The feasibility of using ultra-low-field magnetic resonance (ULF MR) for direct neuronal current imaging (NCI) is investigated by phantom measurements. The aim of NCI is to improve the current localization accuracy for neuronal activity of established methods like electroencephalography (EEG) or magnetoencephalography (MEG) (~1 cm). A measurement setup was developed addressing the main challenge of reaching the necessary sensitivity in order to possibly resolve the faint influence of neuronal magnetic fields on 1H nuclear spin precession. Phantom measurements close to physiology conditions are performed simulating a specific long-lasting neuronal activity evoked in the secondary somatosensory cortex showing that the signal-to-noise ratio (SNR) of the setup needs to be further increased by at least a factor of 2.

A novel technique to extract the quotient of gyromagnetic ratios in a comagnetometer system is presented. This technique aims to probe the quotient in a regime which is free from the spin-relaxation related systematic effects. It is based on the measurement of spin precession frequencies in a gaseous mixture of 129Xe and 3 He at ultralow magnetic field. The resultant quotient value appears to be close to the literature value.

A novel technique to extract the quotient of gyromagnetic ratios in a comagnetometer system is presented. This technique aims to probe the quotient in a regime which is free from the spin-relaxation related systematic effects. It is based on the measurement of spin precession frequencies in a gaseous mixture of Xe-129 and He-3 at ultralow magnetic field. The resultant quotient value appears to be close to the literature value.

A co-located 3He and 129Xe nuclear spin free precession measurement at sub-μT magnetic field was carried out in a magnetically shielded environment. The uncorrected quotient of the gyromagnetic ratios between neutral 3He and 129Xe atoms is determined to be 2.754 082 81(07), accounting for only statistical error. Our measurement shows that this ratio has a stability of 1.4×10-5/ √τ, demonstrating the ability to reach the current precision limit of the quotient in a 10000 s of averaging time τ. This precision is enough for the next-generation EDM search in neutral 129Xe atoms based on a similar comagnetometer scheme.

A co-located He-3 and Xe-129 nuclear spin free precession measurement at sub-mu T magnetic field was carried out in a magnetically shielded environment. The uncorrected quotient of the gyromagnetic ratios between neutral He-3 and Xe-129 atoms is determined to be 2.754 082 81( 07), accounting for only statistical error. Our measurement shows that this ratio has a stability of 1.4x10(-5)/root T, demonstrating the ability to reach the current precision limit of the quotient in a 10000 s of averaging time.. This precision is enough for the next-generation EDM search in neutral Xe-129 atoms based on a similar comagnetometer scheme.

Globally, the demand for improved health care delivery while managing escalating costs is a major challenge. Measuring the biomagnetic fields that emanate from the human brain already impacts the treatment of epilepsy, brain tumours and other brain disorders. This roadmap explores how superconducting technologies are poised to impact health care. Biomagnetism is the study of magnetic fields of biological origin. Biomagnetic fields are typically very weak, often in the femtotesla range, making their measurement challenging. The earliest in vivo human measurements were made with room-temperature coils. In 1963, Baule and McFee (1963 Am. Heart J. 55 95−6) reported the magnetic field produced by electric currents in the heart ('magnetocardiography'), and in 1968, Cohen (1968 Science 161 784−6) described the magnetic field generated by alpha-rhythm currents in the brain ('magnetoencephalography'). Subsequently, in 1970, Cohen et al (1970 Appl. Phys. Lett. 16 278–80) reported the recording of a magnetocardiogram using a Superconducting QUantum Interference Device (SQUID). Just two years later, in 1972, Cohen (1972 Science 175 664–6) described the use of a SQUID in magnetoencephalography. These last two papers set the scene for applications of SQUIDs in biomagnetism, the subject of this roadmap.

Precision measurement of the frequency for a damped sinusoidal signal is important for fundamental symmetry test at the low energy scale. Here we analyzed the signal blockwisely and develop a model that can predict a correct blocksize dependence of the experimental frequency sensitivity. In addition, the model shows a leveling-off of the ultimate frequency precision beyond 2 times the damping time constant.

Recent efforts in the development of ultralow field nuclear magnetic resonance (NMR) have focused on increasing prepolarizing field (B P ) strength. The strong B P , which is up to hundreds of milliteslas, is mandatory for high-quality NMR signals. However, B P needs to be completely removed within milliseconds so that spin relaxation signal measurement can take place before the sample magnetization wears off. In a previous study, where we compared three pick-up coils made of Nb, NbTi, and Pb, we found that only the pick-up coil made of Pb, which is a type-I superconductor, was unaffected by the strong magnetic field from the B P coil and produced a sharp NMR signal. The other coils made of type-II superconductors all began to suffer from a degraded NMR signal with B P above a certain threshold. Here, we show detailed measurement of magnetization loops of NbTi and Pb wires and argue that the counter pulse strategy suggested in our previous study can minimize the trapped flux and recover the spin relaxation signal. We argue that this counter pulse strategy can be applied to superconducting B P coils, so that the counter pulses can neutralize flux trapped inside the B P coil due to its strong internal field, thereby dramatically increasing the limit on the B P strength.

Oscillatory short signal bursts of cortical origin with a frequency around 600 Hz can be measured using magnetoencephalography. These so called somatosensory evoked high frequency oscillations (SE-HFO) are induced by an electrical stimulation at the wrist. Up to now only averages over several thousand stimulations yield an interpretable result. Here the spectral and temporal properties of SE-HFOs are exploited through epoch concatenation followed by temporal decorrelation to study SE-HFO single trial properties. The algorithm is a type of blind source separation and extracts an SE-HFO component, which shows a preferred phase after sorting the single trials using a wave train at 625 Hz as template. The preferred phase is not visible after sorting the raw data trials, which certainly have more noise. This indicates that the epoch concatenation temporal decorrelation is a powerful tool to study transient oscillatory signals in multichannel recordings.

Question: Human high-frequency (>400 Hz) components of somatosensory evoked potentials (hf-SEPs), which can be recorded non-invasively at the scalp, are generated by cortical population spikes, as inferred from microelectrode recordings in non-human primates. It is a critical limitation to broader neurophysiological study of hf-SEPs in that hundreds of responses have to be averaged to detect hf-SEPs reliably. Here, we establish a framework for detecting human hf-SEPs non-invasively in single trials.Methods: Spatio-temporal features were extracted from band-pass filtered (400-900 Hz) hf-SEPs by bilinear Common Spatio-Temporal Patterns (bCSTP) and then classified by a weighted Extreme Learning Machine (w-ELM). The effect of varying signal-to-noise ratio (SNR), number of trials, and degree of w-ELM re-weighting was characterized using surrogate data. For practical demonstration of the algorithm, median nerve hf-SEPs were recorded inside a shielded room in four subjects, spanning the hf-SEP signal-to-noise ratio characteristic for a larger population, utilizing a custom-built 29-channel low-noise EEG amplifier.Results: Using surrogate data, the SNR proved to be pivotal to detect hf-SEPs in single trials efficiently, with the trade-off between sensitivity and specificity of the algorithm being obtained by the w-ELM re-weighting parameter. In practice, human hf-SEPs were detected non-invasively in single trials with a sensitivity of up to 99% and a specificity of up to 97% in two subjects, even without any recourse to knowledge of stimulus timing. Matching with the results of the surrogate data analysis, these rates dropped to 62-79% sensitivity and 18-31% specificity in two subjects with lower SNR.Conclusions: Otherwise buried in background noise, human high-frequency EEG components can be extracted from low-noise recordings. Specifically, refined supervised filter optimization and classification enables the reliable detection of single-trial hf-SEPs, representing non-invasive correlates of cortical population spikes.Significance: While low-frequency EEG reflects summed postsynaptic potentials, and thereby neuronal input, we suggest that high-frequency EEG (>400 Hz) can provide non-invasive access to the unaveraged output of neuronal computation, i.e., single-trial population spike activity evoked in the responsive neuronal ensemble. (C) 2014 Elsevier Inc. All rights reserved.

BACKGROUND:Non-invasively recorded somatosensory high-frequency oscillations (sHFOs) evoked by electric nerve stimulation are markers of human cortical population spikes. Previously, their analysis was based on massive averaging of EEG responses. Advanced neurotechnology and optimized off-line analysis can enhance the signal-to-noise ratio of sHFOs, eventually enabling single-trial analysis. METHODS:The rationale for developing dedicated low-noise EEG technology for sHFOs is unfolded. Detailed recording procedures and tailored analysis principles are explained step-by-step. Source codes in Matlab and Python are provided as supplementary material online. RESULTS:Combining synergistic hardware and analysis improvements, evoked sHFOs at around 600 Hz ('σ-bursts') can be studied in single-trials. Additionally, optimized spatial filters increase the signal-to-noise ratio of components at about 1 kHz ('κ-bursts') enabling their detection in non-invasive surface EEG. CONCLUSIONS:sHFOs offer a unique possibility to record evoked human cortical population spikes non-invasively. The experimental approaches and algorithms presented here enable also non-specialized EEG laboratories to combine measurements of conventional low-frequency EEG with the analysis of concomitant cortical population spike responses.

In ultra-low field nuclear magnetic resonance (ULF-NMR) with strong prepolarization field (Bp), type-II superconducting pick-up coils may be vulnerable to flux pinning from the strong Bp. Pick-up coils made of NbTi, Nb, and Pb were evaluated in terms of acquired NMR signal quality. The type-II pick-up coils showed degraded signals above 61 mT maximum exposure, while the Pb pick-up coil exhibited no such degradation. Furthermore, a negative counter pulse following a strong Bp was shown to follow magnetic hysteresis loop to unpin the trapped flux in the type-II pick-up coil and restore the NMR signal.

Very low residual magnetic field and field gradients are essential for a number of high resolution fundamental physical experiments and for further improvement of very sensitive magnetic measurement devices. The scope ranges from spin precession experiments, e.g. with 3 He or neutrons, to biomagnetic measurements, like magnetoencephalograms, and to low field MR spectroscopy. One method of reducing environmental magnetic noise is to use a magnetically shielded room (MSR). Here, measures are demonstrated to improve residual field and field gradient inside a common MSR by a factor of more than 10 by a specific degaussing procedure, material selection of prefabricated parts and active shielding. The process is independent of the shielding factor and works also properly for heavily shielded rooms.

In ultra-low-field (ULF) NMR/MRI, a common scheme is to magnetize the sample by a polarizing field of up to hundreds of mT, after which the NMR signal, precessing in a field on the order of several mu T, is detected with superconducting quantum interference devices (SQUIDs). In our ULF-NMR system, we polarize with up to 50 mT and deploy a single-stage DC-SQUID current sensor with an integrated input coil which is connected to a wire-wound Nb gradiometer. We developed this system (white noise 0.50 fT root Hz) for assessing the feasibility of imaging neuronal currents by detecting their effect on the ULF-NMR signal. Magnetoencephalography investigations of evoked brain activity showed neuronal dipole moments below 50 nAm. With our instrumentation, we have studied two different approaches for neuronal current imaging. In the so-called DC effect, long-lived neuronal activity shifts the Larmor frequency of the surrounding protons. An alternative strategy is to exploit fast neuronal activity as a tipping pulse. This so-called AC effect requires the proton Larmor frequency to match the frequency of the neuronal activity, which ranges from near-DC to similar to kHz. We emulated neuronal activity by means of a single dipolar source in a physical phantom, consisting of a hollow sphere filled with an aqueous solution of CuSO4 and NaCl. In these phantom studies, with physiologically relevant dipole depths, we determined resolution limits for our set-up for the AC and the DC effect of similar to 10 mu Am and similar to 50 nAm, respectively. Hence, the DC effect appears to be detectable in vivo by current ULF-NMR technology. (C) 2013 Elsevier Inc. All rights reserved.

The detection of the free precession of co‐located 3He/129Xe nuclear spins (clock comparison) is used as ultra‐sensitive probe for non‐magnetic spin interactions, since the magnetic dipole interaction (Zeeman‐term) drops out in the weighted frequency difference, i.e., Δω = ωHe‐ γHe/γXe·ωXe of the respective Larmor frequencies. Recent results are reported on searches for (i) short‐range P‐ and T‐violating interactions between nucleons, and (ii) Lorentz violating signatures by monitoring the Larmor frequencies as the laboratory reference frame rotates with respect to distant stars (sidereal modulation). Finally, a new experimental initiative to search for an electric dipole moment of 129Xe (CP‐violation) is discussed, which strongly benefits from the long spin‐coherence times obtained, reaching > 100 h and > 8 h in case of 3He and 129Xe, respectively.

The spin lattice (T-1) relaxation rates of materials depend on the strength of the external magnetic field in which the relaxation occurs. This T-1 dispersion has been suggested to offer a means to discriminate between healthy and cancerous tissue by performing magnetic resonance imaging (MRI) at low magnetic fields. In prepolarized ultra-low-field (ULF) MRI, spin precession is detected in fields of the order of 10-100 mu T. To increase the signal strength, the sample is first magnetized with a relatively strong polarizing field. Typically, the polarizing field is kept constant during the polarization period. However, in ULF MRI, the polarizing field strength can be easily varied to produce a desired time course. This paper describes how a novel variation of the polarizing field strength and duration can optimize the contrast between two types of tissue having different T-1 relaxation dispersions. In addition, NMR experiments showing that the principle works in practice are presented. The described procedure may become a key component for a promising new approach of MRI at ultra-low fields.

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.

Objective: Median nerve somatosensory evoked potentials (SEP) contain a brief oscillatory wavelet burst at about 600 Hz (r-burst) superimposed on the initial cortical component (N20). While invasive single-cell recordings suggested that this burst is generated by increased neuronal spiking activity in area 3b, recent non-invasive scalp recordings could not reveal concomitant single-trial added-activity, suggesting that the SEP burst might instead be generated by phase-reset of ongoing high-frequency EEG. Here, a statistical model and exemplary data are presented reconciling these seemingly contradictory results.Methods: A statistical model defined the conditions required to detect added-activity in a set of single-trial SEP. Its predictions were tested by analyzing human single-trial scalp SEP recorded with custom-made low-noise amplifiers.Results: The noise level in previous studies did not allow to detect single-trial added-activity in the period concomitant with the trial-averaged r-burst. In contrast, optimized low-noise recordings do reveal added-activity in a set of single-trials.Conclusions: The experimental noise level is the decisive factor determining the detectability of added-activity in single-trials. A low-noise experiment provided direct evidence that the SEP r-burst is at least partly generated by added-activity matching earlier invasive single-cell recordings.Significance: Quantitative criteria are provided for the feasibility of single-trial detectability of band-limited added-activity. (C) 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.