CAREER: Optimal Control of Encapsulated Ultrasound Microbubbles for Biomedicine

University Of Colorado At Colorado Springs, Colorado Springs CO

Investigators

Abstract

CBET - 1653992 PI: 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.