Chemical Analysis of an Isotopically Labeled Molecule Using Two-Dimensional NMR Spectroscopy at 34 µT.

Low-field nuclear magnetic resonance (NMR) spectroscopy, conducted at or below a few millitesla, provides only limited spectral information due to its inability to resolve chemical shifts. Thus, chemical analysis based on this technique remains challenging. One potential solution to overcome this limitation is the use of isotopically labeled molecules. However, such compounds, particularly their use in two-dimensional (2D) NMR techniques, have rarely been studied. This study presents the results of both experimental and simulated correlation spectroscopy (COSY) on 1-13C-ethanol at 34.38 µT. The strong heteronuclear coupling in this molecule breaks the magnetic equivalence, causing all J-couplings, including homonuclear coupling, to split the 1H spectrum. The obtained COSY spectrum clearly shows the spectral details. Furthermore, we observed that homonuclear coupling between 1H spins generated cross-peaks only when the associated 1H spins were coupled to identical 13C spin states. Our findings demonstrate that a low-field 2D spectrum, even with a moderate spectral line width, can reveal the J-coupling networks of isotopically labeled molecules.

Detection of the 40 Hz auditory steady-state response with optically pumped magnetometers.

Magnetoencephalography (MEG) is a functional neuroimaging technique that noninvasively detects the brain magnetic field from neuronal activations. Conventional MEG measures brain signals using superconducting quantum interference devices (SQUIDs). SQUID-MEG requires a cryogenic environment involving a bulky non-magnetic Dewar flask and the consumption of liquid helium, which restricts the variability of the sensor array and the gap between the cortical sources and sensors. Recently, miniature optically pumped magnetometers (OPMs) have been developed and commercialized. OPMs do not require cryogenic cooling and can be placed within millimeters from the scalp. In the present study, we arranged six OPM sensors on the temporal area to detect auditory-related brain responses in a two-layer magnetically shielded room. We presented the auditory stimuli of 1 kHz pure-tone bursts with 200 ms duration and obtained the M50 and M100 components of auditory-evoked fields. We delivered the periodic stimuli with a 40 Hz repetition rate and observed the gamma-band power changes and inter-trial phase coherence of auditory steady-state responses at 40 Hz. We found that the OPM sensors have a performance comparable to that of conventional SQUID-MEG sensors, and our results suggest the feasibility of using OPM sensors for functional neuroimaging and brain-computer interface applications.

Dynamic nuclear polarisation of liquids at one microtesla using circularly polarised RF with application to millimetre resolution MRI.

Magnetic resonance imaging in ultra-low fields is often limited by mediocre signal-to-noise ratio hindering a higher resolution. Overhauser dynamic nuclear polarisation (O-DNP) using nitroxide radicals has been an efficient solution for enhancing the thermal nuclear polarisation. However, the concurrence of positive and negative polarisation enhancements arises in ultra-low fields resulting in a significantly reduced net enhancement, making O-DNP far less attractive. Here, we address this issue by applying circularly polarised RF. O-DNP with circularly polarised RF renders a considerably improved enhancement factor of around 150,000 at 1.2 µT. A birdcage coil was adopted into an ultra-low field MRI system to generate the circularly polarised RF field homogeneously over a large volume. We acquired an MR image of a nitroxide radical solution with an average in-plane resolution of 1 mm. De-noising through compressive sensing further improved the image quality.

Development of a bio-magnetic measurement system and sensor configuration analysis for rats.

Magnetoencephalography (MEG) based on superconducting quantum interference devices enables the measurement of very weak magnetic fields (10-1000 fT) generated from the human or animal brain. In this article, we introduce a small MEG system that we developed specifically for use with rats. Our system has the following characteristics: (1) variable distance between the pick-up coil and outer Dewar bottom (∼5 mm), (2) small pick-up coil (4 mm) for high spatial resolution, (3) good field sensitivity (45∼ 80fT/cm/Hz), (4) the sensor interval satisfies the Nyquist spatial sampling theorem, and (5) small source localization error for the region to be investigated. To reduce source localization error, it is necessary to establish an optimal sensor layout. To this end, we simulated confidence volumes at each point on a grid on the surface of a virtual rat head. In this simulation, we used locally fitted spheres as model rat heads. This enabled us to consider more realistic volume currents. We constrained the model such that the dipoles could have only four possible orientations: the x- and y-axes from the original coordinates, and two tangentially layered dipoles (local x- and y-axes) in the locally fitted spheres. We considered the confidence volumes according to the sensor layout and dipole orientation and positions. We then conducted a preliminary test with a 4-channel MEG system prior to manufacturing the multi-channel system. Using the 4-channel MEG system, we measured rat magnetocardiograms. We obtained well defined P-, QRS-, and T-waves in rats with a maximum value of 15 pT/cm. Finally, we measured auditory evoked fields and steady state auditory evoked fields with maximum values 400 fT/cm and 250 fT/cm, respectively.

Dynamic nuclear polarization in the hyperfine-field-dominant region.

Dynamic nuclear polarization (DNP) allows measuring enhanced nuclear magnetic resonance (NMR) signals. Though the efficiency of DNP has been known to increase at low fields, the usefulness of DNP has not been throughly investigated yet. Here, using a superconducting quantum interference device-based NMR system, we performed a series of DNP experiments with a nitroxide radical and measured DNP spectra at several magnetic fields down to sub-microtesla. In the DNP spectra, the large overlap of two peaks having opposite signs results in net enhancement factors, which are significantly lower than theoretical expectations and nearly invariant with respect to magnetic fields below the Earth's field. The numerical analysis based on the radical's Hamiltonian provides qualitative explanations of such features. The net enhancement factor reached 325 at maximum experimentally, but our analysis reveals that the local enhancement factor at the center of the rf coil is 575, which is unaffected by detection schemes. We conclude that DNP in the hyperfine-field-dominant region yields sufficiently enhanced NMR signals at magnetic fields above 1 µT.

T 1 relaxation measurement of ex-vivo breast cancer tissues at ultralow magnetic fields.

We investigated T 1 relaxations of ex-vivo cancer tissues at low magnetic fields in order to check the possibility of achieving a T 1 contrast higher than those obtained at high fields. The T 1 relaxations of fifteen pairs (normal and cancerous) of breast tissue samples were measured at three magnetic fields, 37, 62, and 122 µT, using our superconducting quantum interference device-based ultralow field nuclear magnetic resonance setup, optimally developed for ex-vivo tissue studies. A signal reconstruction based on Bayesian statistics for noise reduction was exploited to overcome the low signal-to-noise ratio. The ductal and lobular-type tissues did not exhibit meaningful T 1 contrast values between normal and cancerous tissues at the three different fields. On the other hand, an enhanced T 1 contrast was obtained for the mucinous cancer tissue.

Three-dimensional reconstruction of a cardiac outline by magnetocardiography.

A 3-D cardiac visualization is significantly helpful toward clinical applications of magnetocardiography (MCG), but the cardiac reconstruction requires a segmentation process using additional image modalities. This paper proposes a 3-D cardiac outline reconstruction method using only MCG measurement data without further imaging techniques. The cardiac outline was reconstructed by a combination of both spatial filtering and coherence mapping method. The strength of cardiac activities was first estimated by the array-gain constraint minimum-norm spatial filter with recursively updated gram matrix (AGMN-RUG). Then, waveforms were reconstructed at whole source grids, and the maximum source points of an atrium and ventricle were selected as a reference, respectively. Next, the coherence between each maximum source point and whole source points was compared by the coherence mapping method. A reconstructed cardiac outline was validated by comparing with an overlapped volume ratio when the reconstructed volume was identically matched with the original volume. The results obtained by the AGMN-RUG were compared to the results by other spatial filters. The accuracy of numerical simulation and phantom experiment by the AGMN-RUG was superior 10% and 8%, respectively, than the accuracy by the standardized low-resolution electromagnetic tomography. This accuracy demonstrated the efficacy of the proposed 3-D cardiac reconstruction method.

Note: optical receiver system for 152-channel magnetoencephalography.

An optical receiver system composing 13 serial data restore/synchronizer modules and a single module combiner converted optical 32-bit serial data into 32-bit synchronous parallel data for a computer to acquire 152-channel magnetoencephalography (MEG) signals. A serial data restore/synchronizer module identified 32-bit channel-voltage bits from 48-bit streaming serial data, and then consecutively reproduced 13 times of 32-bit serial data, acting in a synchronous clock. After selecting a single among 13 reproduced data in each module, a module combiner converted it into 32-bit parallel data, which were carried to 32-port digital input board in a computer. When the receiver system together with optical transmitters were applied to 152-channel superconducting quantum interference device sensors, this MEG system maintained a field noise level of 3 fT/√Hz @ 100 Hz at a sample rate of 1 kSample/s per channel.

Two-dimensional NMR spectroscopy of (13)C methanol at less than 5 µT.

Two-dimensional (2D) spectroscopy is one of the most significant applications of nuclear magnetic resonance (NMR). Here, we demonstrate that the 2D NMR can be performed even at a low magnetic field of less than 5µT, which is ten times less than the Earth's magnetic field. The pulses used in the experiment were composed of circularly polarized fields for coherent as well as wideband excitations. Since the excitation band covers the entire spectral range, the simplest two-pulse sequence delivered the full 2D spectrum. At 5µT, methanol with (13)C enriched up to 99% belongs to a strongly coupled regime, and thus its 2D spectrum exhibits complicated spectral correlations, which can be exploited as a fingerprint in chemical analysis. In addition, we show that, with compressive sensing, the acquisition of the 2D spectrum can be accelerated to take only 45% of the overall duration.

Toward a brain functional connectivity mapping modality by simultaneous imaging of coherent brainwaves.

Matching the proton-magnetic-resonance frequency to the frequency of a periodic neural oscillation (e.g., alpha or gamma band waves) by magnetic resonance imaging techniques, enables direct visualization of brain functional connectivity. Functional connectivity has been studied by analyzing the correlation between coherent neural oscillations in different areas of the brain. In electro- or magneto-encephalography, coherent source reconstruction in a source-space is very tricky due to power leaking from the correlation among the sources. For this reason, most studies have been limited to sensor-space analyses, which give doubtful results because of volume current mixing. The direct visualization of coherent brain oscillations can circumvent this problem. The feasibility of this idea was demonstrated by conducting phantom experiments with a SQUID-based, micro-Tesla NMR/MRI system. We introduce an experimental trick, an effective step-up of the measurement B-field in a pulse sequence, to decouple the magnetic resonance signal from the strong magneto-encephalographic signal at the same frequency.

Strong pulsed excitations using circularly polarized fields for ultra-low field NMR.

A pulse, which is produced by a single coil and thereby has a linear polarization, cannot coherently drive nuclear spins if the pulse is stronger than the static field B0. The inaccuracy of the pulse, which arises from the failure of the rotating wave approximation, has been an obstacle in adopting multiple pulse techniques in ultra-low field NMR where B0 is less than a few µT. Here, we show that such a limitation can be overcome by applying pulses of circular polarization using two orthogonal coils. The sinusoidal nutation of the nuclear spins was experimentally obtained, which indicates that coherent and precise controls of the nuclear spins can be achieved with circularly polarized pulses. Additional demonstration of the Carl-Purcell-Meiboom-Gill sequence verifies the feasibility of adopting multiple pulse sequences to ultra-low field NMR studies.

Optical transmission modules for multi-channel superconducting quantum interference device readouts.

We developed an optical transmission module consisting of 16-channel analog-to-digital converter (ADC), digital-noise filter, and one-line serial transmitter, which transferred Superconducting Quantum Interference Device (SQUID) readout data to a computer by a single optical cable. A 16-channel ADC sent out SQUID readouts data with 32-bit serial data of 8-bit channel and 24-bit voltage data at a sample rate of 1.5 kSample/s. A digital-noise filter suppressed digital noises generated by digital clocks to obtain SQUID modulation as large as possible. One-line serial transmitter reformed 32-bit serial data to the modulated data that contained data and clock, and sent them through a single optical cable. When the optical transmission modules were applied to 152-channel SQUID magnetoencephalography system, this system maintained a field noise level of 3 fT/√Hz @ 100 Hz.

Non-invasive magnetocardiography for the early diagnosis of coronary artery disease in patients presenting with acute chest pain.

BACKGROUND: Accurate identification of patients with acute coronary syndrome (ACS) is often difficult especially when an electrocardiogram (ECG) does not show typical elevation of ST segment. The aim of the present study was therefore to evaluate the efficacy of magnetocardiography (MCG) for diagnosis of ACS in patients with acute chest pain presenting without ST segment elevation. METHODS AND RESULTS: In the present retrospective study 364 patients with the suspected ACS without ST segment elevation were selected. Significant coronary artery disease (CAD) was defined as a stenosis > or =50% in at least one of 16 segments of the 3 major coronary arteries and their branches. The MCG recordings were obtained at resting state using a 64-channel MCG system in a magnetically shielded room. The patients were classified on the basis of the probability distribution. The presence of significant CAD was identified with a sensitivity of 84.0% and a specificity of 85.0%, compared to 44.7% and 89.8% on ECG. In the subgroup of patients without specific findings on ECG or biomarker test, MCG had a sensitivity of 73.5% and a specificity of 82.3%. CONCLUSIONS: MCG was acceptably sensitive and specific in identifying patients with ACS even in the absence of specific findings on ECG and positive biomarker tests. Thus, MCG seems beneficial for the early triage of patients with acute chest pain.

Can magnetocardiography detect patients with non-ST-segment elevation myocardial infarction?

BACKGROUND AND AIM: Magnetocardiography (MCG) has been proposed as a noninvasive diagnostic tool to risk-stratify patients with myocardial infarction (MI) and ischemia. The purpose of this study is to find the MCG parameters that are sensitive enough to detect the non-ST-segment elevation myocardial infarction (NSTEMI) patients. METHODS: MCG data were recorded and analyzed from 165 young controls (mean age = 27.2 +/- 9.0 years), 57 age-matched controls (mean age = 55.9 +/- 10.5 years) and 83 NSTEMI patients (mean age = 59.7 +/- 11.1 years). The MCG recordings were obtained using a 64-channel MCG system in a magnetically shielded room. Statistical analyses were performed for 24 parameters derived from QRS-, R-, T-wave, and ST-T period. Binary boundaries to detect NSTEMI patients out of control subjects were found using the receiver operating characteristic (ROC) curve for each parameter. RESULTS: Fifteen parameters showed a significant difference (P < 0.05 and P < 0.01) between NSTEMI and both of the control groups. For detection of NSTEMI, the angle of the maximum current and the filed map angle on T-wave peak showed the highest diagnostic performance from 75% to 92% including accuracy, sensitivity, specificity, positive predictive value, and negative predictive value (area under ROC curve = 0.87 approximately 0.93). CONCLUSIONS: Our study showed that MCG has potential clinical application for detection of NSTEMI and should be further investigated.