Vessel Rupture Thresholds for Microbubble-Assisted High-Intensity Therapeutic Ultrasound - Renewal Application

PI：Kismatullin，Damir高强度聚焦超声(HITU)最近被认为是一种无创、无电离、无辐射的治疗方法。它正在被探索用于治疗癌症、神经疾病和循环系统相关的心血管疾病。为了避免永久性损伤并确定HITU设备的血管破裂阈值，将对血管中的气泡动力学进行实验和建模。该项目将为HITU安全阈值评估带来一个计算工具和一个新的公式，使美国的患者能够更快地获得治疗严重衰弱疾病的安全设备。它将直接支持少数民族研究生的研究工作。学生将接受计算流体力学和通过聚焦超声刺激体外组织的实验技术方面的培训。高强度治疗性聚焦超声(HITU)的结果在很大程度上取决于组织中微米大小的气泡的存在，这些气泡可以作为声空化的结果。例如，微泡在超声场中的振荡会对附近的细胞和组织产生机械应力，导致血栓溶解或血脑屏障(BBB)瞬间打开，从而将药物输送到脑组织。PI将开发一种最先进的计算模型，用于研究暴露在聚焦超声下的血管和组织中脂质涂层微泡的空化。该模型将考虑组织粘弹性和非均质性，并与HITU关于移植血管破裂的实验进行验证，以确定血管破裂时管壁上的临界压力和应力。

PI: Khismatullin, Damir High-intensity focused ultrasound (HITU) has recently gained recognition as a noninvasive ionizing radiation-free therapeutic method. It is being explored for treatment of cancer, neurological diseases, and circulatory system-related cardiovascular diseases. To avoid permanent damage and to identify vessel rupture thresholds for HITU devices experiments and modeling of bubble dynamics in blood vessels will be performed. This project will lead to a computational tool and a new formula for HITU safety threshold assessment that will give patients in the U.S. faster access to safe devices for treating severely debilitating diseases. It will directly support the research work of a minority graduate student. The student will receive training in computational fluid dynamics and experimental techniques for stimulation of ex vivo tissues by focused ultrasound. The outcomes of high-intensity therapeutic focused ultrasound (HITU) significantly depend on the presence of micrometer-size bubbles that can be formed in tissues as a result of acoustic cavitation. The oscillation of microbubbles in an ultrasound field generates mechanical stresses on nearby cells and tissues, leading, for example, to thrombolysis or transient opening of the blood-brain barrier (BBB) for drug delivery to brain tissue. The PI will develop a state-of-the-art computational model of cavitation of lipid-coated microbubbles in blood vessels and tissues exposed to focused ultrasound. The model will account for tissue viscoelasticity and inhomogeneity and be validated against HITU experiments on rupture of explanted vessels, to determine the critical pressure and stresses on the vessel wall above which the vessel ruptures.