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

高强度聚焦超声(HIFU)是目前正在探索的一种新的靶向药物输送方式，通过温和的热疗，靶向消融良性肿瘤，如子宫肌瘤和前列腺、肝脏、肾脏、胰腺或骨骼的恶性肿瘤。然而，提供足够的声能以克服某些解剖学限制(即骨骼和致密组织)一直是阻碍HIFU更广泛应用的挑战。例如，磁共振引导的HIFU已用于治疗特发性震颤，这种震颤需要较高的声强来克服被头骨吸收或反射的声音。这种声学强度的增加还会增加焦点和目标区域以外的加热，可能会导致皮肤和皮下脂肪烧伤。因此，需要一种方法来提高HIFU在较低声强下的局部温度，以将附带损害降至最低。气泡增强加热(BEH)是在HIFU期间管理造影剂微气泡，可以缓解这一挑战，因为微气泡空化增强了声能转换过程，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在聚焦超声存在的情况下帮助实现组织内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针对高中生的推广活动。拟议研究的技术目标是使用实验和数值研究相结合的方法来了解和量化聚焦超声与微泡造影剂云的相互作用。一种新的控制良好的体外实验装置将被开发出来，以在存在和不存在微泡的情况下实现组织模体中的焦点加热。不同时空点的温度和压力形式的实验数据将被用来验证可以预测震源温度升高的多尺度数值模式。然后，经过验证的模型将被用来开发声屏蔽的比例定律，这种现象是指较高浓度的微泡基本上可以屏蔽超声波到达目标区域。这项拟议的研究将通过准确描述存在微泡时的声场和热场，并提供治疗的操作范围，有助于为癌症治疗带来革命性的聚焦超声治疗。这将使研究人员能够在开发基于超声的聚焦疗法时自信地探索广泛的治疗相关参数并优化设计环境。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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 (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.