Biochemical, Biomechanical & Morphological Properties of Quantitative Ultrasound

描述（由申请人提供）：背景。全球每年有110万婴儿在出生后的前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，也是非洲裔美国人婴儿死亡的主要原因。如能将分娩时间从孕30周推迟到孕34周，住院死亡率可从8.1%降至0.4%，脑性瘫痪可从6.3%降至0.7%，呼吸窘迫综合征可从44%降至3%。将小于29孕周的婴儿推迟到足月（= 37周）出生估计可节省至少122 000美元/例。早产的治疗集中在治疗宫缩，而不是早产前宫颈成熟的长期过程。阻止早产的药物具有改变收缩平滑肌的功能，而不是宫颈成熟，5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非侵入性定量超声（QUS）技术，该技术将：检测人类早期宫颈成熟;并导致科学干预以改变早产。该R21应用的目标是验证QUS宫颈成熟的生物化学，生物力学和生物结构特性，作为检测人类宫颈成熟的重要步骤。目标1.确定大鼠子宫颈成熟时频率依赖性QUS衍生参数与子宫颈组织生化（胶原和水）、生物结构（双折射、组织学、3-D阻抗图）生物力学（应力-应变）特性之间的关系。目标二。确定适当模拟妊娠子宫颈组织的形状因子。方法.这是一项前瞻性纵向重复测量实验设计，包括2个实验，以实现目标1，包括：初步实验（1），以确定样本量和更确定的实验（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当地对妊娠子宫颈组织进行建模的形状因子。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，翻译定量超声的子宫颈用于人类的生物化学（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）的基础上，在体内动物模型中的定量超声。 公共卫生相关性声明：足月生下一个健康的婴儿是准父母的普遍期望。然而，2006年有50万婴儿早产。分娩前的潜在机制尚未完全了解。1990年至2006年，美国早产发生率增加了21%（2006年占所有出生人数的12.8%），这表明了这一问题的严重性。2006年，18.4%的非洲裔美国妇女、14.2%的美洲土著妇女和12.2%的西班牙裔妇女早产，而白色妇女的早产率为11.7%。早产是美国婴儿死亡的第二大原因（仅次于先天性畸形），也是非洲裔美国婴儿死亡的主要原因。2与足月出生的婴儿相比，妊娠≥ 28周出生的早产儿脑瘫的发病率增加了100倍（1/1000足月出生婴儿vs 100/1000早产婴儿）。将小于29孕周的婴儿推迟到足月（= 37周）出生估计可节省至少122 000美元/例。将美国的早产率降低到7%是“健康人2010”倡议的目标，只有通过降低早产发生率，美国的婴儿死亡率才能得到解决。

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.