Dynamics of the use of magnetocardiography in the study of the cardiac conduction system of the chick embryo.

INTRODUCTION: Human fetal magnetocardiography (fMCG) has been done for several decades to evaluate fetal arrhythmias using a superconducting quantum interference device (SQUID) magnetometer, but there is little work in embryonic/fetal animal models. This study uses an optically-pumped magnetometer (OPM) to obtain an fMCG in the chick embryo. METHODS: White Leghorn chick embryos were examined from incubation Day #10-19. Different examination chambers were tested to optimize embryonic thermal stability and magnetic signal acquisition. All examinations were done with magnetic shielding. The OPM sensors were placed next to the egg shell. The embryo's position was localized by transilluminating the intact egg or ultrasound imaging the egg with an open air cell to optimize sensor placement. The raw data for each embryo was postprocessed to obtain a fMCG composite waveform. RESULTS: fMCG's were obtained in embryos from Day #12 to 19. The best success with intact eggs was obtained using five sensors; one at the bottom and four around the lower perimeter of the egg at 90° intervals with the egg oriented vertically and the air cell up. Using ultrasound imaging with the air cell open only two sensors were necessary, one at the bottom and one laterally next to the embryo. fMCGs were analyzed for heart rate and rhythm, each portion of the PQRST waveform, and the PR interval, QRS complex, RR interval, and QT interval. CONCLUSIONS: This study validates the chick embryo as an animal model to study in a longitudinal and noninvasive fashion the fetal cardiac conduction system by using OPM magnetocardiography.

Repolarization Predictors of Fetal Long QT Syndrome.

BACKGROUND: Diagnosis of fetal long QT syndrome (LQTS) using fetal magnetocardiography (fMCG) is straightforward in cases of overt QTc prolongation accompanied by LQTS rhythms; however, cases of isolated QTc prolongation can be challenging. OBJECTIVE: To characterize repolarization in normal and phenotype-positive LQTS fetuses with the goal of utilizing additional parameters of repolarization to improve the accuracy of fMCG diagnosis of LQTS. METHODS: FMCG recordings were taken from 37 phenotype-positive fetuses with confirmed LQTS and 132 normal controls. The normal fetuses were grouped into those with T-and U-waves and those with only T-waves. We compared the repolarization characteristics of normal fetuses with only T-waves with those of LQTS fetuses. We also compared the repolarization characteristics of normal fetuses with T-and U-waves with those of LQTS fetuses with two-component T-waves. RESULTS: Late-peaking T-waves were strongly associated (35/37= 95%) with LQTS. No normal fetuses showed both QTc prolongation (QTc> 500 ms) and a late-peaking T-wave. U-waves were seen in 11 normal fetuses (8%) and resulted in waveforms that often mimicked those of the 19 LQTS fetuses with two-component T-waves; however, in normal fetuses the polarities of the T-and U-waves were the same, whereas in LQTS fetuses with two-component T-waves the polarity of the components was usually opposite. CONCLUSION: A late-peaking T-wave in association with QTc prolongation is a distinctive, reliable indicator of fetal LQTS. U-waves confound assessment of QTc; however, normal U-waves can usually be distinguished from LQTS T-waves based on polarity.

Low-Cost Fetal Magnetocardiography: A Comparison of Superconducting Quantum Interference Device and Optically Pumped Magnetometers.

Background Fetal magnetocardiography (fMCG) is a highly effective technique for evaluation of fetuses with life-threatening arrhythmia, but its dissemination has been constrained by the high cost and complexity of Superconducting Quantum Interference Device (SQUID) instrumentation. Optically pumped magnetometers (OPMs) are a promising new technology that can replace SQUIDs for many applications. This study compares the performance of an fMCG system, utilizing OPMs operating in a person-sized magnetic shield, to that of a conventional fMCG system, utilizing SQUID magnetometers operating in a magnetically shielded room. Methods and Results fMCG recordings were made in 24 subjects using the SQUID system with the mother lying supine in a magnetically shielded room and the OPM system with the mother lying prone in a person-sized, cylindrical shield. Signal-to-noise ratios of the OPM and SQUID recordings were not statistically different and were adequate for diagnostic purposes with both technologies. Although the environmental noise was higher using the small open-ended shield, this was offset by the higher signal amplitude achieved with prone positioning, which reduced the distance between the fetus and sensors and improved patient comfort. In several subjects, fMCG provided a differential diagnosis that was more precise and/or definitive than was possible with echocardiography alone. Conclusions The OPM-based system was portable, improved patient comfort, and performed as well as the SQUID-based system at a small fraction of the cost. Electrophysiological assessment of fetal rhythm is now practical and will have a major impact on management of fetuses with long QT syndrome and other life-threatening arrhythmias.

Fetal QT Interval Estimation Using Sequential Hypothesis Testing.

Objective: Recent studies utilizing fetal magnetocardiography have demonstrated the efficacy of corrected QT interval (QTc) measurement for in utero diagnosis and prognosis of long QT syndrome, a leading cause of sudden death in early life. The objective of the study was to formulate and test a novel statistical estimation method to detect the end of the fetal T-wave and thereby improve the accuracy of fetal QT interval measurement. Methods: To detect the end of the T-wave, we apply a sequential composite hypothesis test to decide when the T-wave has returned to baseline. The method uses the generalized likelihood ratio test in conjunction with a low-rank spatiotemporal model that exploits the repetitive nature of cardiac signals. The unknown model parameters are determined using maximum likelihood estimation. Results: In realistic simulations, the detector was shown to be accurate to within 10 ms (95% prediction interval), even at noise-to-signal ratios as high as 6. When applied to real data from normal fetuses, the detector agreed well with measurements made by cardiologists ( 1.4 6.9 ms). Conclusions: The method was effective and practical. Detector performance was excellent despite the continual presence of strong maternal interference. Significance: This detector serves as a valuable adjunct to traditional measurement based on subjective assessment.Objective: Recent studies utilizing fetal magnetocardiography have demonstrated the efficacy of corrected QT interval (QTc) measurement for in utero diagnosis and prognosis of long QT syndrome, a leading cause of sudden death in early life. The objective of the study was to formulate and test a novel statistical estimation method to detect the end of the fetal T-wave and thereby improve the accuracy of fetal QT interval measurement. Methods: To detect the end of the T-wave, we apply a sequential composite hypothesis test to decide when the T-wave has returned to baseline. The method uses the generalized likelihood ratio test in conjunction with a low-rank spatiotemporal model that exploits the repetitive nature of cardiac signals. The unknown model parameters are determined using maximum likelihood estimation. Results: In realistic simulations, the detector was shown to be accurate to within 10 ms (95% prediction interval), even at noise-to-signal ratios as high as 6. When applied to real data from normal fetuses, the detector agreed well with measurements made by cardiologists ( 1.4 6.9 ms). Conclusions: The method was effective and practical. Detector performance was excellent despite the continual presence of strong maternal interference. Significance: This detector serves as a valuable adjunct to traditional measurement based on subjective assessment.

Fetal Atrial Flutter: Electrophysiology and Associations With Rhythms Involving an Accessory Pathway.

BACKGROUND: Atrial flutter (AFl) accounts for up to one third of all fetal tachyarrhythmias and can result in premature delivery, hydrops, and fetal death in 10% of cases; however, the electrophysiology of AFl in utero is virtually unstudied. METHODS AND RESULTS: In this observational study, we reviewed 19 fetal magnetocardiography studies from 16 fetuses: 15 fetuses (21-38 weeks' gestation) referred with an echocardiographic diagnosis of AFl and 1 fetus (20 weeks' gestation) referred with a diagnosis of tachycardia that was shown by fetal magnetocardiography to have transient AFl in addition to atrioventricular reciprocating tachycardia. Thirteen fetuses showed AFl during the fetal magnetocardiography session, including 4 that presented prior to the third trimester. Five fetuses had incessant AFl; all but 1 of the others with AFl showed additional significant rhythms. Specifically, AFl showed a strong association with rhythms involving an accessory pathway: atrioventricular reciprocating tachycardia, blocked reentrant premature atrial contractions, and ventricular preexcitation. The observed initiations and terminations of AFl most often involved reentrant premature atrial contractions. Spontaneous termination of AFl showed AFl cycle length oscillations. Nine fetuses with 2:1 AFl also showed periods of 4:1 conduction or variable conduction that oscillated between 2:1 and 4:1; however, 3:1 AFl was relatively rare. CONCLUSIONS: Fetal AFl can occur as early as midgestation and is often accompanied by atrioventricular reciprocating tachycardia and other rhythms associated with an accessory pathway. The findings depict critical differences in the electrophysiology of AFl in the fetus versus the neonate.

Indices and detectors for fetal MCG actography.

Several recent studies have demonstrated the usefulness of fetal magnetocardiogram (fMCG) actography, a relatively new method of detecting fetal movement that can be performed in conjunction with fMCG assessment of fetal heart rate and rhythm. In this study, we formulate indices of fetal activity that incorporate information from all channels to achieve improved sensitivity. We also utilize statistical detection to provide an objective means of inferring significant fetal activity.

Independent component analysis of normal and abnormal rhythm in twin pregnancies.

We investigated the utility of ICA for evaluation of fetal rhythm in five uncomplicated twin pregnancies and in five twin pregnancies complicated by fetal arrhythmia. Using objective and subjective criteria, we sought to determine how the signal-to-noise ratio, signal fidelity and interference rejection are affected when synthesizing the fetal signal using all the signal-containing ICA components (rank-p ICA) versus using the single dominant component (rank-1 ICA). The signal of each fetus was most commonly distributed over 1 or 2 ICA components, as previously observed in studies of singleton pregnancies; however, in 8 of 26 (31%) cases the signal of each fetus was distributed over 3, 4 or even 5 ICA components. Rank-1 ICA provided the highest SNR and interference rejection, but at the cost of reduced signal fidelity. Our results corroborate that in twin pregnancies, including twin pregnancies complicated by fetal arrhythmia, rank-1 ICA is very effective in isolating the QRS complexes of each fetus; however, it has some limitations when used for fetal rhythm evaluation due to signal distortion. Occasionally, rank-1 ICA completely separates the P-wave and the T-wave from the QRS complex, thus requiring the mixing of several ICA components to achieve acceptable signal fidelity.

Matched-filter template generation via spatial filtering: application to fetal biomagnetic recordings.

We have developed a two-step procedure for signal processing of fetal biomagnetic recordings that removes cardiac interference and noise. First, a modified matched filter (MF) is applied to remove maternal cardiac interference; then, a simple signal space projection (SSP) is applied to remove noise. The key difference between our MF and a conventional one is that the interference template and the template scaling are derived from a signal that has been spatially filtered to isolate the interference, rather than from the raw signal. Unlike conventional MFs, ours is able to separate maternal and fetal cardiac complexes, even when they have similar morphology and overlap strongly. When followed by a SSP that preserves only the signal subspace, the noise is reduced to a low level.