A new “blinking microbubble” technique that images deeper inside the body for improved breast cancer diagnostics has won the grand prize at the University of California, San Diego’s Jacob School of Engineering Research Expo 2012. Bioengineering doctoral student Carolyn Schutt developed a method that bridges optical and ultrasound imaging to get the best of both technologies: the chemical sensitivity of visible light and the tissue-penetrating properties of ultrasound. Such a “smart particle contrast agent” would render biological tissues transparent to light and enable highly sensitive light imaging deeper inside the body. Conventional x-ray mammography shows only the tissue density, which indicates the presence of a mass, but it cannot determine any of the biochemical differences between a benign mass and a malignant tumor. Bioengineering graduate student Carolyn Schutt won the Rudee Outstanding Poster Award for her research into a new imaging technique for breast cancer research. (Image: UC San Diego Jacobs School of Engineering) “There is a very high false positive rate with just x-ray mammography,” Schutt said. “By being able to extract chemical information, we hope to avoid unnecessary biopsies that are done on benign lesions.” She used gas-filled microbubble contrast agents that change their fluorescence intensity, or “blink,” only in response to focused ultrasound. A solution of these microbubbles would be injected into the body to circulate through the bloodstream. When they encounter an ultrasound pressure wave, these bubbles contract and expand their outer surface in response to the pressure peaks and troughs. By loading the microbubble surface with a fluorescent dye that turns off when it is in close proximity to other dye molecules, the ultrasound creates a blinking signal. Initially, this modulating fluorescence was produced by less than 10 percent of the bubbles. Upon analysis of the nanostructure using superresolution microscopy, Schutt determined that most of the dye partitioned into isolated clusters, which were probably preventing the dye from blinking in response to ultrasound. She manipulated the nanostructure of the bubbles by heating their outer surface to distribute the dye more evenly, and then rapidly cooled them to lock in this distributed state. This melting and rapid cooling process increased the fraction of blinking microbubbles to more than 50 percent, making this a more viable imaging platform. Schutt was selected from among six individuals or teams representing each of the academic departments at the Jacobs School. For more information, visit: www.ucsd.edu