthesis was adapted to form ZnxFe₃₋ₓO₄ nanoparticles, with greater amounts of substitution into the nanoparticles seen when performing the synthesis in microreactors rather than batch.The 2D continuous flow focussed technique would therefore prove a useful tool for the synthesis of biomedical nanoparticles. Not only those it produce nanoparticles with the correct physical and magnetic properties, but also allows for their adaptation and manipulation of these properties to be tailored for specific applications

A new 3D model for magnetic particle imaging using realistic magnetic field topologies for algebraic reconstruction

We derive a new 3D model for magnetic particle imaging (MPI) that is able to incorporate realistic magnetic fields in the reconstruction process. In real MPI scanners, the generated magnetic fields have distortions that lead to deformed magnetic low-field volumes (LFV) with the shapes of ellipsoids or bananas instead of ideal field-free points (FFP) or lines (FFL), respectively. Most of the common model-based reconstruction schemes in MPI use however the idealized assumption of an ideal FFP or FFL topology and, thus, generate artifacts in the reconstruction. Our model-based approach is able to deal with these distortions and can generally be applied to dynamic magnetic fields that are approximately parallel to their velocity field. We show how this new 3D model can be discretized and inverted algebraically in order to recover the magnetic particle concentration. To model and describe the magnetic fields, we use decompositions of the fields in spherical harmonics. We complement the description of the new model with several simulations and experiments.Comment: 27 pages, 11 figure, 3 table

Magnetic Nanoparticle Sensors

Many types of biosensors employ magnetic nanoparticles (diameter = 5–300 nm) or magnetic particles (diameter = 300–5,000 nm) which have been surface functionalized to recognize specific molecular targets. Here we cover three types of biosensors that employ different biosensing principles, magnetic materials, and instrumentation. The first type consists of magnetic relaxation switch assay-sensors, which are based on the effects magnetic particles exert on water proton relaxation rates. The second type consists of magnetic particle relaxation sensors, which determine the relaxation of the magnetic moment within the magnetic particle. The third type is magnetoresistive sensors, which detect the presence of magnetic particles on the surface of electronic devices that are sensitive to changes in magnetic fields on their surface. Recent improvements in the design of magnetic nanoparticles (and magnetic particles), together with improvements in instrumentation, suggest that magnetic material-based biosensors may become widely used in the future

Localization of dexamethasone within dendritic core-multishell (CMS) nanoparticles and skin penetration properties studied by multi-frequency electron paramagnetic resonance (EPR) spectroscopy

The skin and especially the stratum corneum (SC) act as a barrier and protect epidermal cells and thus the whole body against xenobiotica of the external environment. Topical skin treatment requires an efficient drug delivery system (DDS). Polymer-based nanocarriers represent novel transport vehicles for dermal application of drugs. In this study dendritic core-multishell (CMS) nanoparticles were investigated as promising candidates. CMS nanoparticles were loaded with a drug (analogue) and were applied to penetration studies of skin. We determined by dual-frequency electron paramagnetic resonance (EPR) how dexamethasone (Dx) labelled with 3-carboxy-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (PCA) is associated with the CMS. The micro-environment of the drug loaded to CMS nanoparticles was investigated by pulsed high-field EPR at cryogenic temperature, making use of the fact that magnetic parameters (g-, A-matrices, and spin-lattice relaxation time) represent specific probes for the micro-environment. Additionally, the rotational correlation time of spin-labelled Dx was probed by continuous wave EPR at ambient temperature, which provides independent information on the drug environment. Furthermore, the penetration depth of Dx into the stratum corneum of porcine skin after different topical applications was investigated. The location of Dx in the CMS nanoparticles is revealed and the function of CMS as penetration enhancers for topical application is shown

Rapid-Scan EPR and Imaging

EPR imaging at low frequency is a powerful tool to obtain important biological information in vivo in a non-invasive way. Properties of nitroxide and trityl radical imaging reagents have been studied. Developments in rapid scan imaging techniques are reported that improve efficiency of experiments and user-friendliness of software. Relaxation and signal-to-noise ratio (S/N) in pulse experiments on trityl radicals were measured at frequencies between 400 MHz and 1.5 GHz. Relaxation time increases as the frequency increases and the radical concentration decreases. Since relaxation time is a sensitive and accurate measure of oxygen pressure, this study provides criteria for the selection of the frequencies for in vivo applications. Rapid-scan EPR of irradiated solids at L-band was studied. The results show that for the same data acquisition time, S/N for rapid-scans was significantly higher than for conventional continuous wave spectra. Rapid scan EPR imaging of nitroxide was performed at 250 MHz. Experimental parameters for the sinusoidal single-sweep method were varied to get better image quality. The results show that larger gradient strength provides higher spatial resolution while smaller gradient step size provides finer texture. Another method based on field-stepped linear-scans was developed; field step size, rapid-scan segment width, rapid-scan frequencies and some other parameters were varied. The field-stepped linear-scan method was compared with the sinusoidal single-sweep method using criteria including linewidth and S/N, and the former turned out to be a less effective alternative to the latter. New developments have been made to expand what can be achieved with EPR imaging, such as reduced data acquisition time, quantification of image features, efficient use of instrument time, and simplified experimental procedures from data acquisition to spectral analysis. The Python programming language was used successfully as a new and comprehensive approach to run EPR imaging experiments compared to the prior method that used multiple software packages. These developments will make EPR imaging more accessible for a much wider user group