Antivascular ultrasound is a novel approach that uses low-amplitude ultrasound and microbubbles to treat cancers. In the presence of ultrasound irradiation, microbubbles act as microscopic sources that convert acoustic energy into heat through viscous damping of oscillating bubbles. The localized intravascular heating damages endothelial cells and disrupt tumor vasculature. Thus microbubbles function as both energy source and ultrasound wave beacons to deliver acoustic energy locally to the vascular endothelium. The goals of the research are to model ultrasound-enhanced heating mathematically and to use the model to guide the synthesis of microbubbles using novel microfluidics techniques. The proposal has three Specific Aims.
Specific Aim 1 is to use computational modeling to identify mechanical properties and bubble size distribution that produce maximum thermal effects.
Specific Aim 2 will be to synthesize microbubbles of desired size distribution and shell properties.
Specific Aim 3 will test the efficacy of microbubble preparations in flow phantoms and preclinical animal model. The experimental results will be compared with theoretical calculations. Thus both mathematical modeling and the unique method of synthesis will provide an integrated approach for antivascular therapy. The proposed research develops a completely new ultrasound cancer treatment with significant advantages over existing techniques. We anticipate that the knowledge gained from the proposed research will lead to a new form of antivascular therapy for treating cancers.

Public Health Relevance

Cancer is the second leading cause of death in the United States and around the world. We propose a new cancer treatment that uses low-intensity ultrasound and microbubbles to disrupt tumor vasculature. In this application we will use mathematical models and experiments with phantoms and animals to determine conditions that are most effective for destroying cancer vasculature. A successful outcome will establish low- intensity ultrasound as a promising modality for cancer treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
1R01EB022612-01
Application #
9157676
Study Section
Biomedical Imaging Technology B Study Section (BMIT-B)
Program Officer
Krosnick, Steven
Project Start
2016-09-30
Project End
2020-07-31
Budget Start
2016-09-30
Budget End
2017-07-31
Support Year
1
Fiscal Year
2016
Total Cost
$394,828
Indirect Cost
$149,593
Name
University of Pennsylvania
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Pulsipher, Katherine W; Hammer, Daniel A; Lee, Daeyeon et al. (2018) Engineering Theranostic Microbubbles Using Microfluidics for Ultrasound Imaging and Therapy: A Review. Ultrasound Med Biol 44:2441-2460
Jeong, Heon-Ho; Yadavali, Sagar; Issadore, David et al. (2017) Liter-scale production of uniform gas bubbles via parallelization of flow-focusing generators. Lab Chip 17:2667-2673