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: 10133130
• 负责人: THOMAS R PORTER
• 金额: $ 72.8万
• 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/10133130
• 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; 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.

项目摘要 商业上可获得的磷脂包裹的全氟丙烷微泡可以压缩成 液滴大小为亚微米，即使在体温下仍以液体形式存在于其外壳内。 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，并可在发展中的心肌疤痕区域内积累。 此外，我们已经将这些液滴汽化，诊断为高机械指数(MI)。 超声在大小心肌缺血再灌注(I/R)动物模型中的应用。我们现在有了 显示在血管外位置存在液滴，包括下列肌浆 缺血再灌注后静脉注射选择性激活/空化的诊断和治疗潜力 在这项应用中，将探索正在形成的疤痕区域(DSZ)内的液滴。中心假说 该项目的特点是，在该区域内静脉注射的全氟丙烷液滴可以通过 高MI诊断超声，以及随后背景减去的强度将与 液滴浓度。此外，我们预测这些形成的微泡的活化和空化 会增加组织中一氧化氮的产生，从而缩小DSZ的大小。这项建议 寻求解决必须克服的重大知识差距，以充分检验这一假说。这个 必须确定液滴蒸发的诊断超声阈值，以及什么具体行为 形成的微泡表现为合并、空化或随后的再冷凝。 汽化。我们将使用超高速(&gt；106兆赫帧速率)摄像头来检测激活 (汽化)阈值，并检查形成的微泡行为。我们将利用体外流动系统 用被动空化探测器确定微血管和微血管的激活和空化阈值 血管流动状况。我们将分析液滴(血管或血管外)的微血管位置。 正常情况下和大鼠提睾肌I/R后。然后，我们将选择性地应用 激活/空化脉冲刺激大鼠心肌I/R模型中的dSZ--选择性激活一氧化氮 还将验证疤痕区域内的氧化物活性，以及它是如何受到应用时间的影响的 与再灌流有关的激活/空化脉冲。然后我们将评估选择的能力 激活/空化以量化心肌I/R大型动物模型中的梗塞范围。最后，我们将评估 静脉注射后选择性活化/空化成像治疗脱氧核糖核酸的远期疗效 在猪I/R模型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，以检测正在进行的 瘢痕区域，以及这种激活/空化过程如何改变损伤后的左心室重构。