Tracking evoked responses to auditory and visual stimuli in fetuses exposed to maternal high-risk conditions.

Magnetoencephalography (MEG) has been successfully applied to record fetal auditory (auditory evoked response [AER]) and visual evoked responses (VER). In this study, we report the AER and VER development trajectory by tracking the evoked response detectability and latency from recordings starting at 27 weeks of gestation in pregnancies classified as high risk. Fetal MEG and ultrasound recordings were performed on 158 pregnant women, and the total number of fetal auditory and visual tests conducted was 321 and 237, respectively. The overall evoked response analysis showed 237 AER (73.8%) and 164 VER detections (69.2%). The mean AER latency was 290.7 (SD 125.5) ms and the mean VER latency was 293.7 (SD 114.5) ms. The rate of decrease (95% confidence limits) in average AER and VER first-peak latency between 100-350 ms was 1.97 (-1.86, +5.81) ms/week and 1.35 (-3.83, +6.53) ms/week, respectively. This trend in high-risk fetuses conforms to the general trajectory of decrease in latency with gestational age progression, even though this decrease was non-significant, as reported in the case of normal growing fetuses. Although there was a significant difference in detection rates between male and female fetuses, this was not reflected in either latency values or the sensory modality applied. Furthermore, the main factors that had the most significant effect on response detectability included the presence of intervening layers of adipose tissue between the fetal head and stimulus source and an increase in the maternal body mass index.

Comparing the performance of a new disposable pneumatic tocodynamometer with a standard tocodynamometer.

INTRODUCTION: The goal was to test a newly developed pneumatic tocodynamometer (pTOCO) that is disposable and lightweight, and evaluate its equivalence to the standard strain gauge-based tocodynamometer (TOCO). MATERIAL AND METHODS: The equivalence between the devices was determined by both mechanical testing and recording of contractile events on women. The data were recorded simultaneously from a pTOCO prototype and standard TOCO that were in place on women who were undergoing routine contraction monitoring in the Labor and Delivery unit at the University of Arkansas for Medical Sciences. In this prospective equivalence study, the output from 31 recordings on 28 pregnant women that had 171 measureable contractions simultaneously in both types of TOCO were analyzed. The traces were scored for contraction start, peak and end times, and the duration of the event was computed from these times. RESULTS: The response curve to loaded weights and applied pressure were similar for both devices, indicating their mechanical equivalence. The paired differences in times and duration between devices were subjected to mixed-models analysis to test the pTOCO for equivalence with standard TOCOs using the two-one-sided tests procedure. The event times and duration analyzed simultaneously from both TOCO types were all found to be significantly equivalent to within ±10 s (all p-values ≤0.0001). CONCLUSION: pTOCO is equivalent to the standard TOCO in the detection of the timing and duration of uterine contractions. pTOCO would provide a lightweight, disposable alternative to commercially available standard TOCOs.

Characterizing the Propagation of Uterine Electrophysiological Signals Recorded with a Multi-Sensor Abdominal Array in Term Pregnancies.

The objective of this study was to quantify the number of segments that have contractile activity and determine the propagation speed from uterine electrophysiological signals recorded over the abdomen. The uterine magnetomyographic (MMG) signals were recorded with a 151 channel SARA (SQUID Array for Reproductive Assessment) system from 36 pregnant women between 37 and 40 weeks of gestational age. The MMG signals were scored and segments were classified based on presence of uterine contractile burst activity. The sensor space was then split into four quadrants and in each quadrant signal strength at each sample was calculated using center-of-gravity (COG). To this end, the cross-correlation analysis of the COG was performed to calculate the delay between pairwise combinations of quadrants. The relationship in propagation across the quadrants was quantified and propagation speeds were calculated from the delays. MMG recordings were successfully processed from 25 subjects and the average values of propagation speeds ranged from 1.3-9.5 cm/s, which was within the physiological range. The propagation was observed between both vertical and horizontal quadrants confirming multidirectional propagation. After the multiple pairwise test (99% CI), significant differences in speeds can be observed between certain vertical or horizontal combinations and the crossed pair combinations. The number of segments containing contractile activity in any given quadrant pair with a detectable delay was significantly higher in the lower abdominal pairwise combination as compared to all others. The quadrant-based approach using MMG signals provided us with high spatial-temporal information of the uterine contractile activity and will help us in the future to optimize abdominal electromyographic (EMG) recordings that are practical in a clinical setting.

Tracking the changes in synchrony of the electrophysiological activity as the uterus approaches labor using magnetomyographic technique.

The objective of the study was to perform serial magnetomyographic examinations in order to detect changes in synchrony characteristics of myometrial electrophysiological activity as women approach labor. Of the total of 56 patients recruited, the results of 149 examinations from 29 patients were included in the analysis. The global synchrony across each sensor spread over the abdomen was computed and quantified as synchronization index. The mean and the median value of the global synchrony were computed and correlated with time to active labor from the last recording. Overall, synchrony increased as the patient approached active labor (P = .035). Furthermore, mean synchronization index increased twice as fast in the nonnulliparous group compared to the nulliparous group (P = .039). The changes in synchrony of uterine electrophysiological activity near term could aid in prediction of labor.

Decrement of uterine myometrial burst duration as a correlate to active labor: a Hilbert phase approach.

We propose a novel approach based on Hilbert phase to identify the burst in the uterine myometrial activity. We apply this approach to 24 serial magnetomyographic signals recorded from four pregnant women using a 151 SQUID array system. The bursts identified with this approach are evaluated for duration and are correlated with the gestational age. In all four subjects, we find a decrease in the duration of burst as the subject approaches active labor. As was shown in animal studies, this result indicates a faster conduction time between the muscle cells which activate a larger number of muscle units in a synchronous manner.

Fetal neurological assessment using noninvasive magnetoencephalography.

SQUID Array for Reproductive Assessment is a unique magnetoencephalography device designed for the noninvasive recording of fetal brain activity. In this article, we provide a general overview of the technology and its potential application to fetal medicine. A large number of studies that have been conducted and published describing this device since it was brought into operation are referenced throughout the article.

Extraction, quantification and characterization of uterine magnetomyographic activity--a proof of concept case study.

OBJECTIVE: The objective was to extract, quantify and characterize the uterine magnetomyographic (MMG) signals that correspond to the electrophysiological activity of the uterus. METHODS: Transabdominal MMG recordings with high spatial-temporal resolution were performed with the use of the 151 non-invasive magnetic sensor system. The extraction, quantification and characterization procedures were developed and applied to representative MMG signals that were recorded from a pregnant woman at regular intervals starting at 37 weeks of gestation until the subject reached active labor. RESULTS: Multiple MMG recordings were successfully performed on the subject before she went into active labor. The extracted MMG burst activity showed a statistically significant correlation (r=0.2; p<0.001) with the contractile events perceived by mothers. The time-frequency analysis of the burst activity showed a power shift towards higher-frequency at 48 h before the subject went into active labor as compared to earlier recordings. Further there was a gradual increase in the synchrony in the higher-frequency band as the subject reached close to active labor. CONCLUSIONS: The non-invasive recording of the magnetic signals of pregnant uterus with high spatial-temporal resolution can provide an insight into the preparatory phase of labor and has the potential of predicting term and preterm labor.

Non-invasive detection and identification of brain activity patterns in the developing fetus.

OBJECTIVE: Utilizing a MEG-based device specifically designed to study the fetus, we investigated the presence of salient patterns in spontaneous fetal brain activity. METHODS: We performed 91 MEG recordings from 30 fetuses at various gestational ages. The tracings were evaluated and compared to the well-established electroencephalographic (EEG) features in premature infants. Also, we looked at the correlation of the gestational age (GA) on the occurrence of these patterns and complexes. RESULTS: We were able to identify specific patterns and track changes in fetal brain activity starting at 28 weeks of gestation. The patterns and trends were similar to the established EEG features in premature infants at comparable ages. Of the 30 fetuses, 18 (60%) had at least one recording with discontinuity, 7 (23%) had sharp transients, and 8 (27%) had delta brush activity. Further there was a decrease in the presence of discontinuous patterns after 35 weeks. CONCLUSIONS: We have shown that fetal spontaneous brain activity features can be recorded and identified using MEG technique. The observation of more discontinuity at early gestational ages is consistent with the overall pattern of maturation seen in EEGs of premature infants. SIGNIFICANCE: With refinements, this method can aid in understanding the maturation process of fetal brain activity and further develop as a tool for fetal neurological evaluation.

Synchronization analysis of the uterine magnetic activity during contractions.

BACKGROUND: Our 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. METHODS: The 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. RESULTS: The 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. DISCUSSION: These results show that synchronization indices and their spatial distributions depict uterine contractions and relaxations.

Spatial-temporal analysis of uterine smooth muscle activity recorded during pregnancy.

We performed recording of the magnetic fields (Magnetomyography - MMG) corresponding to the electrical activity of the uterine smooth muscle with a device called SARA, (SQuid Array for Reproductive Assessment). Past studies suggest that the uterus passes through a preparatory process before entering labor and resulting in delivery of the fetus. But the electrophysiological mechanism of this process is not completely understood. We propose four parameters that will allow us quantify the characteristics of the uterine MMG signal obtained from 151 sensors spread over the pregnant abdomen. In summary, we believe that spatial-temporal analysis mapping of uterine activity will help us better understand the process of labor.

Fetal magnetoencephalography--a multimodal approach.

Past studies have shown the feasibility of recording fetal evoked responses to external stimuli using a non-invasive technique called magnetoencephalography (MEG). These studies were all performed using either auditory or visual stimuli and showed a fairly low detection rate for each modality, thus making this technology currently unreliable for fetal clinical applications. This study is based on the hypothesis that a multimodal approach of applying both auditory and visual stimulation paradigms in successive recording sessions could improve the probability of obtaining a fetal evoked response. A total of 34 studies were performed on 11 normal healthy fetuses at different stages of gestation starting as early as 28 weeks with a 151-channel fetal MEG system. The success rate of obtaining a response to either (or both) stimuli from a study at a given gestation age was 91%. All the 11 fetuses showed a response at least once over the gestation period the recordings were performed. A multimodal testing approach can improve the ability of the MEG technique to reliably monitor the functional development of the fetal brain.

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.

Prediction of labor in term and preterm pregnancies using non-invasive magnetomyographic recordings of uterine contractions.

OBJECTIVE: The purpose of this study was to characterize the noninvasive magnetic field recordings of the uterine electrophysiological activity in patients reporting onset of uterine contractions. STUDY DESIGN: Transabdominal magnetomyographic (MMG) recordings were performed with the use of the SARA system's 151 primary magnetic sensors (CTF Systems Inc, Coquitlam, British Columbia, Canada). Eleven term and 4 preterm patients participated in the study. On all patients, cervical dilation and outcomes were recorded. RESULTS: Of 8 patients having a peak MMG activity exceeding 8 pT (pico Tesla), all but 1 delivered within 48 hours of our recordings. Of the 7 patients with peak activity below 8 pT, 5 failed to deliver within 48 hours of the recordings. This observation reflects an increase in the electrophysiologic activity of the myometrium as labor progresses. CONCLUSION: MMG evaluation provides a new noninvasive method for the prediction of labor. Further studies are in progress to determine the temporal relationship of MMG changes with the onset of labor.

Noninvasive antepartum recording of fetal S-T segment with a newly developed 151-channel magnetic sensor system.

OBJECTIVE: The objective of this study was to evaluate the efficiency of the detection of the S-T segment in the fetal PQRST complex that is recorded in the antepartum period with the use of a newly developed noninvasive 151-channel magnetic sensor array. STUDY DESIGN: One hundred two fetal magnetocardiographic recordings were performed on normal fetuses with gestational ages that ranged from 27.5 to 39.5 weeks. After the removal of the interfering maternal heart signals, the fetal heart data were inspected to detect the presence of P, QRS, and T segments. RESULTS: The QRS complex was detectable in 100%, the P wave was detectable in 95.1%, and the T wave was detectable in 87.3% of the recordings. CONCLUSION: Fetal magnetocardiography was recorded successfully, the QRS complex was observed in all subjects, and the T detection rate increased, with the gestational age reaching a peak of 97%. Further study of the S-T segment through the antepartum period could lead to advances in the detection of fetal jeopardy before labor.

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.

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.

First magnetomyographic recordings of uterine activity with spatial-temporal information with a 151-channel sensor array.

OBJECTIVE: The purpose of this study was to examine the feasibility of recording the spatial-temporal magnetomyographic activity from the pregnant uterus with the use of the newly developed 151-channel noninvasive device, known as the superconducting quantum interference device array for reproductive assessment. STUDY DESIGN: Uterine magnetomyographic signals were recorded from 10 pregnant subjects with the 151-channel sensor array curved to fit the pregnant abdomen. The recording sessions were 16 minutes in length, with a sampling rate of 250 Hz. RESULTS: Uterine activity bursts were successfully recorded with the superconducting quantum interference device array for reproductive assessment system. By obtaining a contour plot of the magnetic field distribution, we were able to localize the areas of activation over the uterus during a contraction. Also, it was possible to calculate the time delay in the propagation of the activity across the uterus. CONCLUSION: Using superconducting quantum interference device array for reproductive assessment system, we have established the feasibility of recording uterine contractile activity with spatial-temporal resolution that is high enough to determine the regions of localized activation and propagation over the uterus.