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: 9199589
• 负责人: Helen Feltovich
• 金额: $ 51.1万
• 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 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9199589
• 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; Discipline of obstetrics; Drug usage; Event; Fetus; Foundations; Future; Generations; Goals; Human; Hysterectomy; Image; Individual; Investigation; Knowledge; Language; Lead; Logistics; 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; individual patient; innovation; microscopic imaging; nonhuman primate; novel therapeutic intervention; novel therapeutics; optical imaging; pregnant; public health relevance; quantitative ultrasound; second harmonic; simulation; soft tissue; 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，在整个妊娠过程中，胶原微结构瓦解，宫颈软化，最终分娩胎儿。时机就是一切；错误会导致早产或过期分娩，这两种情况都是昂贵且病态的。值得注意的是，目前没有工具可以客观地量化这些变化，使得临床医生无法精确确定风险，甚至无法使用语言来准确传达患者宫颈的状态。这项工作的主要目标是进一步开发和测试技术，以客观地描述和量化宫颈微观结构胶原排列和软化。第二个目标是建立非人类灵长类动物（NHP）模型来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评估微观结构组织和柔软度的变化：波束控制定量超声（QUS）和声辐射力脉冲（ARFI）。在这项拟议的工作中，我们将使用这些技术来研究 NHP 正常妊娠期间子宫颈所经历的微观结构变化。有两个分支：第一个涉及子宫切除标本，第二个涉及活体 NHP。对于前者，我们将研究因不相关的研究项目而被安乐死的动物的正常标本。该组中的一半将在引产前使用临床上用于使宫颈成熟的药物进行宫颈成熟，另一半将不接受任何治疗。将比较这两组的声散射特性（用于描述胶原蛋白结构）和组织柔软度的定量超声测量，并且将使用非线性光学显微镜（用于胶原蛋白成像）来证实超声结果。 （这种比较与人类子宫切除标本的类似研究中正在进行的比较相似。）另一个分支将是对正常月经期间几个时间点的定量超声参数进行系列研究（以确定潜在的生物变异性），然后是正常怀孕（以描述怀孕期间的胶原蛋白重组和宫颈软化）。妊娠期宫颈成熟的成功 NHP 模型将显着丰富有关宫颈的知识，并加速向体内人体研究的过渡。最终，对妊娠期宫颈变化的全面了解可以实现（a）选择合适的过期引产候选者，（b）预测早产风险最大的患者，（c）监测早产或过期催产失败的治疗，最重要的是，（d）基于对特定具体情况的透彻理解，通过对相关分子事件进行有针对性的研究，制定针对早产和过期分娩的创新治疗策略。 导致异常宫颈重塑的微观结构变化。