Ultrasound induced vessel thrombosis for treatment of Gastric varices

描述（由申请人提供）： 该研究职业奖提案的目的是概述高强度治疗性超声领域的多学科研究路线，其潜在应用于胃肠道出血，将用作在指导环境中获得额外科学和工程研究经验的工具。本提案的总体目标是培养一套技能，使我能够成为一名高度胜任和具有竞争力的独立科学研究者，应用工程和科学原理解决胃肠病学领域的临床问题。此外，一个补充的职业发展计划，其中包括额外的课程，职业发展研讨会，并成立一个科学/职业发展监督委员会的建议。 拟议研究的总体目的是研究超声靶向血管闭塞治疗胃静脉曲张的作用。虽然超声最常用于临床诊断目的，但它也能够将能量输送到组织用于治疗目的。在更高的强度下，超声具有已知的生物效应，例如组织加热和由于空化引起的机械破坏。最初的研究已经调查了血管暴露于HIFU所导致的生物效应，特别是在循环超声造影剂（UCA）的情况下。已经证明，脉冲HIFU与微泡造影剂组合可导致内皮损伤，从而导致血小板活化和血管内血栓形成。此外，已证明该方法可用于靶向血管闭塞。该项目旨在将基本的超声生物效应研究转化为治疗胃静脉曲张的临床有效方法。拟议的研究将检查超声介导的血管闭塞在活跃出血血管中实现止血的能力。将构建原型内窥镜换能器，以在大型动物模型中测试超声介导血管闭塞治疗胃静脉曲张的可行性。该项目的总体假设是，超声介导的血管闭塞可以在活跃出血的血管中实现止血，并闭塞和闭塞血管的目标段。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静脉曲张的临床有用方法

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