Ronald T. Wakai

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.

Theta Oscillations and Human Navigation: A Magnetoencephalography Study

Magnetoencephalography (MEG) was used to study alpha and theta activity while subjects navigated through a computer-generated virtual reality town. The subjects were first allowed to explore the environment freely. They then had to navigate from a starting point to a destination, knowing that an obstruction would appear at one of several possible locations along the main route and force them to take a detour. Spatiotemporal analysis of the theta and alpha bands were performed (1) prior to the start of navigation, (2) from the start of navigation until the obstruction was encountered, (3) during the time subjects were contemplating a detour and were not navigating, and (4) from the resumption of navigation until the destination was reached. In all subjects, theta power was strongest during the two periods of navigation. The peak frequency of the oscillations was approximately 3.7 Hz. Control studies consisted of a motor task similar to that required for navigation, passive viewing of a tour through the same virtual reality town, and a mental concentration task. No consistent increases in theta power were seen in the MEG during any of the control tasks. The results suggest an association between theta rhythm and the performance of navigational tasks in humans.

Cortical patch basis model for spatially extended neural activity

A new source model for representing spatially distributed neural activity is presented. The signal of interest is modeled as originating from a patch of cortex and is represented using a set of basis functions. Each cortical patch has its own set of bases, which allows representation of arbitrary source activity within the patch. This is in contrast to previously proposed cortical patch models which assume a specific distribution of activity within the patch. We present a procedure for designing bases that minimize the normalized mean squared representation error, averaged over different activity distributions within the patch. Extension of existing algorithms to the basis function framework is straightforward and is illustrated using linearly constrained minimum variance (LCMV) spatial filtering and maximum-likelihood signal estimation/generalized likelihood ratio test (ML/GLRT). The number of bases chosen for each patch determines a tradeoff between representation accuracy and the ability to differentiate between distinct patches. We propose choosing the minimum number of bases that satisfy a constraint on the normalized mean squared representation accuracy. A mismatch analysis for LCMV and ML/GLRT is presented to show that this is an appropriate strategy for choosing the number of bases. The effectiveness of the patch basis model is demonstrated using real and simulated evoked response data. We show that significant changes in performance occur as the number of basis functions varies, and that very good results are obtained by allowing modest representation error

Electrophysiological characteristics of fetal atrioventricular block.

OBJECTIVES The purpose of our work was to define the complex electrophysiological characteristics seen in second- (2 degrees) and third-degree (3 degrees) atrioventricular block (AVB) and to longitudinally follow the development of atrial and ventricular heart rate and rhythm patterns with a goal of identifying heart rate and rhythm patterns associated with urgent delivery or neonatal pacing. BACKGROUND The electrophysiological characteristics of congenital AVB before birth have not been extensively studied, yet the mortality from this disease is substantial. Along with advances in fetal therapies and interventions, a comprehensive natural history specific to the etiology of AVB, as well as the electrophysiological factors influencing outcome, are needed to best select treatment options. METHODS Twenty-eight fetuses with AVB were evaluated by fetal magnetocardiography; 21 fetuses were evaluated serially. RESULTS Fetuses with 2 degrees AVB and isolated 3 degrees AVB showed: 1) diverse atrial rhythms and mechanisms of atrioventricular conduction during 2 degrees AVB; 2) junctional ectopic tachycardia and ventricular tachycardia during 3 degrees AVB; 3) reactive ventricular and atrial fetal heart rate (FHR) tracings at ventricular rates >56 beats/min; and 4) flat ventricular FHR tracings at ventricular rates <56 beats/min despite reactive atrial FHR tracings. In contrast, fetuses with 3 degrees AVB associated with structural cardiac disease exhibited predominantly nonreactive heart rate tracings and simpler rhythms. CONCLUSIONS Second-degree AVB, isolated 3 degrees AVB, and 3 degrees AVB associated with structural cardiac disease manifest distinctly different electrophysiological characteristics and outcome. Fetuses with 2 degrees AVB or isolated 3 degrees AVB commonly exhibited complex, changing heart rate and rhythm patterns; all 19 delivered fetuses are alive and healthy. Fetuses with structural cardiac disease and 3 degrees AVB exhibited largely monotonous heart rate and rhythm patterns and poor prognosis. Junctional ectopic tachycardia and/or ventricular tachycardia may be characteristic of an acute stage of heart block.

Fetal cardiac arrhythmia detection and in utero therapy

The human fetal heart develops arrhythmias and conduction disturbances in response to ischemia, inflammation, electrolyte disturbances, altered load states, structural defects, inherited genetic conditions, and many other causes. Yet sinus rhythm is present without altered rate or rhythm in some of the most serious electrophysiological diseases, which makes detection of diseases of the fetal conduction system challenging in the absence of magnetocardiographic or electrocardiographic recording techniques. Life-threatening changes in QRS or QT intervals can be completely unrecognized if heart rate is the only feature to be altered. For many fetal arrhythmias, echocardiography alone can assess important clinical parameters for diagnosis. Appropriate treatment of the fetus requires awareness of arrhythmia characteristics, mechanisms, and potential associations. Criteria to define fetal bradycardia specific to gestational age are now available and may allow detection of ion channelopathies, which are associated with fetal and neonatal bradycardia. Ectopic beats, once thought to be entirely benign, are now recognized to have important pathologic associations. Fetal tachyarrhythmias can now be defined precisely for mechanism-specific therapy and for subsequent monitoring of response. This article reviews the current and future diagnostic techniques and pharmacologic treatments for fetal arrhythmia.

Assessment of fetal neurodevelopment via fetal magnetocardiography

Fetal magnetocardiography (fMCG) offers unique capabilities for assessment of fetal heart rate (FHR) and fetal behavior, which are fundamental aspects of neurodevelopment. The most important attribute of fMCG for FHR monitoring is its high precision, which allows accurate assessment of beat-to-beat fetal heart rate variability (FHRV), including respiratory sinus arrhythmia. Using mathematical indices to assess FHRV, we find that short- and long-term FHRV both increase during gestation but not in the same manner. The largest increases in short-term FHRV occur during the last trimester, while the largest increases in long-term FHRV occur early on, with smaller changes occurring during the last trimester. The fMCG also allows assessment of fetal activity. This results from the high sensitivity of the signal to the position and orientation of the fetal heart. FMCG actograms are therefore specific for fetal trunk movement, which are thought to be more important than isolated extremity movements and other small fetal movements. The ability to assess FHR, FHRV, and fetal trunk movement simultaneously makes fMCG a valuable tool for neurodevelopment research.

A Compact, High Performance Atomic Magnetometer for Biomedical Applications

We present a highly sensitive room-temperature atomic magnetometer (AM), designed for use in biomedical applications. The magnetometer sensor head is only 2 × 2 × 5 cm3 and is constructed using readily available, low-cost optical components. The magnetic field resolution of the AM is <10 fT Hz–1/2, which is comparable to cryogenically cooled superconducting quantum interference device (SQUID) magnetometers. We present side-by-side comparisons between our AM and a SQUID magnetometer, and show that equally high quality magnetoencephalography and magnetocardiography recordings can be obtained using our AM.

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.

In Utero Diagnosis of Long QT Syndrome by Magnetocardiography

Background— The electrophysiology of long QT syndrome (LQTS) in utero is virtually unstudied. Our goal here was to evaluate the efficacy of fetal magnetocardiography (fMCG) for diagnosis and prognosis of fetuses at risk of LQTS. Methods and Results— We reviewed the pre/postnatal medical records of 30 fetuses referred for fMCG because of a family history of LQTS (n=17); neonatal/childhood sudden cardiac death (n=3), or presentation of prenatal LQTS rhythms (n=12): 2° atrioventricular block, ventricular tachycardia, heart rate < 3rd percentile. We evaluated heart rate and reactivity, cardiac time intervals, T-wave characteristics, and initiation/termination of Torsade de Pointes, and compared these with neonatal ECG findings. After birth, subjects were tested for LQTS mutations. Based on accepted clinical criteria, 21 subjects (70%; 9 KCNQ1, 5 KCNH2, 2 SCN5A, 2 other, 3 untested) had LQTS. Using a threshold of corrected QT= 490 ms, fMCG accurately identified LQTS fetuses with 89% (24/27) sensitivity and 89% (8/9) specificity in 36 sessions. Four fetuses (2 KCNH2 and 2 SCN5A), all with corrected QT ≥ 620 ms, had frequent episodes of Torsade de Pointes, which were present 22–79% of the time. Although some episodes initiated with a long-short sequence, most initiations showed QRS aberrancy and a notable lack of pause dependency. T-wave alternans was strongly associated with severe LQTS phenotype. Conclusions— Corrected QT prolongation (≥490 ms) assessed by fMCG accurately identified LQTS in utero; extreme corrected QT prolongation (≥620 ms) predicted Torsade de Pointes. FMCG can play a critical role in the diagnosis and management of fetuses at risk of LQTS.

Whole head mapping of magnetic fields following painful electric finger shock

Painful intracutaneous electric finger shock was delivered to the fifth digit of the non-dominant hand of five healthy volunteers. Whole head evoked magnetic field maps were collected and cortical localizations were calculated using local sphere equivalent current dipole fits. MRI scans were used to identify the anatomical structures where magnetic field sources were located. Anatomically, sources were identified bilaterally in the primary somatosensory region and SII-Insula regions. Additionally, frontal operculum sources were observed contralaterally in two subjects. Temporally, an initial contralateral SI activation at 40-60 ms was followed by several SII-Insula responses over the next several hundred milliseconds (ms). These SII-Insula responses were often interspersed with additional activations of the SI region. These later responses were observed in both hemispheres.