Detection and Description of Tissue Disease: Advances in the Use of Nanomedicine for Medical Imaging - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 252

between the lumen of the vessel and its surroundings. Ultrasound
contrast agents (UCAs) have a number of desirable characteristics
that they share with CT contrast agents, such as low toxicity and ease
of formulation and administration. Additionally, as with CT contrast
agents, the mass of imaging agent concentrating at the site of disease
is important in achieving a good signal-to-noise ratio. However, the
nature of the imaging modality adds additional constraints above
those required for CT contrast agents. For example, large bubbles
are required for good echogenicity, but if they are too large, they
become trapped in microvasculature, especially in the lung. Initially,
the microbubbles that were used were of the order of 100 μm, while
the current microbubbles are <5 μm in diameter. The microbubbles
must flex to produce signal, but at the same time, they must be strong
enough to withstand the pressures in the left side of the heart without
rupturing if they are to have a long circulation time, a requirement
for optimal concentration at the site of interest. As with all contrast
agents, the optimal UCA will depend on the purpose of the imaging
study. It must have adequate echogenicity to produce a high-contrast
image and also strong enough to withstand the US beam used for
detection, but if it is designed to be susceptible to rupture by more
intense US radiation, then local signal can be artificially reduced
to enable repeated studies. Another way in which the ability of
microbubbles to be “fractured on demand” can be exploited is as
targeted drug delivery vehicles. A drug can be encapsulated in the
microbubbles, the bubbles are then administered intravenously, and
an US beam can be used to fracture the bubbles at the target site,
delivering the drug specifically to that site.
In the development of UCAs, three components must be optimized:
the shell, the core, and the targeting moiety. We will discuss each of
these in turn.
8.3.1 Shell
The composition of the UCA's shell determines its physical properties,
most important, its mechanical elasticity. If it is too brittle, then it
will fracture too easily, but if it is too elastic, then it will not produce
an adequate signal (see McCulloch et al . [26]). The optimal UCA for
each purpose varies — for example, a more brittle shell might be
used as a drug delivery vehicle so that it can be ruptured more easily
at the target site.