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

高强度聚焦超声（HIFU）是一种新兴的治疗方式，目前正在探索通过轻度热疗靶向给药，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，传递足够的声能通过某些解剖限制（即骨骼和致密组织）一直是阻碍HIFU更广泛应用的挑战。例如，磁共振引导下的HIFU已被用于治疗特发性震颤，这种疾病需要高强度的声波来克服颅骨吸收或反射的声音量。声强度的增加也增加了焦点和目标区域外的加热，可能导致皮肤和皮下脂肪的烧伤。因此，需要一种方法在较低的声强下局部升高HIFU的温度，以尽量减少附带损伤。气泡增强加热（BEH），即在HIFU过程中使用造影剂微泡，可以缓解这一挑战，因为微泡空化增强了声能转换过程，可以用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外展活动。拟议研究的技术目标是使用实验和数值相结合的研究来理解和量化聚焦超声与包封微泡造影剂云的相互作用。一个新的良好控制的体外实验装置将被开发，以实现在组织幻影焦加热在存在和不存在微泡。在不同时空点的温度和压力形式的实验数据将用于验证多尺度数值模型，该模型可以预测焦点温度高程。经过验证的模型将用于开发声屏蔽的标度定律，即高浓度的微泡基本上可以屏蔽超声波到达目标区域。提出的研究将通过准确表征微泡存在时的声场和热场，并提供治疗的操作界限，有助于彻底改变聚焦超声治疗癌症的治疗方法。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 (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.