Imaging the Developing Fetal Brain: Novel Markers of Risk for Maternal Smoking

描述(由申请人提供)：本申请响应PAR-12-066；成像-科学轨道研究过渡奖；I/START)。这项拟议的研究将有助于将神经机制添加到PI的母亲吸烟/后代行为研究计划中。孕期母亲吸烟与婴儿的发病率和死亡率以及年龄较大儿童的行为缺陷(注意力缺陷、物质使用、破坏性行为)有关。尽管普遍禁止怀孕期间吸烟，但13%-30%的婴儿出生时就暴露在空气中。鉴于持续的高接触率以及与代价高昂的后代后果的联系，需要采用创新的方法来识别和保护高风险后代，并帮助怀孕的吸烟者戒烟。识别子代风险的出生前标志物为开发新的治疗目标和早期干预努力减轻不良后果提供了可能性。我们小组以前使用2D超声来揭示母亲吸烟对胎儿行为缺陷的影响。然而，尽管结构性脑缺陷被认为是母亲吸烟和子女神经行为缺陷之间潜在联系的关键候选机制，但还没有研究包括母亲吸烟导致胎儿风险的神经标记物。拟议的I/START将允许PI通过包括新的胎儿风险神经标记物来扩大和增加她的母亲吸烟研究计划的影响。三维超声的出现提供了更高分辨率的胎儿图像，并允许在临床研究中对特定的胎儿结构进行体积表征。拟议的I/START研究将首次确定应用3D超声技术在发育中的胎儿中识别母亲吸烟风险的神经标记物的可行性。I/START研究将利用基础设施和PI正在进行的关于母亲吸烟和婴儿行为的研究(R01 DA031188)的参与者。正在进行的研究中的孕妇吸烟者和对照组将完成三项胎儿超声评估，包括对胎儿神经(额叶-小脑区域)和神经内分泌(肾上腺)结构的3D体积评估。将对超声方案的可接受性和遵守情况以及容量评估的可靠性进行评估。我们的目标是：1)证明我们新的超声方法用于胎儿神经和神经内分泌结构容量评估的可行性，以及2)初步表征怀孕期间母亲吸烟对胎儿神经和神经内分泌结构的影响，为更大规模的R01研究做准备。如果成功，这项试验性研究的结果将提供未来的潜力：a)促进在怀孕期间实时发现母亲吸烟的机制，b)改善对怀孕吸烟者的临床护理，c)确定保护暴露在风险中的胎儿的新治疗目标，以及d)开发针对怀孕吸烟者戒烟努力的新焦点。

DESCRIPTION (provided by applicant): This application is responsive to PAR-12-066; Imaging-Science Track Award for Research Transition; I/START). The proposed study will facilitate the addition of neural mechanisms to the PI's program of maternal smoking/offspring behavior research. Maternal smoking during pregnancy is associated with morbidity and mortality in infants and behavioral deficits (attention deficits, substance use, disruptive behaviors) in older children. Despite pervasive sanctions against smoking during pregnancy, 13-30% of infants are born exposed. Given continued high exposure rates and links to costly offspring outcomes, innovative approaches are needed to identify and protect high risk offspring and help pregnant smokers quit. Identification of pre-birth markers of offspring risk offers potential for developing novel therapeutic targets and early intervention efforts to mitigate adverse outcomes. Our group previously utilized 2D ultrasound to reveal effects of maternal smoking on fetal behavioral deficits. However, although structural brain deficits have been proposed as a key candidate mechanism underlying links between maternal smoking and offspring neurobehavioral deficits, no studies have included neural markers of fetal risk from maternal smoking. The proposed I/START will allow the PI to expand and increase the impact of her program of maternal smoking research by including novel neural markers of fetal risk. The advent of 3D ultrasound offers higher resolution fetal images and allows volumetric characterization of specific fetal structures in clinical studies. The proposed I/START study will determine, for the first time, the feasibility of applying 3D ultrasound technology to identify neural markers of risk from maternal smoking in the developing fetus. The I/START study will capitalize on infrastructure and participants from the PI's ongoing study of maternal smoking and infant behavior (R01 DA031188). Pregnant smokers and controls from the ongoing study will complete three fetal ultrasound assessments involving 3D volumetric assessment of fetal neural (fronto-cerebellar regions) and neuroendocrine (adrenal gland) structures. Acceptability and adherence to ultrasound protocols and reliability of volumetric assessments will be assessed. Our goals are: 1) to demonstrate feasibility of our novel ultrasound methodology for volumetric assessment of fetal neural and neuroendocrine structures, and 2) to conduct a preliminary characterization of effects of maternal smoking on fetal neural and neuroendocrine structures over pregnancy in preparation for a larger R01 study. If successful, results from this pilot study offer future potential for: a) promoting discovery of mechanisms of maternal smoking in real-time during pregnancy, b) improving clinical care for pregnant smokers, c) identifying novel therapeutic targets to protect exposed fetuses, and d) developing new foci for cessation efforts with pregnant smokers.