CAREER: Optimal Control of Encapsulated Ultrasound Microbubbles for Biomedicine

CBET-1653992PI：Calvisi，Michael L.常规使用造影剂以提高医学图像的质量。对于超声成像，造影剂是微米大小的气泡，当它们暴露在超声波下时，它们的大小会振荡。微泡提供的图像增强取决于它们的详细动力学和它们对特定超声波形的响应。微泡还被用于医疗治疗，如静脉给药的载体和超声消融组织的试剂。这项职业奖将为开发模型和算法提供支持，以确定驱动超声波形，优化成像和其他疗法所需的脂质涂层微泡的反应。该项目将包括数学建模和经过实验验证的数值计算。该项目还将支持针对K-12学生的教育活动。将为参加科罗拉多大学科罗拉多斯普林斯分校的STEM夏令营的学生开发与生物技术有关的教育模块。此外，还将开发一款在线教育游戏《虚拟泡泡》，让学生和公众了解微泡和超声波在医学上的生物医学用途。该项目的目标是应用最优控制理论来确定在生物医学中使用的胶囊微泡中能够产生所需非球形响应的最佳超声波形。研究的目的是确定在患者安全的约束下，产生最佳声强迫的成本函数，以增强亚谐声学响应，并激发被包裹的微泡的破裂。将探索单频、双频和宽带声强迫方案，并将通过与所需微泡响应相关的指标来比较每种方案的有效性。将开发一个非球形脂质涂层微泡的分析模型，以确定产生最佳声强迫波形的成本函数。这些预测将使用物理上更真实的数值模型进行验证和改进。预测的波形将通过一种新的设置进行进一步的实验验证，该设置使用声波捕捉来成像超声驱动的微泡的动力学并检测其声学特征。控制被包裹的微泡的非球形振荡的能力有可能提供高度专业化的强化治疗，并通过提高成像的信噪比和减少药物输送的剂量来减少不必要的副作用。

CBET - 1653992PI: Calvisi, Michael L.Contrast agents are used routinely to enhance the quality of medical images. For ultrasound imaging, the contrast agents are micron-sized bubbles, which oscillate in size when they are exposed to ultrasound. The image enhancement provided by the microbubbles depends on their detailed dynamics and their responses to the specific waveform of the ultrasound. Microbubbles are also used for medical therapies, such as carriers for intravenous drug delivery and as agents for ultrasonic ablation of tissue. This CAREER award will provide support to develop models and algorithms for determining the driving ultrasound waveforms that optimize desired responses of lipid-coated microbubbles for imaging and other therapies. The project will comprise mathematical modeling and numerical computations validated by experiments. The project will also support educational activities for K-12 students. Educational modules related to biotechnology will be developed for students participating in STEM summer camps at the University of Colorado Colorado Springs. In addition, an online educational game, "The Virtual Bubble," will be developed to acquaint students and the public with biomedical uses of microbubbles and ultrasound in medicine. The goal of this project is to apply optimal control theory to determine optimal ultrasound waveforms that elicit a desired nonspherical response in encapsulated microbubbles used in biomedicine. The research objective is to determine the cost functions that yield the optimal acoustic forcing for enhancing the subharmonic acoustic response, and for inciting breakup of encapsulated microbubbles, subject to constraints dictated by patient safety. Single frequency, dual frequency, and broadband acoustic forcing schemes will be explored, and the effectiveness of each will be compared through metrics related to the desired microbubble response. An analytical model of nonspherical lipid-coated microbubbles will be developed to determine the cost functions that yield the optimal acoustic forcing waveforms. These predictions will be validated and refined using a more physically realistic numerical model. The predicted waveforms will be further validated experimentally with a novel setup that uses acoustic trapping to image the dynamics of ultrasonically-driven microbubbles and to detect their acoustic signatures. The capability to control nonspherical oscillations of encapsulated microbubbles has the potential to provide enhanced treatment that is highly specialized and reduces unwanted side effects by improving signal to noise ratios in imaging and reducing dosages in drug delivery.