Placental Functional Imaging to Predict Preeclampsia Therapeutic Outcomes

胎盘功能成像预测先兆子痫的治疗结果

基本信息

批准号：
10680400
负责人：
Carolyn Louise Bayer
金额：
$ 31.65万
依托单位：
TULANE UNIVERSITY OF LOUISIANA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-15 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10680400
关键词：
Acceleration Angiogenesis Inhibitors Angiogenesis Promoter Angiogenic Factor Blood Vessels Data Development Disease Environment Equilibrium Functional Imaging Functional disorder Goals Growth Hand Health Human Hypoxia Imaging Device Incidence Invaded Ischemia Laboratories Measurement Measures Methods Mission Modeling Monitor Outcome Oxidative Stress Patient-Focused Outcomes Perfusion Physiological Placenta Pre-Clinical Model Pre-Eclampsia Pregnancy Prevention Public Health Rattus Research Sampling Symptoms Technology Testing Therapeutic Therapeutic Effect Therapeutic Studies Therapy Clinical Trials Tissues Traction Treatment Efficacy Ultrasonography United States National Institutes of Health Uterus Validation Vascular remodeling angiogenesis contrast enhanced effective therapy fetal imaging modality improved in vivo in vivo imaging in vivo imaging system in vivo monitoring innovation maternal hypertension method development multimodality novel novel therapeutics pathophysiology of preeclampsia photoacoustic imaging pre-clinical pressure response serial imaging therapy outcome tissue oxygenation tool treatment response ultrasound

项目摘要

There is a lack of reliable tools to assess the impact of promising treatments for preeclampsia on placental function and development; assessment of treatment efficacy is typically determined through measurements of maternal mean arterial pressure, which are not always correlated with fetal outcome. In the absence of such technology, the promise of an improved mechanistic understanding of preeclampsia pathophysiology — necessary for the development of novel treatments to improve patient outcomes — will likely remain unfulfilled. The long-term goal of this effort is to develop new functional imaging methods to improve the treatment of preeclampsia. The overall objective in this application is to establish new functional imaging methods to longitudinally measure in vivo placental perfusion, ischemia, and placental angiogenesis. Our central hypothesis is that fetal outcomes can be predicted by longitudinally monitoring placental perfusion, hypoxia, and angiogenesis using spectral photoacoustic (sPA) and targeted contrast enhanced ultrasound (CEUS) imaging. This hypothesis was formulated based on preliminary data from our lab and others establishing sPA imaging as a method to estimate longitudinal placental tissue oxygenation in vivo, and CEUS as a method to quantify in vivo tissue perfusion and angiogenesis. The rationale for the proposed research is that improved methods for longitudinal in vivo monitoring of preeclampsia will provide more accurate preclinical validation of potential treatments for preeclampsia. Guided by strong preliminary data, this hypothesis will be tested by pursuing two specific aims: 1) the development of methods to image in vivo placental oxygenation changes in response to therapy; and 2) the development of methods to image the longitudinal impact of therapies on placental growth. Under the first aim, spectral photoacoustic imaging will be implemented to estimate placental oxygenation during treatment; the imaging methods and the model of preeclampsia which will be used in this project, the reduced uterine perfusion pressure (RUPP) rat, have both been established as feasible in the applicants' hands. Under the second aim, contrast-enhanced ultrasound will be implemented to longitudinally track alterations in placental perfusion during preeclampsia treatment. Preliminary data in support of this objective demonstrates CEUS as a method of assessing placental perfusion and angiogenesis. This approach is innovative, because it represents a substantive departure from the status quo by shifting the research focus from maternal systemic dysfunction, to placental dysfunction, long recognized as the dominant underlying regulator in the development of preeclampsia. The establishment of multimodal in vivo imaging of placental function will constitute a significant improvement towards characterizing the physiological environment of the placenta during preeclampsia; acquiring this missing information is expected to open up new therapeutic options and move the field substantially towards improved treatment. This contribution is expected to have broad translational importance in the prevention and treatment of a range of pregnancy-associated diseases.

缺乏可靠的工具来评估诺言对preeclamsia对placenal的影响功能和发展；通常通过测量来确定治疗效率的评估母体平均动脉压，并不总是与胎儿结局相关。在没有这样的情况下技术，有望改善对前学病理生理学的机械理解的希望 - 开发新型治疗以改善患者预后所必需的 - 可能仍然无法实现。这项工作的长期目标是开发新的功能成像方法，以改善子痫前期。此应用程序的总体目的是建立新的功能成像方法纵向测量体内灌注，缺血和斑点血管生成。我们的中心假设是，可以通过纵向监测斑点灌注，缺氧，缺氧来预测胎儿结局。使用光谱光声（SPA）和靶向对比度增强超声（CEUS）的血管生成（CEUS）成像。该假设是根据我们实验室和其他建立水疗中心的初步数据提出的成像作为估计体内纵向位置组织氧合的方法，而CEUS作为一种方法量化体内组织灌注和血管生成。拟议研究的理由是改善纵向体内监测子痫的方法将提供更准确的临床前验证先兆子痫的潜在治疗方法。在强大的初步数据的指导下，该假设将通过追求两个具体的目的：1）开发在体内含量变化的方法的发展对治疗的反应； 2）开发方法以对疗法的纵向影响进行成像胎盘生长。在第一个目标下，将实施光谱光声成像以估计胎盘治疗期间的氧合；成像方法和先兆子痫的模型将在此使用项目，降低的子宫灌注压力（RUPP）大鼠，都在可行的申请人的手。在第二个目标下，将实施对比增强的超声在先兆子痫治疗期间跟踪斑点灌注的改变。初步数据支持此目的证明CEU是评估斑点灌注和血管生成的一种方法。这种方法具有创新性，因为它通过转移研究重点来代表与现状的实质性不同从孕产妇的全身功能障碍到位置功能障碍，长期以来被认为是主要的基础先兆子痫发展中的调节剂。建立位置多模式的体内成像功能将构成表征的物理环境的重大改进先兆子痫期间的lopeta；预计这些丢失的信息有望开放新的疗法选择并大大将现场转移到改善治疗方面。预计这项贡献将有在预防和治疗一系列妊娠相关疾病方面的广泛翻译重要性。