While magnetomyography (MMG) using optically pumped magnetometers (OPMs) is a promising method for non-invasive investigation of the neuromuscular system, it has almost exclusively been performed in magnetically shielded rooms (MSRs) to date. MSRs provide extraordinary conditions for biomagnetic measurements but limit the widespread adoption of measurement methods due to high costs and extensive infrastructure. In this work, we address this issue by exploring the feasibility of mobile OPM-MMG in a setup of commercially available components. From field mapping and simulations, we find that the employed zero-field OPM can operate within a large region of the mobile shield, beyond which residual magnetic fields and perturbations become increasingly intolerable. Moreover, with digital filtering and moderate averaging a signal quality comparable to that in a heavily shielded MSR is attained. These findings facilitate practical and cost-effective implementations of OPM-MMG systems in clinical practice and research.

ABSTRACTObjectiveMagnetomyography (MMG) is currently a rather unexplored neurophysiological modality and it is not known to which extent the number of motor units have an influence on the amplitude and the direction of the MMG-signal.MethodsA simultaneous invasive electromyography (iEMG), surface EMG (sEMG) and MMG using optically pumped magnetometer (OPM-MMG) of the right abductor digiti minimi muscle (ADM) of two healthy participants was recorded during a stepwise increasing electrical stimulation of the ADM innervating ulnar nerve. Then, the number of electrically evoked motor units was estimated (MUNE), the magnetic field vectors were reconstructed and aligned to the muscular anatomy. In addition, a finite element simulation of the ADM muscle was performed and compared to the experimental data.ResultsThe more motor units were activated by increasing electrical stimulation, the stronger the MMG signal became, which was the same for iEMG&sEMG (r>0.96). The finite element simulation showed the same relation between the magnetic and electric signal. Further, based on the simulation the number of activated muscular fibers and neuromuscular units could be estimated the ratio of signal to fibers determined.In addition, the precise vector direction of the magnetomyography (MMG) signal can reliably be recorded following the electric stimulation of the ulnar nerve and followed the muscle fiber direction.ConclusionThe MMG signal can be used to determine the amount of activated motor units, but also analysis of the magnetic field vector corresponds to the muscle fiber direction, offering a functional as well as structural characterization of muscles. The modelling and simulation is especially helpful to understand the magnetic muscular signal in detail.SignificanceNext to establishing MUNE in MMG, our results provide the first quantitative comparison between MMG vs. iEMG&sEMG and highlight the possibilities of the vector component analysis in MMG.Highlights- Comparative study of MMG, iEMG&sEMG using electrically induced activation of motor units.- MUNE in MMG is possible and is potentially superior to surface EMG.- The vector components of the MMG-signal correspond to the muscle fiber direction of the muscle.- Finite element simulation of the muscular magnetic and electric signal

We present a fast and robust optically pumped magnetometer that is based on a feedback-controlled spin ensemble of cesium atoms in spin-polarized vapor. The table-top system is intended for operation in unshielded environment, and its design allows conversion into a handheld sensor head. Under strongly disturbed environmental conditions in the laboratory, the sensor exhibits a speed of more than 56 kHz, while having a slew rate of 39 mT/s and a full dynamic range of 10 - 120 mu T. Under these conditions a sensitivity of 33 pT/root Hz is reached. By reducing the speed to 3.6 kHz the sensitivity can be improved to 6 pT/root Hz, which is close to the shot noise limit. We describe the sensor design and its optimization and demonstrate the performance of the sensor under conditions appropriate for magnetic susceptometry measurements.

Abstract The electrophysiological activities in the human body generate electric and magnetic fields that can be measured noninvasively by electrodes on the skin, or even, not requiring any contact, by magnetometers. This includes the measurement of electrical activity of brain, heart, muscles and nerves that can be measured in vivo and allows to analyze functional processes with high temporal resolution. To measure these extremely small magnetic biosignals, traditionally highly sensitive superconducting quantum-interference devices have been used, together with advanced magnetic shields. Recently, they have been complemented in usability by a new class of sensors, optically pumped magnetometers (OPMs). These quantum sensors offer a high sensitivity without requiring cryogenic temperatures, allowing the design of small and flexible sensors for clinical applications. In this letter, we describe the advantages of these upcoming OPMs in two exemplary applications that were recently carried out at Physikalisch-Technische Bundesanstalt (PTB): (1) magnetocardiography (MCG) recorded during exercise and (2) auditory-evoked fields registered by magnetoencephalography.

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.

In the endeavor to perform in vivo magnetic resonance imaging in very low fields, we developed a dedicated SQUID based NMR/MRI measurement system. The low noise performance of < 30 fT/\(\surd\)Hz above 1 Hz enables the measurement of nuclear magnetic precession at magnetic fields well below 50 μT down to 100 nT. The system is operated inside a heavily magnetically shielding - the Berlin Magnetically Shielded Room BMSR-2.

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 (1)H-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.

In this study, we revisited nuclear magnetic relaxation of (1)H in water at very low Larmor frequencies that has been studied intensively in earlier years. We make use of the recently developed superconducting quantum interference device based ultra-low field NMR technique, which enables much easier access to the longitudinal spin-lattice relaxation time T(1) and the transversal spin-spin relaxation time T(2) below several kHz than traditional field cycling methods. Our data reproduce and complement the earlier results, in that they corroborate the finding of an exchange process with a correlation time of about 0.34 ms at room temperature which can be attributed to the migration of hydronium and hydroxyl ions in neutral water via hydrogen bridges. The corresponding relaxation process is driven by the interaction of the protons with (17)O and contributes to the T(1) and the T(2) relaxation rate by about 0.12 s(-1). In addition, we found evidence of a very slow exchange process at about 100 Hz that has hitherto not been reported.

Magnetoencephalography measurements of somatosensory evoked brain activity taken inside an extremely magnetically shielded room are reported. The massive low frequency shielding in combination with a high sampling rate enabled the simultaneous observation of AC and near-DC effects. Neuronal activation was achieved by repetitive electrostimulation of the right median nerve above motor threshold using repetition rates from 3 Hz to 12 Hz. Stimulation sequences lasted for 10 s and were interspersed with periods of rest of equal length. The recorded magnetic fields, inferred for the N20m and a sustained near-DC component, revealed mainly dipolar patterns with mutually rotated orientations with angles of rotation of 30° and 75°. At the start of the stimulation we observed a fast rise within 100 ms in the evoked magnetic near-DC fields for which a maximum equivalent current dipole strength of 65 nAm was obtained. The sustained fields decayed by a factor of ∼4 to a lower DC-level B(γ) with a time constant τ of order of seconds. For 12 Hz repetition rate B(γ) was decreased. We suggest that the sustained neuronal activity evoked by repetitive electrostimulation could provide a suitable scheme to realize the direct detection of DC effects of neuronal currents via low field magnetic resonance.

We describe a nuclear magnetic resonance (NMR) spectrometer operating at 20 μT with a frequency resolution of 2 mHz to determine the intrinsic linewidth of the proton resonance in the human brain to be about 3 Hz. Using the same system we measured a biomagnetic field of 0.5 to 1 pT amplitude, which was generated by sustained brain activity evoked during repetitive median nerve stimulation. From these data, the effect of neuronal currents on the proton NMR signal was estimated. We conclude that neuronal currents may cause a measurable shift of the proton NMR line of brain tissue in low-fields.

The noninvasive detection of neuronal currents in active brain networks [or direct neuronal imaging (DNI)] by means of nuclear magnetic resonance (NMR) remains a scientific challenge. Many different attempts using NMR scanners with magnetic fields >1 T (high-field NMR) have been made in the past years to detect phase shifts or magnitude changes in the NMR signals. However, the many physiological (i.e., the contemporarily BOLD effect, the weakness of the neuronal-induced magnetic field, etc.) and technical limitations (e.g., the spatial resolution) in observing the weak signals have led to some contradicting results. In contrast, only a few attempts have been made using low-field NMR techniques. As such, this paper was aimed at reviewing two recent developments in this front. The detection schemes discussed in this manuscript, the resonant mechanism (RM) and the DC method, are specific to NMR instrumentations with main fields below the earth magnetic field (50 microT), while some even below a few microteslas (ULF-NMR). However, the experimental validation for both techniques, with differentiating sensitivity to the various neuronal activities at specific temporal and spatial resolutions, is still in progress and requires carefully designed magnetic field sensor technology. Additional care should be taken to ensure a stringent magnetic shield from the ambient magnetic field fluctuations. In this review, we discuss the characteristics and prospect of these two methods in detecting neuronal currents, along with the technical requirements on the instrumentation.

A SQUID magnetometer system was developed for measuring sustained brain activity by magnetoencephalogmphy (DC-MEG) and to record the free precession decay of protons (FPD) of the human brain at very low fields. The SQUID system has a white noise level of about 4 fT/root Hz. To generate the MR signal, two magnetic fields are used: a static polarisation field of a few mT and a static detection field of a few microtesla. To test the spectral resolution of the system, we measured the FPD of protons in distilled water having a spectral line width of about 156 mHz with an instrumental resolution of 2 mHz. The proton resonance line width of the human brain was found to be about 3.0 Hz. Using the same SQUID system we recorded a DC-MEG signal with an amplitude of about 1.5 pT upon motor stimulation. On the basis of these data, we discuss the possibility of detecting a shift of the resonance line due to the superposition of the neuromagnetic field generated by sustained brain activity.

Nuclear magnetic resonance (NMR) spectra of liquids were studied at fields from 470nTto65μT using a nitrogen cooled radio frequency superconducting quantum interference device. The authors demonstrated that low field NMR measurements with this device are feasible and may yield useful information. In particular, they determined the natural linewidth of distilled water to be 0.17±0.06Hz. In addition, they recorded J-coupled spectra of 2,2,2-trifluoroethanol in a measurement field regime that was determined to provide the best signal-to-noise ratio. Four peaks with frequency differences of about 2Hz were well separated.

In ultralow magnetic fields, liquid state nuclear magnetic resonance (NMR) spectra of homonuclear spin systems exhibit line widths dominated by their natural lifetime. Chemical shifts become negligible, and heteronuclear NMR spectra show predominantly the electron-mediated field-independent J-coupling. However, weak polarization and Larmor frequencies down to a few hertz require special detectors, such as Superconducting Quantum Interference Devices (SQUID), that also enable the simultaneous detection of broad band spectra of heteronuclear spin systems. We acquired spectra of 2,2,2-trifluoroethanol and trimethyl phosphate at detection fields varying from 444 nT to 3.34 muT after prepolarizing the sample in a field of 250 muT. Down to a 1H Larmor frequency of 40 Hz, the spectra of trifluoroethanol exhibited four clearly resolvable peaks. The numerical simulation agreed well with the measured spectra. Trimethyl phosphate exhibited two major groups of nonresolved proton lines. At 1H Larmor frequencies below 150 Hz, the separation of the two groups decreased, reflecting the transition from weakly to strongly coupled spin systems. Direct determination of 3J(H,P) from the peak separation is possible only at Larmor frequencies above 150 Hz. The experimental setup allowed an easy adjustment of the detection field over several octaves. This enabled us to adapt the detection field to the best-suited measurement window providing the maximum spectral information. Low-field NMR may open new applications, such as monitoring heteronuclear reactions, low-field imaging, simultaneous NMR/magnetoencephalography measurements, or quantum computing.

Introduction. Coated magnetic nanoparticles (MNP) serve as probes for the investigation of biological binding reactions in Magnetic Relaxation ImmunoAssays (MARIA) [1, 2]. MARIA is based on MagnetoRelaXometry (MRX) which is an integral and sensitive methode to quantify the binding behaviour of functionalized MNP. In contrast to flourescence and radioactive assays, MRX allows to distinguish between bound and unbound MNP-labeled reagents without washing steps. Non-aggregated well separated probes are required for immunological detection tasks. MRX also allows to assess quantitatively the aggregation of MNP in suspension. Here, we studied the effect of different MNP coatings (polar, nonpolar, biological) in different suspension media such as aqua dest., phosphate buffered saline (PBS) or serum on the aggregation behaviour of the magnetic probes. This serves to estimate the non-specific binding of functionalized magnetic probes which makes the analysis of the specific bindings more difficult. Specific binding of biological molecules was studied by the coupling between biotinylated latex spheres and streptavidin linked MNP. Magnetorelaxometry is the measurement of the relaxation of the magnetic moment of magnetic nanoparticles (MNP) after switching off the external polarisation field. There are two mechanisms of the relaxation of the particle moments: (i) Néel-relaxation, i.e., the flipping of the moment inside the particle, (ii) the Brownian relaxation: movement of the entire particle in the suspension. If the particles become immobilised, the latter mechanism is suppressed and the relaxation prolongs [3]. By separation of fast and slow relaxation contributions we can quantify the amount of bound and unbound magnetic probes [4]. The size, here the hydrodynamic diameter dhyd, of the relaxating structures (MNP, aggregates) determines the time constant of the Brownian relaxation

The ion exchange mediated binding of magnetic nanoparticles (MNP) to modified latex spheres and yeast cells was quantified using magnetorelaxometry. By fitting subsequently recorded relaxation curves, the kinetics of the binding reactions was extracted. The signal of MNP with weak ion exchanger groups bound to latex and yeast cells scales linearly with the concentration of latex beads or yeast cells whereas that of MNP with strong ion exchanger groups is proportional to the square root of concentration. The binding of the latter leads to a much stronger aggregation of yeast cells than the former MNP.

Large magnetosomes of 40nm diameter were characterised by altogether four different methods, i.e. DC-magnetometry and magnetorelaxometry as integral tools, and atomic and magnetic force microscopy as microscopic tools. The results suggest that the integral hysteretic behaviour of magnetosomes can be understood as a superposition of their microscopic behaviour, ignoring interaction between the particle moments.

A novel SQUID vector magnetometer system is introduced which has been specially designed for the use inside the strongly magnetically shielded room BMSR-2 of PTB. The system is housed in a dewar with a flat bottom and an inner diameter of Ø 250 mm. The SQUIDs are arranged so that in addition to the usually measured Z-component of the field the horizontal magnetic fields are measured too. A total of 304 DC-SQUID magnetometers are divided up into 19 identical modules. The 16 low-Tc SQUIDs of each module are located in such a way that an estimation of the magnetic field in all three dimensions is possible at three points inside the module. The 57 SQUIDs of the lowest Z plane of all modules form a hexagonal grid with a base length of 29 mm. The design criteria and the physical principle behind the complex SQUID arrangement are explained.