Ultrasound induced vessel thrombosis for treatment of Gastric varices

描述(由申请人提供)： 这项研究事业奖提案的目的是勾勒出高强度治疗性超声领域的多学科研究路线，潜在地应用于胃肠道出血，将被用作在指导环境中获得更多科学和工程研究经验的载体。这项提议的总体目标是发展一套技能，使我能够成为一名高度胜任和有竞争力的独立科学研究员，应用工程和科学原理来解决胃肠病领域的临床问题。此外，还提出了一项补充职业发展计划，其中包括额外的课程作业、职业发展研讨会和成立一个科学/职业发展监督委员会。 这项拟议研究的总体目的是调查超声靶向血管闭塞治疗胃底静脉曲张的作用。虽然超声在临床上最常用于诊断目的，但它也能够将能量传递给组织用于治疗目的。在较高的强度下，超声波具有已知的生物效应，如组织加热和空化造成的机械破坏。初步研究已经调查了血管暴露在HIFU下的生物效应，特别是在循环超声造影剂(UCA)的环境中。研究表明，脉冲HIFU联合微泡造影剂可导致血管内皮细胞损伤，导致血小板活化和血管内血栓形成。此外，还证明了该方法可以用于血管闭塞的目标识别。该项目建议将基本的超声生物效应研究转化为治疗胃底静脉曲张的临床有用方法。建议的研究将检验超声介导的血管闭塞在活动性出血的血管中实现止血的能力。将构建一个原型内窥镜换能器，以测试超声介导的血管闭塞在大型动物模型中治疗胃底静脉曲张的可行性。该项目的总体假设是，超声介导的血管闭塞可以在活动性出血的血管中实现止血，并闭塞和闭塞目标血管的一段。随着基于内窥镜的超声换能器的发展，这种方法可以转化为治疗胃底静脉曲张的临床有用的方法。

DESCRIPTION (provided by applicant): This purpose of this Research Career Award proposal is to outline a multidisciplinary line of investigation in the field of high-intensity therapeutic ultrasound with potential applications to gastrointestinal bleeding that will be used as a vehicle to gain additional scientific and engineering research experience in a mentored setting. The overall goal of this proposal is to develop a skill set that will enable me to become a highly competent and competitive independent scientific investigator applying engineering and scientific principles to solve clinical problems in the field of gastroenterology. In addition, a supplemental career development plan that includes additional coursework, career development seminars, and the formation of a scientific/career development supervisory committee is proposed. The overall purpose of the proposed research is to investigate the role of ultrasound-targeted vessel occlusion for the treatment of gastric varices. Although ultrasound is most commonly used for diagnostic purposes clinically, it is also capable of delivering energy to tissue for therapeutic purposes. At higher intensities, ultrasound has known bioeffects such as tissue heating and mechanical disruption due to cavitation. Initial studies have investigated the bioeffects that result from the exposure of blood vessels to HIFU, particularly in the setting of circulating ultrasound contrast agent (UCA). It has been demonstrated that pulsed HIFU in combination with microbubble contrast agent can lead to endothelial damage resulting in platelet activation and intravascular thrombus formation. Furthermore, it has been demonstrated that this method can be used to target vessel occlusion. This project proposes to translate basic ultrasound bioeffects studies into a clinically useful approach for treating gastric varices. The proposed studies will examine the ability of ultrasound-mediated vascular occlusion in achieving hemostasis in actively bleeding blood vessels. A prototype endoscopic transducer will be constructed to test the feasibility of ultrasound-mediated vessel occlusion in treating gastric varices in a large animal model. The overall hypothesis of this project is that ultrasound-mediated vascular occlusion can achieve hemostasis in actively bleeding blood vessels and occlude and obliterate a targeted segment of a blood vessel. This method can be translated to a clinically useful approach for the treatment of gastric varices with the development of an endoscopic-based ultrasound transducer