Scar Detection and Treatment with Droplet Activation

通过液滴激活进行疤痕检测和治疗

• 批准号: 10376846
• 负责人: THOMAS R PORTER
• 金额: $ 74.51万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10376846
• 关键词: Acoustics; Acute; Address; Affect; Animal Experimentation; Animal Model; Behavior; Blood Vessels; Body Temperature; Caliber; Cicatrix; Contrast Media; Detection; Diagnostic; Encapsulated; Environment; Exhibits; Family suidae; Fluoroscopy; Frequencies; Gender; Heart; Hour; Image; In Vitro; Infarction; Inflammation; Inflammatory; Injury; Intravenous; Ischemia; Knowledge; Left; Left Ventricular Remodeling; Liquid substance; Location; Mechanics; Microbubbles; Microcirculation; Modeling; Muscle; Myocardial; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion; Myocardium; Nitric Oxide; Operating System; Phase; Phospholipids; Physical condensation; Physiologic pulse; Physiological; Process; Production; Property; Rattus; Reperfusion Therapy; Sarcoplasm; Scheme; Speed; System; Temperature; Testing; Therapeutic; Therapeutic Effect; Time; Tissues; Transducers; Transmission Electron Microscopy; Troponin; Ultrasonography; Ventricular; base; cremaster muscle; detector; evaporation; follow-up; indexing; intravenous injection; intravital microscopy; myocardial infarct sizing; nanoscale; optical imaging; porcine model; pressure; submicron; time interval; ultrasound; vapor; vaporization

Project Summary Commercially available phospholipid encapsulated perfluoropropane microbubbles can be compressed into droplets that are submicron in size and remain in a liquid form within their shell even at body temperatures. We have demonstrated that these shelled droplets have significantly different acoustic properties than the microbubbles they are formed from, and can accumulate within a developing myocardial scar zone. Moreover, we have vaporized these droplets with diagnostic high mechanical index (MI) transthoracic ultrasound in small and large animal models of myocardial ischemia and reperfusion (I/R). We have now demonstrated droplet presence within extravascular locations including the sarcoplasm following intravenous injection after I/R. The diagnostic and therapeutic potential of selective activation/cavitation of droplets within the developing scar zone (DSZ) will be explored in this application. The central hypothesis of this project is that intravenously injected perfluoropropane droplets within the DSZ can be vaporized with high MI diagnostic ultrasound, and that subsequent background-subtracted intensities will correlate with droplet concentration. Furthermore, we project that activation and cavitation of these formed microbubbles will increase tissue nitric oxide production, resulting in a reduction in the size of the DSZ. This proposal seeks to address significant knowledge gaps that must be overcome to adequately test this hypothesis. The diagnostic ultrasound thresholds for droplet vaporization must be determined, and what specific behavior the formed microbubbles exhibit in terms of coalescence, cavitation, or re-condensation following vaporization. We will employ an ultra-high speed (>106 Megahertz frame rate) camera to detect activation (vaporization) thresholds and examine the formed microbubble behavior. We will utilize in vitro flow systems with passive cavitation detectors to determine activation and cavitation thresholds in microvascular and vascular flow conditions. We will analyze the microvascular location of droplets (vascular or extravascular) under normal conditions and following I/R in the rat cremaster muscle. We will then apply selective activation/cavitation pulses to the DSZ in a rat model of myocardial I/R. The selective activation of nitric oxide activity within the scar zone will also be verified, and how it is affected by the timing of the applied activation/cavitation impulses in relation to reperfusion. We will then assess the ability of selective activation/cavitation to quantify infarct size in a large animal model of myocardial I/R. Finally, we will assess the long-term therapeutic effect of selective activation/cavitation imaging of the DSZ following intravenous injections of perfluoropropane droplets at different time points following reperfusion in porcine models of I/R. This project will determine the potential for selective droplet activation and cavitation to detect the developing scar zone, and how this activation/cavitation process may alter left ventricular remodeling following injury.

项目概要 市售的磷脂封装的全氟丙烷微泡可被压缩成 尺寸为亚微米级的液滴，即使在体温下也能在其壳内保持液态。 我们已经证明，这些带壳液滴的声学特性与 它们是由微泡形成的，并且可以在正在形成的心肌疤痕区域内积聚。 此外，我们还通过诊断性高机械指数 (MI) 经胸腔蒸发了这些液滴 超声在小型和大型动物心肌缺血和再灌注（I/R）模型中的应用。我们现在有 证明液滴存在于血管外位置，包括随后的肌浆 I/R后静脉注射。选择性激活/空化的诊断和治疗潜力 本应用将探讨形成疤痕区 (DSZ) 内的液滴。中心假设 该项目的主要特点是 DSZ 内静脉注射的全氟丙烷液滴可以通过以下方式蒸发： 高 MI 诊断超声，并且随后的背景扣除强度将与 液滴浓度。此外，我们预计这些形成的微泡的活化和空化 会增加组织一氧化氮的产生，从而导致 DSZ 尺寸减小。这个提议 旨在解决必须克服的重大知识差距，以充分检验这一假设。这 必须确定液滴汽化的诊断超声阈值，以及什么具体行为 形成的微泡表现出聚结、空化或再凝结 汽化。我们将采用超高速（>106 兆赫兹帧速率）相机来检测激活 （蒸发）阈值并检查形成的微泡行为。我们将利用体外流动系统 使用被动空化探测器来确定微血管和中的激活和空化阈值 血管血流状况。我们将分析液滴的微血管位置（血管或血管外） 在正常条件下以及大鼠提睾肌 I/R 后。然后我们将选择性地应用 大鼠心肌 I/R 模型中 DSZ 的激活/空化脉冲。选择性激活硝酸 疤痕区域内的氧化物活性也将得到验证，以及它如何受到所施加的时间的影响 与再灌注相关的激活/空化脉冲。然后我们将评估选择性的能力 激活/空化来量化大型动物心肌 I/R 模型中的梗塞面积。最后，我们将评估 静脉注射后 DSZ 选择性激活/空化成像的长期治疗效果 在 I/R 猪模型再灌注后的不同时间点注射全氟丙烷液滴。 该项目将确定选择性液滴激活和空化的潜力，以检测正在发展的 疤痕区，以及这种激活/空化过程如何改变受伤后的左心室重塑。