Chemistry Reference
In-Depth Information
differential enhancement. Microbubbles may serve as a MR contrast agent for imaging tumour angiogenesis. The limited
in
vivo
lifetime and stability can be a challenge in various microbubble applications, but optimisation of physiological prop-
erties should be sought for future study.
14.5
aPPlIcatIons beyond us IMagIng and MrI
14.5.1
Positron emission tomography
Positron emission tomography (PET) detects annihilation photons emitted from radionuclides administered as positrons
interact with electrons, hence generating images depicting distributions of radionuclides in the body. It is often coupled with
computed tomography to acquire anatomical and functional images simultaneously. In PET, suitable radionuclides are gen-
erally short half-lived positron-emitting isotopes, including
11
C,
13
N,
15
o,
18
F,
62
Cu,
68
Ga, and
82
Rb. These radioisotopes can
replace atoms in molecules that are essential for metabolism or in molecules that bind to receptors or other sites of drug
action, enabling tracing the biological pathway of radiolabelled compounds for studies of functional processes in the body.
To date, most clinical PET applications utilise
18
F-labelled fluorodeoxyglucose, an analogue of glucose, to probe regional
glucose uptake for diagnosis, staging, and monitoring treatment of cancers.
The use of
18
F-labelled lipids, incorporated into microbubble shells, for measuring biodistribution of nontargeted micro-
bubbles in rats was reported [113]. With the use of therapeutic US, microbubbles could be destructed at a specific site for
characterisation of microbubble-mediated therapy.
Ex vivo
studies also confirmed that an increased deposition of lipid shells
occurs locally after US sonication [113].
In vivo
monitoring of biodistribution of targeted microbubbles in mice was also
performed using
18
F-labelled lipids [114]. In general, PET provides a sensitive and quantitative means for evaluation of
microbubble biodistribution via radiolabelling.
14.5.2
diffraction-enhanced Imaging (deI)
Diffraction-enhanced imaging (DEI) is an X-ray phase contrast technique using diffraction contrast rather than absorption
contrast. DEI is based on the use of a perfect crystal analyser placed between the region of interest and the imaging detector.
After irradiating the sampling tissues with monochromatic X-rays, the analyser acts as an angular filter that selectively
accepts those X-rays that have traversed the sample by satisfying the bragg law for diffraction, thereby producing a
two-dimensional spatial intensity mapping of the diffracted X-ray. Compared with conventional computed tomography, DEI
can provide better soft tissue contrast with less radiation, and it has shown promise in breast lesion and bone and vascular
imaging [115-117].
The feasibility of microbubbles levovist and optison as DEI scattering contrast agents was investigated [118]. Imaging
contrast produced by microbubbles can be manipulated by varying the reflectivity of the analyser. Studies are warranted to
further explore the values of microbubbles in enhancing DEI scattering for clinical applications.
14.6
conclusIons: lIMItatIons, bIoeffects, and safety
Despite the advantages of the unique capability of gas-filled microbubbles, there are several limitations. Microbubble-based
applications are limited by the inherent short plasma half-lives, primarily as a result of their destruction in the alveoli due to
gaseous exchange [15]. Possible toxicity is another issue that needs to be taken into consideration.
The potential hazards usually involve cavitation of microbubbles. At low acoustic pressures, microbubbles exhibit
low amplitude volumetric oscillations following the changes in the local pressure, which is known as stable cavitation
[119]. While exposed to higher pressures, the microbubble oscillation becomes increasingly asymmetric and eventually
the shell may be broken, leading to the release of filling gas, which may lead to further cavitations. This nonlinear
behaviour is called inertial cavitation [119]. Therefore, its potential risks increase with the acoustic pressure, which is
defined by the mechanical index. Caution should be made in choosing the mechanical index for US to avoid undesired
cavitation effects.
Generally, gas-filled microbubbles are relatively safe to use with no specific renal, liver, or cerebral toxicity [17]. The
adverse reactions are rare, usually transient, and of mild intensity [17, 120]. Most frequently, local pain, warmth or cold, and
tissue irritation may occur at the injection site or along the draining vein [121-123]. Recently, deaths and serious
cardiopulmonary reactions following administration of microbubbles were reported [124]. However, the associated risk is
1:500000, which is advantageous with the 1:1000 mortality risk associated with diagnostic coronary angiography and the
