Real-Time Magnetocardiography with Passive Miniaturized Coil Array in Earth Ambient Field.

We demonstrate a magnetocardiography (MCG) sensor that operates in non-shielded environments, in real-time, and without the need for an accompanying device to identify the cardiac cycles for averaging. We further validate the sensor's performance on human subjects. Our approach integrates seven (7) coils, previously optimized for maximum sensitivity, into a coil array. Based on Faraday's law, magnetic flux from the heart is translated into voltage across the coils. By leveraging digital signal processing (DSP), namely, bandpass filtering and averaging across coils, MCG can be retrieved in real-time. Our coil array can monitor real-time human MCG with clear QRS complexes in non-shielded environments. Intra- and inter-subject variability tests confirm repeatability and accuracy comparable to gold-standard electrocardiography (ECG), viz., a cardiac cycle detection accuracy of >99.13% and averaged R-R interval accuracy of <5.8 ms. Our results confirm the feasibility of real-time R-peak detection using the MCG sensor, as well as the ability to retrieve the full MCG spectrum as based upon the averaging of cycles identified via the MCG sensor itself. This work provides new insights into the development of accessible, miniaturized, safe, and low-cost MCG tools.

Magnetocardiography on an isolated animal heart with a room-temperature optically pumped magnetometer.

Optically pumped magnetometers are becoming a promising alternative to cryogenically-cooled superconducting magnetometers for detecting and imaging biomagnetic fields. Magnetic field detection is a completely non-invasive method, which allows one to study the function of excitable human organs with a sensor placed outside the human body. For instance, magnetometers can be used to detect brain activity or to study the activity of the heart. We have developed a highly sensitive miniature optically pumped magnetometer based on cesium atomic vapor kept in a paraffin-coated glass container. The magnetometer is optimized for detection of biological signals and has high temporal and spatial resolution. It is operated at room- or human body temperature and can be placed in contact with or at a mm-distance from a biological object. With this magnetometer, we detected the heartbeat of an isolated guinea-pig heart, which is an animal widely used in biomedical studies. In our recordings of the magnetocardiogram, we can detect the P-wave, QRS-complex and T-wave associated with the cardiac cycle in real time. We also demonstrate that our device is capable of measuring the cardiac electrographic intervals, such as the RR- and QT-interval, and detecting drug-induced prolongation of the QT-interval, which is important for medical diagnostics.

Fetal rhythm-based language discrimination: a biomagnetometry study.

Using fetal biomagnetometry, this study measured changes in fetal heart rate to assess discrimination of two rhythmically different languages (English and Japanese). Two-minute passages in English and Japanese were read by the same female bilingual speaker. Twenty-four mother-fetus pairs (mean gestational age=35.5 weeks) participated. Fetal magnetocardiography was recorded while the participants were presented first with passage 1, a passage in English, and then, following an 18 min interval, with passage 2, either a different passage in English (English-English condition: N=12) or in Japanese (English-Japanese condition: N=12). The fetal magnetocardiogram was reconstructed following independent components analysis decomposition. The mean interbeat intervals were calculated for a 30 s baseline interval directly preceding each passage and for the first 30 s of each passage. We then subtracted the mean interbeat interval of the 30 s baseline interval from that of the first 30 s interval, yielding an interbeat interval change value for each passage. A significant interaction between condition and passage indicated that the English-Japanese condition elicited a more robust interbeat interval change for passage 2 (novelty phase) than for passage 1 (familiarity phase), reflecting a faster heart rate during passage 2, whereas the English-English condition did not. This effect indicates that fetuses are sensitive to the change in language from English to Japanese. These findings provide the first evidence for fetal language discrimination as assessed by fetal biomagnetometry and support the hypothesis that rhythm constitutes a prenatally available building block in language acquisition.

Noninvasive Determination of HV Interval Using Magnetocardiography.

BACKGROUND: The His-ventricular (HV) interval is an important index of atrioventricular conduction, but at present can be reliably measured only during an invasive electrophysiology (EP) study. Magnetocardiography (MCG) is a noninvasive measurement of weak magnetic fields generated by the heart. We compared HV interval noninvasively assessed using MCG with the corresponding values measured directly in an EP study. METHODS: MCG was measured using a 37-channel system inside a magnetically shielded room in patients who had previously undergone an EP study. His-bundle potential was identified in the PR segment after signal averaging. Magnetic field maps representing the spatial distribution of ramp-like signals in the PR segment generated at various instants of time were used to identify His-bundle signals in cases where the deflection representing the His was ambiguous. RESULTS: The study included 23 patients (14 male, nine female) with a wide range of HV intervals measured during EP study (49 ± 17 ms, range 35-120 ms). In 21 (91%) subjects, discernible His-bundle signals are observed in the PR segment of MCG traces. HV intervals measured between the two methods showed a correlation (r2 = 0.87, P < 0.0001) with a mean difference of 5.4 ± 3.2 ms. CONCLUSION: With the use of new criteria to identify the His-bundle deflection in signal-averaged MCG signals, we report a high success rate in noninvasive HV interval measurement and a good agreement with those from EP study. The results encourage the use of MCG as a noninvasive method for measurement of the HV interval.

The encoding of auditory objects in auditory cortex: insights from magnetoencephalography.

Auditory objects, like their visual counterparts, are perceptually defined constructs, but nevertheless must arise from underlying neural circuitry. Using magnetoencephalography (MEG) recordings of the neural responses of human subjects listening to complex auditory scenes, we review studies that demonstrate that auditory objects are indeed neurally represented in auditory cortex. The studies use neural responses obtained from different experiments in which subjects selectively listen to one of two competing auditory streams embedded in a variety of auditory scenes. The auditory streams overlap spatially and often spectrally. In particular, the studies demonstrate that selective attentional gain does not act globally on the entire auditory scene, but rather acts differentially on the separate auditory streams. This stream-based attentional gain is then used as a tool to individually analyze the different neural representations of the competing auditory streams. The neural representation of the attended stream, located in posterior auditory cortex, dominates the neural responses. Critically, when the intensities of the attended and background streams are separately varied over a wide intensity range, the neural representation of the attended speech adapts only to the intensity of that speaker, irrespective of the intensity of the background speaker. This demonstrates object-level intensity gain control in addition to the above object-level selective attentional gain. Overall, these results indicate that concurrently streaming auditory objects, even if spectrally overlapping and not resolvable at the auditory periphery, are individually neurally encoded in auditory cortex, as separate objects.

Effects of docosahexaenoic acid supplementation during pregnancy on fetal heart rate and variability: a randomized clinical trial.

DHA (22:6n-3) supplementation during infancy has been associated with lower heart rate (HR) and improved neurobehavioral outcomes. We hypothesized that maternal DHA supplementation would improve fetal cardiac autonomic control and newborn neurobehavior. Pregnant women were randomized to 600 mg/day of DHA or placebo oil capsules at 14.4 (+/-4) weeks gestation. Fetal HR and HRV were calculated from magnetocardiograms (MCGs) at 24, 32 and 36 weeks gestational age (GA). Newborn neurobehavior was assessed using the Neonatal Behavioral Assessment Scale (NBAS). Post-partum maternal and infant red blood cell (RBC) DHA was significantly higher in the supplemented group as were metrics of fetal HRV and newborn neurobehavior in the autonomic and motor clusters. Higher HRV is associated with more responsive and flexible autonomic nervous system (ANS). Coupled with findings of improved autonomic and motor behavior, these data suggest that maternal DHA supplementation during pregnancy may impart an adaptive advantage to the fetus.

The effect of routine magnesium supplementation on fetal cardiac time intervals: a fetal magnetocardiographic study.

OBJECTIVES: Magnesium deficiency in pregnancy is frequent, and in consequence magnesium supplementation is widely used. As magnesium crosses the placental barrier and since the fetal kidney does not excrete magnesium as efficiently as the mature kidney, effects on fetal cardiac time intervals are probable, but still unknown. STUDY DESIGN: Sixty pregnant women were included in an observational study: 31 patients received oral routine magnesium supplementation. In addition to routine fetal echocardiography, fetal magnetocardiography (fMCG) was used to investigate electrophysiological rhythm patterns with high temporal resolution. fMCG tracings were analyzed according to a predefined procedure for fetal cardiac time interval (CTI)-detection. fCTI findings (P-wave, PQ-segment, PR-interval, QRS complex, ST segment, T-wave and QTc interval) were registered. RESULTS: Significant widening of the QRS-complex (p=0.004) was demonstrated in fetuses whose mothers received magnesium supplementation (240 mg/day) relative to the control group. CONCLUSION: Magnesium exposed fetuses demonstrated a prolonged ventricular arousal, but healthy neonatal outcome was found in all exposed fetuses. Although fMCG is a preclinical method and limited in its availability, the procedure could help to monitor fetuses.

Electrogram organization predicts left atrial reverse remodeling after the restoration of sinus rhythm by catheter ablation in patients with persistent atrial fibrillation.

BACKGROUND: Despite the informative nature of atrial fibrillation (AF) electrograms, electrophysiological aspects of predicting reversal of structural remodeling of the left atrium (LA) have not been evaluated. OBJECTIVES: To identify predictors of reverse remodeling after restoration of sinus rhythm by catheter ablation in patients with persistent AF. METHODS: This study included 90 patients with persistent AF and enlarged LA (left atrial volume indexed to body surface area [LAVi] ≥32 mL/m(2)). LAVi was measured by echocardiography before ablation and 12 months after sinus rhythm restoration. We divided 73 (81%) patients free from recurrences into 2 groups according to reduction in LAVi: responders, reduction ≥23% (n = 35); nonresponders, reduction <23% (n = 38). Serological testing and electrophysiological characteristics on electrocardiogram and magnetocardiogram were analyzed. RESULTS: LAVi decreased from 43 ± 12 to 27 ± 7 mL/m(2) in responders and from 37 ± 8 to 33 ± 8 mL/m(2) in nonresponders. Higher LAVi at baseline (P = .01), lower age (59 ± 7 years vs 63 ± 7 years; P <.05), higher brain natriuretic peptide level (median = 92, interquartile range [IQR] = 98 pg/mL vs median = 60, IQR = 64 pg/mL; P = 0.01), higher atrial natriuretic peptide level (median = 73, IQR = 74 pg/mL vs median = 54, IQR = 70 pg/mL; P = .02), and higher organization index of AF signals (0.51 ± 0.11 vs 0.42 ± 0.09; P = .0001) were observed in responders. There was a linear correlation between organization index and % reduction in LAVi (R = 0.63; P <.0001). Multiple linear regression analysis showed relations between reverse remodeling and age (ß = -0.28; P = .002), atrial natriuretic peptide level (ß = 0.21; P = .03), and organization index (ß = 0.53; P <.0001). CONCLUSIONS: Electrogram organization was a robust predictor of reverse remodeling of the enlarged LA after sinus rhythm restoration by catheter ablation in patients with persistent AF.

An increase in right atrial magnetic strength is a novel predictor of recurrence of atrial fibrillation after radiofrequency catheter ablation.

BACKGROUND: Differences in electrical properties between left and right atria (LA and RA) after pulmonary vein isolation (PVI) for atrial fibrillation (AF) are currently poorly understood. Magnetocardiograms were used to investigate the effect of PVI on bi-atrial magnetic field changes and their relationship to clinical outcomes. METHODS AND RESULTS: This study included 71 patients undergoing PVI for paroxysmal AF. Magnetocardiograms were recorded at baseline and 1 day, 8 weeks, and 24 weeks after ablation. Peak magnitude of LA and RA segments on P waves was separately compared before and after PVI. During a 16-month post-ablation period, 53 (75%) patients were free from AF recurrences. LA magnetic strength in patients without recurrence persistently decreased for 24 weeks and was significantly lower at 8 weeks than that in patients with recurrence (1.28±0.69 vs. 1.74±0.71 pico-Tesla, P=0.02). RA magnetic strength in patients with recurrence persistently rose for 24 weeks and was significantly higher at 8 weeks than that in patients without recurrence (2.17±0.82 vs. 3.00±1.12 pico-Tesla, P=0.001). Multivariate analysis showed RA magnetic strength at 8 weeks to be the strongest predictor of AF recurrence (odds ratio=3.335; 95% confidence interval=1.181-9.416; P=0.02). CONCLUSIONS: PVI resulted in distinct changes in magnetic strength in both the LA and the RA. A persistent rise in RA magnetic strength might be a robust predictor of AF recurrence after ablation.

Increased left prefrontal activation during an auditory language task in adolescents born preterm at high risk.

Although individuals born preterm are at risk for cognitive dysfunction, few studies have examined functional brain reorganization in these individuals. We used magnetoencephalography (MEG) to examine cortical reorganization related to preterm birth. Thirty-one adolescents systemically selected from a longitudinal study on child development based on gestational age, birth weight and medical complications (full term, low risk preterm, high-risk preterm) performed real-word and non-word auditory rhyme tasks during MEG recording. Equivalent current dipoles were localized every 4ms during the 50- to 250-ms period following the onset of the auditory stimulus. The association between the number of dipoles (NODs) and birth group, language task, latency and phonological skills was examined. Adolescents born preterm at high risk demonstrated a greater NODs in the left Broca's and prefrontal areas combined, left cingulate gyrus and left superior temporal gyrus and a fewer NODs in the right superior temporal gyrus as compared to those born preterm at low risk and term. A greater NODs in the left Broca's and prefrontal areas combined and fewer NODs in the left cingulate gyrus was associated with better phonological skills only in adolescents born preterm at high risk. These results suggest that the language networks are reorganized in adolescents born preterm at high risk. Increased prefrontal activity has also been seen in adolescents born preterm during a reading task and in young adults with a history of dyslexia who are well compensated for their disorder. We suggest that this increased prefrontal activation may represent increased top-down control of weak posterior language networks.

Premotor cortex mediates perceptual performance.

Articulatory goals have long been proposed to mediate perception. Examples include direct realist and constructivist (analysis by synthesis) theories of speech perception. Although the activity in brain regions involved with action production has been shown to be present during action observation (Mirror Neuron System), the relationship of this activity to perceptual performance has not been clearly demonstrated at the event level. To this end we used functional magnetic resonance imaging fMRI and magnetoencephalography MEG to measure brain activity for correct and incorrect trials of an auditory phonetic identification in noise task. FMRI analysis revealed activity in the premotor cortex including the neighboring frontal opercular part of Broca's area (PMC/Broca's) for both perception and production tasks involving the same phonetic stimuli (potential mirror system site) that was significantly greater for correct over incorrect perceptual identification trials. Time-frequency analysis of single trials conducted over MEG current localized to PMC/Broca's using a hierarchical variational Bayesian source analysis technique revealed significantly greater event-related synchronization ERS and desynchronization ERD for correct over incorrect trials in the alpha, beta, and gamma frequency range prior to and after stimulus presentation. Together, these fMRI and MEG results are consistent with the hypothesis that articulatory processes serve to facilitate perceptual performance, while further dispelling concerns that activity found in ventral PMC/Broca's (mirror system) is merely a product of covert production of the perceived action. The finding of performance predictive activity prior to stimulus onset as well as activity related to task difficulty instead of information available in stimulation are consistent with constructivist and contrary to direct realist theories of perception.

Non-invasive detection of conduction pathways to left atrium using magnetocardiography: validation by intra-cardiac electroanatomic mapping.

AIMS: Alteration in conduction from right to left atrium (LA) is linked to susceptibility to atrial fibrillation (AF). We examined whether different inter-atrial conduction pathways can be identified non-invasively by magnetocardiographic mapping (MCG). METHODS AND RESULTS: In 27 patients undergoing catheter ablation of paroxysmal AF, LA activation sequence was determined during sinus rhythm using invasive electroanatomic mapping. Before this, 99-channel magnetocardiography was recorded over anterior chest. The orientation of the magnetic fields during the early (40-70 ms from P onset) and later part (last 50%) of LA depolarization was determined using pseudocurrent conversion. Breakthrough of electrical activation to LA occurred through Bachmann bundle (BB) in 14, margin of fossa ovalis (FO) in 3, coronary sinus ostial region (CS) in 2, and their combinations in 10 cases by invasive reference in total of 29 different P-waves. Based on the combination of pseudocurrent angles over early and late parts of LA activation, the MCG maps were divided to three types. These types correctly identified the LA breakthrough sites to BB, CS, FO, or their combinations in 27 of 29 (93%) cases. CONCLUSION: Magnetocardiographic mapping seems capable of distinguishing inter-atrial conduction pathways. Recognizing the inter-atrial conduction pattern may assist in understanding the pathogenesis of AF and identifying the subgroups for patient-tailored therapy.

High-resolution signal-averaged analysis of atrial electromagnetic characteristics in patients with paroxysmal lone atrial fibrillation.

BACKGROUND: Abnormalities in the electromagnetic signal of the atria during sinus rhythm could serve as markers of triggering foci or substrate for atrial fibrillation (AF). We examined atrial electrophysiologic properties noninvasively by using magnetocardiographic mapping (MCG) in patients with paroxysmal lone AF to find whether any difference exists between those who have frequent triggers of AF and who don't. METHODS: MCG was recorded over anterior chest during sinus rhythm in 80 patients with paroxysmal lone AF (44 +/- 12 years, 61 males) and 80 matched controls. Atrial wave duration (Pd) and root mean square amplitudes of the last 40 ms (RMS40) of the averaged filtered atrial complex were determined automatically. Patients expressing atrial arrhythmias triggering AF episodes were classified as focal AF. RESULTS: The Pd was 109 ms in patients and 104 ms in controls (P = 0.007). In focal AF (72%) the Pd was slightly prolonged and its proportion of the PR interval was larger, but RMS40 was normal compared to controls. In other patients, the Pd was close to controls, but the RMS40 was reduced (59 +/- 17 vs74 +/- 36 fT, P = 0.006). Pd and atrial RMS amplitudes were unrelated to duration of AF history or frequency of recurrences. CONCLUSION: Clinical subclasses of lone AF seem to possess distinct signal profiles of atrial depolarization. Differences in electrophysiological properties between these subclasses may reflect pathogenetic variation and could have implications on diagnostics and therapy.

Supraventricular tachycardia in fetus: how can we treat ?

The normal fetal cardiac rhythm is characterized by a regular heart rate ranging between 100 and 160 -180 beats/min with a normal 1: 1 atrioventricular electromechanical relationship during each cardiac cycle. Fetal tachycardia occurring in approximately 0.5% of all pregnancies and it is an important cause of fetal morbidity and mortality. A fetal tachycardic heart is at risk for developing low cardiac output, hydrops and ultimately fetal death or significant neurological morbidity. Different conditions can play a role to determine the natural history of tachycardic fetus as gestational age, underlying pathophysiology of the arrhythmia, fetal heart rate, duration of the tachyarrhythmia, and presence or absence of cardiac dysfunction. Reliable diagnosis in utero of fetal arrhythmia is possible by ultrasound examination of the fetal heart. In fact pulsed wave Doppler guided by two-dimensional echocardiography provided important information on cardiac rhythm as it study the blood flow from different chambers. With the introduction of the latest myocardial deformation methodology, the fetal tachyarrhythmias can be diagnosed more accu notrately. Precise diagnosis of cardiac arrhythmias in the fetus is crucial for a managed therapeutic approach. The choice of management is correlated to many factors: gestational age, underlying pathophysiology of the arrhythmia, fetal heart rate, duration of the tachyarrhythmia, and presence or absence of cardiac dysfunction. A large review of fetal arrhythmias was been reported in our work.

Dietary n-3 polyunsaturated fatty acids and direct renin inhibition improve electrical remodeling in a model of high human renin hypertension.

We compared the effect n-3 polyunsaturated fatty acids (PUFAs) with direct renin inhibition on electrophysiological remodeling in angiotensin II-induced cardiac injury. We treated double-transgenic rats expressing the human renin and angiotensinogen genes (dTGRs) from week 4 to 7 with n-3 PUFA ethyl-esters (Omacor; 25-g/kg diet) or a direct renin inhibitor (aliskiren; 3 mg/kg per day). Sprague-Dawley rats were controls. We performed electrocardiographic, magnetocardiographic, and programmed electrical stimulation. Dietary n-3 PUFAs increased the cardiac content of eicosapentaenoic and docosahexaenoic acid. At week 7, mortality in dTGRs was 31%, whereas none of the n-3 PUFA- or aliskiren-treated dTGRs died. Systolic blood pressure was modestly reduced in n-3 PUFA-treated (180+/-3 mm Hg) compared with dTGRs (208+/-5 mm Hg). Aliskiren-treated dTGRs and Sprague-Dawley rats were normotensive (110+/-3 and 119+/-6 mm Hg, respectively). Both n-3 PUFA-treated and untreated dTGRs showed cardiac hypertrophy and increased atrial natriuretic peptide levels. Prolonged QRS and QT(c) intervals and increased T-wave dispersion in dTGRs were reduced by n-3 PUFAs or aliskiren. Both treatments reduced arrhythmia induction from 75% in dTGRs to 17% versus 0% in Sprague-Dawley rats. Macrophage infiltration and fibrosis were reduced by n-3 PUFAs and aliskiren. Connexin 43, a mediator of intermyocyte conduction, was redistributed to the lateral cell membranes in dTGRs. n-3 PUFAs and aliskiren restored normal localization to the intercalated disks. Thus, n-3 PUFAs and aliskiren improved electrical remodeling, arrhythmia induction, and connexin 43 expression, despite a 70-mm Hg difference in blood pressure and the development of cardiac hypertrophy.

Biomagnetism in perinatal medicine. Our experience in Greece.

This is a report on our experience in the application of biomagnetism in perinatal medicine. We provide a brief description of our research work in fetal magnetoencephalography and fetal magnetocardiography in normal, preeclamptic and IUGR pregnancies, together with hemodynamics of the umbilical cord and uterine arteries, providing a new approach to biomagnetism as a non invasive imaging modality in the investigation of perinatal complications.