Embolotherapy involves the occlusion of blood flow for therapy. This type of approach has primarily been used for treating a variety of cancers by starving tumors of blood flow, and for treating uterine fibroids. One example of a cancer that is well suited to treatment by embolotherapy is hepatocellular carcinoma, the most common form of liver cancer. Systemic chemotherapy has no appreciable impact on survival rates. Previous attempts at embolotherapy have used solid emboli, such as blood clot, gelatin sponge, particulates, balloons and streamers. A major difficulty in embolotherapy is restricting delivery of the emboli to the tumor, i.e. minimizing ischemia of healthy tissue, without extremely invasive procedures. The novelty of our gas embolotherapy approach lies in the use of gas bubbles rather than solid emboli. The bubbles originate as encapsulated liquid droplets that can be vaporized in vivo by focused high intensity ultrasound to form gas bubbles which then lodge in the tumor vasculature. This minimally invasive technique would allow selective delivery of gas emboli to the target region, and is well suited to repeated doses and long term use. Droplets small enough to pass through capillaries would allow venous injection. Our preliminary work suggests the potential of this treatment modality for many applications, yet many questions remain regarding delivery of droplets/bubbles and their interaction with vessels and blood. The proposed research will experimentally and computationally investigate the dynamics of vascular bubbles and droplets to provide new knowledge that is essential to developing this potentially revolutionary treatment.
The specific aims of this proposal are: 1. Characterize the process of acoustic droplet vaporization (ADV), including the mechanisms involved and the effects of droplet and flow parameters. 2. Evaluate the processes by which by the resulting bubbles are transported through the vasculature prior to lodging, and evaluate the effects of bubble and flow parameters on the ability to target specific locations for bubble delivery. 3. Assess the dynamics of bubble lodging and the ability of lodged bubbles to occlude blood flow. This work is relevant to public health by providing a fundamental understanding of how to use the controlled formation of cardiovascular gas bubbles, which originate from liquid droplets, to locally occlude blood flow for therapy. This approach could potentially be used to treat a variety of cancers and uterine fibroids.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB006476-04
Application #
7851091
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Peng, Grace
Project Start
2007-09-12
Project End
2013-04-30
Budget Start
2010-06-01
Budget End
2013-04-30
Support Year
4
Fiscal Year
2010
Total Cost
$471,916
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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Valassis, Doug T; Dodde, Robert E; Esphuniyani, Brijesh et al. (2012) Microbubble transport through a bifurcating vessel network with pulsatile flow. Biomed Microdevices 14:131-43
Qamar, Adnan; Wong, Zheng Z; Fowlkes, J Brian et al. (2012) Evolution of acoustically vaporized microdroplets in gas embolotherapy. J Biomech Eng 134:031010
Samuel, Stanley; Duprey, Ambroise; Fabiilli, Mario L et al. (2012) In vivo microscopy of targeted vessel occlusion employing acoustic droplet vaporization. Microcirculation 19:501-9
Eshpuniyani, Brijesh; Fowlkes, J Brian; Bull, Joseph L (2008) A Boundary Element Model of Microbubble Sticking and Sliding in the Microcirculation. Int J Heat Mass Transf 51:5700-5711