Page 34 - Bio Engineering Approaches to Cancer Diagnosis and Treatment

2.3 Ultrasound 31

2.3.1 Microbubbles-based contrast agent
The density of blood vessels in tumorogenic side is proportional to the size and
pathological condition of the tumors. To visualize vascular morphology and tissue
surrounded by different vascular morphology, contrast-enhanced ultrasound imaging
has been administrated.
As already mentioned, these kinds of CAs are generally gas-filled microbubbles
ranging 1–5 µm in diameter. The acoustic response of microbubbles is around MHz
range which is optimal for ultrasound imaging [23]. Microbubbles are able to reduce
backscattering from the vasculature.
In order to increase blood circulation time and improve the stability of micro-
bubbles, a lipid shells such as lipid [24], polymers [25], protein [26], or a mixture of
them [27] are surrounded them. Beside the shells, the type of encapsulated micro-
bubbles affects the stability and in vivo half-life of the CA. It has been shown that
low solubility of the encapsulated microbubble (Ex., perfluorochemicals) enjoys
high stability and circulation time [28]. It would be worth noting that, the amount of
shell’s oscillating after insonication is determined. In this context to types of shells
have been described: soft shells mainly used for hormonic imaging and hard shells
applied for destructive ultrasound imaging. One of the commonly used microbubbles
is SonoVue which is a perfluoro agent gas surrounded by a phospholipid shell.
The ultrasound molecular imaging involves the use of targeted microbubbles to
selective bind to the desired region in intravascular space. Target-specific microbub-
bles mostly are achieved by attaching antibodies or peptides to the surface of micro-
bubbles either during the production process of microbubbles or after its synthesize.
The main aims for target-specific microbubbles are molecules expressed on the
activated endothelium in response to either angiogenic stimuli or inflammation. The
main targeted molecules in this field of interest are including vascular cell adhesion
molecule (VCAM-1), intercellular adhesion molecule (ICAM-1), interleukins (IL-
1), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF),
fibroblast growth factor (FGF), and endoglin.
Due to the difference in compressibility and acoustic impedance between the
surrounding media and the microbubbles, contrast-enhanced ultrasound imaging
mainly acts as nonlinear scatters. Nonlinear imaging technic, which includes subhar-
monic imaging and intermittent power Doppler, improves the quality of the images
by reducing bubble destruction.

2.3.2 Advantages and disadvantages
The advantages of using ultrasound imaging are as follow:
• Being portable
• Easy to use
• Appropriate for soft tissue
• Cost-effective
• Extensive database for some species