Prenatal Diagnosis Of Congenital Anomalies

先天性异常的产前诊断

• 批准号: 10266486
• 负责人: ROBERTO ROMERO
• 金额: $ 723.75万
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10266486
• 关键词: Address; Alternative Splicing; Amniotic Fluid; Anatomy; Biometry; Brain; Breathing; Cardiac; Cardiac Myocytes; Cells; Code; Complex; Computers; Congenital Abnormality; Data Set; Dependence; Detection; Development; Dextrocardia; Diagnosis; Discipline; Discipline of obstetrics; Disease; Echocardiography; Education; Educational process of instructing; Evaluation; Feedback; Fetal Development; Fetal Heart; Fetal Liver; Fetal Organ Maturity; Fetus; Four-dimensional; Frequencies; Gene Expression; Genes; Genomics; Goals; Growth; Heart Abnormalities; Image; Immune; Immunity; Intelligence; Learning; Lung; Maternal-fetal medicine; Measurement; Medical; Methods; Motion; Optics; Organ; Pathologic Processes; Pathway interactions; Pattern; Performance; Physiological; Physiological Processes; Population; Positioning Attribute; Pregnancy; Prenatal Diagnosis; Process; RNA; RNA Splicing; Reporting; Role; Salivary Glands; Sampling; Second Pregnancy Trimester; Self-Examination; Sensitivity and Specificity; Sleep; System; Technology; Testing; Third Pregnancy Trimester; Time; Tissues; Trachea; Training; Transducers; Ultrasonography; Untranslated RNA; Uterus; Voice; Woman; animation; base; biomarker identification; cell type; congenital anomaly; congenital heart disorder; differential expression; fetal; fetal medicine; genomic signature; heart function; imaging modality; improved; infant morbidity/mortality; instrument; interest; laptop; novel; organ growth; portability; screening; simulation; skills; spatiotemporal; success; transcriptome; transcriptomics

1. New and Advanced Features of Fetal Intelligent Navigation Echocardiography (FINE): Congenital heart disease (CHD) is the leading organ-specific birth defect, as well as the leading cause of infant morbidity and mortality from congenital malformations. Therefore, a comprehensive screening examination of the fetal heart should be performed in all women to maximize the detection of CHD. Four-dimensional sonography with spatiotemporal image correlation (STIC) technology displays a cine loop of a complete single cardiac cycle in motion. A novel method known as Fetal Intelligent Navigation Echocardiography (FINE) was previously developed to interrogate STIC volume datasets using intelligent navigation technology. Such method allows the automatic display of nine standard fetal echocardiography views required to diagnose most cardiac defects. FINE considerably simplifies fetal cardiac examinations and reduces operator dependency. It has both high sensitivity and specificity for the detection of CHD. Indeed, FINE has been integrated into several commercially available ultrasound platforms. Recently, eight novel and advanced features have been developed for the FINE method and they are described in this article. Such features can be categorized based upon their broad goals. The first goal is to simplify FINE further, and consists of the following features: 1) Auto fetal positioning (or FINE align); 2) Skip points; 3) Predictive cursor; 4) Static mode volume; and 5) Breech sweep. The second goal is to allow quantitative measurements to be performed on the cardiac views generated by FINE: 6) Automatic cardiac axis; and 7) Cardiac biometry. Finally, the last goal is to improve the success of obtaining fetal echocardiography view(s), and consists of: 8) Maestro planar navigation. 2. Optical Ultrasound Simulation Based Training in Obstetric Sonography: Ultrasound is an imaging modality that is highly operator dependent. In this article, we reviewed the challenges in learning how to perform obstetric sonography, as well as the processes necessary to acquire expert performance skills in sonography. Simulation-based education and learning, and the value of medical simulation were also discussed. Ultrasound simulators are an effective means of teaching obstetric sonography, because it provides training, deliberate practice, and performance evaluation/feedback which allows continuous and critical self-evaluation. We reviewed evidence that simulation can improve performance in obstetric ultrasound examination, reviewed current simulators, and discussed the current problems/gaps in ultrasound simulation. Optical positioning ultrasound simulation is a novel high-fidelity simulation learning system, which addresses many of these problems/gaps, and we introduced this for the first time in this article. The technology uses a camera-based optical tracking system and has a limited amount of hardware, making the simulator compact, portable, and personal. A computer or laptop is used to load actual (vs. artificially created) ultrasound cases, which are organ-specific. The goal of the trainee is to achieve a sonographic target plane. The Guided mode uniquely provides: 1) simulator voice commands which instruct the user on how to manipulate the transducer; 2) contextual videos and animation; and 3) graphic feedback to guide the user towards obtaining the correct target plane of interest (e.g. four-chamber view). 3. The Amniotic Fluid Cell-Free Transcriptome: The amniotic fluid cell-free RNA (cfRNA) is modulated with physiologic and pathologic processes during pregnancy, and hence, we sought to define amniotic fluid normal expression and splicing patterns to aid the identification of biomarkers for assessing fetal development and obstetrical disease. About one hundred amniotic fluid transcriptomes were profiled in samples collected during midtrimester and at term, and we quantified the expression of tissue-specific and cell-type specific signatures defined by single-cell genomics. We found that 11% of the coding and 6% of the non-coding amniotic fluid genes were differentially expressed between midtrimester and term gestation. Expression changes with advancing gestation featured increased expression of genes specific to the trachea, salivary glands, and lung; and decreased expression of genes specific to the cardiac myocytes, uterus, and fetal liver, among others. We also found that differential splicing with advancing gestation involved genes related brain development and immunity pathways, including some that were missed based on differential expression analysis alone. Therefore, this is the largest amniotic fluid transcriptomics study in normal pregnancy, reporting for the first time that single-cell genomic signatures can be tracked in the amniotic fluid and display complex patterns of expression during gestation. We also demonstrated a role for alternative splicing in tissue-identity acquisition, organ development, and immune processes. The results herein may have implications for the development of fetal testing to assess placental function and fetal organ maturity.

1.胎儿智能导航超声心动图（FINE）的新功能和高级功能： 先天性心脏病（CHD）是主要的器官特异性出生缺陷，也是先天性畸形导致婴儿发病和死亡的主要原因。因此，应对所有孕妇进行全面的胎儿心脏筛查，以最大限度地检测CHD。四维超声与时空图像相关（STIC）技术显示一个完整的单一心动周期的运动电影循环。先前开发了一种称为胎儿智能导航超声心动图（FINE）的新方法，用于使用智能导航技术询问STIC体积数据集。这种方法允许自动显示诊断大多数心脏缺陷所需的九个标准胎儿超声心动图视图。FINE大大简化了胎儿心脏检查，减少了对操作员的依赖。它对冠心病的检测具有较高的敏感性和特异性。事实上，FINE已被集成到几个商用超声平台中。最近，八个新的和先进的功能已经开发的精细方法，他们在这篇文章中进行了描述。这些功能可以根据其广泛的目标进行分类。第一个目标是进一步简化FINE，包括以下功能：1）自动胎儿定位（或FINE对齐）; 2）跳过点; 3）预测光标; 4）静态模式体积;以及5）臀位扫描。第二个目标是允许对FINE生成的心脏视图执行定量测量：6）自动心脏轴;和7）心脏生物测量。最后，最后一个目标是提高获得胎儿超声心动图视图的成功率，包括：8）Maestro平面导航。 2.基于光学超声模拟的产科超声成像培训： 超声是一种高度依赖于操作者的成像方式。在这篇文章中，我们回顾了学习如何进行产科超声检查的挑战，以及必要的过程，以获得专业的超声检查技能。讨论了基于仿真的教育和学习以及医学仿真的价值。超声模拟器是产科超声教学的有效手段，因为它提供培训、刻意练习和绩效评估/反馈，从而允许持续和批判性的自我评估。我们回顾了仿真可以提高产科超声检查性能的证据，回顾了当前的仿真器，并讨论了当前超声仿真中存在的问题/差距。光学定位超声模拟是一种新型的高保真模拟学习系统，它解决了许多这些问题/差距，我们在这篇文章中首次介绍了这一点。该技术使用基于摄像头的光学跟踪系统，硬件数量有限，使模拟器紧凑，便携和个人化。计算机或笔记本电脑用于加载实际（与人工创建的）超声病例，这些病例是器官特异性的。受训者的目标是实现超声目标平面。引导模式独特地提供：1）模拟器语音命令，指导用户如何操作探头; 2）上下文视频和动画;以及3）图形反馈，指导用户获得正确的目标平面（例如，四腔视图）。 3.羊水无细胞转录组： 羊水无细胞RNA（cfRNA）在妊娠期间受到生理和病理过程的调节，因此，我们试图定义羊水正常表达和剪接模式，以帮助鉴定用于评估胎儿发育和产科疾病的生物标志物。在妊娠中期和足月时收集的样本中，分析了约100个羊水转录组，我们量化了由单细胞基因组学定义的组织特异性和细胞类型特异性签名的表达。我们发现，11%的编码和6%的非编码羊水基因之间的差异表达的中期妊娠和足月妊娠。随着妊娠的进展，表达变化的特点是气管、唾液腺和肺特异性基因表达增加;心肌细胞、子宫和胎肝特异性基因表达减少。我们还发现，随着妊娠的进展，差异剪接涉及与大脑发育和免疫途径相关的基因，包括一些仅基于差异表达分析而遗漏的基因。因此，这是正常妊娠中最大的羊水转录组学研究，首次报告可以在羊水中追踪单细胞基因组签名，并在妊娠期间显示复杂的表达模式。我们还证明了选择性剪接在组织身份获得，器官发育和免疫过程中的作用。本文的结果可能对胎儿测试的发展有影响，以评估胎盘功能和胎儿器官成熟度。