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World J Gastroenterol. Jan 7, 2011; 17(1): 28-41
Published online Jan 7, 2011. doi: 10.3748/wjg.v17.i1.28
Contrast-enhanced and targeted ultrasound
Michiel Postema, Odd Helge Gilja
Michiel Postema, Emmy Noether Research Group, Institute of Medical Engineering, Department of Electrical Engineering and Information Sciences, Ruhr-Universität Bochum, 44780 Bochum, Germany
Michiel Postema, Department of Physics and Technology, University of Bergen, 5007 Bergen, Norway
Michiel Postema, Department of Engineering, The University of Hull, Kingston upon Hull HU6 7RX, United Kingdom
Michiel Postema, Centre de Biophysique Moléculaire, UPR 4301 CNRS affiliated to the University of Orléans, 45071 Orléans, France
Odd Helge Gilja, National Center for Ultrasound in Gastroenterology, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway
Odd Helge Gilja, Institute of Medicine, University of Bergen, 5007 Bergen, Norway
Author contributions: Postema M and Gilja OH wrote the paper.
Correspondence to: Dr. Michiel Postema, Professor, Department of Physics and Technology, University of Bergen, Allégaten 55, 5007 Bergen, Norway. michiel.postema@rub.de
Telephone: +47-555-82880 Fax: +47-555-89440
Received: July 2, 2010
Revised: September 3, 2010
Accepted: September 10, 2010
Published online: January 7, 2011
Abstract

Ultrasonic imaging is becoming the most popular medical imaging modality, owing to the low price per examination and its safety. However, blood is a poor scatterer of ultrasound waves at clinical diagnostic transmit frequencies. For perfusion imaging, markers have been designed to enhance the contrast in B-mode imaging. These so-called ultrasound contrast agents consist of microscopically small gas bubbles encapsulated in biodegradable shells. In this review, the physical principles of ultrasound contrast agent microbubble behavior and their adjustment for drug delivery including sonoporation are described. Furthermore, an outline of clinical imaging applications of contrast-enhanced ultrasound is given. It is a challenging task to quantify and predict which bubble phenomenon occurs under which acoustic condition, and how these phenomena may be utilized in ultrasonic imaging. Aided by high-speed photography, our improved understanding of encapsulated microbubble behavior will lead to more sophisticated detection and delivery techniques. More sophisticated methods use quantitative approaches to measure the amount and the time course of bolus or reperfusion curves, and have shown great promise in revealing effective tumor responses to anti-angiogenic drugs in humans before tumor shrinkage occurs. These are beginning to be accepted into clinical practice. In the long term, targeted microbubbles for molecular imaging and eventually for directed anti-tumor therapy are expected to be tested.

Keywords: Ultrasound; Drug delivery systems; Drug targeting; Sonoporation; Contrast media; Liver; Pancreas; Gastrointestinal tract