154th ASA Meeting, New Orleans, LA

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Multitasking Microbubbles

Vesna Zderic, zderic@gwu.edu
George Washington University

Shahram Vaezy
University of Washington

Popular Version of Paper 2aBB3, "Acoustic hemostasis: underlying mechanisms"
Presented at 9:15 a.m. on Wednesday, November 28, 2007
154th ASA Meeting, New Orleans, LA

Popular Version of Paper 4pBB3, "Therapeutic potential of stable cavitation: from enhanced drug delivery to faster hemorrhage control" 
Presented at 2:10 p.m. on Friday, November 30, 2007
154th ASA Meeting, New Orleans, LA

Recent studies are showing that microbubbles can help us address a variety of current clinical needs. These important needs range from clinical diagnosis of hidden tumors or hard to detect deep internal bleeding using ultrasound imaging, to facilitating novel therapeutic ultrasound therapies such as targeted delivery of anticancer drugs and genes, hemorrhage control and tumor ablation.

Ultrasound that is most known for imaging unborn babies has a long track record of being completely safe due to very low levels of applied energy that does not harm tissues.  However, the picture may change when microbubbles (about 1-10 µm) are introduced either by injection of what’s known as ultrasound contrast agents or by using high-intensity ultrasound fields that produce bubbles right there in the tissue. These microbubbles become active in the ultrasound field by either singing peacefully in resonance to the tone of ultrasound (stable cavitation) or crying their swan song before violent implosion (inertial cavitation).  With stable cavitation, the microbubbles usually act as beacons of visualization of tumors or bleeding sites.  With inertial cavitation, they become vehicles of energy delivery resulting in destruction of tumor cells around them, punching holes in cell membranes for transport of drugs and genes to a specific diseased site, and promoting clotting in the treatment of internal bleeding.

In our work, we have utilized stable cavitation for detection and localization of internal bleeding sites. In pre-clinical studies, liver and vascular injuries, while staying hidden in regular ultrasound images, were clearly visualized using stable microbubbles. Also, producing microbubbles helped us target a high-intensity focused ultrasound (HIFU) beam for the purposes of hemorrhage control and tumor treatment.  Furthermore, the bubbles at the treated area have provided an effective method to monitor HIFU therapy.

We have also utilized inertial cavitation in delivery of drugs to specific sites of interest. In pre-clinical trials, ocular medications (such as antibiotics and anti-inflammatory compounds) that have a hard time penetrating inside the eye were delivered through tiny holes punctured in the eye surface (cornea). These holes were healed within an hour to restore normal barrier function to protect the eye from bacteria, viruses and fungi.  Additionally, we have used inertial cavitation to achieve hemorrhage control in blood vessels and solid organs such as liver in a shorter time as compared to when microbubbles were not present.  Not only the extra energy boost from imploding bubbles was helpful in promoting coagulation, but also the release and exposure of tissue factors (normally unexposed to blood) from the surrounding tissues expedited clotting at the wound site.

The great promise of multitasking microbubbles can be realized in ultrasound-image guided therapy. As an example, microbubbles can be used to target and monitor the HIFU energy delivery at a desired site while allowing better and faster treatment at the same time. OK, let’s use microbubbles in what they can do best, “see and treat”!

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