BRIGE - The role of vaporized perfluorocarbon nanoemulsions in enhanced ultrasound-induced lesion formation for cancer therapy

0926909PorterIntellectual MeritFocused ultrasound（FUS）是一种用于治疗局部实体瘤的非侵入性医疗程序。FUS可迅速加热组织，导致凝固性坏死。 凝固组织的体积被称为病变，FUS治疗可以以毫米精度破坏实体肿瘤。然而，大多数临床相关实体瘤的治疗需要放置多个病灶，这可能需要数小时而不是数分钟才能实现。有充分证据表明，气泡加速FUS介导的病变形成并增加病变体积。因此，有效治疗实体肿瘤所需的时间和声能可以显著减少。使用气泡的一个挑战是不受控制的气泡形成和活动可能导致不可预测的加热和损伤形成。我们开发了一种相移纳米乳液（PSNE），可以高度空间和时间控制地使气泡成核。损伤形成的速率以及损伤体积取决于气泡场的大小和密度。通过了解PSNE浓度、所施加的声压、气泡场的活性和病变形成之间的关系，我们可以设计一种系统，以更有效地利用聚焦超声治疗癌症。所提出的研究的目标是：1）阐明PSNE密度、声压和气泡云演变之间的关系，（2）研究空化场的大小和活动性与病变空间演变的关系。将使用与白蛋白混合并填充PSNE的聚丙烯酰胺凝胶进行体外研究。凝胶是光学透明的，因此允许观察和测量气泡场和病变的空间演变。光学和声学技术将用于监测聚丙烯酰胺凝胶体模中的PSNE蒸发，并测量所得气泡场的大小。 实验结果将进行比较，在粘性牛顿介质中的气泡增强加热的理论模型所提供的损伤形成的预测。从拟议的研究中获得的知识将提高我们的理解的方式，其中空化气泡重新分配声能和增强热沉积在超声hypothermia.broaderimpactsA研究生课程的基本原理和应用的医疗声学将开发。本课程将涵盖粘弹性介质中的声波传播和吸收，以及与声空化相关的生物效应，包括组织中增强的热沉积和用于药物和基因递送的细胞膜的透化。一名研究生将接受纳米乳液合成和声学技术和数值方法的培训，以研究空化气泡在超声介导的热疗中的作用。此外，在夏季的几个月里，将为代表性不足的少数民族本科生提供研究机会。最后，外展工作将使当地高中代表性不足的少数民族学生接触基本声学，能量转换，相变和基本工程设计。这将分两个阶段实现：（1）讲座和动手演示将被开发来描述基本的声学和光学，以及（2）学生将构建和测试定制设计的超声造影剂的声学特性。

0926909PorterIntellectual MeritFocused ultrasound (FUS) is a noninvasive medical procedure for the treatment of localized solid tumors. FUS can heat tissue rapidly, which leads to coagulative necrosis. The volume of coagulated tissue is known as a lesion, and FUS therapy can destroy solid tumors with millimeter precision. However, the treatment of most clinically relevant solid tumors requires placement of multiple lesions, which can take hours instead of minutes to achieve. It is well documented that bubbles accelerate FUS-mediated lesion formationand increase the lesion volume. As a result, the time and acoustic energy required for effective treatment of solid tumors can be significantly reduced. One challenge to using bubbles is that uncontrolled bubble formation and activity can lead to unpredictable heating and lesion formation. We have developed a phase-shift nanoemulsion (PSNE)to nucleate bubbles with a high degree of spatial and temporal control. The rate of lesion formation as well as the lesion volume depends upon the size and density of the bubble field. By understanding the relationship between the PSNE concentration, applied acoustic pressure, activity of the bubble field, and lesion formation, we can design a system to more efficiently treat cancer with focused ultrasound.The objectives of the proposed research are to 1) elucidate the relationship between PSNE density, acoustic pressure, and the evolution of bubble clouds, and 2) investigate the relationship between the size and activity of the cavitation field and the spatial evolution of lesions. In vitro studies will be performed with polyacrylamide gels mixed with albumin and populated with PSNE. The gels are optically transparent, thus allowing for observation and measurement of the spatial evolution of bubble fields and lesions. Optic and acoustic techniques will be used to monitor for PSNE vaporization in polyacrylamide gel phantoms and measure the size of the resultant bubble field. Experimental results will be compared with predictions of lesion formation provided by theoretical models of bubble-enhanced heating in viscous Newtonian media. The knowledge gained from the proposed research will improve our understanding of the manner in which cavitating bubbles redistribute acoustic energy and enhance heat deposition during ultrasound hyperthermia.Broader ImpactsA graduate course on the fundamental principles and applications of medical acoustics will be developed. The course will cover acoustic wave propagation and absorption in viscoelastic media, and bioeffects associated with acoustic cavitation, including enhanced heat deposition in tissue and permeabilization of cell membranes for drug and gene delivery. One graduate student will receive training on the synthesis of nanoemulsions and acoustic techniques and numerical methods for investigating the role of cavitating bubbles in ultrasound-mediated hyperthermia. Additionally, research opportunities will be made available for underrepresented minority undergraduate students during the summer months. Finally, outreach efforts will be made to expose underrepresented minority students from local high schools to fundamental acoustics, energy conversion, phase transitions, and basic engineering design. This will be achieved in two stages: (1) lectures and hands-on demonstrations will be developed to describe basic acoustics and optics, and (2) students will construct and test the acoustic properties of a custom-designed ultrasound contrast agent.