Naoaki Sato

Recent Advances in Fetal Electrocardiography

Since the first observations of Cremer in 1906, fetal electrocardiogram (ECG) measurements via the maternal abdominal wall have remained a formidable challenge for clinical technicians and engineers in the cutting-edge field of information theory. Previous obstacles in extracting fetal ECG still complicate their acquisition at the present. These include three main difficulties for non-invasive measurement of fetal ECG: first, the low signal to noise ratio; second, the lack of a standard lead system for fetal ECG on the maternal abdomen; and third, the factor of fetal movement or non-stationarity during recording. A new extraction system based on blind source separation with reference signals (BSSR) was utilized and our detection rates, both off-line (91%) and on-line (60%), in pregnancies of 20 to 41 weeks of gestation have shown a marked improvement from earlier attempts. With this development, we discuss the potentials and limitations of this new system.

Model-Based Estimation of Aortic and Mitral Valves Opening and Closing Timings in Developing Human Fetuses

Electromechanical coupling of the fetal heart can be evaluated noninvasively using doppler ultrasound (DUS) signal and fetal electrocardiography (fECG). In this study, an efficient model is proposed using K-means clustering and hybrid Support Vector Machine-Hidden Markov Model (SVM-HMM) modeling techniques. Opening and closing of the cardiac valves were detected from peaks in the high frequency component of the DUS signal decomposed by wavelet analysis. It was previously proposed to automatically identify the valve motion by hybrid SVM-HMM[1] based on the amplitude and timing of the peaks. However, in the present study, six patterns were identified for the DUS components which were actually variable on a beat-to-beat basis and found to be different for the early gestation (16-32 weeks), compared to the late gestation fetuses (36-41 weeks). The amplitude of the peaks linked to the valve motion was different across the six patterns and this affected the precision of valve motion identification by the previous hybrid SVM-HMM method. Therefore in the present study, clustering of the DUS components based on K-means was proposed and the hybrid SVM-HMM was trained for each cluster separately. The valve motion events were consequently identified more efficiently by beat-to-beat attribution of the DUS component peaks. Applying this method, more than 98.6% of valve motion events were beat-to-beat identified with average precision and recall of 83.4% and 84.2% respectively. It was an improvement compared to the hybrid method without clustering with average precision and recall of 79.0% and 79.8%. Therefore, this model would be useful for reliable screening of fetal wellbeing.

Understanding congenital heart defects through abdominal fetal electrocardiography: Case reports and clinical implications

Aims:  Congenital heart defects are the most common fetal structural anomalies of which a significant number remain unrecognized during postnatal life. Fetal electrocardiography (FECG) is an ideal clinical tool to complement ultrasonography for the screening and management of these cases where early and accurate diagnoses would allow definite rather than palliative treatment. The objective of this report was to correlate the particular FECG results found with the different types of congenital heart defects involved and to further demonstrate the usefulness of FECG in clinical settings.

Evaluation of cardiac performance by abdominal fetal ECG in twin‐to‐twin transfusion syndrome

To investigate fetal cardiac performance by abdominal fetal electrocardiography (ECG) in monochorionic diamniotic pregnancies with twin‐to‐twin transfusion syndrome (TTTS‐MCDA).

Intrauterine Ischemic Reperfusion Switches the Fetal Transcriptional Pattern from HIF-1α- to P53-Dependent Regulation in the Murine Brain

Ischemic reperfusion (IR) during the perinatal period is a known causative factor of fetal brain damage. So far, both morphologic and histologic evidence has shown that fetal brain damage can be observed only several hours to days after an IR insult has occurred. Therefore, to prevent fetal brain damage under these circumstances, a more detailed understanding of the underlying molecular mechanisms involved during an acute response to IR is necessary. In the present work, pregnant mice were exposed to IR on day 18 of gestation by clipping one side of the maternal uterine horn. Simultaneous fetal electrocardiography was performed during the procedure to verify that conditions resulting in fetal brain damage were met. Fetal brain sampling within 30 minutes after IR insult revealed molecular evidence that a fetal response was indeed triggered in the form of inhibition of the Akt-mTOR-S6 synthesis pathway. Interestingly, significant changes in mRNA levels for both HIF-1α and p53 were apparent and gene regulation patterns were observed to switch from a HIF-1α-dependent to a p53-dependent process. Moreover, pre-treatment with pifithrin-α, a p53 inhibitor, inhibited protein synthesis almost completely, revealing the possibility of preventing fetal brain damage by prophylactic pifithrin-α treatment.

Vaginal LPS changed gene transcriptional regulation response to ischemic reperfusion and increased vulnerability of fetal brain hemorrhage

During pregnancy, both ischemic reperfusion and bacterial agent LPS are known risk factors for fetal brain damage. However, there is a lack of evidence to explain whether vaginal LPS affects the fetus response to ischemic reperfusion. Here we reported that there was more than 2 folds higher vulnerability of fetal brain hemorrhage response to ischemic reperfusion when mother mouse was treated with vaginal LPS. As our previously reported, ischemic reperfusion induces P53-dependent fetal brain damage was based on a molecular mechanism: the transcriptional pattern was changed from HIF-1alpha-dependent to P53-dependent immediately. In the present work, only with vaginal LPS precondition, phosphorylation of activated transcriptional factor (ATF) 2 at Thr71 appeared in response to ischemic reperfusion. Moreover, this phosphorylation was completely blocked by pre-treatment with a P53 inhibitor, pifithrin-α. We concluded that vaginal LPS precondition trigged the p53-dependent phosphorylation of ATF2 in response to ischemic reperfusion, which played an important role of increasing vulnerability to hemorrhage in fetus.

Non-invasive evaluation of opening and closing timings of the cardiac valves in the fetal cardiac cycle

In this study, we propose a non-invasive system to recognize the timings of fetal cardiac events on the basis of analysis of fetal ECG and Doppler ultrasound signal together. Fetal ECG was extracted from transabdominal ECG (10 normal subjects, 38-41 weeks of gestation) using blind source separation with the reference signal. Multiresolution wavelet analysis enabled the frequency contents of the Doppler signals to be linked to the opening(o) and closing(c) of the heartpsilas valves (Aortic (A) and mitral(M)). M-mode, B-mode and pulsed Doppler ultrasound were used to examine and verify the timings of opening and closure of aortic as well as mitral valves. The time intervals from Q-wave of QRS complex of fetal ECG to opening and closing of aortic valve, i.e. Q-Ao and Q-Ac were found to be 75.0plusmn11.9 (msec) and 221.6plusmn29.0 (msec) respectively. As for the mitral valve, Q-Mc and Q-Mo were found to be 45.0plusmn18.9 (msec) and 301.6plusmn20.7 (msec) respectively.