William B. Drake

Magnetographic assessment of fetal hiccups and their effect on fetal heart rhythm

Fetal hiccups emerge as early as nine weeks post-conception, being the predominant diaphragmatic movement before 26 weeks of gestation. They are considered as a programmed isometric inspiratory muscle exercise of the fetus in preparation for the post-natal respiratory function, or a manifestation of a reflex circuitry underlying the development of suckling and gasping patterns. The present paper provides the first evidence of non-invasive biomagnetic measurements of the diaphragm spasmodic contractions associated with fetal hiccups. The magnetic field patterns generated by fetal hiccups exhibit well-defined morphological features, consisting of an initial high frequency transient waveform followed by a more prolonged low frequency component. This pattern is consistent across recordings obtained from two fetal subjects, and it is confirmed by signals recorded in a neonatal subject. These results demonstrate that fetal biomagnetometry can provide insights into the electrophysiological mechanisms of diaphragm motor function in the fetus. Additionally, we study the correlation between hiccup events and fetal cardiac rhythm and provide evidence that hiccups may modulate the fetal heart rate during the last trimester of pregnancy.

Bioengineered human and allogeneic pulmonary valve conduits chronically implanted orthotopically in baboons: Hemodynamic performance and immunologic consequences

OBJECTIVE This study assesses in a baboon model the hemodynamics and human leukocyte antigen immunogenicity of chronically implanted bioengineered (decellularized with collagen conditioning treatments) human and baboon heart valve scaffolds. METHODS Fourteen baboons underwent pulmonary valve replacement, 8 with decellularized and conditioned (bioengineered) pulmonary valves derived from allogeneic (N = 3) or xenogeneic (human) (N = 5) hearts; for comparison, 6 baboons received clinically relevant reference cryopreserved or porcine valved conduits. Panel-reactive serum antibodies (human leukocyte antigen class I and II), complement fixing antibodies (C1q binding), and C-reactive protein titers were measured serially until elective sacrifice at 10 or 26 weeks. Serial transesophageal echocardiograms measured valve function and geometry. Differences were analyzed with Kruskal-Wallis and Wilcoxon rank-sum tests. RESULTS All animals survived and thrived, exhibiting excellent immediate implanted valve function by transesophageal echocardiograms. Over time, reference valves developed a smaller effective orifice area index (median, 0.84 cm(2)/m(2); range, 1.22 cm(2)/m(2)), whereas all bioengineered valves remained normal (effective orifice area index median, 2.45 cm(2)/m(2); range, 1.35 cm(2)/m(2); P = .005). None of the bioengineered valves developed elevated peak transvalvular gradients: 5.5 (6.0) mm Hg versus 12.5 (23.0) mm Hg (P = .003). Cryopreserved valves provoked the most intense antibody responses. Two of 5 human bioengineered and 2 of 3 baboon bioengineered valves did not provoke any class I antibodies. Bioengineered human (but not baboon) scaffolds provoked class II antibodies. C1q(+) antibodies developed in 4 recipients. CONCLUSIONS Valve dysfunction correlated with markers for more intense inflammatory provocation. The tested bioengineering methods reduced antigenicity of both human and baboon valves. Bioengineered replacement valves from both species were hemodynamically equivalent to native valves.

Reconstruction of Fetal Cardiac Vectors From Multichannel fMCG Data Using Recursively Applied and Projected Multiple Signal Classification

Previous attempts at unequivocal specification of signal strength in fetal magnetocardiographic (fMCG) recordings have used an equivalent current dipole (ECD) to estimate the cardiac vector at the peak of the averaged QRS complex. However, even though the magnitude of fetal cardiac currents are anticipated to be relatively stable, ECD-based estimates of signal strength show substantial and unrealistic variation when comparing results from different time windows of the same recording session. The present study highlights the limitations of the ECD model, and proposes a new methodology for fetal cardiac source reconstruction. The proposed strategy relies on recursive subspace projections to estimate multiple dipoles that account for the distributed myocardial currents. The dipoles are reconstructed from spatio-temporal fMCG data, and are subsequently used to derive estimators of the cardiac vector over the entire QRS. The new method is evaluated with respect to simulated data derived from a model of ventricular depolarization, which was designed to account for the complexity of the fetal cardiac source configuration on the QRS interval. The results show that the present methodology overcomes the drawbacks of conventional ECD fitting, by providing robust estimators of the cardiac vector. Additional evaluation with real fMCG data show fetal cardiac vectors whose morphology closely resembles that obtained in adult MCG

The effect of volume conductor modeling on the estimation of cardiac vectors in fetal magnetocardiography

Previous studies based on fetal magnetocardiographic (fMCG) recordings used simplified volume conductor models to estimate the fetal cardiac vector as an unequivocal measure of the cardiac source strength. However, the effect of simplified volume conductor modeling on the accuracy of the fMCG inverse solution remains largely unknown. Aiming to determine the sensitivity of the source estimators to the details of the volume conductor model, we performed simulations using fetal-maternal anatomical information from ultrasound images obtained in 20 pregnant women in various stages of pregnancy. The magnetic field produced by a cardiac source model was computed using the boundary-element method for a piecewise homogeneous volume conductor with three nested compartments (fetal body, amniotic fluid and maternal abdomen) of different electrical conductivities. For late gestation, we also considered the case of a fourth highly insulating layer of vernix caseosa covering the fetus. The errors introduced for simplified volume conductors were assessed by comparing the reconstruction results obtained with realistic versus spherically symmetric models. Our study demonstrates the significant effect of simplified volume conductor modeling, resulting mainly in an underestimation of the cardiac vector magnitude and low goodness-of-fit. These findings are confirmed by the analysis of real fMCG data recorded in mid-gestation.

Cardiac vectors in the healthy human fetus: developmental changes assessed by magnetocardiography and realistic approximations of the volume conductor

This study sought to characterize the developmental changes of three measures used to describe the morphology of the fetal cardiac vector: QRS peak-amplitude, QRS duration and QRS time-amplitude integral. To achieve this objective, we rely on a recently developed methodology for fetal cardiac vector estimation, using multichannel fetal magnetocardiographic (fMCG) recordings and realistic approximations of the volume conductors obtained from free-hand ultrasound imaging. fMCG recordings and 3D ultrasound images were obtained from 23 healthy, uncomplicated pregnancies for a total of 77 recordings performed at gestational ages between 22 and 37 weeks. We report the developmental changes of the cardiac vector parameters with respect to gestational age and estimated fetal weight, as well as their dependence on the estimated ventricular mass derived from cardiac dimensions measured with M-mode ultrasound. The normative values can be used along with the cardiac time intervals reported by previous fMCG studies to assist future clinical studies investigating conditions that affect fetal cardiac function.

Cardiac Vector Estimation in Fetal Magnetocardiography Using Realistic Approximations of the Volume Conductor

Fetal magnetocardiography (fMCG) records the magnetic field generated by the electrical activity associated with the fetal cardiac muscle contraction and has emerged as an attractive tool for monitoring the fetal heart in-utero. The magnetic sensor array is placed above the maternal abdomen to receive the extremely weak magnetic signal of the fetal heart from 20 weeks of gestation onward. fMCG outperforms fetal electrocardiography (fECG) in its notably superior signal quality, as the magnetic field is considerably less affected by tissues with low electrical conductivity surrounding the fetal heart [1], which can drastically diminish the fECG signal amplitude.Copyright