Biochemical, Biomechanical & Morphological Properties of Quantitative Ultrasound

生物化学、生物力学

• 批准号: 7738734
• 负责人: BARBARA L MCFARLIN
• 金额: $ 28.17万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-20 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7738734
• 关键词: 3-Dimensional; Acoustics; Address; Affect; African American; Anatomy; Animal Model; Animals; Biochemical; Biomechanics; Birefringence; Birth; Birth Rate; Cerebral Palsy; Cervical; Cervical Dilatations; Cervical Ripening; Cervix Uteri; Collagen; Contracts; Data; Data Set; Detection; Etiology; Experimental Designs; Extracellular Matrix; Fetus; Frequencies; Gestational Age; Goals; Gold; Healthy People 2010; Hispanics; Histology; Hospital Mortality; Human; Incidence; Infant; Infant Mortality; Intervention; Lead; Length; Life; Maps; Measures; Methods; Modeling; Native Americans; Parents; Pathway interactions; Phase; Pregnancy; Premature Birth; Premature Infant; Premature Labor; Process; Property; Radio; Rattus; Research; Role; Sample Size; Savings; Smooth Muscle; Stress; Techniques; Testing; Thick; Three-dimensional analysis; Tissue Model; Tissues; Translating; Ultrasonics; Ultrasonography; United States; Uterine Contraction; Uterine cavity; Water; Woman; Work; base; electric impedance; expectation; improved; in vivo; infant death; innovation; instrumentation; novel; pregnant; premature; programs; prospective; public health relevance; quantitative ultrasound; research study; respiratory distress syndrome

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.

描述（由申请人提供）：背景。在全球范围内，每年有 110 万婴儿在出生后的前 4 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。如果可以将分娩从妊娠 30 周推迟到 34 周，则： 院内死亡率可以从 8.1% 降低到 0.4%；脑瘫发生率可从6.3%降低至0.7%；呼吸窘迫综合征的发生率可从 44% 降至 3%。将妊娠 <29 周至足月（= 37 周）的婴儿出生延迟估计每例可节省至少 122,000 美元。早产的治疗重点是治疗宫缩，而不是早产前宫颈成熟的漫长过程。阻止早产的药物具有改变平滑肌收缩而非宫颈成熟的功能，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无创定量超声 (QUS) 技术，该技术将： 检测人类早期宫颈成熟；并采取科学干预措施来改变早产。该 R21 应用的目标是使用 QUS 验证宫颈成熟的生化、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. 确定成熟时大鼠宫颈中频率依赖性 QUS 衍生参数与宫颈组织生化（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）之间的关系特性。目标 2. 确定适当模拟怀孕子宫颈组织的形状因子。方法。这是一个前瞻性纵向重复测量实验设计，由 2 个实验组成，旨在实现目标 1，其中包括：确定样本量的初步实验 (1) 和更明确的实验 (2)。实验 3 将使用 3 维组织学数据集的 3 维阻抗建模来确定适当模拟怀孕子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进我们的目标，即通过验证生化（胶原蛋白和水）、生物结构（双折射、组织学、3D 阻抗图）、生物力学（应力），将子宫颈定量超声应用于人类。 -应变）体内动物模型中定量超声的基础。 公共卫生相关声明：足月健康婴儿的出生是准父母的普遍期望。然而，2006 年有 500,000 名婴儿早产。临产前的潜在机制尚未完全了解。 1990 年至 2006 年间，美国早产发生率增加了 21%（2006 年占所有出生婴儿的 12.8%），这表明了这一问题的严重性。 2006年，18.4%的非裔美国妇女、14.2%的美洲原住民妇女和12.2%的西班牙裔妇女生下了早产儿，而白人妇女的这一比例为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，早产儿=孕 28 周出生，有脑瘫的发病率增加一百倍（足月出生的婴儿为 1/1000，早产婴儿为 100/1000）。据估计，将妊娠 <29 周至足月（= 37 周）的婴儿出生延迟每例至少可节省 122,000 美元。将美国早产率降低至7%是“健康人民2010”倡议的目标，只有降低早产发生率才能解决美国婴儿死亡率问题。