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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.

目前缺乏可靠的工具来评估先兆子痫有希望的治疗对胎盘的影响。功能和发育;治疗效果的评估通常通过测量母体平均动脉压，并不总是与胎儿结局相关。如果没有这种技术，改善先兆子痫病理生理学的机制理解的承诺- 开发新的治疗方法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，以改善对先兆子痫本申请的总体目标是建立新的功能成像方法，纵向测量体内胎盘灌注、缺血和胎盘血管生成。我们的中央有一种假说认为，通过纵向监测胎盘灌注，缺氧，以及使用光谱光声（sPA）和靶向对比增强超声（CEUS）的血管生成显像这一假设是根据我们实验室和其他建立sPA的实验室的初步数据提出的。成像作为体内估计纵向胎盘组织氧合的方法，CEUS作为量化体内组织灌注和血管生成。拟议研究的理由是，先兆子痫的纵向体内监测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有力的初步数据的指导下，这一假设将得到检验，追求两个具体的目标：1）开发在体内对胎盘氧合变化进行成像的方法，对治疗的反应;和2）开发方法来成像治疗的纵向影响，胎盘生长在第一个目标下，将实施光谱光声成像来估计胎盘治疗过程中的氧合;将用于本研究的成像方法和先兆子痫模型项目，子宫灌注压降低（RUPP）大鼠，都已建立为可行的，申请人的手。在第二个目标下，将纵向实施对比增强超声，跟踪先兆子痫治疗期间胎盘灌注的变化。支持这一观点的初步数据目的探讨超声造影评价胎盘血流灌注和血管新生的方法。这种方法是创新的，因为它通过转移研究重点，从母体系统功能障碍到胎盘功能障碍，长期以来被认为是主要的潜在疾病，先兆子痫的发展中的调节剂。胎盘多模式在体成像技术的建立功能将构成对表征患者的生理环境的显著改进。先兆子痫期间胎盘;获得这些缺失的信息有望开辟新的治疗方法选择，并将该领域大幅推向改善治疗。预计这一贡献将在一系列妊娠相关疾病的预防和治疗中具有广泛的转化重要性。