Investigating the role of microbubbles and focused ultrasound in tissue temperature elevation

研究微泡和聚焦超声在组织温度升高中的作用

• 批准号: 2301709
• 负责人: Aswin Gnanaskandan
• 金额: $ 27.5万
• 依托单位: Worcester Polytechnic Institute
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2301709&HistoricalAwards=false
• 关键词: Investigating; role; microbubbles; focused; ultrasound

High-intensity focused ultrasound (HIFU) is an emerging therapeutic modality currently being explored for targeted drug delivery by mild hyperthermia, targeted ablation of benign tumors, such as uterine fibroids and malignant tumors in the prostate, liver, kidney, pancreas, or bone. However, delivering sufficient acoustic energy past certain anatomical constraints (i.e., bones and dense tissue) has been a challenge that prevented HIFU from being more widely applicable. For instance, magnetic resonance guided HIFU has been used for treatment of essential tremor, which requires high acoustic intensities to overcome the amount of sound that is absorbed or reflected by the skull. This increase in acoustic intensities also increases the heating outside the focus and the targeted region, potentially leading to burns in the skin and subcutaneous fat. Therefore, there is a need for a method to elevate temperature locally with HIFU at lower acoustic intensities to minimize collateral damage. Bubble-enhanced heating (BEH), administration of contrast agent microbubbles during HIFU, can mitigate this challenge as microbubble cavitation enhances the acoustic energy conversion process, enabling heat generation with less acoustic energy. The main goal of this project is to enhance the fundamental understanding of how microbubbles help in achieving increased temperature elevation in tissues in the presence of focused ultrasound. The project will also encompass significant educational activities including undergraduate research projects and outreach activities for high school students.The technical goal of the proposed research is to use a combined experimental and numerical study to understand and quantify the interaction of focused ultrasound with a cloud of encapsulated microbubble contrast agents. A novel well controlled in vitro experimental setup will be developed to achieve focal heating in tissue phantoms both in the presence and absence of microbubbles. The experimental data in the form of temperature and pressure at various spatial and temporal points will be used to validate a multiscale numerical model that can predict focal temperature elevation. The validated model will then be used to develop scaling laws for acoustic shielding, a phenomenon where microbubbles at higher concentrations can essentially shield the ultrasound from reaching the target region. The proposed research will help in revolutionizing focused ultrasound therapy for cancer treatment by accurately characterizing the acoustic and thermal fields in the presence of microbubbles and by providing operational bounds of the therapy. This will enable researchers to explore a wide range of therapeutically relevant parameters and optimize design settings with confidence when developing focused ultrasound-based therapies.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

高强度聚焦超声（HIFU）是一种新兴的治疗模式，目前正在探索通过轻度高温靶向药物输送，靶向消融良性肿瘤，如子宫肌瘤和前列腺，肝脏，肾脏，胰腺或骨骼中的恶性肿瘤。然而，传递足够的声能超过某些解剖约束（即，骨和致密组织）一直是阻碍HIFU更广泛应用的挑战。例如，磁共振引导的HIFU已经用于治疗特发性震颤，其需要高的声强度来克服被颅骨吸收或反射的声音的量。声强度的这种增加也增加了焦点和目标区域外部的加热，可能导致皮肤和皮下脂肪的烧伤。因此，需要一种在较低声强度下用HIFU局部升高温度以使附带损伤最小化的方法。气泡增强加热（BEH），即在HIFU期间给予造影剂微泡，可以缓解这一挑战，因为微泡空化增强了声能转换过程，从而能够以更少的声能产生热量。该项目的主要目标是加强对微泡如何帮助在聚焦超声存在下实现组织中温度升高的基本理解。该项目还将包括重要的教育活动，包括本科生研究项目和高中生的推广活动，拟议研究的技术目标是使用实验和数值相结合的研究，以了解和量化的相互作用，聚焦超声与云封装微泡造影剂。将开发一种新的控制良好的体外实验装置，以实现在存在和不存在微泡的情况下在组织模型中的局部加热。在不同的空间和时间点的温度和压力的形式的实验数据将被用来验证多尺度的数值模型，可以预测焦点温度升高。然后将使用经验证的模型来开发声屏蔽的比例定律，这是一种高浓度微泡基本上可以屏蔽超声到达目标区域的现象。拟议的研究将有助于通过准确表征微泡存在下的声场和热场以及提供治疗的操作范围来彻底改变用于癌症治疗的聚焦超声治疗。 这将使研究人员能够探索广泛的治疗相关参数，并在开发聚焦超声治疗时充满信心地优化设计设置。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。