Ultra-low field NMR measurements of liquids and gases with short relaxation times

Interest in nuclear magnetic resonance measurements at ultra-low magnetic fields (ULF, approximately microT fields) has been motivated by various benefits and novel applications including narrow NMR peak-width, negligible susceptibility artifacts, imaging of samples inside metal containers, and possibility of directly imaging neuronal currents. ULF NMR/MRI is also compatible with simultaneous measurements of biomagnetic signals. However the most widely used technique in ULF NMR-prepolarization at high field and measurement at lower field-results in large transient signals which distort the free induction decay signal. This is especially severe for the measurement of signals from samples and materials with short T1 time. We have devised an approach that largely cancels the transient signals. The technique was successfully used to measure NMR signals from liquids and gases with T1 in the range 1-4 ms.     

Are brain currents detectable by means of low-field NMR? A phantom study

A number of different methods have been developed in order to detect the spreading of neuronal currents by means of noninvasive imaging techniques. However, all of these are subjected to limitations in the temporal or spatial resolution. A new approach of neuronal current detection is based on the use of low-field nuclear magnetic resonance (LF-NMR) that records brain activity directly. In the following, we describe a phantom study in order to assess the feasibility of neuronal current detection using LF-NMR. In addition to that, necessary preliminary subject studies examining somatosensory evoked neuronal currents are presented. During the phantom study, the influences of two different neuronal time signals on ¹H-NMR signals were observed. The measurements were carried out by using a head phantom with an integrated current dipole to simulate neuronal activity. Two LF-NMR methods based on a DC and an AC (resonant) mechanism were utilized to study the feasibility of detecting both types of magnetic brain signals. Measurements were made inside an extremely magnetically shielded room by using a superconducting quantum interference device magnetometer system. The measurement principles were validated applying currents of higher intensity than those typical of the neuronal currents. Through stepwise reduction of the amplitude of the current dipole strength, the resolution limits of the two measuring procedures were found. The results indicate that it is necessary to improve the signal-to-noise ratio of the measurement system by at least a factor of 38 in order to detect typical human neuronal activity directly by means of LF-NMR. In addition to that, ways of achieving this factor are discussed.     

High-resolution NMR spectra in inhomogeneous and unstable fields via the three-pulse method

In modern solution nuclear magnetic resonance (NMR), the spectral resolution is mainly dependent on the spatial homogeneity and temporal stability of the magnetic field. The spectral linewidths are usually proportional to the overall field homogeneity and the stability experienced by the sample. Many high-resolution NMR methods have been developed, but few are applicable in inhomogeneous and unstable fields. In this paper, a high-resolution three-pulse method based on intermolecular zero-quantum coherences (iZQCs) is proposed. Since this method is insensitive to field inhomogeneity and instability, spectral information such as the chemical shift can be retained in the resulting spectra. In comparison with the CPMG-HOMOGENIZED method, the new method provides almost pure solvent–solute iZQC signals.     

Direct detection of neuronal activity with MRI: Fantasy, possibility, or reality?

Hemodynamic-based functional magnetic resonance imaging (fMRI) techniques have proven to be extremely robust and sensitive methods for noninvasive detection and mapping of human brain activation. Nevertheless, limitations in temporal and spatial resolution as well as interpretation remain because hemodynamic changes accompanying brain activation are relatively sluggish and variable and therefore imprecise measures of neuronal activity. A hope among brain imagers would be to possess a technique that would allow direct mapping of brain activity with spatial resolution on the order of a cortical column and temporal resolution on the order of an action potential or at least a postsynaptic potential. Recent efforts in understanding the direct effects of neuronal activity on MRI signal have provided some degree of hope for those who want a more precise noninvasive brain activation mapping technique than fMRI as we know it now. While the manner in which electrical currents influence MRI signal is well understood, the manner in which neuronal firing spatially and temporally integrates on the spatial scale of an MRI voxel to produce a magnetic field shift and subsequently an NMR phase and/or magnitude change is not well understood. It is also not established that this field shift would be large or long enough in duration to be detected. The objective of this paper is to provide a perspective of the work that has been performed towards the direction of achieving direct neuronal current imaging with MRI. A specific goal is to further clarify what is understood about the theoretical and practical possibilities of neuronal current imaging. Specifically discussed are modeling efforts, phantom studies, in vitro studies, and human studies.     

High-field NMR using resistive and hybrid magnets

Resistive and resistive-superconducting hybrid magnets can generate dc magnetic fields much higher than conventional superconducting NMR magnets but the field spatial homogeneity and temporal stability are usually not sufficient for high-resolution NMR experiments. Hardware and technique development addressing these issues are presented for high-resolution NMR at magnetic fields up to 40T. Passive ferromagnetic shimming and magic-angle spinning are used effectively to reduce the broadening from inhomogeneous magnetic field. A phase correction technique based on simultaneous heteronuclear detection is developed to compensate magnetic field fluctuations to achieve high spectral resolution.     

基于高温超导SQUID的低场核磁共振研究

采用一高温超导射频量子干涉器(HTS rf-SQUID)作为信号探测器件,研究了多种液体样品的低场核磁共振信号。通过改变测量场(简称Bm)的大小,可以探测到质子拉莫频率(简称fL)从2Hz到40kHz的信号。由于在低场核磁共振中,Bm的均匀性能很好的得到满足,因而可能得到很窄的谱线宽度。实验发现,对自来水样品,在7μT以下均可接近谱线的自然宽度。同时,在低场核磁共振条件下,样品的化学位移很小以至于消失,因而可以研究"纯"的异核间的自旋耦合谱。作者研究了低场下2,2,2-三氟乙醇的低场自旋耦合谱。另外,作者首次采用SQUID在户外探测到地球磁场下的核磁共振现象,并研究了地球磁场的涨落对测量的影响,为SQUID的低场核磁共振研究开辟了一个新的研究方向。     

Avoiding eddy-current problems in ultra-low-field MRI with self-shielded polarizing coils

In ultra-low-field magnetic resonance imaging (ULF MRI), superconductive sensors are used to detect MRI signals typically in fields on the order of 10-100 μT. Despite the highly sensitive detectors, it is necessary to prepolarize the sample in a stronger magnetic field on the order of 10-100 mT, which has to be switched off rapidly in a few milliseconds before signal acquisition. In addition, external magnetic interference is commonly reduced by situating the ULF-MRI system inside a magnetically shielded room (MSR). With typical dipolar polarizing coil designs, the stray field induces strong eddy currents in the conductive layers of the MSR. These eddy currents cause significant secondary magnetic fields that may distort the spin dynamics of the sample, exceed the dynamic range of the sensors, and prevent simultaneous magnetoencephalography and MRI acquisitions. In this paper, we describe a method to design self-shielded polarizing coils for ULF MRI. The experimental results show that with a simple self-shielded polarizing coil, the magnetic fields caused by the eddy currents are largely reduced. With the presented shielding technique, ULF-MRI devices can utilize stronger and spatially broader polarizing fields than achievable with unshielded polarizing coils.     

Failure to direct detect magnetic field dephasing corresponding to ERP generation

Functional magnetic resonance imaging (fMRI) has become the method of choice for mapping brain activity in human subjects and detects changes in regional blood oxygenation and volume associated with local changes in neuronal activity. While imaging based on blood oxygenation level dependent (BOLD) contrast has good spatial resolution and sensitivity, the hemodynamic signal develops relatively slowly and is only indirectly related to neuronal activity. An alternative approach termed magnetic source magnetic resonance imaging (msMRI) is based on the premise that neural activity may be mapped by magnetic resonance imaging (MRI) with greater temporal resolution by detecting the local magnetic field perturbations associated with local neuronal electric currents. We used a hybrid ms/BOLD MRI method to investigate whether msMRI could detect signal changes that occur simultaneously at the time of the production of well-defined event-related potentials, the P300 and N170, in regions that previously have been identified as generators of these electrical signals. Robust BOLD activations occurred after some seconds, but we were unable to detect any significant changes in the T2*-weighted signal in these locations that correlated temporally with the timings of the evoked response potentials (ERPs).     

Simulating the effects of time-varying magnetic fields with a realistic simulated scanner

Transient magnetic fields induce changes in magnetic resonance (MR) images ranging from small, visually undetectable effects (caused, for instance, by neuronal currents) to more significant ones, such as those created by the gradient fields and eddy currents. Accurately simulating these effects may assist in correcting or optimising MR imaging for many applications (e.g., diffusion imaging, current density imaging, use of magnetic contrast agents, neuronal current imaging, etc.). Here we have extended an existing MR simulator (POSSUM) with a model for changing magnetic fields at a very high-resolution time-scale. This simulator captures a realistic range of scanner and physiological artifacts by modeling the scanner environment, pulse sequence details and subject properties (e.g., brain geometry and air-tissue boundaries).     

Single point measurements of magnetic field gradient waveform

Pulsed magnetic field gradients are fundamental to spatial encoding and diffusion weighting in magnetic resonance. The ideal pulsed magnetic field gradient should have negligible rise and fall times, however, there are physical limits to how fast the magnetic field gradient may change with time. Finite gradient switching times, and transient, secondary, induced magnetic field gradients (eddy currents) alter the ideal gradient waveform and may introduce a variety of undesirable image artifacts. We have developed a new method to measure the complete magnetic field gradient waveform. The measurement employs a heavily doped test sample with short MR relaxation times (T(1), T(2), and T(2)(*)<100 micros) and a series of closely spaced broadband radiofrequency excitations, combined with single point data acquisition. This technique, a measure of evolving signal phase, directly determines the magnetic field gradient waveform experienced by the test sample. The measurement is sensitive to low level transient magnetic fields produced by eddy currents and other short and long time constant non-ideal gradient waveform behaviors. Data analysis is particularly facile permitting a very ready experimental check of gradient performance.     

Investigation of MR signal modulation due to magnetic fields from neuronal currents in the adult human optic nerve and visual cortex

Neuronal currents produce weak transient magnetic fields, and the hypothesis being investigated here is that the components of these parallel to the B0 field can potentially modulate the MR signal, thus providing a means of direct detection of nerve impulses. A theory for the phase and amplitude changes of the MR signal over time due to an external magnetic field has been developed to predict this modulation. Experimentally, a fast gradient-echo EPI sequence (TR = 158 ms, TE = 32.4 ms) was employed in an attempt to directly detect these neuronal currents in the adult human optic nerve and visual cortex using a 280-mm quadrature head coil at 1.5 T. A symmetrical intravoxel field distribution, which can be plausibly hypothesized for the axonal fields in the optic nerve and visual cortex, would result in phase cancellation within a voxel, and hence, only amplitude changes would be expected. On the other hand, an asymmetrical intravoxel field distribution would produce both phase and amplitude changes. The in vivo magnitude image data sets show a significant nerve firing detection rate of 56%, with zero detection using the phase image data sets. The percentage magnitude signal changes relative to the fully relaxed equilibrium signal fall within a predicted RMS field range of 1.2-2.1 nT in the optic nerve and 0.4-0.6 nT in the visual cortex, according to the hypothesis that the axonal fields create a symmetrical Lorentzian field distribution within the voxel.     

Calculation of electric fields induced by body and head motion in high-field MRI

In modern magnetic resonance imaging (MRI), patients are exposed to strong, nonuniform static magnetic fields outside the central imaging region, in which the movement of the body may be able to induce electric currents in tissues which could be possibly harmful. This paper presents theoretical investigations into the spatial distribution of induced electric fields and currents in the patient when moving into the MRI scanner and also for head motion at various positions in the magnet. The numerical calculations are based on an efficient, quasi-static, finite-difference scheme and an anatomically realistic, full-body, male model. 3D field profiles from an actively shielded 4T magnet system are used and the body model projected through the field profile with a range of velocities. The simulation shows that it possible to induce electric fields/currents near the level of physiological significance under some circumstances and provides insight into the spatial characteristics of the induced fields. The results are extrapolated to very high field strengths and tabulated data shows the expected induced currents and fields with both movement velocity and field strength.     

Easy-axis kagome antiferromagnet: local-probe study of Nd3Ga5SiO14

We report a local-probe investigation of the magnetically anisotropic kagome compound Nd3Ga5SiO14. Our zero-field muon spin relaxation (muSR) results provide direct evidence of a fluctuating collective paramagnetic state down to 60 mK, supported by a wipeout of the Ga nuclear magnetic resonance (NMR) signal below 25 K. At 60 mK a dynamics crossover to a much more static state is observed by muSR in magnetic fields above 0.5 T. Accordingly, the NMR signal is recovered at low T above a threshold field, revealing a rapid temperature and field variation of the magnetic fluctuations.     

A new strategy for fast radiofrequency CW EPR imaging: direct detection with rapid scan and rotating gradients

Rapid field scan on the order of T/s using high frequency sinusoidal or triangular sweep fields superimposed on the main Zeeman field, was used for direct detection of signals without low-frequency field modulation. Simultaneous application of space-encoding rotating field gradients have been employed to perform fast CW EPR imaging using direct detection that could, in principle, approach the speed of pulsed FT EPR imaging. The method takes advantage of the well-known rapid-scan strategy in CW NMR and EPR that allows arbitrarily fast field sweep and the simultaneous application of spinning gradients that allows fast spatial encoding. This leads to fast functional EPR imaging and, depending on the spin concentration, spectrometer sensitivity and detection band width, can provide improved temporal resolution that is important to interrogate dynamics of spin perfusion, pharmacokinetics, spectral spatial imaging, dynamic oxymetry, etc.     

A Superconducting Quantum Interference Device Measurement System for Ultra Low-Field Nuclear Magnetic Resonance

We describe a superconducting quantum interference device (SQUID)-based nuclear magnetic resonance (NMR) spectrometer operating at ultralow magnetic fields far below the Earth’s field. The spectrometer consists of a helium-cooled magnetic sensor system and two Helmholtz coils, one for pre-polarizing the sample by fields of up to 5 mT, and one for the detection in fields of the nanotesla and microtesla range. The spectrometer represents the current state of the art in ultralow-field NMR and enables the observation of phenomena that are difficult or impossible to achieve by a conventional NMR setting. In particular, one can obtain broad band spectra covering different nuclei, such as ¹H and ³¹P, with a frequency resolution in the millihertz range, observe the variation of their heteronuclear coupling with the detection field strength, and investigate relaxation processes that reflect molecular dynamics in the millisecond range.     

Initial attempts at directly detecting alpha wave activity in the brain using MRI

The “direct detection” of neuronal activity by MRI could offer improved spatial and temporal resolution compared to the blood oxygenation level-dependent (BOLD) effect. Here we describe initial attempts to use MRI to detect directly the neuronal currents resulting from spontaneous alpha wave activity, which have previously been shown to generate the largest extracranial magnetic fields. Experiments were successfully carried out on four subjects at 3 T. A single slice was imaged at a rate of 25 images per second under two conditions. The first (in darkness with eyes-closed) was chosen to promote alpha wave activity, while the second (eyes-open viewing a visual stimulus) was chosen to suppress it. The fluctuations of the phase and magnitude of the resulting MR image data were frequency analysed, and tested for the signature of both alpha wave activity and neuronal activity evoked by the visual stimulus.

Regions were found that consistently showed elevated power in fluctuations of the phase of the MR signal, in the frequency range of alpha waves, during the eyes-closed condition. It was conservatively assumed that if oscillations occurred at the same frequency in the magnitude signal from the same region or at the same frequency in the phase or magnitude signal from other regions overlying large vessels or cerebrospinal fluid (CSF), then the phase changes were not due to neuronal activity related to alpha waves. Using these criteria the data obtained were consistent with direct detection of alpha wave activity in three of the four volunteers. No significant MR signal fluctuations due to evoked activity were identified.     

Magnetic resonance imaging at frequencies below 1 kHz

Within the magnetic resonance imaging (MRI) community the trend is going to higher and higher magnetic fields, ranging from 1.5 T to 7 T, corresponding to Larmor frequencies of 63.8–298 MHz. Since for high-field MRI the magnetization increases with the applied magnetic field, the signal-to-noise-ratio increases as well, thus enabling higher image resolutions. On the other hand, MRI is possible also at ultra-low magnetic fields, as was shown by different groups. The goal of our development was to reach a Larmor frequency range of the low-field MRI system corresponding to the frequency range of human brain activities ranging from near zero-frequency (near-DC) to over 1 kHz. Here, first 2D MRI images of phantoms taken at Larmor frequencies of 100 Hz and 731 Hz will be shown and discussed. These frequencies are examples of brain activity triggered by electrostimulation of the median nerve. The method will allow the magnetic fields of the brain currents to influence the magnetic resonance image, and thus lead to a direct functional imaging modality of neuronal currents.     

不均匀场下空间编码超快速高分辨NMR研究进展

二维核磁共振(2D NMR)的提出和发展,为NMR技术的研究和应用提供了广阔的空间. 然而当样品或磁场本身不均匀时,高分辨的2D NMR谱难以获得. 此外,常规2D NMR实验通常需要长的采样时间. 空间编码超快速采样方法利用空间编码技术,只需单次扫描即可获得2D甚至多维NMR谱,极大地缩短了采样时间. 目前相位补偿、相干转移和分子间多量子相干等技术与空间编码技术相结合,已成功实现不均匀场下超快速获得高分辨NMR谱. 该文对不均匀场下空间编码超快速NMR方法进行了介绍,对其未来发展进行了展望.     

NMR signal averaging in 62T pulsed fields

Nuclear Magnetic Resonance (NMR) experiments in pulsed high magnetic fields up to 62T at the Dresden High Magnetic Field Laboratory (Hochfeld-Magnetlabor Dresden) are reported. The time dependence of the magnetic field is investigated by observing various free induction decays (FIDs) in the vicinity of the maximum of the field pulse. By analyzing each FID's phase and its evolution with time the magnetic field's time dependence can be determined with high precision. Assuming a quadratic or cubic dependence on time near the field maximum its confidence is found to be better than ± 0.03ppm at low fields and ± 0.8ppm near 62T. In turn, the thus obtained time dependence of the field can be used to demodulate and phase-correct all FIDs so that they appear phase-locked to each other. As a consequence signal averaging is possible. The increase in signal-to-noise ratio is found to be close to that expected theoretically. This shows that the intrinsic time dependence of the pulsed fields can be removed so that the NMR signals appear to be taken at rather stable static field. This opens up the possibility of performing precise shift measurements and signal averaging also of unknown, weak signals if a reference signal is measured during the same field pulse with a double-resonance probe.     

NMR imaging of white button mushroom (Agaricus bisporis) at various magnetic fields

Nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) have been applied to visualize physiological phenomena in plants and agricultural crops. Imaging sequences that result in contrast of a combination of parameters (e.g., proton density, ) cannot be used for a correct and unique interpretation of the results. In this study multiecho imaging together with monoexponential T₂ decay fitting was applied to determine reliable proton density and T₂ distributions over a mushroom. This was done at three magnetic field strengths (9.4, 4.7, and 0.47 T) because susceptibility inhomogeneities were suspected to influence the T₂ relaxation times negatively, and because the inflences of susceptibility inhomogeneities increase with a rise in magnetic field strength. Electron microscopy was used to understand the different T₂'s for the various tissue types in mushrooms. Large influences of the tissue ultrastructure on the observed T₂ relaxation times were found and explained. Based on the results, it is concluded that imaging mushrooms at low fields (around or below 0.47T) and short echo times has strong advantages over its high-field counterpart, especially with respect to quantitative imaging of the water balance of mushrooms. These conclusions indicate general validity whenever NMR imaging contrast is influenced by susceptibility inhomogeneities.