A concept for a magnetic particle imaging scanner with Halbach arrays.

Magnetic particle imaging (MPI) is a new medical imaging technique visualizing the concentration distribution of superparamagnetic nanoparticles used as tracer material. MPI is not yet in clinical routine, since one of the challenges is the upscaling of scanners. Typically, the magnetic fields of MPI scanners are generated electromagnetically, resulting in an immense power consumption but providing high flexibility in terms of adjusting the field strengths and very fast image acquisition rates. Permanent magnets provide high flux densities and do not need any power supply. However, the flux density is not adjustable, and a mechanical movement is slow compared to electromagnetically varying fields. The MPI scanner concept proposed here uses permanent magnets and provides high flexibility, with the possibility to choose between fast overview scanning and detailed image acquisition. By mechanical rotation of magnetic rings in Halbach array configuration, it is possible to adjust the field or gradient strengths. The latter allows for determining the spatial resolution and the size of the field of view. A continuous mechanical rotation defines the coarseness of the scanning trajectory and image acquisition rate. This concept provides a comparable flexibility, as an alternating magnetic field and an adjustable field gradient can be applied as known from electromagnetically driven MPI systems, and therefore yields high potential for an enlarged system. We present the idea of an arrangement of Halbach arrays and how to calculate the generated magnetic fields. Simulations for an exemplary geometry are provided to show the potential of the proposed setup.

Optimized Continuous Application of Hyperpolarized Xenon to Liquids.

In recent years, NMR with hyperpolarized (HP) xenon inside functionalized host structures (e.g., cryptophanes) have become a potential candidate for the direct observation of metabolic processes (i.e., molecular imaging). A critical issue for real applications is the dissolution of the HP-gas in the liquid which contains the host. In this work, we present recent developments for an improved and controlled dissolution of HP-Xe in liquids using hollow fiber membranes and different compressor systems. The designed apparatus consists of a compressor and a membrane unit. The compressor provides HP-129Xe continuously at small adjustable pressures and in a polarization-preserving way. The membrane unit enables a molecular solution of the HP-gas in aqueous liquids, avoiding the formation of bubbles or even foams. Two different types of compressors were tested in terms of function and useful materials. Special emphasis was put on a systematic reduction of transfer losses in the gas and liquid phase. In order to optimize the system parameters, several physical models were developed to describe the transport and the losses of nuclear polarization. Finally, the successful implementation was demonstrated in several experiments. HP-Xe was dissolved in an aqueous cryptophane-A-(OCH2COOH)6 solution, and stable Xe signals could be measured over 35 min, only limited by the size of the gas reservoir. Such long and stable experimental conditions enabled the study of chemical exchange of xenon between cryptophane and water environments even for a time-consuming 2D NMR experiment. The good signal stability over the measurement time allowed an exact determination of the residence time of the Xe atom inside the cryptophane, resulting in an average residence time of 44.5 ± 2.7 ms.

HP-Xe to go: Storage and transportation of hyperpolarized (129)Xenon.

Recently the spin-lattice relaxation time T1 of hyperpolarized (HP)-(129)Xe was significantly improved by using uncoated and Rb-free storage vessels of GE180 glass. For these cells, a simple procedure was established to obtain reproducible wall relaxation times of about 18 h. Then the limiting relaxation mechanism in pure Xe is due to the coupling between the nuclear spins and the angular momentum of the Xe-Xe van-der-Waals-molecules. This mechanism can be significantly reduced by using different buffer gases of which CO2 was discovered to be the most efficient so far. From these values, it was estimated that for a 1:1 mixture of HP-Xe with CO2 a longitudinal relaxation time of about 7 h can be expected, sufficient to transport HP-Xe from a production to a remote application site. This prediction was verified for such a mixture at a total pressure of about 1 bar in a 10 cm glass cell showing a storage time of T1≈9 h (for T1(wall)=(34±9) h) which was transported inside a magnetic box over a distance of about 200 km by car.

Intrinsic superoxide dismutase activity of MnO nanoparticles enhances the magnetic resonance imaging contrast.

Superoxide radicals are associated with the development of many severe diseases, such as cancer. Under nonpathogenic conditions, the natural enzyme superoxide dismutase (SOD) regulates the intracellular superoxide concentrations, but nearly all tumor tissues show reduced SOD levels. Selective imaging in early progression stages remains a key requirement for efficient cancer diagnosis and treatment. Magnetic resonance imaging (MRI) as a noninvasive tool with high spatial resolution may offer advantages here, but MRI contrast agents exhibiting a redox-triggered change in the image contrast towards superoxide radicals have not been reported so far. Here we show that manganese oxide (MnO) nanoparticles (NPs) exhibit an intrinsic SOD-like activity, which is higher than that of the native Mn-dependent SOD. In addition, MnO NPs significantly enhance the MRI contrast when exposed to superoxide radicals, making them responsive MRI contrast agents for the treatment and imaging of cancer cells with reduced SOD levels.

Magnetic resonance imaging of dissolved hyperpolarized 129Xe using a membrane-based continuous flow system.

A technique for continuous production of solutions containing hyperpolarized (129)Xe is explored for MRI applications. The method is based on hollow fiber membranes which inhibit the formation of foams and bubbles. A systematic analysis of various carrier agents for hyperpolarized (129)Xe has been carried out, which are applicable as contrast agents for in vivo MRI. The image quality of different hyperpolarized Xe solutions is compared and MRI results obtained in a clinical as well as in a nonclinical MRI setting are provided. Moreover, we demonstrate the application of (129)Xe contrast agents produced with our dissolution method for lung MRI by imaging hyperpolarized (129)Xe that has been both dissolved in and outgassed from a carrier liquid in a lung phantom, illustrating its potential for the measurement of lung perfusion and ventilation.

Design of a permanent magnet with a mechanical sweep suitable for variable-temperature continuous-wave and pulsed EPR spectroscopy.

A magnetic system is introduced which consists of three nested rings of permanent magnets of a Halbach dipolar layout and is capable for EPR spectroscopy. Two of the rings can be rotated independently to adjust the magnetic flux in the center and even allow for mechanical field sweeps. The presented prototype achieves a magnetic flux range of 0.0282-0.3013T with a minimal sweep of 0.15mT and homogeneity of about 10(-3). First applications with CW and pulsed Mims ENDOR as well as ESEEM experiments on a sample of a glycine single crystal doped with 1% copper nitrate demonstrate that flux range, sweep accuracy and homogeneity of this prototype is sufficient for EPR experiments on most solid samples. Together with a recently improved design magnets can be build which could serve as compact and easily transportable replacement of standard electromagnets with negligible consumption of power or coolants.

Resolution enhancement in MRI of laser polarized 3He by control of diffusion.

Diffusion of atoms or molecules in presence of magnetic field gradients not only attenuates the NMR signal but also leads to distortions close to restricting boundaries. This phenomenon is most evident in imaging with laser polarized (LP) noble gases. Diffusion of gases can be manipulated, however, by admixing inert gases of different molecular weight. In this work we analyze the effect of mixing LP-(3)He with SF(6) on the image quality of a phantom consisting of an arrangement of capillaries with different diameters. Admixing buffer gases of higher molecular weight changes the contrast and offers a means to record images with high spatial and time resolution. Additionally we demonstrate how distortions due to edge enhancement can be reduced even for long timed MRI-sequences.

Diffusion in binary gas mixtures studied by NMR of hyperpolarized gases and molecular dynamics simulations.

The dependence of the individual mean square displacement of rare gases in binary mixtures is studied by a combined experimental and theoretical approach. We show that the diffusion constant can be varied in a considerable range by changing the molar fractions of the mixtures. On the experimental side, NMR diffusion measurements are done on hyperpolarized 3He and 129Xe, mixed with several inert buffer gases, in the presence of a magnetic field gradient. The results are compared to diffusion coefficients obtained from atomistic molecular dynamics simulations based on Lennard-Jones type potentials of the corresponding gas mixtures, and to appropriate analytical expressions, yielding very good mutual agreement. This study is the first quantitative validation of the effects of the mutual interactions between gas particles on the individual diffusion properties. It is shown that the dependency of gas phase diffusion properties on the local chemical environment may not be neglected, e.g. in diffusion-controlled chemical reactions.

Imaging of a mixture of hyperpolarized 3He and 129Xe.

With the use of hyperpolarized gases, a great number of experiments have been carried out in order to improve the diagnostics of the lung, both from a structural and a functional point of view. 3He is best suited for structural studies, whereas 129Xe gives more detailed information about the functionality of the lung because it enters the bloodstream. In this work, we propose the use of a gas mixture to perform consecutive analysis of lung structure and functionality upon the delivery of a single bolus of gas. We show images of a helium-xenon gas mixture in the presence of a small amount of liquid toluene in order to demonstrate how both nuclei can be detected independently, extracting the spectroscopic information provided by the 129Xe spectra and obtaining an image with high sensitivity for 3He. A second experiment performed on a dissected mouse lung was used to demonstrate how the mixture of gases can enhance sensitivity in the larger airways of the lung.

[A software program for quantitative analysis of alveolar oxygen partial pressure (p(A)O(2)) with oxygen-sensitive (3)He-MRI]. / Ein Auswerteprogramm zur quantitativen Analyse von Messungen des alveolären Sauerstoffpartialdrucks (p(A)O(2)) mit der sauerstoffsensitiven (3)He-MR-Tomographie.

PURPOSE: To develop a software tool for quantitative analysis of alveolar oxygen partial pressure (p(A)O(2)) as well as its time course during apnea. MATERIAL AND METHODS: T (1)-relaxation times of hyperpolarized (3)He are reduced by paramagnetic oxygen rendering (3)He-MRI sensitive to oxygen and thus allowing the assessment of the local oxygen partial pressure in the pulmonary airspaces. Oxygen-related relaxation and loss of polarization by RF-excitation can be discriminated by acquiring two image series with varying interscan delay and/or flip angles. Software was developed to calculate the p(A)O(2) and the decay rate in user-defined regions of interest (ROIs) automatically. Moreover, parameter maps can be calculated. In addition to the analysis of 2-dimensional data sets, the software allows the evaluation of 3-dimensional measurements for the first time. Artifacts due to lung motion were reduced by implementing a motion correction algorithm. RESULTS: The software was successfully applied to data sets from healthy volunteers and from patients with various lung diseases. The parameter maps demonstrated a more homogeneous distribution of p(A)O(2) for the volunteers than for the patients. A regional increase in p(A)O(2) was found in a few patients. CONCLUSION: The described software allows the absolute quantification of p(A)O(2) as well as its variation over time. In the future, therefore, the software may gain importance for detecting mismatches between ventilation and perfusion, e. g., in patients with pulmonary embolism or chronic obstructive lung diseases.

Surface normal imaging with a hand-held NMR device.

Recently the capabilities of single sided nuclear magnetic resonance (NMR) devices have been extended towards three-dimensional imaging. This paper details the use of a magnetic field sweep coil to obtain spatial resolution in the plane normal to the surface of a hand-held NMR device-the NMR-Mobile Universal Surface Explorer (MOUSE). One-dimensional depth profiles can be recorded by varying the current in the sweep coils. Preliminary results from multi-layer rubber and glass sample phantoms demonstrate a sample penetration depth of 7 mm. Two-dimensional images were acquired via the inclusion of phase encoding coils. Non-destructive cross-sectional images of small rubber phantoms were successfully recorded.

The NMR-mouse: construction, excitation, and applications.

A mobile nuclear magnetic resonance (NMR) device similar to a bore-hole probe has been developed for applications in materials science and biomedicine. Inhomogeneous polarizing and radio-frequency (rf) magnetic fields are applied to arbitrarily large samples from one side. Different experimental techniques have been tested to measure transverse and longitudinal relaxation times and translational diffusion constants. Good contrast for discrimination of material properties is gained when the residual dipolar coupling is retained in soft matter by avoiding spinlock effects in multi-pulse techniques. Applications to characterization of products from technical elastomers, skin, and coatings on iron sheets are reported.

Analysis of polymer materials by surface NMR via the MOUSE.

Applications are discussed of a novel NMR device, the NMR MOUSE (mobile universal surface explorer), for characterization of polymers. Different properties of elastomers can be related to an effective transverse relaxation parameter T2eff. Effects of multi-echo sequences influence the decay curve and can be described in terms of B0 inhomogeneity and spin-lock effects. Furthermore, the signal-to-noise ratio (SIN) can be improved by use of steady-state free precession (SSFP) pulse sequences modified for use in inhomogeneous magnetic fields.

Hadamard NMR imaging with slice selection.

Stochastic NMR imaging is one of the less common NMR imaging techniques. Nevertheless, stochastic rf excitation is characterized by some remarkable features: the rf excitation power is at least two orders of magnitude lower in comparison to conventionally pulsed NMR imaging schemes. Thus, the technique is of interest for imaging of large objects. The systematic noise inherent in images obtained with random noise excitation has been eliminated by using pseudorandom noise together with Hadamard transformation for data evaluation. Data acquisition times are comparable to those of ultrafast imaging techniques. For slice selection, z magnetization is destroyed outside the slice region with specially designed low power pulses. Thus, gradient switching times are only limited by T1 and not T2*. Images are reconstructed by the backprojection algorithm. We have set up a stochastic imaging procedure on a conventional Bruker MSL 300 spectrometer, and have drawn a comparison between images obtained by the pseudorandom noise excitation and by conventional Fourier imaging.

Two-dimensional one-pulse rotational echo spectra.

Recently a two-dimensional representation of one-dimensional spinning sideband magic-angle spinning (MAS) spectra has been published with applications to deuteron MAS nuclear magnetic resonance (NMR). The introduction of a new time axis, based on the rotor period, allows the separation of isotropic and anisotropic chemical shifts. It is shown here that, in addition to untangling spinning sideband spectra, data-processing steps can be incorporated which enabled applications of the method to signals from nuclei with anisotropies smaller than those of the quadrupole coupling of deuterons. This is achieved by linear prediction of the rotary echo signals. Advantages and limitations of the algorithm are discussed and demonstrated with experimental results of 13C cross-polarization (CP) MAS spectra of glycine.

Presentation of sideband envelopes by two-dimensional one-pulse (TOP) spectroscopy.

A novel way of representing 1D MAS spinning sideband spectra in a 2D-resolved fashion is explained. The method is illustrated with 2H MAS data of deuterated polycarbonate. From the resulting 2D spectrum, the isotropic shifts can be identified on one axis and the rotary echo decay spectra along the other axis.

Magnetization filters: applications to NMR imaging of elastomers.

The general Fourier scheme for parameter selective imaging is subdivided into three periods: A preparation period for application of magnetization filters, an evolution period for space encoding, and a detection period for acquisition of the spectroscopic dimension. Depending on sample requirements and available time, the first and the last period can be omitted. Preparation of the initial magnetization for space encoding by appropriate filters is a powerful and time-saving way to introduce parameter-selective image contrast. This is illustrated by filters of molecular dynamics, which are sensitive to segmental motion in different time windows for contrast enhancement in composite and aged elastomers. Further contrast amplification is achieved by computing the difference of images acquired with different filter settings.