Fine-resolution mapping of micro vasculature after placental transport of acoustic nanodrops

声学纳米滴胎盘运输后微脉管系统的精细分辨率绘图

• 批准号: 9983114
• 负责人: Jeffrey Ketterling
• 金额: $ 20.54万
• 依托单位: RIVERSIDE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9983114
• 关键词: 3-Dimensional; Acoustics; Affect; Age; Blood Circulation; Blood Vessels; Caliber; Charge; Chemicals; Contrast Media; Data; Development; Developmental Biology; Disease; Dose; Dyes; Embryo; Embryonic Development; Exposure to; Fluorocarbons; Focused Ultrasound Therapy; Frequencies; Gases; Genetic; Goals; Harvest; Image; Image Enhancement; Individual; Injections; Label; Lateral; Length; Location; Longitudinal Studies; Magnetic Resonance Imaging; Maps; Methods; Michigan; Microbubbles Ultrasound Contrast Medium; Modeling; Morphogenesis; Morphology; Mus; Organ; Organogenesis; Pathway interactions; Pattern; Physiologic pulse; Placenta; Process; Reporting; Resolution; Role; Shapes; Source; Surface; Tail; Techniques; Testing; Ultrasonic wave; Ultrasonography; Veins; angiogenesis; body system; contrast enhanced; hemodynamics; imaging agent; imaging approach; imaging modality; improved; in utero; in vivo; microCT; mouse model; particle; pressure; temporal measurement; transmission process; uptake; vapor; vaporization; virtual

Project Summary/Abstract A fundamental question in developmental biology is how specific molecules and genetic pathways control mor- phogenesis during embryonic development. Recent studies have shown that many of the same molecules and genetic pathways affecting organogenesis are also involved in vascular development and patterning during an- giogenesis. A major challenge is to develop rapid, in vivo mouse-embryo imaging methods that provide the ability to analyze organ and vascular patterning with fine resolution. The goal of this proposal is to establish the feasibility of transporting acoustic nanodrops (NDs) through the pla- centa in order to map vasculature of the embryonic mouse, in utero, with super-resolution, plane-wave ultrasonic imaging. Perfluorocarbon NDs can be vaporized by an acoustic excitation and converted to gas filled acoustic contrast agents. After vaporization, the NDs reach a size on the order of 1 m and appear as bright points in an ultrasound image. We will formulate ND compositions of different size, charge and perfluorocarbon core. We will evaluate fluorescent ND compositions to determine which NDs, after injection into the maternal mouse tail vein, pass through the placenta into the embryonic circulation and select the most promising composition in terms of size and transport efficiency. We will quantify the acoustic pressures at which the selected NDs vaporize. The most promising ND in terms of vaporization threshold will be injected into the maternal tail vein of a mouse and, after entering the embryonic circulation, the NDs will be activated with an acoustic pulse. Plane-wave ul- trasound and super-resolution methods will then be utilized to detect and localize activated NDs at fine-spatial and -temporal resolution as they move through the embryonic circulation. Feasibility of vascular mapping in a single plane will be evaluated. Because this approach relies on tracking point targets, the length scale that can be resolved, on the order of 20 m, is much less than the lateral beamwidth of the 18-MHz linear-array acous- tic field. The ability to activate NDs that have passed through the placenta and to perform noninvasive, in utero contrast-enhanced imaging has high potential to revolutionize the way we study organogenesis and angiogenesis in widely utilized models of normal and abnormal embryonic development.

项目概要/摘要 发育生物学的一个基本问题是特定分子和遗传途径如何控制发育。 最近的研究表明，许多相同的分子和胚胎发育过程中的光发生。 影响器官发生的遗传途径也参与血管发育和模式形成 一个主要的挑战是开发能够提供这种能力的快速体内小鼠胚胎成像方法。 以高分辨率分析器官和血管模式。 该提案的目标是确定通过平面传输声纳米滴（ND）的可行性 centa 旨在利用超分辨率平面波超声波绘制子宫内胚胎小鼠的脉管系统图 全氟化碳 ND 可以通过声学激发而汽化并转化为气体填充的声学。 造影剂蒸发后，ND 的尺寸达到 1 m 左右，并在造影剂中显示为亮点。 我们将配制不同尺寸、电荷和全氟化碳核的 ND 组合物。 评估荧光 ND 成分以确定哪些 ND 在注射到母鼠尾静脉后， 通过胎盘进入胚胎循环并选择最有希望的成分 我们将量化所选 ND 汽化的声压。 就汽化阈值而言最有希望的 ND 将注射到小鼠母体尾静脉中 并且，进入胚胎循环后，ND 将被平面波 ul- 激活。 然后将利用超声和超分辨率方法在精细空间中检测和定位激活的 ND -它们在胚胎循环中移动时的时间分辨率。 由于这种方法依赖于跟踪点目标，因此将评估单个平面。 被解析，大约20 m，远小于18 MHz线性阵列声学的横向波束宽度 能够激活已穿过胎盘的 ND 并在子宫内进行非侵入性操作。 对比增强成像具有彻底改变我们研究器官发生和血管生成的方式的巨大潜力 在广泛使用的正常和异常胚胎发育模型中。