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

Worcester Polytechnic Institute, Worcester MA

Investigators

Abstract

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.