Chemistry Reference
In-Depth Information
14.2.2.1 Perfluorochemicals
Perflubron® (Alliance Pharmaceutical Corporation, San Diego, CA) is liquid perfluoro-
carbon emulsion with size ranges from 0.06 to 0.25 μm composed of carbon and bromine; it is inert with low surface tension
and immiscible with water. Upon emulsification, it accumulates in the reticuloendothelial system and leaks from inflammatory
or tumoural capillaries into the interstitial space for US imaging after intravenous injection [23, 24].
14.2.2.2 Perfluorocarbon-Filled Microbubbles with a Phospholipid Shell
bR14 (bracco Diagnostics, Geneva,
Switzerland) is a perfluorobutane-filled microbubble stabilised using phospholipid. It can produce persistent contrast
enhancement of tissue perfusion for liver and spleen imaging [25, 26]. Definity® (bristol-Myers Squibb Medical Imaging,
North billerica, MA) is a phospholipid-coated microbubble filled with octafluoropropane with a mean diameter of 2.5 μm.
other phospholipid microbubbles include perfluorohexane-filled Imagent® (Imcor Pharmaceutical, San Diego, CA) and
perfluorobutane-filled Sonazoid® (Amersham Health, osla, Norway). both Imagent and Sonazoid show a late liver-specific
enhancement post-injection [27-29].
14.2.2.3 Perfluorocarbon-Filled Microbubbles with an Albumin Shell
optison® (Amersham Health, Princeton, NJ) is
very similar to Albunex except the filling gas is octafluoropropane, with diameter ranges from 2 to 4.5 μm. When the micro-
bubble shell collapses, the relatively inert octafluoropropane gas is released into the plasma and vents out via the lung. It has
been reported that the Kupffer cells in the liver uptake albumin that includes both intact microbubbles and deflated albumin
shells or fragments [30, 31]. It is approved for clinical use to provide opacification of cardiac chambers and to improve left
ventriclar endocardial border delineation for cardiac imaging.
14.2.2.4 Phase Shift Perfluorocarbon-Filled Microbubbles
EchoGen® (Sonus Pharmaceuticals, bothell, WA) is a
liquid/liquid emulsion with size of 0.4 μm [17], containing dodecafluoropentane in a dispersed phase. Dodecafluoropentane
is a low diffusibility and low solubility perfluorocarbon gas, with a low boiling point of 28.5°C. Upon administration, dode-
cafluoropentane shifts to gas phase at body temperature, forming microbubbles with a diameter of 2 to 5 μm. The phase
transition from liquid to gas state is achieved by producing a hypobaric pressure followed by an intense shock within the
syringe immediately prior to administration [32].
14.2.3
sulphur Hexafluoride-filled Microbubbles
Sulphur hexafluoride presents a low diffusibility through the phospholipid layer and a low solubility in blood, extending
microbubble circulation time
in vivo
. SonoVue® (bracco Diagnostics, Milan, Italy) consists of sulphur hexafluoride gas
stabilised in an aqueous dispersion by a phospholipid monolayer. With its long plasma half-life of 6 min. and a narrow size
distribution [33], SonoVue can improve the acoustic backscattering at low power insonation [34].
14.3
aPPlIcatIons In ultrasound IMagIng
US imaging utilises typical frequency ranges from 2 to 18 MHz to visualise internal structures for diagnosis and therapeutic
applications. Image contrast in US imaging is determined by the tissue acoustic impedance and the mode of imaging. The
contrast mechanism of gas-filled microbubbles comes from the difference in acoustic impedance between the filling gas
and the surrounding materials, as well as the compressed gas of the microbubbles compared to the incompressible mate-
rials being displaced. Compared to the wavelength of the US beam, microbubbles are small and hence act as a point
source for reflections. Moreover, the compressible microbubbles resonate in the US field, generating a nonlinear acoustic
response that can be detected using harmonic imaging [35]. Under higher acoustic power, microbubble destruction occurs
with the emission of an irregular nonlinear signal [36]. behaviours of lipid and polymer microbubbles under different
acoustic powers are depicted in Figure 14.2. Current applications of microbubbles in US imaging include, but are not
limited to, morphological enhancement, microvascular perfusion, as well as molecular imaging and therapeutic
intervention.
14.3.1
as an us Intravascular contrast agent
Due to the relatively large size of gas-filled microbubbles, they do not pass through the vascular endothelium and hence
serve as pure intravascular contrast agents [37]. They have been used to improve the endocardial border of left ventricles
for better delineation of left ventricular function and myocardial thickening [38]. Strong echoes were produced within
the heart, due to the acoustic mismatch between microbubbles and the surrounding blood. Recent applications include
