Monitoring Changes in Cervical Microstructure During Pregnancy

监测怀孕期间宫颈微观结构的变化

• 批准号: 8605088
• 负责人: Helen Feltovich
• 金额: $ 53.23万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-15 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8605088
• 关键词: Acoustics; Animals; Anisotropy; Biological; Biomechanics; Birth; Breeding; Caliber; Cervical; Cervical Ripening; Cervix Uteri; Clinical; Collagen; Communication; Computerized Medical Record; Data; Date of birth; Development; Diffuse; Drug usage; Event; Fetus; Foundations; Future; Generations; Goals; Human; Hysterectomy; Image; Individual; Investigation; Knowledge; Language; Lead; Left; Life; Macaca mulatta; Measurement; Measures; Menstrual cycle; Menstruation; Methodology; Methods; Microscopy; Modeling; Molecular; Monitor; Morbidity - disease rate; Noise; Optics; Patients; Physiologic pulse; Pregnancy; Premature Birth; Primates; Process; Property; Provider; Public Health; Radiation; Research; Research Project Grants; Resources; Risk; Role; Sampling; Scanning; Signal Transduction; Specimen; Speed; Structure; Study models; Techniques; Technology; Testing; Therapeutic; Thick; Time; Tissues; Ultrasonography; Work; attenuation; base; cohort; cost; human subject; improved; in vivo; innovation; nonhuman primate; novel; novel therapeutic intervention; optical imaging; pregnant; public health relevance; quantitative ultrasound; second harmonic; simulation; tool

DESCRIPTION (provided by applicant): An essential part of normal pregnancy is cervical remodeling, the process by which the collagen microstructure disorganizes and the cervix softens throughout pregnancy to allow eventual delivery of a fetus. Timing is everything; errors result in preterm or post-dates birth, both of which are costly and morbid. Remark- ably, there are currently no tools to objectively quantify these changes, leaving clinicians without a means to precisely determine risk or even a language to accurately communicate the status of a patient's cervix. The primary objective of this proposed effort is to further develop and test technology to objectively describe and quantify cervical microstructural collagen arrangement and softening. A secondary objective is to establish a nonhuman primate (NHP) model for the study of cervical remodeling in pregnancy. Our preliminary studies suggest that two quantitative ultrasound techniques can accurately assess changes in microstructural organization and softness: quantitative ultrasound with beamsteering (QUS) and acoustic radiation force impulse (ARFI). Within this proposed effort we will use these techniques to study the microstructural changes that the cervix undergoes during normal pregnancy in NHPs. There are two branches: the first involves hysterectomy specimens and the second live NHPs. For the former, we will study normal specimens from animals being euthanized for unrelated research projects. Half of the group will undergo cervical ripening with a drug used clinically to ripen the cervix prior to induction of labor, and half will receive no treatment. Quantitative ultrasound measurements of acoustic scattering properties (to describe collagen structure) and tissue softness will be compared in these two groups, and nonlinear optical microscopy (for imaging collagen) will be used to corroborate the ultrasound findings. (This comparison parallels that underway in similar studies of human subject hysterectomy specimens.) The other branch will be a serial study of quantitative ultrasound parameters at several time points throughout normal menstruation (to establish underlying biological variability), and then normal pregnancy (to describe collagen reorganization and cervical softening in pregnancy). A successful NHP model of cervical ripening in pregnancy would add significantly to the body of knowledge about the cervix and accelerate transition to in vivo human studies. Ultimately, a comprehensive understanding of cervical change in pregnancy could allow (a) selection of appropriate candidates for post-dates induction of labor, (b) prediction of patients at greatest risk for preterm delivery, (c) monitorin of treatments for preterm birth or failed post-dates ripening, and most importantly, (d) development of innovative therapeutic strategies for both preterm and post-dates birth via targeted investigation of associated molecular events based on thorough understanding of specific microstructural changes that lead to abnormal cervical remodeling.

描述（由申请人提供）：正常妊娠的一个重要部分是宫颈重塑，在整个妊娠期间，胶原微结构解体和宫颈软化的过程，最终允许胎儿分娩。时机就是一切;错误会导致早产或晚生，这两种情况都是昂贵和病态的。值得注意的是，目前还没有客观量化这些变化的工具，使得临床医生没有精确确定风险的手段，甚至没有准确传达患者宫颈状态的语言。这项工作的主要目的是进一步开发和测试客观描述和量化宫颈微结构胶原蛋白排列和软化的技术。第二个目的是建立一个非人灵长类动物（NHP）模型，用于研究妊娠期宫颈重塑。我们的初步研究表明，两种定量超声技术可以准确地评估微结构组织和柔软度的变化：定量超声波束转向（QUS）和声辐射力脉冲（ARFI）。在这项拟议的努力，我们将使用这些技术来研究的微观结构的变化，子宫颈在正常妊娠期间经历的NHP。有两个分支：第一个涉及子宫切除标本，第二个活的NHP。对于前者，我们将研究从动物的正常标本被安乐死无关的研究项目。一半的人将在引产前接受临床上用于使宫颈成熟的药物使宫颈成熟，另一半人将不接受任何治疗。将在这两组中比较声散射特性（描述胶原结构）和组织柔软度的定量超声测量，并将使用非线性光学显微镜（用于胶原成像）来证实超声结果。(This与人类受试者子宫切除术标本的类似研究中进行的比较相似。另一个分支是在正常月经（以建立潜在的生物学变异性）和正常妊娠（以描述妊娠中的胶原重组和宫颈软化）的几个时间点对定量超声参数进行的系列研究。一个成功的NHP妊娠期宫颈成熟模型将显著增加有关宫颈的知识体系，并加速向体内人体研究的过渡。最终，全面了解妊娠期宫颈变化可以（a）选择适当的候选人进行过期引产，（B）预测早产风险最大的患者，（c）监测早产或过期成熟失败的治疗，最重要的是，（d）为早产儿和产后婴儿制定创新的治疗战略，基于对导致宫颈异常的特定微结构变化的全面了解，通过有针对性地调查相关分子事件来确定出生日期重塑