Biochemical, Biomechanical & Morphological Properties of Quantitative Ultrasound

描述（由申请人提供）：背景。在全球范围内，每年有110万婴儿在出生后的头四周内因早产而死亡。在美国，早产是婴儿死亡的第二大原因，也是非裔美国人婴儿死亡的主要原因。如果能将分娩从妊娠30周推迟到34周，住院死亡率可从8.1%降至0.4%；脑瘫可从6.3%降至0.7%；呼吸窘迫综合征可以从44%下降到3%。将妊娠期<29周的婴儿推迟到足月（= 37周），估计每例至少可节省12.2万美元。治疗早产的重点是治疗宫缩，而不是治疗早产前宫颈成熟的漫长过程。阻止早产的药物作用是改变收缩的平滑肌而不是宫颈成熟，并且在过去40年中未能降低早产率。该研究计划的长期目标是开发一种无创定量超声（QUS）技术，该技术将：检测人类早期宫颈成熟；并引导科学干预来改变早产。本R21应用的目的是利用QUS验证宫颈成熟的生化、生物力学和生物结构特性，这是检测人类宫颈成熟的重要步骤。目的1。确定成熟发生时大鼠子宫颈中频率相关的qs衍生参数与子宫颈组织生化（胶原蛋白和水）、生物结构（双折射、组织学、三维阻抗图）生物力学（应力-应变）特性之间的关系。目标2。确定适当地模拟怀孕子宫颈组织的形状因子。方法。这是一个前瞻性的纵向重复测量实验设计，由两个实验组成，以实现目标1：一个初步实验(1)，以确定样本量和一个更明确的实验(2)。实验3将使用三维组织学数据集的三维阻抗建模来确定适合模拟妊娠宫颈组织的形状因子。结论。我们预计，这项研究的成功完成将进一步推动我们的目标，通过在体内动物模型中验证定量超声的生化（胶原蛋白和水），生物结构（双折射，组织学，3-D阻抗图）生物力学（应力-应变）基础，将子宫颈定量超声翻译为人类使用。

DESCRIPTION (provided by applicant): Background. Globally,1.1 million infants die each year during the first four weeks of life due to prematurity.In the United States, prematurity is the second leading cause of infant mortality and the leading cause of infant mortality for African Americans. If birth could be delayed from 30 to 34 weeks gestation, the incidence of: inhospital mortality could be reduced from 8.1% to 0.4%; cerebral palsy could be reduced from 6.3% to 0.7%; and respiratory distress syndrome could be decreased from 44% to 3%. Delaying the birth of an infant <29 weeks gestation to term (= 37 weeks) is estimated to result in at least $122,000 savings/case. Treatment of preterm labor has focused on treating contractions rather than the long process of cervical ripening that precedes preterm labor. Pharmacologic agents to arrest preterm labor have functions to modify contracting smooth muscle not cervical ripening,5 and have failed to reduce preterm birth rates in the last 40 years. The long-term goal of this research program is to develop a noninvasive quantitative ultrasound (QUS) technique that will: detect early cervical ripening in humans; and lead to scientific interventions to modify preterm birth. The goal of this R21 application is to validate the biochemical, biomechanical and biostructural properties of cervical ripening with QUS, as an essential step to detect cervical ripening in humans. Aim 1. Determine the relationship among frequency-dependent QUS-derived parameters in the rat cervix as ripening occurs, with cervix tissue biochemical (collagen and water), biostructural (birefringence, histology, 3-D impedance map) biomechanical (stress-strain) properties. Aim 2. Determine the form factor that appropriately models pregnant cervix tissue. Methods. This is a prospective longitudinal repeated-measures experimental design consisting of 2 experiments to achieve aim 1 consisting of: a preliminary experiment (1) to determine sample size and a more definitive experiment (2). Experiment 3 will use 3-dimensional impedance modeling of a 3-dimensional histological data set to determine the form factor that appropriately models pregnant cervix tissue. Conclusion. We anticipate that the successful completion of this research will have furthered our goal of translating quantitative ultrasound of the cervix for use in humans by validating the biochemical (collagen and water), biostructural (birefringence, histology, 3-D impedance map) biomechanical (stress-strain) basis of quantitative ultrasound in the in vivo animal model. PUBLIC HEALTH RELEVANCE STATEMENT: The birth of a healthy baby at term is a universal expectation of prospective parents. However, 500,000 infants were born preterm in 2006. The underlying mechanisms preceding labor are not yet fully understood. The 21% increase in the incidence of preterm birth (to 12.8% of all births in 2006) in the United States between 1990 and 2006 is an indication of the seriousness of this problem. In 2006, 18.4% of African-American women, 14.2% of Native American women and 12.2% of Hispanic women delivered a preterm infant compared to 11.7% of White women. Preterm birth is the second leading cause (after congenital anomalies) of infant mortality in the United States and the leading cause of infant death among African-American infants.2 Compared with infants born full-term, premature infants born = 28 weeks gestation, have a one hundred-fold increase in the incidence of cerebral palsy (1/1000 infants born at term versus 100/1000 born premature). Delaying the birth of an infant <29 weeks gestation to term (= 37 weeks) is estimated to result in at least $122,000 savings/case. Reducing the preterm birth rate to 7% in the United States is a goal of the Healthy People 2010 initiative, and it is only by reducing the incidence of preterm birth that infant mortality in the United States can be addressed.