Hari Eswaran

Magnetoencephalographic recordings of visual evoked brain activity in the human fetus

We investigated the feasibility of recording visual evoked brain activity in the human fetus by use of non-invasive magnetoencephalography (MEG). Each recording lasted 6 min and consisted of a sequence of 180 flashes with 33 ms duration delivered 2 s apart over the maternal abdomen. Four of ten fetuses included showed a response; the ranges of amplitude and latency of peak response were 15-30 x 10(-15) Tesla and 180-390 ms, respectively. Six fetuses showed no discernible response. With improvement, this method could aid in the testing of fetal neurological status throughout pregnancy.

Fetal MEG redistribution by projection operators

The fetal magnetoencephalogram (fMEG) is measured in the presence of large interference from the maternal and fetal magnetocardiograms. This interference can be efficiently attenuated by orthogonal projection of the corresponding spatial vectors. However, the projection operators redistribute the fMEG signal among sensors. Although redistribution can be readily accounted for in the forward solution, visual interpretation of the fMEG signal topography is made difficult. We have devised a general, model-independent method for correction of the redistribution effect that utilizes the assumption that we know in which channels the fMEG should be negligible (such channels are distant from the known fetal head position). In a simplified case where the fMEG can be explained by equivalent current dipoles, the correction can also be obtained from fitting the dipoles to the fMEG signal. The corrected fMEG signal topography then corresponds to the dipole forward solution, but without orthogonal projection. We illustrate the redistribution correction on an example of experimentally measured flash evoked fMEG.

Development of auditory evoked fields in human fetuses and newborns: A longitudinal MEG study

OBJECTIVE To investigate the maturation of the auditory cortex by non-invasive recording of auditory evoked magnetic fields in human fetuses and newborns with the relatively novel and completely non-invasive technology of MEG. METHODS Serial recordings were performed every 2 weeks on 18 fetuses beginning from week 27 of gestational age until term with a follow-up recording on the newborn. Auditory stimulation consisted of tone bursts in an oddball design with standard tones and deviant tones. RESULTS In 52 of 63 fetal and in all of the neonatal recordings an auditory evoked magnetic field was obtained. A decrease in latency with increasing age of the subjects was observed in the combined analysis of fetuses and neonates. CONCLUSIONS With advanced study using MEG, 83% of the measurements showed auditory evoked fields in fetuses that correspond with existing literature in electrophysiology in the past. These findings indicate that MEG is a technique that can be used to investigate maturation of the auditory cortex based on auditory evoked fields in fetuses and neonates. SIGNIFICANCE Maturational changes have been examined in the past. With the use of this novel technique, applied to a serial study, it is possible to trace the development of auditory responses in utero and newborns.

Short-term serial magnetoencephalography recordings offetal auditory evoked responses.

The study objective was to determine whether short-term serial magnetoencephalographic (MEG) measurements would increase the odds in favor of obtaining fetal auditory evoked responses in normal fetuses. The recordings were performed in two phases using the newly developed 151-channel fetal MEG system, superconducting quantum interference device array for reproductive assessment. Ten pregnant subjects with gestational ages ranging from 30-35 weeks were recruited to participate. Daily recordings were performed over a minimum of 3 days during 1 week of gestation and repeated in the same subjects between 36 and 40 weeks gestation. In 80% of subjects, auditory evoked responses were detected at least once. In healthy fetuses, serial recordings over a short span of time increased the rate of detecting fetal evoked response.

Fetal magnetoencephalography: current progress and trends.

Multimodal testing is the key to successful fetal neurological assessment. New mutichannel SQUID (Superconducting Quantum Interference Device) sensor devices can now be used to effectively record fetal auditory evoked responses (fAER) and visual evoked responses (VER), spontaneous brain activity, and heart activity. In this paper, we review the current progress in the area of fetal magnetoencephalography (fMEG) and also present an overview of the studies performed using a system called SARA that is specifically designed for fetal MEG studies. With the capability of recording spontaneous and evoked magnetic fields, we believe the monitoring of the neurological status of the fetus can be effectively implemented and can encourage the development of new strategies of intervention for the high-risk fetus.

Functional development of the visual system in human fetus using magnetoencephalography.

The development of the human brain in utero is normally regarded as a dynamic process involving mainly structural and quantitative changes in neurons and their distribution. However, it is generally accepted that a parallel development of functional specialization occurs in certain areas of the brain, especially in the primary cortex. Nearly all knowledge of functional fetal brain development has been obtained from various animal studies rather than human studies. These studies show that the primary sensory areas like auditory, visual, and somatosensory cortex show a basic function similar to that of a fully developed brain. It has been specifically shown that the visual system develops during fetal life and becomes functional before birth. Several studies have demonstrated the feasibility of using visual evoked response (VER) recordings on preterm human infants to follow the functional development of the visual system. With the advent of the noninvasive technique of magnetoencephalography (MEG), human fetal VER recordings are now possible thus providing the opportunity to track its functional development with gestation. We present and discuss the results of VER recordings in human fetuses starting at 28 weeks of gestation performed using a 151-channel MEG system.

Synchronization analysis of the uterine magnetic activity during contractions

BackgroundOur objective was to quantify and compare the extent of synchronization of the spatial-temporal myometrial activity over the human uterus before and during a contraction using transabdominal magnetomyographic (MMG) recordings. Synchronization can be an important indicator for the quantification of uterine contractions.MethodsThe spatialtermporal myometrial activity recordings were performed using a 151-channel noninvasive magnetic sensor system called SARA. This device covers the entire pregnant abdomen and records the magnetic field corresponding to the electrical activity generated in the uterine myometrium. The data was collected at 250 samples/sec and was resampled with 25 samples/sec and then filtered in the band of 0.1–0.2 Hz to study the primary magnetic activity of the uterus related to contractions. The synchronization between a channel pair was computed. It was inferred from a statistical tendency to maintain a nearly constant phase difference over a given period of time even though the analytic phase of each channel may change markedly during that time frame. The analytic phase was computed after taking Hilbert transform of the magnetic field data. The process was applied on the pairs of magnetic field traces (240 sec length) with a stepping window of 20 sec duration which is long enough to cover two cycle of the lowest frequency of interest (0.1 Hz). The analysis was repeated by stepping the window at 10 sec intervals. The spatial patterns of the synchronization indices covering the anterior transabdominal area were computed. For this, regional coil-pairs were used. For a given coil, the coil pairs were constructed with the surrounding six coils. The synchronization indices were computed for each coil pair, averaged over the 21 coil-pairs and then assigned as the synchronization index to that particular coil. This procedure was tested on six pregnant subjects at the gestational age between 29 and 40 weeks admitted to the hospital for contractions. The RMS magnetic field for each coil was also computed.ResultsThe results show that the spatial patterns of the synchronization indices change and follow the periodic pattern of the uterine contraction cycle. Spatial patterns of synchronization indices and the RMS magnetic fields show similarities in few window frames and also show large differences in few other windows. For six subjects, the average synchronization indices were: 0.346 ± 0.068 for the quiescent baseline period and 0.545 ± 0.022 at the peak of the contraction.DiscussionThese results show that synchronization indices and their spatial distributions depict uterine contractions and relaxations.

Human fetal brain imaging by magnetoencephalography: verification of fetal brain signals by comparison with fetal brain models.

Fetal magnetoencephalogram (fMEG) is measured in the presence of a large interference from maternal and fetal magnetocardiograms (mMCG and fMCG). This cardiac interference can be successfully removed by orthogonal projection of the corresponding spatial vectors. However, orthogonal projection redistributes the fMEG signal among channels. Such redistribution can be readily accounted for in the forward solution, and the signal topography can also be corrected. To assure that the correction has been done properly, and also to verify that the measured signal originates from within the fetal head, we have modeled the observed fMEG by two extreme models where the fetal head is assumed to be either electrically transparent or isolated from the abdominal tissue. Based on the measured spontaneous, sharp wave, and flash-evoked fMEG signals, we have concluded that the model of the electrically isolated fetal head is more appropriate for fMEG analysis. We show with the help of this model that the redistribution due to projection was properly corrected, and also, that the measured fMEG is consistent with the known position of the fetal head. The modeling provides additional confidence that the measured signals indeed originate from within the fetal head.

Fetal magnetocardiography measurements with an array of microfabricated optically pumped magnetometers.

Following the rapid progress in the development of optically pumped magnetometer (OPM) technology for the measurement of magnetic fields in the femtotesla range, a successful assembly of individual sensors into an array of nearly identical sensors is within reach. Here, 25 microfabricated OPMs with footprints of 1 cm(3) were assembled into a conformal array. The individual sensors were inserted into three flexible belt-shaped holders and connected to their respective light sources and electronics, which reside outside a magnetically shielded room, through long optical and electrical cables. With this setup the fetal magnetocardiogram of a pregnant woman was measured by placing two sensor belts over her abdomen and one belt over her chest. The fetal magnetocardiogram recorded over the abdomen is usually dominated by contributions from the maternal magnetocardiogram, since the maternal heart generates a much stronger signal than the fetal heart. Therefore, signal processing methods have to be applied to obtain the pure fetal magnetocardiogram: orthogonal projection and independent component analysis. The resulting spatial distributions of fetal cardiac activity are in good agreement with each other. In a further exemplary step, the fetal heart rate was extracted from the fetal magnetocardiogram. Its variability suggests fetal activity. We conclude that microfabricated optically pumped magnetometers operating at room temperature are capable of complementing or in the future even replacing superconducting sensors for fetal magnetocardiography measurements.

Optimal reduction of MCG in fetal MEG recordings

Recording fetal magnetoencephalographic (fMEG) signals in-utero is a demanding task due to biological interference, especially maternal and fetal magnetocardiographic (MCG) signals. A method based on orthogonal projection of MCG signal space vectors (OP) was evaluated and compared with independent component analysis (ICA). The evaluation was based on MCG amplitude reduction and signal-to-noise ratio of fetal brain signals using exemplary datasets recorded during ongoing studies related to auditory evoked fields. The results indicate that the OP method is the preferable approach for attenuation of MCG and for preserving the fetal brain signals in fMEG recordings