Early Fetal Heart Research Articles

Multi-scale input reconstruction network and one-stage instance segmentation for enhancing heart defect prediction rate

<p>Artifacts and unpredictable fetal movements can hinder clear fetal heart imaging during ultrasound scans, complicating anatomical identification. This study presents a new medical imaging approach that combines one-stage instance segmentation with ultrasound (US) video enhancement for precise fetal heart defect detection. This innovation allows real-time identification and timely medical intervention. The study acquired 100 fetal heart US videos from an Indonesian Hospital featuring cardiac septal defects, generating 1,000 frames for training, validation, and testing. Utilizing a combination of the multi-scale input reconstruction network (MIRNet) for image enhancement and YOLOv8l-seg for real-time instance segmentation, the method achieved outstanding validation results, boasting a 99.50% mAP for bounding box prediction and 98.40% for mask prediction. It delivered a remarkable real-time processing speed of 68.4 frames per second. In application to new patients, the method yielded a 65.93% mAP for bounding box prediction and 57.66% for mask prediction. This proposed approach offers a promising solution to early fetal heart defect detection using ultrasound, holding substantial potential for enhancing healthcare outcomes.</p>

Evaluation of cardiac findings using speckle tracking in fetuses with hemoglobin Bart's disease.

Hemoglobin (Hb) Bart's disease is a severe manifestation of alpha thalassemia, resulting in fetal tissue hypoxia and severe anemia. There is limited research available on assessing fetal speckle tracking analysis as a response to fetal anemia caused by Hb Bart's disease and its utility as a sonographic predictor for Hb Bart's disease. This study aimed to assess the diagnostic performance of fetal cardiac parameters derived from speckle tracking echocardiography for distinguishing between affected and unaffected fetuses in pregnancies at risk of Hb Bart's disease during the 17-24 gestational weeks. A total of 115 pregnant women at risk for fetal Hb Bart's disease, who underwent either amniocentesis or cordocentesis at Siriraj Hospital, Bangkok Thailand, were included. Speckle tracking analysis was performed on the 4-chamber view (4CV) of the fetal heart, assessing heart size, shape, ventricular contractility, and left ventricular function prior to invasive prenatal testing. Logistic regression analysis determined significant cardiac predictors and calculated the probability of a fetus having Hb Bart's disease. Among the cohort, 38 fetuses (33%) were diagnosed with Hb Bart's disease, and 9 cases (7.8%) exhibited frank hydropic signs. In comparison to the control group, affected fetuses displayed a notable enlargement of the 4CV and a more globular shape specifically in the right ventricular chamber. Additionally, there were significant differences in the left global and longitudinal contractility between affected and unaffected fetuses. However, at mid-gestation, no significant distinctions were observed in terms of transverse contractility and left ventricular function between the two groups. Based on logistic regression analysis, combined cardiac parameters derived from speckle tracking analysis as a function of head circumference, could differentiate non-hydropic fetuses with Hb Bart's disease from unaffected fetuses, achieving a maximum sensitivity of 100%, specificity of 98.7%, and overall accuracy of 99.06%. Speckle tracking echocardiography has the potential to accurately identify early fetal heart changes in individuals at risk of developing Bart's anemia during the second trimester. This not only offers a novel predictive marker for Hb Bart's disease but also helps address the question of the underlying mechanisms of heart failure associated with anemia. This article is protected by copyright. All rights reserved.

Fetal heart rate patterns and the incidence of adverse events after oral misoprostol administration for cervical ripening among low-risk pregnancies

Objective Though misoprostol is commonly used for inpatient cervical ripening, its use in outpatient settings has been limited by safety concerns. This study was conducted to assess the association between early fetal heart tracing (FHT) and maternal tocodynamometry patterns and the incidence of adverse fetal and pregnancy outcomes after the administration of oral misoprostol for cervical ripening. Methods We conducted a retrospective cohort study of 9908 low-risk patients at ≥37 weeks gestation who received oral misoprostol for cervical ripening prior to rupture of membranes between 01/01/2012 and 12/31/2017 at Kaiser Permanente Northern California hospitals as inpatients. We excluded patients who received a different agent for cervical ripening or had any need for additional inpatient monitoring, including hypertensive disorders of pregnancy, diabetes, or intrauterine growth restriction. Abnormal FHT, abnormal uterine activity, and adverse pregnancy or fetal-related events documented in the electronic health record in the four hours after administration of the first and second doses of misoprostol were assessed using descriptive statistics. Results We found that 0.9% of patients experienced tachysystole after the first dose of misoprostol (0.6% without decelerations; 0.3% with decelerations). The incidence of variable decelerations only and other FHT abnormalities (i.e. bradycardia, late or prolonged decelerations, or absent or minimal variability) in the first hour after misoprostol administration were 7.1% and 6.7% respectively, and diminished over time. The need for tocolytic use was 0.2% in the first hour and declined over time to 0.03% in the fourth hour after the first dose. Urgent cesarean delivery occurred in 0.1% of patients after receiving the first dose of misoprostol. Patients who did not experience variable, prolonged, or late decelerations in the first hour after the initial misoprostol dose were less likely to have such FHT abnormalities in the subsequent three hours compared to patients who had other FHT abnormalities (11.8% among patients with no FHT abnormalities vs. 43.7% among patients with other FHT abnormalities; p <.001). The overall trends in outcomes over time were similar after the second dose of misoprostol. Conclusion The risk of short-term adverse outcomes associated with misoprostol is low among relatively low-risk patients. FHT abnormalities occurred in up to 32% of patients in the first four hours of monitoring post-misoprostol. Patients with no FHT abnormalities in the first hour after receiving misoprostol had a low risk of developing adverse outcomes and FHT abnormalities on continued monitoring, while patients with any type of deceleration in the first hour were at higher risk of adverse outcomes and FHT abnormalities. Our data may inform the development of protocols for cervical ripening that allow reduced monitoring for a subset of low-risk patients, however, more research is needed to validate findings and develop clinical protocols.

Defining cardiac cell populations and relative cellular composition of the early fetal human heart.

While the adult human heart is primarily composed of cardiomyocytes, fibroblasts, endothelial and smooth muscle cells, the cellular composition during early development remains largely unknown. Reliable identification of fetal cardiac cell types using protein markers is critical to understand cardiac development and delineate the cellular composition of the developing human heart. This is the first study to use immunohistochemistry (IHC), flow cytometry and RT-PCR analyses to investigate the expression and specificity of commonly used cardiac cell markers in the early human fetal heart (8-12 post-conception weeks). The expression of previously reported protein markers for the detection of cardiomyocytes (Myosin Heavy Chain (MHC) and cardiac troponin I (cTnI), fibroblasts (DDR2, THY1, Vimentin), endothelial cells (CD31) and smooth muscle cells (α-SMA) were assessed. Two distinct populations of cTnI positive cells were identified through flow cytometry, with MHC positive cardiomyocytes showing high cTnI expression (cTnIHigh) while MHC negative non-myocytes showed lower cTnI expression (cTnILow). cTnI expression in non-myocytes was further confirmed by IHC and RT-PCR analyses, suggesting troponins are not cardiomyocyte-specific and may play distinct roles in non-muscle cells during early development. Vimentin (VIM) was expressed in cultured ventricular fibroblast populations and flow cytometry revealed VIMHigh and VIMLow cell populations in the fetal heart. MHC positive cardiomyocytes were VIMLow whilst CD31 positive endothelial cells were VIMHigh. Using markers investigated within this study, we characterised fetal human cardiac populations and estimate that 75-80% of fetal cardiac cells are cardiomyocytes and are MHC+/cTnIHigh/VIMLow, whilst non-myocytes comprise 20-25% of total cells and are MHC-/cTnILow/VIMHigh, with CD31+ endothelial cells comprising ~9% of this population. These findings show distinct differences from those reported for adult heart.

Diagnostic performance of “Superb Microvascular Imaging” in fetal heart exploration during first trimester of pregnancy in a high-risk population for cardiac malformations fetuses

To evaluate the diagnostic performance of Superb Micro vascular Imaging (SMI) at 11–14 weeks of gestation in an early extended fetal heart examination in a high-risk population of fetal cardiac malformations. We present a moncocentric study in a referral unit of fetal medicine in a university hospital in Lyon, from September 2020 to March 2022. Only transabdominal fetal echocardiography was performed with an Aplio i800 US system, Canon Medical Systems, Tokyo, Japan, in routine care, during the first trimester screening, in a high risk population of fetal heart malformations. Extended cardiac examination was performed using six views (four chamber, pulmonary veins, left outflow, right outflow, three vessel trachea, aorta in sagittal view) with B mode, Color Doppler and SMI. All the pregnancies, which were continued, had second trimester heart scan. In total, 142 fetuses were scanned at 11 to 14 weeks gestation. In total, 100% were performed in transabdominal examination. Congenital heart diseases (CHD) were identified in 31 (23%): 11 to 11 + 6 weeks (8.5%), 12 to 12 + 6 weeks (36.6%) 13 to 14 weeks (54.9%). Ninety-two percent of all views were obtained with SMI, 63% in color doppler ( P < 0.001) and 40% in B Mode ( P < 0.001). When adding SMI to the examination, we obtained a complete 6-views examination for 80.3% up to 90.8% with 5 views out of 6 ( P < 0.001); in comparison, those scores were respectively of 23.5% and 45.6% using only B mode and color doppler ( P < 0.001). In total, 106 (75%) normal scans were confirmed at the second trimester control. In detection of CHD, sensitivity and specificity were high (100%). In diagnostic concordance, sensitivity was 92%, specificity 99%, positive predictive value 83% and negative predictive value 99% ( Fig. 1 ). SMI is a complementary mode with B-Mode and Color Doppler to improve early detection of congenital heart disease in this high-risk population, with transabdominal examination.

Design and Realization of Non Invasive Fetal ECG Monitoring System

Early fetal cardiac diseases and heart abnormalities can be detected and appropriately treated by monitoring fetal health during pregnancy. Advancements in computer sciences and the technology of sensors show that is possible to monitor fetal electrocardiogram (fECG). Both signal processing and experimental aspects are needed to be investigated to monitor fECG. In this study, we aim to design and realize a non invasive fECG monitoring system. In the first part of this work, a remote study process of the electrical activity of the heart is achieved. In fact, our proposed design considers transmitting the detected signals in real time using a WiFi module and then analyzing the results on Raspberry Pi 3. As the signal acquired from the mother’s abdomen is contaminated by several noises, in the second part, we propose a method to extract the fetal electrocardiogram FECG by using Independent Component Analysis (ICA) and Wavelet Transform (WT). The proposed method was tested on real data recordings from the publicly available Physionet database. In this paper, we proposed an efficient hardware design to well monitor the heart activity. Then, we presented our adopted method for fECG extraction. The obtained results with the mentioned method show the effectiveness of our proposed algorithm and it is suggested to be used in the portable designed fECG monitoring system.

The diagnostic value of the early extended fetal heart examination at 13 to 14 weeks gestational age in a high-risk population.

BackgroundCongenital heart disease (CHD) is the most common congenital malformation that affects high-risk populations. A more definite heart diagnosis in the first trimester should be provided to guide clinical treatment. The study aim was to evaluate the diagnostic precision of the early extended fetal heart examination (EFHE) that includes abdominal situs view, four-chamber view (4CV), left ventricular outflow tract view (LVOT), right ventricular outflow tract view (RVOT), 3-vessel and tracheal view (3VT), ductal arch view, and the aortic arch view in the detection of CHD at the gestational age (GA) 13 to 14 weeks in a population with high risks.MethodsThis study was a diagnostic test study. EFHE was performed by transabdominal sonography in women at GA 13 to 14 weeks with singleton pregnancies who were at high risk for CHD. The risk of CHD was determined by family history of CHD, rubella infection, metabolic disorders, exposure to teratogens, conception by in-vitro fertilization (IVF), increased nuchal translucency (NT) thickness, abnormal obstetric ultrasound, etc. The operator had more than 5 years of experience in first-trimester scans and fetal echocardiography. Early scans were compared with a fetal echocardiography in the second trimester (16–24 weeks).ResultsEFHE was performed, and the pregnancy outcomes were obtained in 234 single pregnancies with a high risk of CHD. The average crown-rump length (CRL) was (76.17±7.09) mm. CHD was diagnosed in 43 cases by EFHE; 10 of these cases were misdiagnosed, and 2 cases were missed. Four cases were inconsistent in the main diagnosis of CHD. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and kappa coefficient (Ko) value of EFHE in diagnosing CHD by type and severity was 84.6% [95% confidence interval (CI), 69.5–94.1%], 96.9% (95% CI, 93.4–98.9%), 84.6% (95% CI, 69.5–94.1%), 96.9% (95% CI, 93.4–98.9%), and 0.82 (P<0.001), respectively.ConclusionsEFHE can work as a diagnose examination for most major CHD cases at GA 13 to 14 weeks by an experienced operator; Therefore, this diagnostic system for fetal CHD may be applied in the first trimester. The study has been registered in the Chinese Clinical Trial Registry (www.chictr.org.cn). The registration number is ChiCTR2000038451.

Accuracy of the Standardized Early Fetal Heart Assessment in Excluding Major Congenital Heart Defects in High-Risk Population: A Single-Center Experience.

To evaluate the ability of standardized early fetal heart assessment (EFHA) that includes the 4-chamber view, outflow tract relationship (OTR), and transverse arches views (TAV) of the great arteries in excluding major congenital heart defects (CHDs) in high-risk populations. This retrospective study included high-risk pregnancies for CHDs undergoing EFHA at 11-14 weeks of gestation. Risk factors for CHDs were diabetes mellitus, a family history of CHDs, a history of a CHD use of teratogenic medications, seizure disorder, assisted reproductive treatment-conceived pregnancy, presence of at least one of the ultrasound markers: enlarged nuchal translucency (>95th percentile), tricuspid regurgitation, and reversed a-wave in the ductus venosus, presence of an extracardiac or a suspected cardiac anomaly, a high-risk first trimester combined screen result, and multiple pregnancies. EFHA consisted of visualization of 4ChV, OTR, and TAV, with and without power Doppler ultrasound. The primary outcome was the negative predictive value of EFHA in excluding major CHDs. EFHA was performed on 1055 fetuses. Of these, 1024 were used for the final analysis. Of these, 94.9% (n=923) were singleton. The most common indication for EFHA was maternal DM (n=231, 22.6%). The sensitivity, specificity, false positive, false negative, and accuracy of EFHA were 93.2%, 99.9%, 1.4%, 0.4%, and 99.5% (P < .0001), respectively, in entire included cases. The performance of EFHA was 88%, 99.9%, 1.4%, 0.4%, and 99.5% (P < .0001) respectively when the terminated cases were excluded. Early fetal heart assessment is feasible for screening for major CHDs in high-risk populations. This approach may be expanded to the general obstetric population.

First-trimester fetal heart evaluation: time to move forward.

First-trimester fetal heart evaluation: time to move forward.

Monitoring and Analysis of Early Heart Structure of Fetus in Gynecology and Obstetrics Based on Ultrasound Image

As the core organ of cardiovascular system, fetal heart plays a very important role. With the development of pregnancy, the early fetal heart rate tends to mature, and the corresponding cardiac function tends to mature and stable. But the fetal heart is very fragile during pregnancy. Various diseases during pregnancy directly lead to fetal heart growth restriction, and even lead to fetal heart function damage. Ultrasound image diagnosis is one of the most important diagnostic methods in medical imaging. It is of great significance to detect the early heart structure of the fetus in gynecology and obstetrics. It can detect the early fetal heart in real time and noninvasively. However, the traditional ultrasonic image detection has many disadvantages in the process of application, such as many noise points, low performance of processing algorithm, which to some extent affects the detection performance of ultrasonic image detection in the detection of fetal heart structure in gynecology and obstetrics. Based on the above problems, this paper proposes an adaptive detection algorithm of superimposed moving image based on ultrasonic image detection, which can accurately extract and analyze fetal heart region when the signal-to-noise ratio of ultrasonic image sequence is low. The average anisotropy algorithm is also proposed innovatively in this paper. In order to predict the structure of fetal heart more accurately, the active heart model combining fetal heart structure and motion information is considered in the actual analysis process. Experiments show that the accuracy error of the algorithm is less than 11 pixels.

Novel insights into cardiac regeneration based on differential fetal and adult ovine heart transcriptomic analysis.

The adult mammalian cardiomyocyte has a very limited capacity to reenter the cell cycle and advance into mitosis. Therefore, diseases characterized by lost contractile tissue usually evolve into myocardial remodeling and heart failure. Analyzing the cardiac transcriptome at different developmental stages in a large mammal closer to the human than laboratory rodents may serve to disclose positive and negative cardiomyocyte cell cycle regulators potentially targetable to induce cardiac regeneration in the clinical setting. Thus we aimed at characterizing the transcriptomic profiles of the early fetal, late fetal, and adult sheep heart by employing RNA-seq technique and bioinformatic analysis to detect protein-encoding genes that in some of the stages were turned off, turned on, or differentially expressed. Genes earlier proposed as positive cell cycle regulators such as cyclin A, cdk2, meis2, meis3, and PCNA showed higher expression in fetal hearts and lower in AH, as expected. In contrast, genes previously proposed as cell cycle inhibitors, such as meis1, p16, and sav1, tended to be higher in fetal than in adult hearts, suggesting that these genes are involved in cell processes other than cell cycle regulation. Additionally, we described Gene Ontology (GO) enrichment of different sets of genes. GO analysis revealed that differentially expressed gene sets were mainly associated with metabolic and cellular processes. The cell cycle-related genes fam64a, cdc20, and cdk1, and the metabolism-related genes pitx and adipoq showed strong differential expression between fetal and adult hearts, thus being potent candidates to be targeted in human cardiac regeneration strategies.NEW & NOTEWORTHY We characterized the transcriptomic profiles of the fetal and adult sheep hearts employing RNAseq technique and bioinformatic analyses to provide sets of transcripts whose variation in expression level may link them to a specific role in cell cycle regulation. It is important to remark that this study was performed in a large mammal closer to humans than laboratory rodents. In consequence, the results can be used for further translational studies in cardiac regeneration.

Anatomical structure segmentation from early fetal ultrasound sequences using global pollination CAT swarm optimizer-based Chan-Vese model.

The structure of an early fetal heart provides essential information for the diagnosis of fetus defects. Accurate segmentation of anatomical structure is a major challenging task because of the small size, low signal-to-noise ratio, and rapid movement of the ultrasound images. In recent years, active contour methods have found applications to ultrasound image segmentation. The familiar region-based Chan-Vese (RCV) model is a strong and flexible technique that is able to segment many types of images compared to other active contours. However, the solution trapping in local minima is the main drawback determined on the RCV model with the exposure of improper initial contours. Also, the RCV model showed poor results with this situation. More probably, the images having large intensity differences between global and local structures usually suffered from this problem. To solve this issue, we develop an improved version of the RCV model which is expected to achieve satisfactory segmentation performance, irrespective of the initial selection of the contour. We have formulated a new and hybrid meta-heuristic optimization algorithm namely global pollination-based CAT swarm (GPCATS) optimizer to solve the fitting energy minimization problem. In the GPCATS method, the global pollination step of the flower pollination algorithm (FPA) is used for improving the distance averaging of the CATS algorithm. The performance of the proposed method was analyzed on different fetal heart ultrasound videos acquired from 12 subjects. Each frame of each video was manually annotated in order to provide labels for training and validating the model. Experimental results of the proposed model proved that the precision of locating boundaries is improved greatly and requires only a reduced number of iterations (75% less) for convergence compared to the traditional RCV model. This proposed method also proved that our model not only enhances the accuracy of locating boundaries but also works stronger robustness than some other active contour methods. Graphical Abstract Anatomical structure segmentation from early fetal ultrasound sequences using GPCATS based Chan-Vese Model.

Expression and localisation of thymosin beta-4 in the developing human early fetal heart.

BackgroundThe objective of this study was to investigate the expression and localisation of thymosin β4 (Tβ4) in the developing human heart. Tβ4 is a cardioprotective protein which may have therapeutic potential. While Tβ4 is an endogenously produced protein with known importance during development, its role within the developing human heart is not fully understood. Elucidating the localisation of Tβ4 within the developing heart will help in understanding its role during cardiac development and is crucial for understanding its potential for cardioprotection and repair in the adult heart.MethodsExpression of Tβ4 mRNA in the early fetal human heart was assessed by PCR using both ventricular and atrial tissue. Fluorescence immunohistochemistry was used to assess the localisation of Tβ4 in sections of early fetal human heart. Co-staining with CD31, an endothelial cell marker, and with myosin heavy chain, a cardiomyocyte marker, was used to determine whether Tβ4 is localised to these cell types within the early fetal human heart.ResultsTβ4 mRNA was found to be expressed in both the atria and the ventricles of the early fetal human heart. Tβ4 protein was found to be primarily localised to CD31-expressing endothelial cells and the endocardium as well as being present in the epicardium. Tβ4-associated fluorescence was greater in the compact layer of the myocardial wall and the interventricular septum than in the trabecular layer of the myocardium.ConclusionsThe data presented illustrates expression of Tβ4 in the developing human heart and demonstrates for the first time that Tβ4 in the human heart is primarily localised to endothelial cells of the cardiac microvasculature and coronary vessels as-well as to the endothelial-like cells of the endocardium and to the epicardium.

Applicability of Standardized Early Fetal Heart Examination in the Obese Population.

This study aimed to evaluate the impact of obesity on early evaluation of fetal cardiac landmarks using a standardized examination method at the time of nuchal translucency scan. This was a cross-sectional study of an ongoing prospective cohort at high risk for congenital heart defects. We used a standardized examination protocol using 2-dimensional sonography with power Doppler in the evaluation of fetal cardiac landmarks consisting of 4-chamber view, outflow tract relationship, and transverse arches view. The study population was stratified based on maternal body mass index into nonobese (<30 kg/m2 ) and obese (≥30 kg/m2 ). Groups were compared in terms of satisfactory evaluation of fetal cardiac landmarks, transvaginal sonography use, and scan times required for the evaluations. Subanalysis was performed by further categorizing obesity into nonmorbid obesity (30.0-39.9 kg/m2 ) and morbid obesity (≥40 kg/m2 ). A total of 190 patients were evaluated. Of these, 48.4% (n = 92) were obese. The most common indication for fetal cardiac assessment was maternal pregestational diabetes mellitus (42.6%). Transvaginal sonography was utilized in one nonobese woman (1.4%) and 11 obese women (12%) (P = .002). The satisfactory evaluation of 4-chamber view, outflow tract relationship, transverse arches view, and all views were not significantly different between groups (P > .05). The scan time was about 5 minutes longer in the obese group compared with nonobese group (P = .020). Obesity does not hamper early evaluation of fetal cardiac landmarks around the time of nuchal translucency scan. However, obese patients are more likely to require transvaginal examinations.

Early fetal heart ultrasonography as additional indicator for chromosomopathies

Objective: First trial of estimating values of scans of fetal heart structures (FHS) in first trimester of pregnancy, as more primary facts of possible chromosomopathies. Materials and Methods: The study included 2,643 fetuses that were examined in first trimester of pregnancy on Sono CT convex (C5-2MHz), endovaginal (ev 8-4MHz), and linear transducers (L12-5MHz) during a period of eight years. Fetal heart was evaluated using appropriate software with broad-band transducers and color Doppler, Sono CT, and HD ZOOM technologies. The scan was performed by three experienced physicians. FHS were based on: left and right ventricle morphology; AV valves (atrioventricular) position and existence of primal ostium; relationship of left ventricle outflow tract (LVOT) and right ventricle outflow tract (RVOT) and great vessels on three vessel view (3VV) and estimation of ductal and aortic arch. Results: Several developments, one being the ability to identify fetuses at risk for cardiac defects combining nuchal translucency (NT), ductus venosus (DV) Doppler, and evaluation of tricuspid regurgitation, have prompted reconsideration of the role of the first trimester prognostic factor of fetal evaluation. In low-risk pregnancies group, 36 (1.8%) fetuses were found to have congenital heart disease (CHD), and in high-risk pregnancies the number of fetuses with CHD was 75 (12%). Genetic amniocentesis or chorionic villus sampling (CVS) was performed in all fetuses with CHD. Forty-two (37.8%) fetuses with CHD were found to have chromosomal anomalies. Out of 111 fetuses with CHD 39 (35.1%) had an nuchal translucency (NT) above three mm. Out of 42 fetuses with chromosomal anomalies and CHD, 29 (69%) had an increased NT. Conclusion: Using first trimester fetal echosonography constitutes a further step in the earlier recognition of chromosomopathies, even in low risk groups. Still further steps are necessary as all facts of good clinical practice. In order to offer further benefits during pregnancies, improvements in diagnostics are still required.

Metabolic gene profile in early human fetal heart development.

The primitive cardiac tube starts beating 6-8 weeks post fertilization in the developing embryo. In order to describe normal cardiac development during late first and early second trimester in human fetuses this study used microarray and pathways analysis and created a corresponding 'normal' database. Fourteen fetal hearts from human fetuses between 10 and 18 weeks of gestational age (GA) were prospectively collected at the time of elective termination of pregnancy. RNA from recovered tissues was used for transcriptome analysis with Affymetrix 1.0 ST microarray chip. From the amassed data we investigated differences in cardiac development within the 10-18 GA period dividing the sample by GA in three groups: 10-12 (H1), 13-15 (H2) and 16-18 (H3) weeks. A fold change of 2 or above adjusted for a false discovery rate of 5% was used as initial cutoff to determine differential gene expression for individual genes. Test for enrichment to identify functional groups was carried out using the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Array analysis correctly identified the cardiac specific genes, and transcripts reported to be differentially expressed were confirmed by qRT-PCR. Single transcript and Ontology analysis showed first trimester heart expression of myosin-related genes to be up-regulated >5-fold compared with second trimester heart. In contrast the second trimester hearts showed further gestation-related increases in many genes involved in energy production and cardiac remodeling. In conclusion, fetal heart development during the first trimester was dominated by heart-specific genes coding for myocardial development and differentiation. During the second trimester, transcripts related to energy generation and cardiomyocyte communication for contractile coordination/proliferation were more dominant. Transcripts related to fatty acid metabolism can be seen as early as 10 weeks and clearly increase as the heart matures. Retinol receptor and gamma-aminobutyric acid (GABA) receptor transcripts were detected, and have not been described previously in human fetal heart during this period. For the first time global gene expression of heart has been described in human samples to create a database of normal development to understand and compare with known abnormal fetal heart development.

Natural history and pregnancy outcome in patients with placental chorioangioma

To evaluate the natural history and outcome of pregnancies in patients with placental chorioangioma. A total of 16 placentas with a histologic diagnosis of chorioangioma were identified, and the natural history and outcome of pregnancy were evaluated. This study was approved by the Institutional Ethics Committees of our unit, and written informed consent was obtained from all study participants. Thirteen of the 16 cases were associated with a wide variety of fetal complications. Two-thirds of the cases developed complications that either required elective delivery because of fetal distress (n = 4), fetal heart failure (n = 1), oligohydramnion (n = 1), and premature labor of dichorionic twins (n = 1) or resulted in intrauterine fetal death and termination of pregnancy (n = 2). Placental chorioangioma was associated with the development of polyhydramnios, fetal growth restriction, and fetal distress in a significant number of cases. The size, vascularity, and location of the chorioangioma may be three independent factors of maternal and fetal complications. Any of these three factors can influence the outcome of pregnancy. Close antenatal examination should be routinely practiced to allow the timely diagnosis of early fetal heart failure.

Contribution of Store-Operated Ca2+ Entry to Beat-to-Beat Ca2+ Transient in Early Fetal Mouse Heart

Introduction: Store-operated Ca2+ entry (SOCE) is triggered by ER/SR Ca2+ depletion to maintain intracellular Ca2+ concentration. In adult myocytes, SOCE contributes to cell growth or hypertrophy. However, in fetus, little is known about the role of SOCE. We hypothesize that SOCE may contribute to fetal cardiac contraction. Method: The whole hearts in embryonic day(ED) 9.5/12.5/15.5 and neonate were stained by Fluo-3 AM. Fluorescence signals in beating hearts stimulated electrically were recorded using a photomultiplier, then analyzed as Ca2+ transient(CaT) in each age. 1) SOCE was induced by changing the solutions from zero to 1.8mM Ca2+. With inhibiting voltage-dependent Ca2+ channels(VDCC), we tested whether SOCE was suppressed by 0.2mM Gd3+ application, as SOCE blocker. 2) We tested whether beat-to-beat CaT was suppressed by 0.2mM Gd3+ application. Results: 1) In fetal heart, SOCE was suppressed significantly by Gd3+ application (ED9.5; 46% decreased, p=0.011, n=5. ED12.5; 82% decreased, p<0.0001, n=6). 2) In ED 9.5, CaT was depressed significantly by Gd3+ application (49.2+/-7.6% vs. 2.0+/-2.0%), but after ED 12.5, CaT was not depressed. Conclusion: SOCE would contribute to beat-to-beat CaT in early fetal mouse myocytes.View Large Image | View Hi-Res Image | Download PowerPoint Slide

Active cardiac model and its application on structure detection from early fetal ultrasound sequences

The structure of an early fetal heart provides vital information for the diagnosis of fetus defects. However, early fetal hearts are difficult to detect due to their relatively small size and the low signal-to-noise ratio of ultrasound images. In this paper, a novel method is proposed for automatic detection of early fetal cardiac structure from ultrasound images. The proposed method consists of two major parts which are the preprocessing phase and the active cardiac model: (1) The preprocessing phase consists of two sub-steps. (a) The region of interest is first automatically selected based on an accumulated motion image, which is able to represent the motion information of the fetal heart more accurately. (b) Then by combining Rayleigh-trimmed filter and anisotropic diffusion in 3-dimensional space, a despeckling method is developed to suppress the speckle noise and emphasize the motion information for subsequent cardiac structure detection. (2) The active cardiac model is proposed for the detection of fetal heart structure, which is a key contribution of this paper. It takes into account both the structure and motion information of fetal hearts simultaneously. Both learning and inference of the active cardiac model are described in the paper. Experiments on seven ultrasound sequences demonstrate the effectiveness of the proposed method.

Regulation of Embryonic Cardiac Wall Growth and Vascularization by FGF‐2

The aim of this study was to assess the effect of FGF‐2 signaling on growth of chick embryonic ventricular wall and its vascularization. In the first set of experiments, left ventricular wall of embryonic day 7 (E7) chick embryos was injected with either GFP‐expressing replication‐deficient adenovirus alone or in combination with adenoviral vector encoding human FGF‐2 gene. In the second set of experiments, FGF signaling was blocked in E8 embryos using FGFR1 receptor tyrosine kinase inhibitor SU 5402. Cell proliferation was measured in both cases using BrdU incorporation and immunohistochemistry on E9.Morphological examination of adenovirus‐injected hearts revealed no difference in normal myocardial architecture, but increased levels of myocyte proliferation in hearts injected with FGF‐2 adenovirus. There was no difference in capillary density or coronary artery anomalies. Blocking of FGF signaling with SU 5402 led to hemorrhages in the areas of developing vasculature in the tips of limbs and epicardium. However, the rate of myocyte proliferation was unchanged.We conclude that up‐regulation of FGF‐2 signaling has a positive effect on growth of the early fetal heart, while its inhibition impacts mainly vasculogenesis, pointing to functional redundancy in paracrine control of myocyte proliferation in the developing heart.Supported by MSMT VZ 0021620806, LC 06061, AS CR AVOZ50450515.Grant Funding SourceMSMT VZ 0021620806