CAREER: Optimal Control of Encapsulated Ultrasound Microbubbles for Biomedicine

CBET -1653992 PI：Calvisi，Michael L.常规使用造影剂来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，当它们暴露于超声时，它们的尺寸会振荡。由微泡提供的图像增强取决于它们的详细动力学和它们对超声的特定波形的响应。微泡也用于医学治疗，例如用于静脉内药物递送的载体和作为用于组织的超声消融的试剂。该CAREER奖项将为开发用于确定驱动超声波波形的模型和算法提供支持，这些超声波波形优化了脂质涂层微泡用于成像和其他治疗的所需响应。该项目将包括通过实验验证的数学建模和数值计算。该项目还将支持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STEM夏令营的学生开发与生物技术有关的教育模块。此外，将开发一个在线教育游戏“虚拟气泡”，使学生和公众了解微气泡和超声波在医学中的生物医学用途。本计画的目标是应用最佳控制理论来决定最佳的超音波波形，以使生物医学中所使用的微泡囊产生所需的非球形反应。研究的目的是确定成本函数，产生最佳的声学强迫，以提高次谐波声学响应，并为煽动破裂的封装微泡，受患者安全的约束。单频，双频，和宽带声学强迫计划将进行探讨，并通过所需的微泡响应相关的指标，每一个的有效性进行比较。非球形脂质涂层微泡的分析模型将被开发，以确定成本函数，产生最佳的声学强迫波形。这些预测将使用物理上更现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，该设置使用声学捕获来成像超声驱动的微泡的动态并检测其声学特征。控制封装的微泡的非球形振荡的能力具有提供增强的治疗的潜力，该治疗是高度专业化的，并且通过改善成像中的信噪比和减少药物递送中的剂量来减少不想要的副作用。

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.