ERI:Elucidating the Mechanism and Effects of Enhanced Thermal Ablation of Tissues by Microbubble Assisted High Intensity Focused Ultrasound

高强度聚焦超声热消融是FDA批准的一种使用高频超声热消融癌组织的癌症治疗方法。长期以来，使用这种疗法来实现深层癌症的预期治疗效果的障碍是需要使用高能超声来实现更深的超声穿透，导致邻近波通道区域的有害加热。克服这一障碍的一种潜在方法是在目标区域引入微泡，同时使用中等能量的超声，在不升高邻近健康组织温度的情况下，在目标区域产生更高的温度升高。该项目的主要目的是通过数值模拟来阐明微泡如何在不损害周围组织的情况下帮助有效消融组织的基本理解。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外展活动。本研究的技术目标是模拟和量化微泡辅助聚焦超声热消融治疗中的气泡-声-热场相互作用现象。为了实现这一目标，将开发一个数值模型，可以模拟非线性超声在组织中的传播，它与微泡云的相互作用以及由此产生的热场。该模型将通过体外和离体实验数据进行验证。经过验证的模型将用于回答两个先前未回答的问题：(i)微泡增强从超声波到组织的热量传递的基本机制是什么？（ii）微泡参数和超声参数的什么组合可以在不损伤周围组织的情况下使靶区产生最佳的热沉积？本研究通过准确表征微泡存在时的声场和热场，将有助于实现微泡辅助超声治疗癌症的突破。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。该奖项反映了美国国家科学基金会的法定使命，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。

High Intensity Focused Ultrasound thermal ablation is an FDA approved cancer therapy that uses high frequency ultrasound to thermally ablate cancer tissues. A long-standing barrier in using this therapy to achieve desired therapeutic outcomes for deeper cancers is the need to use high energy ultrasound to achieve deeper ultrasound penetration, leading to detrimental heating of the neighboring wave passage regions. One potential method to overcome this barrier is to introduce microbubbles in the target region, while using moderate energy ultrasound, to generate higher temperature elevations in the target region without elevating the temperature of the neighboring healthy tissues. The main aim of this project is to elucidate through numerical simulations, the fundamental understanding of how microbubbles can help in efficient ablation of tissues without causing damage to surrounding tissues. The project will also encompass significant education activities including undergraduate research projects and outreach activities for high school students.The technical goal of the proposed research is to simulate and quantify the bubble-acoustics-thermal field interaction phenomenon in microbubble assisted focused ultrasound based thermal ablation therapy. To address this goal a numerical model will be developed that can simulate non-linear ultrasound propagation through tissues, its interaction with a microbubble cloud and the resulting thermal field. The model will be validated using both in vitro and ex vivo experimental data. The validated model will then be used to answer two previously unanswered questions: (i) what is the fundamental mechanism through which microbubbles enhance heat transfer from ultrasound to the tissues? (ii) what combination of microbubble parameters and ultrasound parameters can give rise to an optimal heat deposition in the target region without causing damage to the surrounding tissues? The proposed research will help in achieving a breakthrough in using microbubble assisted ultrasound therapy for cancer treatment by accurately characterizing the acoustic and thermal fields in the presence of microbubbles. 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.