Detection and Description of Tissue Disease: Advances in the Use of Nanomedicine for Medical Imaging - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 254

8.3.2 Core
In addition to the above-described issues of size, etc., the nature of the
fluid entrapped within the microbubble also influences its imaging
characteristics. Air is easily incorporated into microbubbles, but
is soluble in blood, so it escapes from the bubble and shortens the
potential imaging time. The rate of diff usion of air from microbubbles
can be reduced by, for example, using biopolymer shells. Heavy gases
have lower solubility in blood and so lead to the UCAs having longer
persistence. Polyfluorinated carbon gases (PFCs) are also poorly
soluble in water and are liquids at room temperature, and their non-
toxicity, stability, and low acoustic impedance make them attractive
fluids to use as the core of microbubble contrast agents.
Marsh et al. [30] systematically investigated the echogenicity
of seven PFCs at a range of temperatures between 25 ° C and 45 ° C.
Their conclusion was that perfluorohexane had the lowest acoustic
impedance within this temperature range (the acoustic impedance
of distilled water at 37 ° C is approximately 1.5 g/cm 2 -s, while
perfluorohexane is approximately 0.8 g/cm 2 -s), and therefore
would provide a good enhancement agent as it has a very diff erent
impedance compared with water, resulting in good contrast. The
group then extended this work by investigating the suitability of
various fluids as the core of targeted microbubbles in vitro [31]. This
study investigated the observation that targeting the microbubbles to
a surface improved their impedance. The authors suggested that this
improvement was due to the development of a reflective interface
between the targeted surface and the medium surrounding it.
The introduction of fluids into nanoparticles and then ensuring
their entrapment, at least for the duration of scanning, presents a
challenge that can be met in various ways. One interesting method of
introducing the gas in vivo was reported by Kang et al. [32], who used
polyesters with carbonate side-chains to produce nanoparticles,
which, when injected intravenously, produce nanobubbles that
coalesce into microbubbles. Water diff uses into the microbubbles
and cleaves the carbonate side-chain forming carbon dioxide in situ .
The viability of this approach was confirmed by ultrasound imaging
in vivo . Another advantage of this technology is that the nanobubbles
are themselves not visible at 100 μm US resolution, but once they
arrive at the target tissue and coalesce into microbubbles, the size
increases and the bubbles become visible by US.