Chemistry Reference
In-Depth Information
14
MIcrobubbles: contrast agents
for ultrasound and MrI
April M. Chow and Ed X. Wu
Laboratory of Biomedical Imaging and Signal Processing and Department of Electrical and Electronic Engineering, The University of
Hong Kong, Pokfulam, Hong Kong SAR, China
14.1
IntroductIon
Gas-filled microbubbles offer new approaches in diagnostic imaging techniques and therapeutic interventions. Current
applications of microbubbles include morphological enhancement and microvascular perfusion, which have been widely
used clinically. Apart from conventional diagnostic purposes, microbubbles have also demonstrated potential in several
exciting areas through various imaging modalities, including molecular imaging and therapeutic intervention. In this chapter,
we will review the commonly used gas-filled microbubbles and their characteristics. We will summarise applications with
several imaging modalities and future uses. Finally, we will discuss the bioeffects and safety issues related to microbubble
applications.
The capability of gas-filled microbubbles in enhancement ultrasound (US) imaging contrast was first reported by
Raymond Gramiak and Pravin Shah in 1968 [1]. During cardiac catheterisation, contrast enhancement was observed in the
aorta following injection of agitated saline. Since the intervention of the gas-filled microbubbles for clinical applications, its
development has been active and exciting in radiology. Gas-filled microbubbles then emerged as an essential adjunct to US
imaging technology, bringing insights and breakthroughs toward therapeutic development and medical diagnosis.
Gas-filled microbubbles were originally developed as an intravascular contrast agent to enhance acoustic backscat-
tering in US imaging. They are generally administered intravenously or in a cavity for better anatomy, measurement of
tissue perfusion, precise drug delivery mechanisms, and determination of elastic properties of the tissue in US imaging
[2-4]. Due to their unique cavitation and sonoporation properties [5-9], gas-filled microbubbles also play an expanding
role in therapeutic applications. The relatively short
in vivo
lifetime of microbubbles may pose challenges in some of
these applications. Nevertheless, the microbubble fabrication technology is advancing for increased
in vivo
lifetimes
using surfactant molecules with multiphase mixing technique and molecular targeting capability by microbubble surface
modification [10, 11].
14.2
classIfIcatIon of MIcrobubbles
Microbubbles are composed of a shell of biocompatible materials, such as proteins, lipids, or polymers, with air, perfluoro-
carbon, or sulphur hexafluoride as the filling gas. In order to be a transpulmonary contrast agent, their size normally ranges
from 3 to 10 μm. Figure 14.1 shows a representative light micrograph of SonoVue
®
microbubble suspensions and its histo-
gram showing diameter distribution.
