Detection of NMR signals with a radio-frequency atomic magnetometer

We demonstrate detection of proton NMR signals with a radio-frequency (rf) atomic magnetometer tuned to the NMR frequency of 62 kHz. High-frequency operation of the atomic magnetometer makes it relatively insensitive to ambient magnetic field noise. We obtain magnetic field sensitivity of 7 fT/Hz1/2 using only a thin aluminum shield. We also derive an expression for the fundamental sensitivity limit of a surface inductive pick-up coil as a function of frequency and find that an atomic rf magnetometer is intrinsically more sensitive than a coil of comparable size for frequencies below about 50 MHz.     

Magnetic Relaxometry with an Atomic Magnetometer and SQUID Sensors on Targeted Cancer Cells

Magnetic relaxometry methods have been shown to be very sensitive in detecting cancer cells and other targeted diseases. Superconducting Quantum Interference Device (SQUID) sensors are one of the primary sensor systems used in this methodology because of their high sensitivity with demonstrated capabilities of detecting fewer than 100,000 magnetically-labeled cancer cells. The emerging technology of atomic magnetometers (AM) represents a new detection method for magnetic relaxometry with high sensitivity and without the requirement for cryogens. We report here on a study of magnetic relaxometry using both AM and SQUID sensors to detect cancer cells that are coated with superparamagnetic nanoparticles through antibody targeting. The AM studies conform closely to SQUID sensor results in the measurement of the magnetic decay characteristics following a magnetization pulse. The AM and SQUID sensor data are well described theoretically for superparamagnetic particles bound to cells and the results can be used to determine the number of cells in a cell culture or tumor. The observed fields and magnetic moments of cancer cells are linear with the number of cells over a very large range. The AM sensor demonstrates very high sensitivity for detecting magnetically labeled cells does not require cryogenic cooling and is relatively inexpensive.     

Detection of 3He spins with ultra-low field nuclear magnetic resonance employing SQUIDs for application to a neutron electric dipole moment experiment

The precession of ³He spins is detected with ultra-low field NMR. The absolute strength of the NMR signal is accurately measured and agrees closely with theoretical calculations. The sensitivity is analyzed for applications to a neutron electric dipole moment (nEDM) fundamental symmetry experiment under development.     

Current-density imaging using ultra-low-field MRI with zero-field encoding

Electric current density can be measured noninvasively with magnetic resonance imaging (MRI). Determining all three components of the current density, however, requires physical rotation of the sample or current injection from several directions when done with conventional methods. However, the emerging technology of ultra-low-field (ULF) MRI, in which the signal encoding and acquisition is conducted at a microtesla-range magnetic field, offers new possibilities. The low applied magnetic fields can even be switched off completely within the pulse sequence, increasing the flexibility of the available sequences. In this article, we present a ULF-MRI sequence designed for obtaining all three components of a current-density pattern without the need of sample rotations. The sequence consists of three steps: prepolarization of the sample, signal encoding in the current-density-associated magnetic field without applying any MRI fields, and spatial encoding in a microtesla-range field using any standard ULF-MRI sequence. The performance of the method is evaluated by numerical simulations. The method may find applications, e.g., in noninvasive conductivity imaging of tissue.     

A practical multinuclear transceiver volume coil for in vivo MRI/MRS at 7 T

A practical multinuclear transceiver RF volume coil with improved efficiency for in vivo small animal ¹H/¹³C/²³Na MR applications at the ultrahigh magnetic field of 7 T is reported. In the proposed design, the coil's resonance frequencies for ¹H and ¹³C are realized by using a traditional double-tuned approach, while the resonant frequency for ²³Na, which is only some 4 MHz away from the ¹³C frequency, is tuned based upon ¹³C channel by easy-operating capacitive “frequency switches”. In contrast to the traditional triple-tuned volume coil, the volume coil with the proposed design possesses less number of resonances, which helps improve the coil efficiency and alleviate the design and operation difficulties. This coil design strategy is advantageous and well suitable for multinuclear MR imaging and spectroscopy studies, particularly in the case where Larmor frequencies of nuclei in question are not separate enough. The prototype multinuclear coil was demonstrated in the desired unshielded design for easy construction and experiment implementation at 7 T. The design method may provide a practical and robust solution to designing multinuclear RF volume coils for in vivo MR imaging and spectroscopy at ultrahigh fields. Finite difference time domain method simulations for evaluating the design and 7-T MR experiment results acquired using the prototype coil are presented.     

Current-density imaging using ultra-low-field MRI with adiabatic pulses

Magnetic resonance imaging (MRI) allows measurement of electric current density in an object. The measurement is based on observing how the magnetic field of the current density affects the associated spins. However, as high-field MRI is sensitive to static magnetic field variations of only the field component along the main field direction, object rotations are typically needed to image three-dimensional current densities. Ultra-low-field (ULF) MRI, on the other hand, with B₀ on the order of 10–100 μT, allows novel MRI sequences. We present a rotation-free method for imaging static magnetic fields and current densities using ULF MRI. The method utilizes prepolarization pulses with adiabatic switch-off ramps. The technique is designed to reveal complete field and current-density information without the need to rotate the object. The method may find applications, e.g., in conductivity imaging. We present simulation results showing the feasibility of the sequence.     

Isolating quantum coherences in structural imaging using intermolecular double-quantum coherence MRI

Intermolecular multiple-quantum coherence (iMQC) MR imaging provides a fundamentally different contrast mechanism. It allows probing tissue microstructure by tuning the direction and strength of the correlation gradient. However, iMQC images of a specific quantum-coherence can easily be contaminated by leakage signals from undesired quantum coherences (zero, single, and triple quantum coherence in this work). Using a modified double-quantum CRAZED imaging sequence, we show that signals originating from various coherence orders (M=0, 1, 2, 3) can be predicted in k-space and effectively isolated by means of a four-step phase cycling scheme and judicious choice of flip angles. Finally, preliminary data suggest the method to be able to provide information on trabecular bone architecture such as regional mean trabecular plate separation.     

Calculation of the optimal imaging parameters for frequency modulation atomic force microscopy

True atomic resolution of conductors and insulators is now routinely obtained in vacuum by frequency modulation atomic force microscopy. So far, the imaging parameters (i.e., eigenfrequency, stiffness and oscillation amplitude of the cantilever, frequency shift) which result in optimal spatial resolution for a given cantilever and sample have been found empirically. Here, we calculate the optimal set of parameters from first principles as a function of the tip–sample system. The result shows that the either the acquisition rate or the signal-to-noise ratio could be increased by up to two orders of magnitude by using stiffer cantilevers and smaller amplitudes than are in use today.     

Guidelines for the achievement of true atomic resolution with noncontact atomic force microscopy

We investigated the conditions to achieve true atomic resolution with an atomic force microscope under noncontact mode (NC-AFM). At first, we derived the equation of vertical resolution as a function of the signal-to-noise ratio and the decay length of frequency shift by assuming an exponential tip-to-sample distance dependence of frequency shift. Next, by assuming a single atom probe, we derived the equation of lateral resolution as a function of the vertical resolution and the tip-to-sample distance, from which we clarified the guidelines to achieve true atomic resolution with NC-AFM. At last, we made clear the attainable decay length of frequency shift both for the van der Waals potential and the electrostatic (Coulomb) potential.     

A novel editing technique for F MRI: Molecule-specific imaging

A novel technique is proposed to facilitate the selective imaging of specific molecules from a mixture. The application of the technique presented here demonstrates the ability to selectively produce ¹⁹F MR images of either trifluoroacetic acid or the perfluorocarbon emulsion Oxypherol-ET (perfluorotributylamine), when both molecules are present simultaneously. Selective detection is based on the presence of homonuclear J-modulation in one molecule and differential spin-spin relaxation time (T₂). Perfluorotributylamine, an A₃B₂ system, is subject to homonuclear J-modulation, which produces a null signal from the antiphase components of the triplet (A₃) when an echo time is used in a spin-echo image. At this echo time the second molecule, in this example trifluoroacetic acid, a non-coupled spin system, is selectively imaged. At longer echo times, e.g., TE = 1/J there is substantial recovery of the J-modulated signal, which may be solely observed due to T₂ decay of the trifluoroacetic acid signal. The method is demonstrated both using phantoms and in vivo.     

A new method for characterization of low grade gliomas using ultra low field magnetic resonance imaging

Low grade gliomas were studied with ultra low field magnetic resonance imaging (ULF MRI). The tumors exhibited high tissue contrast in both T₁ and T₂-weighted images as compared to normal brain tissue. Moreover they were sharply delineated towards the surrounding brain tissue. When compared with X-ray computed tomography the tumors were more readily detected and delineated by using ultra-low field magnetic imaging. A computerassisted classification procedure was used to define new regions of interest for relaxation time estimation. By using this procedure more accurate estimations of the T₁ and T₂ values were obtained.     

Study of brain anatomy with high-field MRI: recent progress

Recent developments in high-field magnetic resonance imaging technology have led to improved contrast and resolution and are opening up new possibilities for the study of human brain anatomy. In particular, techniques sensitized to magnetic susceptibility contrast provide particular advantages at high field that have allowed visualization of brain structures that have been difficult to detect with conventional technology. In this review, some of these developments and techniques will be discussed, and an attempt will be made to interpret magnetic susceptibility contrast based on recent studies.     

Recent advances with association models for practical applications

ABSTRACT

Association models like Cubic Plus Association (CPA) equation of state and other Statistical Associating Fluid Theory variants have found widespread use, especially over the recent 30 or so years, and this is not limited anymore to universities and researchers. Industry is beginning slowly to adopt such models for some applications and a few of the association models are now provided by commercial simulators. Association models account explicitly for hydrogen bonding (and other complex) phenomena, and for this reason, they are potentially more useful and more successful than traditional models like cubic equations of state and activity coefficient models. Still, for practical applications, all models are judged by their results and these depend on the availability of experimental data, the number and type of adjustable parameters and the performance of the models for phase equilibria and occasionally also for other properties. We will consider four case studies in this work which, will illustrate some of the capabilities and limitations of these association models in different applications. We will offer a ‘model developer’s’ point of view showing in several cases all stages of model development in order to illustrate what worked, what did not and how it was corrected (when possible). The ‘physics’ and ‘application’ aspects of the models will be in all cases discussed. All results will be shown with the CPA equation of state, although we expect that the overall conclusions will be the same for a wide range of association models.     

Simultaneous imaging of locus coeruleus and substantia nigra with a quantitative neuromelanin MRI approach

Quantitative MRI of neuromelanin (NM) containing structures (referred to as NM-MRI) in the brainstem, namely the locus coeruleus (LC) and substantia nigra (SN), may assist with the early detection of Parkinson’s disease (PD) and Alzheimer’s disease (AD) as well as differential diagnosis in the early disease stages. In this study, two gradient echo (GRE) sequences with magnetization transfer contrast (MTC) preparation pulses were developed to simultaneously image the LC and SN. This has been a challenge with NM-MRI techniques used in previous studies due to the relatively high specific absorption rate (SAR) induced by these techniques. In addition, a semi-automated quantitative analysis scheme was applied to estimate volumes and contrast-to-noise ratios (CNR) of the LC and SN based on segmentation of both structures. Compared to a T₁-weighted turbo spin echo (TSE) sequence typically used for simultaneous imaging of the LC and SN, the two GRE-MTC sequences exhibited improved performance in terms of higher sensitivity (in CNR) in imaging the SN and lower SAR during the scans. A multiple-measurement protocol was adopted as well so that motion degraded measurements could be removed and artifacts associated with motion could be corrected. The present approach has demonstrated advantages in image acquisition (lower SAR and higher sensitivity), image pre-processing (with motion correction) and quantitative image analysis (segmentation-based estimation of volume and CNR) when compared with existing NM-MRI approaches. This approach has potential for detection and monitoring of neurodegeneration in LC and SN in disease states including AD and PD.     

Distortion correction for a double inversion-recovery sequence with an echo-planar imaging readout

A double inversion-recovery (DIR) sequence with an echo-planar imaging (EPI) readout can be used to image selectively the grey matter of the brain, and this has previously been applied to improve the sensitivity of the statistical analysis of functional magnetic resonance imaging (fMRI) data. If a procedure were to be implemented to remove the distortions that are inherent in the EPI-based fMRI data set, then a similar technique would have to be applied to the DIR-EPI image also to ensure that it matches the geometry of the functional data. A comparison of candidate methodologies for correcting distortions in DIR-EPI images, based on the reversed-gradient method, is presented. A corrected image could be calculated from two DIR-EPI images acquired with k-space traversal in opposite directions, but that method was not able to cope with the large regions of low signal intensity corresponding to the nulled white matter. It was found that the optimal procedure to apply the reversed-gradient method to DIR-EPI images was to acquire two additional EPI images (without the two inversion pulses) with opposite-direction k-space traversal; the distortion-correction information calculated from those EPI images was then applied to the DIR-EPI data.     

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.     

3D imaging with a single-sided sensor: an open tomograph

An open tomograph to image volume regions near the surface of large objects is described. The central achievement in getting such a tomograph to work is the design of a fast two-dimensional pure phase encoding imaging method to produce a cross-sectional image in the presence of highly inhomogeneous fields. The method takes advantage of the multi-echo acquisition in a Carr-Purcell-Meiboom-Gill (CPMG)-like sequence to significantly reduce the experimental time to obtain a 2D image or to spatially resolve relaxation times across the sensitive volume in a single imaging experiment. Depending on T(2) the imaging time can be reduced by a factor of up to two orders of magnitude compared to the one needed by the single-echo imaging technique. The complete echo train decay has been also used to produce T(2) contrast in the images and to spatially resolve the T(2) distribution of an inhomogeneous object, showing that variations of structural properties like the cross-link density of rubber samples can be distinguished by this method. The sequence has been implemented on a single-sided sensor equipped with an optimized magnet geometry and a suitable gradient coil system that provides two perpendicular pulsed gradient fields. The static magnetic field defines flat planes of constant frequency parallel to the surface of the scanner that can be selected by retuning the probe frequency to achieve slice selection into the object. Combining the slice selection obtained under the presence of the static gradient of the open magnet with the two perpendicular pulsed gradient fields, 3D spatial resolution is obtained.     

Elliptical magnetic resonance spectroscopic imaging with GRAPPA for imaging brain tumors at 3 T

Magnetic Resonance Spectroscopic Imaging (MRSI) is a technique for imaging spatial variation of metabolites and has been very useful in characterizing biochemical changes associated with disease as well as response to therapy in malignant pathologies. This work presents a self-calibrated undersampling to accelerate 3D elliptical MRSI and an extrapolation-reconstruction algorithm based on the GRAPPA method. The accelerated MRSI technique was tested in three volunteers and five brain tumor patients. Acceleration allowed larger spatial coverage and consequently, less lipid contamination in spectra, compared to fully sampled acquisition within the same scantime. Metabolite concentrations measured from the accelerated acquisitions were in good agreement with measurements obtained from fully sampled MRSI scans.     

Feasibility of diffusional kurtosis tensor imaging in prostate MRI for the assessment of prostate cancer: Preliminary results

Purpose

To assess the feasibility of full diffusional kurtosis tensor imaging (DKI) in prostate MRI in clinical routine. Histopathological correlation was achieved by targeted biopsy.

Materials and Methods

Thirty-one men were prospectively included in the study. Twenty-one were referred to our hospital with increased prostate specific antigen (PSA) values (> 4 ng/ml) and suspicion of prostate cancer. The other 10 men were volunteers without any history of prostate disease. DKI applying diffusion gradients in 20 different spatial directions with four b-values (0, 300, 600, 1000 s/mm²) was performed additionally to standard functional prostate MRI. Region of interest (ROI)-based measurements were performed in all histopathologically verified lesions of every patient, as well as in the peripheral zone, and the central gland of each volunteer.

Results

DKI showed a substantially better fit to the diffusion-weighted signal than the monoexponential apparent diffusion coefficient (ADC). Altogether, 29 lesions were biopsied in 14 different patients with the following results: Gleason score 3 + 3 = 6 (n = 1), 3 + 4 = 7 (n = 7), 4 + 3 = 7 (n = 6), 4 + 4 = 8 (n = 1), and 4 + 5 = 9 (n = 2), and prostatitis (n = 12). Values of axial (K_ax) and mean kurtosis (K_mean) were significantly different in the tumor (K_ax 1.78 ± 0.39, K_mean 1.84 ± 0.43) compared with the normal peripheral zone (K_ax 1.09 ± 0.12, K_mean 1.16 ± 0.13; p < 0.001) or the central gland (K_ax 1.40 ± 0.12, K_mean 1.44 ± 0.17; p = 0.01 respectively). There was a minor correlation between axial kurtosis (r = 0.19) and the Gleason score.

Conclusion

Full DKI is feasible to utilize in a routine clinical setting. Although there is some overlap some DKI parameters can significantly distinguish prostate cancer from the central gland or the normal peripheral zone. Nevertheless, the additional value of DKI compared with conventional monoexponential ADC calculation remains questionable and requires further research.     

Use of an advanced composite material in construction of a high pressure cell for magnetic ac susceptibility measurements

The applicability of fibre-reinforced polymers for fabrication of high pressure cells was assessed using finite element analysis and experimental testing. Performance and failure modes for the key components of the cell working in tension and in compression were evaluated and the ways for optimising the designs were established. These models were used in construction of a miniature fully non-metallic diamond anvil cell for magnetic ac susceptibility measurements in a magnetic property measurement system. The cell is approximately 14 mm long, 8.5 mm in diameter and was demonstrated to reach a pressure of 5.6 GPa. AC susceptibility data collected on Dy₂O₃ demonstrate the performance of the cell in magnetic property measurements and confirm that there is no screening of the sample by the environment which typically accompanies the use of conventional metallic high pressure cells in oscillating magnetic fields.