1. Fetal Intelligent Navigation Echocardiography (FINE): A novel method, Fetal Intelligent Navigation Echocardiography or FINE, was developed for the visualization of standard fetal echocardiography views from volume datasets obtained with STIC and application of intelligent navigation technology. This method was established to demonstrate nine cardiac diagnostic planes and spontaneously navigate the anatomy surrounding each of the nine planes (Virtual Intelligent Sonographer Assistance, VIS-Assistance). The method consists of marking seven anatomical structures of the fetal heart. The following echocardiography views are then automatically generated: 1) four chamber;2) five chamber;3) left ventricular outflow tract;4) short-axis view of great vessels/right ventricular outflow tract;5) three vessels and trachea;6) abdomen/stomach;7) ductal arch;8) aortic arch;and 9) superior and inferior vena cava. The FINE method was tested in a separate set of 50 STIC volumes of normal hearts (18.6-37.2 weeks of gestation), and visualization rates for fetal echocardiography views using diagnostic planes and/or VIS-Assistance were calculated. In normal cases, the FINE method was able to generate nine fetal echocardiography views using: 1) diagnostic planes in 78%-100% of cases;2) VIS-Assistance in 98-100% of cases;and 3) a combination of diagnostic planes and/or VIS-Assistance in 98-100% of cases. To examine the feasibility of identifying abnormal cardiac anatomy, we tested the FINE method in 4 cases with proven congenital heart defects (coarctation of aorta, tetralogy of Fallot, transposition of the great vessels, and pulmonary atresia with intact ventricular septum). In all 4 abnormal cases, the FINE method demonstrated evidence of abnormal fetal cardiac anatomy. In conclusion, the FINE method can be used to visualize nine standard fetal echocardiography views in normal hearts by applying intelligent navigation technology to STIC volume datasets. This method can simplify examination of the fetal heart and reduce operator dependency. The observation of abnormal echocardiography views in the diagnostic planes and/or VIS-Assistance should raise the index of suspicion for congenital heart disease. 2. Evaluation of fetal cardiac function: Abnormal umbilical artery (UA) Doppler velocimetry reflects increased impedance to blood flow in the placenta. Placental insufficiency with increased placental vascular resistance may lead to fetal cardiovascular compromise, and even fetal metabolic acidosis and death. Fetuses with abnormal UA Doppler velocimetry have been shown to have similar changes to those observed in adults with atherosclerosis. This, along with fetal cardiac dysfunction, may have important consequences in the fetal programming of cardiac disease and the early onset of disease. Four-dimensional sonography with STIC allows evaluation of the volume of the cardiac chambers without geometrical assumptions. Our objective was to determine if increased placental vascular impedance to flow is associated with changes in fetal cardiac function using STIC and virtual organ computer-aided analysis (VOCAL). A cross-sectional study was performed in 34 fetuses with umbilical artery pulsatility index >95th percentile (abnormal). Ventricular volume (end-systole, end-diastole), stroke volume, cardiac output (CO), adjusted CO, and ejection fraction were compared to those of 184 normal fetuses. In the presence of increased placental vascular impedance to flow: 1) fetal ventricular volume (end-systole and end-diastole), stroke volume, and CO were lower when compared to normal fetuses;2) right ventricular volume, stroke volume, and CO exceeded those of the left side;3) ejection fraction was higher when compared to normal fetuses;and 4) left ejection fraction was greater than that of the right side. These findings suggest that increased placental vascular impedance to flow is associated with changes in fetal cardiac function. 3. Evaluation of cervical stiffness during pregnancy using semiquantitative ultrasound elastography: Elastography can be used to determine the degree of cervical stiffness/softness, which may constitute a complementary method to identify patients at risk for preterm delivery, or alternatively, those with a short cervix not at risk for a preterm delivery. The average cervical displacement (strain) was calculated when manual oscillatory compression was applied (a low strain value is associated with a stiff tissue). We found that: 1) the endocervical canal was 33% softer than the rest of the cervix;2) the internal cervical os was significantly stiffer than the external cervical os;3) the internal cervical os became softer as pregnancy progressed;and 4) women having a previous preterm delivery had a softer cervix than patients without previous preterm deliveries. Our results confirmed that ultrasound-derived elastography is able to detect differences in tissue strain. These findings suggest that ultrasound-derived elastography may be helpful in assessing the risk for preterm delivery. 4. In utero functional magnetic resonance imaging (fMRI) quantification of human fetal brain functional connectivity: Functional connections between different areas of the human brain develop and mature over time. Abnormalities in such connections have been implicated in many disorders such as attention deficit hyperactivity disorder, autism, schizophrenia, and Alzheimer's disease. Abnormal patterns of brain connections underlying developmental disorders likely originate in utero, but it is difficult to determine what happens in the brain during the prenatal period. We reported a method for non-invasive mapping of brain connections in healthy singleton fetuses between 24 and 39 weeks of gestation. We found evidence of bilateral functional connections in the fetal brain, as well as regional connections within each hemisphere. The connection pattern varied with gestational age, such that connection strength increased as the fetuses approached term. This work lays the foundation to study fetal functional neuroconnectivity in pregnancies at risk for neurodevelopmental disorders.

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Yeo, Lami; Romero, Roberto (2016) How to Acquire Cardiac Volumes for Sonographic Examination of the Fetal Heart: Part 2. J Ultrasound Med 35:1043-66
Tang, Xiangna; Hernandez-Andrade, Edgar; Ahn, Hyunyoung et al. (2016) Intermediate Diastolic Velocity as a Parameter of Cardiac Dysfunction in Growth-Restricted Fetuses. Fetal Diagn Ther 39:28-39
Krishnamurthy, Uday; Szalai, Gabor; Shen, Yimin et al. (2016) Longitudinal Changes in Placental Magnetic Resonance Imaging Relaxation Parameter in Murine Pregnancy: Compartmental Analysis. Gynecol Obstet Invest 81:193-201
Yeo, Lami; Romero, Roberto (2016) Intelligent navigation to improve obstetrical sonography. Ultrasound Obstet Gynecol 47:403-9
Yeo, Lami; Romero, Roberto (2016) How to Acquire Cardiac Volumes for Sonographic Examination of the Fetal Heart: Part 1. J Ultrasound Med 35:1021-42
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Lee, W; Deter, R; Sangi-Haghpeykar, H et al. (2013) Prospective validation of fetal weight estimation using fractional limb volume. Ultrasound Obstet Gynecol 41:198-203

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