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 可以将市售的磷脂封装的全氟丙烷微泡被压缩到 液滴的尺寸是亚微米，即使在体温下，也可以在其壳内保持液体形式。 我们已经证明了这些炮弹的液滴具有明显不同的声学特性 它们是由它们形成的微泡，并且可以在发育中的心肌疤痕区域内积聚。 此外，我们已经用诊断性高机械指数（MI）经胸腔蒸发了这些液滴 超声检查的心肌缺血和再灌注的大型动物模型（I/R）。我们现在有 在包括肌浆在内的血管外部位表现出了液滴的存在 I/R后静脉注射。选择性激活/空化的诊断和治疗潜力 在此应用程序中将探索发育中的疤痕区域（DSZ）内的液滴。中心假设 这个项目的是，DSZ中静脉注射的全氟丙烷液滴可以用 高MI诊断超声，随后的背景提取强度将与 液滴浓度。此外，我们预测这些形成的微泡的激活和空化 将增加组织一氧化氮的产生，从而减少DSZ的大小。这个建议 试图解决必须克服的重大知识差距，以充分检验这一假设。这 必须确定用于液滴汽化的诊断超声阈值，以及哪种特定行为 形成的微泡在结合，气蚀或重新降低后表现出 汽化。我们将采用超高速度（> 106兆赫框架速率）来检测激活 （蒸发）阈值并检查形成的微泡行为。我们将利用体外流系统 使用被动气射检测器，以确定微血管和 血管流量条件。我们将分析液滴（血管或血管外）的微血管位置 在正常条件下并遵循大鼠cremaster肌肉的I/R。然后，我们将应用选择性 在心肌I/R大鼠模型中，激活/空化脉冲与DSZ。硝酸的选择性激活 疤痕区域内的氧化活性也将得到验证，以及如何受到施加的时间的影响 与再灌注有关的激活/空化冲动。然后，我们将评估选择性的能力 在心肌I/R的大动物模型中量化梗塞大小的激活/气蚀。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的猪模型中再灌注后不同时间点的全氟丙烷液滴注射。 该项目将确定选择性液滴激活和空化的潜力 疤痕区以及这种激活/气蚀过程如何改变受伤后的左心室重塑。