Characterizing atomic magnetic gradiometers for fetal magnetocardiography.

Atomic magnetometers (AMs) offer many advantages over superconducting quantum interference devices due to, among other things, having comparable sensitivity while not requiring cryogenics. One of the major limitations of AMs is the challenge of configuring them as gradiometers. We report the development of a spin-exchange relaxation free vector atomic magnetic gradiometer with a sensitivity of 3 fT cm-1 Hz-1/2 and common mode rejection ratio >150 in the band from DC to 100 Hz. We introduce a background suppression figure of merit for characterizing the performance of gradiometers. It allows for optimally setting the measurement baseline and for quickly assessing the advantage, if any, of performing a measurement in a gradiometric mode. As an application, we consider the problem of fetal magnetocardiography (fMCG) detection in the presence of a large background maternal MCG signal.

Assessment of atrioventricular conduction by echocardiography and magnetocardiography in normal and anti-Ro/SSA-antibody-positive pregnancies.

OBJECTIVES: The objectives of this study were, first, to evaluate the association between fetal echocardiographic atrioventricular (AV) and magnetocardiographic (fMCG) PR intervals at different gestational ages (GAs) in normal and anti-Ro/SSA-antibody-positive pregnancies; second, to determine if PR interval could be predicted by AV interval; and third, to assess the neonatal outcome of fetuses with prolonged AV and PR intervals, with the goal of developing criteria for fetal first-degree AV block (AVB-I). METHODS: This was a retrospective study of anti-Ro/SSA-antibody-positive pregnancies (cases) and controls that underwent fMCG and fetal echocardiography at the same recording session. Cardiac cycle length, GA and AV (by mitral inflow/aortic outflow Doppler) and PR (by fMCG) intervals were measured. We tested for significant differences between AV and PR intervals using generalized estimating equations to account for repeat measurements, and assessed whether PR interval could be predicted reliably by AV interval. After delivery, infants with fetal AV or PR interval Z-score ≥ 3 underwent 12-lead electrocardiography. RESULTS: Thirty-nine controls and 31 cases underwent 46 and 36 simultaneous fMCG and echocardiographic examinations, respectively; 101 controls and nine cases underwent fMCG only. AV and PR intervals increased with GA (P < 0.05 for both). Overall, AV and PR intervals were significantly different from each other (P < 0.001); this difference was not significant when compared between cases and controls (P = 0.222). PR interval could not be predicted accurately from AV interval and GA alone. Three of four cases with AV and PR interval Z-scores > + 3 had postnatal AVB-I despite treatment. The fourth fetus, which had predominately second-degree AVB and rare periods of AVB-I, progressed to third-degree AVB despite treatment with dexamethasone. CONCLUSIONS: The diagnostic threshold for AVB-I, defined by AV interval Z-score, is GA dependent. Based on the observed data, an AV interval Z-score threshold of 3 (AV interval, 151-167 ms) may be appropriate. Echocardiographic AV interval was not predictive of fMCG-PR interval. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Slow rhythms and sleep spindles in early infancy.

OBJECTIVE: To investigate the slow rhythm and its relationship to spindling in early infancy. METHODS: We analyzed sleep MEG recordings containing sleep spindles, taken from 7 normal, healthy subjects at conceptional age 46-63 weeks in 21 sessions. RESULTS: We show that the sleep MEG in early infancy contains a slow rhythm, centered at approximately 0.2Hz, which showed a striking association with spindling. The slow rhythm grouped sleep spindles, which were clock-like with a recurrence rate of approximately 0.1Hz. CONCLUSIONS: The association of the 0.2Hz oscillation and low delta rhythms with spindling was so strong as to suggest that they may play a critical role during brain development in the genesis of sleep spindles. SIGNIFICANCE: Infant brain rhythms exhibit relatively simple, regular behavior, allowing the relationships between them to be more easily discerned.

Diffusive suppression of AC-Stark shifts in atomic magnetometers.

In atomic magnetometers, the vector AC-Stark shift associated with circularly polarized light generates spatially varying effective magnetic fields, which limit the magnetometer response and serve as sources of noise. We describe a scheme whereby optically pumping a small subvolume of the magnetometer cell and relying on diffusion to transport polarized atoms allows a magnetometer to be operated with minimal sensitivity to the AC-Stark field.

Magnetocardiography with a modular spin-exchange relaxation-free atomic magnetometer array.

We present a portable four-channel atomic magnetometer array operating in the spin-exchange relaxation-free regime. The magnetometer array has several design features intended to maximize its suitability for biomagnetic measurement, specifically foetal magnetocardiography, such as a compact modular design and fibre-coupled lasers. The modular design allows the independent positioning and orientation of each magnetometer. Using this array in a magnetically shielded room, we acquire adult magnetocadiograms. These measurements were taken with a 6-11 fT Hz(-1/2) single-channel baseline sensitivity that is consistent with the independently measured noise level of the magnetically shielded room.

Dependent component analysis for the magnetogastrographic detection of human electrical response activity.

The detection of the basic electric rhythm (BER), composed of a 3 cycles min(-1) oscillation, can be performed using SQUID magnetometers. However, the electric response activity (ERA), which is generated when the stomach is performing a mechanical activity, was detected mainly by invasive electrical measurements and only recently was one report published describing its detection by magnetic measurements. This study was performed with the aim of detecting the ERA noninvasively after a meal. MGG recordings were made with a 74-channel first-order gradiometer (Magnes II, biomagnetic technologies) housed in a shielded room. Seven nonsymptomatic volunteers were measured in the study. Initially a 10 min recording was performed with the subject in the fasted state. A 250 kcal meal was given to the subject without moving out of the magnetometers and two epochs of 10 min each were acquired. The signals were processed to remove cardiac interference by an algorithm based on a variation of independent component analysis (ICA), then autoregressive and wavelet analysis was performed. Preliminary results have shown that there is an increase in the signal power at higher frequencies around (0.6 Hz-1.3 Hz) usually associated with the basic electric rhythm. The center of the frequency band and its width varied from subject to subject, demonstrating the importance of pre-prandial acquisition as a control. Another interesting finding was an increase in power after about 5 min of meal ingestion. This period roughly agrees with the lag phase of gastric emptying, measured by scintigraphy and other techniques. We confirm that MGG can detect the electric response activity in normal volunteers. Further improvements in signal processing and standardization of signal acquisition are necessary to ascertain its possible use in clinical situations.

On and Off magnetic auditory evoked responses in early infancy: a possible marker of brain immaturity.

OBJECTIVE: To follow the development of the auditory evoked on- and off-responses in early infancy. METHODS: The subjects were healthy infants, studied at conceptional age (CA) 39-66 weeks. Serial auditory evoked responses (AERs) were recorded in 17 subjects in response to tones of frequency 1.5 kHz and duration 1.0 s in order to follow the development of the AERs. Two small substudies were performed to examine off-responses evoked by tones of varying duration. The first used 0.2, 0.3, 0.4, and 0.5s tones; the second used 0.5, 1.0, and 2.0 s tones. RESULTS: For the 1.0 s tones, the on- and off-responses consisted of three components: P250, P400, and N750 m. The on- and off-responses had similar amplitude, in contrast to adult AERs in which the on-responses are typically much larger. Prior to about CA 47 weeks, the on-responses were actually smaller on average than the off-responses, and in infants born prior to CA 38 weeks the AERs were dominated by the off-response. Off-responses were seen for tones as brief as 0.2 s; however, the P400m component was often absent in the off-responses for tone durations < or = 0.5 s. An interaction was observed in which the N750 m-On component was strongly suppressed when it overlapped the P250 m-Off. CONCLUSIONS: Off-responses are much more prominent in infant than in adult AERs, especially in pre-term infants and at early CAs. On- and off-responses also exhibit more complex behavior in infants than in adult; the individual components can interact and behave independently. SIGNIFICANCE: Measurement of auditory off-responses can improve the assessment of infant neurodevelopment, potentially providing a marker of brain immaturity.

Development of MEG sleep patterns and magnetic auditory evoked responses during early infancy.

OBJECTIVE: To follow the development of MEG sleep patterns and auditory evoked responses (AERs) during the first six months of life. METHODS: The subjects were 18 neonates, born at conceptional age (CA) 36-42 weeks, following uncomplicated pregnancies. During each session, several 10-min MEG recordings were acquired in the presence of auditory stimulation. The recordings were classified into three distinct MEG patterns-low amplitude irregular; high-amplitude slow; and mixed-based largely on MEG amplitude and frequency. Averaged AERs were computed for the entire recording and for each MEG pattern within the recording. The results were based on analysis of 61 recording sessions of the 10 subjects who yielded three or more sessions of usable data. RESULTS: Developmental changes in the MEG sleep patterns were most pronounced at the earliest ages. By CA 48 weeks the patterns had progressed to a more mature form, characterized by the prevalence of delta wave sleep, absence of discontinuity, and development of spindling and higher amplitude delta rhythms. In contrast to the MEG patterns, the AERs did not change markedly during the first 8 weeks (CA 40-48 weeks) and showed a simple morphology, consisting of a prominent deflection at 250 ms (P250m) and a more diffuse one at around 750 ms (N750m). During the period CA 48-54 weeks, however, a relatively abrupt transition occurred to a more complex morphology, characterized by a double peak with peak latencies 150ms (P150m) and 350 ms (P350m). Beyond this period the AERs continued to evolve, showing biphasic complexes and the emergence of late components arising from outside the auditory cortex. CONCLUSIONS: Over the age range of this study the MEG sleep patterns and AER developed in succession, rather than concurrently; i.e. development of the sleep patterns was most rapid during the first 8 weeks (CA 40-48 weeks) while major development of the AERs commenced after this time. SIGNIFICANCE: This finding suggests that the brain must achieve a certain level of overall maturity, reflected in the character of the MEG sleep patterns at CA 48 weeks, before the cortex enters a phase of significant functional development, reflected in the more rapid evolution of the AER after CA 48 weeks. The results of this study affirm the efficacy of MEG for spatiotemporal characterization of neonatal brain activity.

MEG sleep pattern dependence of auditory evoked fields in young infants.

We recorded magnetic auditory evoked responses (AERs) to brief 1 kHz tones in infants ranging in age from 1.5-8.5 weeks. Long continuous MEG recordings were collected with a 37-channel sensor and were classified into one of four patterns: low-amplitude irregular, high-amplitude slow, mixed, and REM-like sleep. The AERs were characterized by a monophasic deflection with nominal latency 250 msec, followed by a broader peak with opposite polarity and approximate latency 600 msec. No strong dependences on MEG sleep pattern were observed. The latency of the 250 msec component decreased with age, but the 600 msec component showed variable latency. The signal topography of both components was compatible with a source in the auditory cortex. We conclude that sleep state does not appreciably confound recording of the AER in young infants.

Maximum likelihood dipole fitting in spatially colored noise.

We evaluated a maximum likelihood dipole-fitting algorithm for somatosensory evoked field (SEF) MEG data in the presence of spatially colored noise. The method exploits the temporal multiepoch structure of the evoked response data to estimate the spatial noise covariance matrix from the section of data being fit, which eliminates the stationarity assumption implicit in prestimulus based whitening approaches. The performance of the method, including its effectiveness in comparison to other localization techniques (dipole fitting, LCMV and MUSIC) was evaluated using the bootstrap technique. Synthetic data results demonstrated robustness of the algorithm in the presence of relatively high levels of noise when traditional dipole fitting algorithms fail. Application of the algorithm to adult somatosensory MEG data showed that while it is not advantageous for high SNR data, it definitely provides improved performance (measured by the spread of localizations) as the data sample size decreases.

Linearly constrained minimum variance source imaging using cortical bases.

An approach is presented for representing spatially extended cortical activity using a basis function expansion. The bases are designed to represent patches on the cortical surface. The basis function expansion coefficients are estimated for each patch by scanning modified linearly constrained minimum variance (LCMV) spatial filters over the entire surface. Next, a generalized likelihood ratio test (GLRT) is performed to detect patches with significant activity. In the last step, an image of the activity within each patch is reconstructed using a minimum norm solution to a local inverse problem. We show that the basis function representation enables the LCMV approach to identify patches of coherent activity that are missed by the conventional LCMV method and has potential for extended source detection and localization.

HTS magnetometers for fetal magnetocardiography.

High temperature superconducting (HTS) SQUID sensors have adequate magnetic field sensitivity for adult magnetocardiography (MCG) measurements, but it remains to be seen how well they perform for fetal MCG (fMCG), where the heart signals are typically ten times smaller than the adult signals. In this study, we assess the performance of a prototype HTS SQUID system; namely, a three-SQUID gradiometer formed from three vertically-aligned HTS dc-SQUID magnetometers integrated into a fiberglass liquid nitrogen dewar of diameter 12.5 cm and height 30 cm. Axial gradiometers with short or long baseline, as well as a second order gradiometer, can be formed out of these magnetometers via electronic subtraction. The calibrated magnetometer sensitivities at 1 kHz are 109 fT/square root of Hz, 155 fT/square root of Hz and 51 fT/square root of Hz. Direct comparison is made between the HTS SQUID system and a LTS SQUID system by making recordings with both systems during the same session on adult and fetal subjects. Although the fMCG could be resolved with the HTS SQUID system in most near-term subjects, the signal-to-noise ratio was relatively low and the system could not be operated outside of a shielded room.

Magnetocardiographic rhythm patterns at initiation and termination of fetal supraventricular tachycardia.

BACKGROUND: Using fetal magnetocardiography (fMCG), we characterize for the first time the electrophysiological patterns of initiation and termination of reentrant fetal supraventricular tachycardia (SVT), the most common form of life-threatening fetal arrhythmia. METHODS AND RESULTS: In contrast to the expectation that reentrant SVT is initiated by spontaneous premature atrial contractions (PACs) and is terminated by spontaneous block, 5 distinct patterns of initiation and 4 patterns of termination were documented, with the most common patterns of initiation involving reentrant PACs. Waveform morphology and timing, including QRS and ventriculoatrial interval, were assessed. This enabled detection of such phenomena as Wolff-Parkinson-White syndrome, QRS aberrancy, and multiple reentrant pathways that were crucial for defining the rhythm patterns. In addition, fMCG actocardiography revealed an unexpectedly strong association between fetal trunk movement and the initiation and termination of SVT, suggesting that autonomic influences play a key role. CONCLUSIONS: This study demonstrates that the patterns of initiation and termination of fetal SVT are more diverse than is generally believed and that the most common patterns of initiation involve reentrant PACs. The ability to discern such patterns can help elucidate the underlying mechanisms and guide antiarrhythmic drug therapy. fMCG provides a noninvasive means of analyzing complex tachyarrhythmia in utero, with efficacy approaching that of postnatal electrocardiographic rhythm monitoring.

Improved neuromagnetic detection of fetal and neonatal auditory evoked responses.

OBJECTIVE: To assess the quality of fetal and neonatal auditory evoked responses (fAERs and nAERs) obtainable with a low-noise, high-channel count SQUID gradiometer in a well-shielded environment. METHODS: Measurement of long-latency fAERs was attempted in 19 normal fetuses in 28 sessions at 29-40 weeks' gestation, using a 37-channel SQUID gradiometer. Postnatal measurement was attempted in 16 neonates in 25 sessions at age 2-6 weeks. RESULTS: Signals of amplitude 8 fT or greater were detected in 15 of 28 fetal measurement sessions, yielding a higher success rate (54%) than in a previous study of ours. Signals of amplitude greater than 25 fT were detected in 23 of 25 (92%) of neonatal measurement sessions. The spatial and temporal characteristics of the signals were studied in greater detail. Dipole patterns consistent with a source in the auditory cortex were observable in nearly all neonates and in many fetuses. The dominant component of the nAER was compatible with the P250 seen in neonatal EEG recordings; however, the largest component of the fAERs had longer latency and in many subjects had opposite polarity. CONCLUSION: A higher success rate, earlier detection, and improved characterization of signal morphology and topography were demonstrated for fAER recordings.

Eigenvector based spatial filtering of fetal biomagnetic signals.

In this paper we demonstrate the usefulness of an eigenvector based spatial filtering method for signal processing of multi-channel fetal magnetocardiogram (fMCG) and fetal magnetoencephalogram (fMEG) recordings. This method of filtering can separate signal and interference by exploiting the considerable spatial information contained in multi-channel recordings. Typically, fMCGs and fMEGs suffer from large cardiac interference and low signal-to-noise ratio. To isolate the signal from the interference, we identify their respective subspaces using one portion of the record dominated by the signal and another dominated by the interference. Each subspace is approximately rank two since the sources of the signal and interference can be modeled as current dipoles. The spatial filter consists of a linear transformation that preserves the signal subspace and annihilates the interference subspace. It is easier to implement than a matched filter, preserves the morphology and topography of the fetal signal, and effectively removes maternal cardiac interference, even when the maternal and fetal complexes overlap strongly in time or when small maternal movements or maternal arrhythmias alter the temporal character of the interference.

Transmission of electric and magnetic foetal cardiac signals in a case of ectopia cordis: the dominant role of the vernix. caseosa.

Foetal electrocardiograms (fECGs) and foetal magnetocardiograms (fMCGs) were recorded in the 26th, 29th and 31st weeks of gestation from a foetus with ectopia cordis-a rare condition in which the heart lies outside the chest wall. This provided an opportunity to study foetal cardiograms uninfluenced by the insulating effects of the foetal skin and vernix caseosa. The fECG of the ectopia cordis foetus was striking. Unlike recordings from age-matched normal foetuses, recordings from this subject had very high signal-to-noise ratio and showed no anomalous signal transmission properties. In contrast, fMCGs recorded from the ectopia cordis foetus and normal foetuses were largely similar. Both showed high signal-to-noise ratio and signal transmission properties consistent with volume conduction. The findings corroborate the hypothesis that high foetal skin resistance due primarily to the vernix caseosa is responsible for the low amplitude and anomalous transmission properties of the normal fECG, and demonstrate that the fMCG is relatively insensitive to conductivity inhomogeneities.

Assessment of fetal rhythm in complete congenital heart block by magnetocardiography.

We report high precision assessment of fetal rhythm in utero in a case of isolated congenital complete heart block using fetal magnetocardiography. The recordings reveal a remarkably strong tendency for the atria and ventricles to synchronize, which is manifested by the continual presence of ventriculophasic sinus arrhythmia and frequent episodes of accrochage and isorhythmic AV dissociation.

Noninvasive in utero assessment of PR and QRS intervals from the fetal magnetocardiogram.

Fetal cardiac waveform intervals were assessed from fetal magnetocardiogram (FMCG) recordings taken from 59 pregnant women at 17-41 weeks gestation. Beyond 27 weeks' gestation PR and QRS intervals, measured from averaged waveforms, could be obtained from all subjects; however, prior to 21 weeks' gestation the success rate was 50% or less due to low signal-to-noise ratio. QT interval could not be assessed accurately in most subjects. Weak, but statistically significant, correlations with gestational age were found for PR interval (n = 145, R2 = 0.033, P = 0.028) and QRS interval (n = 145, R2 = 0.140, P < 0.0005). Abnormal waveform morphology was documented in several patients with cardiac malformations.

Atrial and ventricular fetal heart rate patterns in isolated congenital complete heart block detected by magnetocardiography.

Atrial and ventricular fetal heart rate tracings from a patient with isolated congenital complete heart block treated with dexamethasone showed a remarkable degree of correlation and greater reactivity for the ventricular than the atrial fetal heart rate. Ventriculophasic sinus arrhythmia was present continually in the atrial fetal heart rate tracings.

Association of fetal junctional rhythm and respiratory arrhythmia detected by magnetocardiography.

Magnetocardiographic recordings from a fetus at 34 weeks' gestation with a complex heart malformation revealed an unusual fetal arrhythmia, where the rhythm was observed to alternate between extended periods of sinus and junctional rhythms. Fetal heart rate measurement showed that the junctional rhythm was strongly associated with respiratory arrhythmia. We hypothesize that changes in autonomic balance due to the onset and cessation of fetal breathing movements were largely responsible for the rhythm alternations. To our knowledge this is the first report of a fetal junction rhythm and the first observation of fetal respiratory arrhythmia during nonsinus rhythm.