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

• 批准号: 10215581
• 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
• 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/10215581
• 关键词: Angiogenesis Inhibitors; Angiogenesis Promoter; Blood Vessels; Data; Development; Disease; Environment; Equilibrium; Functional Imaging; Functional disorder; Goals; Growth; Hand; Health; Human; Hypoxia; Imaging Device; Incidence; 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; base; 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

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有希望的先兆子痫治疗方法对胎盘的影响 功能和发育；治疗效果的评估通常通过测量来确定 母亲平均动脉压，在没有这种情况的情况下并不总是与胎儿结局相关。 技术，有望改善对先兆子痫病理生理学的机制理解—— 开发新疗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治疗 本申请的总体目标是建立新的功能成像方法来诊断先兆子痫。 体内胎盘灌注、缺血和胎盘血管生成的纵向测量。 假设胎儿结局可以通过纵向监测胎盘灌注、缺氧、 使用光谱光声 (sPA) 和靶向对比增强超声 (CEUS) 进行血管生成 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制定的。 成像作为估计体内纵向胎盘组织氧合的方法，而超声造影作为估计胎盘组织纵向氧合的方法 量化体内组织灌注和血管生成拟议研究的基本原理是改善。 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 在强有力的初步数据的指导下，这一假设将得到检验。 追求两个具体目标：1）开发体内胎盘氧合变化成像的方法 对治疗的反应；以及2）开发对治疗的纵向影响进行成像的方法。 在第一个目标下，将采用光谱光声成像来估计胎盘。 治疗期间的氧合；本研究中将使用的成像方法和先兆子痫模型 降低子宫灌注压（RUPP）大鼠项目均已在 根据第二个目标，超声造影将纵向实施。 跟踪先兆子痫治疗期间胎盘灌注的变化支持这一点。 这种方法证明了客观的超声造影是一种评估胎盘灌注和血管生成的方法。 具有创新性，因为它通过转移研究重点代表了对现状的实质性偏离 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基础 先兆子痫发展中的调节因子。胎盘多模式体内成像的建立。 功能将显着改善表征生理环境 先兆子痫期间的胎盘；获取这一缺失的信息有望开辟新的治疗方法 的选择并大大推动该领域改善治疗。 在预防和治疗一系列妊娠相关疾病方面具有广泛的转化重要性。