Enhancing ultrasound-mediated tumor ablation with phase-shift nanoemulsion It is well documented that microbubbles can enhance the absorption of ultrasound in tissue. Thus, it may be possible to improve the efficiency and clinical utility of ultrasound ablation for cancer therapy by introducing or creating microbubbles within the tumor. Unfortunately, the pressure required for creating bubbles in tissue exceeds 100 atmospheres, and the bubbles created collapse violently and damage tissue mechanically before fragmenting into smaller, less responsive gas bodies. In order to reduce the pressure required for bubble formation in vivo, we have developed a liquid perfluorocarbon phase-shift nanoemulsion (PSNE) that can be vaporized in a controlled and predictable manner, forming microbubbles when and where needed. We have shown in previous studies that PSNE can be vaporized with short acoustic pulses, and the threshold for vaporization depends upon the size, composition of the liquid perfluorocarbon core, and ambient temperature. Furthermore, we have shown that PSNE can extravasate through fenestrae in leaky tumor vasculature and populate the tumor interstitium with cavitation nuclei. Upon acoustic vaporization of the PSNE, the bubbles formed are used to enhance tissue absorption of transmitted ultrasound, resulting in the ablation of larger tumor volumes using shorter and less powerful ultrasound exposures. This work will test the use of PSNE to enhance noninvasive focused ultrasound thermal ablation guided by magnetic resonance imaging and thermometry in renal cancer. A combination of in vitro and in vivo studies will be conducted to assess the biodistribution and tumor accumulation of PSNE as function of physicochemical properties, identify vaporization and cavitation thresholds as a function of perfluorocarbon composition, evaluate the spatial correlation between sustained cavitation activity and heat deposition, and assess the response of tumors and animal survival to bubble-enhanced ablation therapy.

Public Health Relevance

Kidney cancer is difficult to eradicate due to limited treatment options. The research outlined in this proposal will develop technology and protocols for localized treatment of solid tumors within the kidney using focused ultrasound with negligible adverse side effects. Ultimately, this technology has the potential to increase patient survival and improve the quality of patient care.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01EB016102-02
Application #
8656622
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Krosnick, Steven
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Boston University
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02215
Kopechek, Jonathan A; Park, Eun-Joo; Zhang, Yong-Zhi et al. (2014) Cavitation-enhanced MR-guided focused ultrasound ablation of rabbit tumors in vivo using phase shift nanoemulsions. Phys Med Biol 59:3465-81