Biomedical Engineering Reference
In-Depth Information
phantoms revealed the potential for stem-cell imaging by NaYF4 nanocrystals doped with
Tm
3+
, with up to a 3-mm detection depth [103]. That was followed by a successful modification
based on replacing yttrium with lutetium, which lead to a dramatic intensification of the
signal by NaLuF
4
-based upconversion nanophosphors, reaching a sensitivity applicable to
imaging in large animals [104].
Nanobubbles
Echogenic microbubles are routinely used contrast agents in ultrasonography [105, 106].
The advantage of a background-free signal was achieved by the detection of the second
harmonic wave [107]. However, the second harmonic wave depends on the bubble size; thus,
their diameter must fit the needs of clinical ultrasonography. While the micrometer-size bub-
bles are produced for clinical purposes and they are easily available on the market, their large
size is not compatible with stem cell labeling. The appropriate formulation of nanobubbles is
very important, as the toxicity of some nanobubble types has been reported [108] and clinical
application should be approached cautiously. Fortunately, there is continuous research and
further advances in the detection of nanobubbles with ultrasound microscopy [109], as well
as the development of nanobubbles with sufficient stability and safety [110, 111], indicating
an important role for ultrasonography in stem-cell imaging.
Multimodal Nanoparticles
Homogeneous Nanoparticles
There are a few nanostructures that can be detected by multiple imaging modalities, making
them desirable in specific experimental conditions. Europium doping of mesoporous gadolinium
nanoparticles produced not only a MRI signal, but also the emission phosphorescence, which
enables optical imaging. The applicability of cellular imaging with this probe was confirmed on
HeLa cells [112]. The exchange of europium to lanthanum within gadolinium oxide results in an
addition of upconversion luminescence [113].
The excellent production of a MR signal that is well-known for iron oxide is even exceeded
by metals with higher magnetic moments, such as cobalt. However, the suboptimal stability
of cobalt nanoparticles precluded their use in medical applications [114]. A recently manufac-
tured alloy made of hollow cobalt and platinum (CoPt) surmounted the obstacle of stability
while not influencing the strength of the MRI signal, and adding platinum-based X-ray
visibility [115]. The nanoparticles made of this CoPT alloy were shown to be a viable option
for stem-cell labeling [116]. The embedding of CoPt within the dendrimer matrix resulted in
nanoparticles of novel architecture [117].
The major advantage of radionuclides is an extreme sensitivity with almost imperceptible
amounts of label sufficient for signal acquisition. The short life-span of radionuclides, how-
ever, is a major obstacle [118]. Fortunately, nanotechnology has provided a tool with which
to incorporate radionuclides into existing types of nanoparticles. Due to the rapid decay of
radioactivity, which prohibits storage of the radionuclides, the production of such multi-
modal nanoparticles must be rapid and simple to accommodate at the application site just
before use. This challenge has been addressed by the fast and straightforward microwave-
based production of dextran-coated
64
Cu-doped iron oxide [119].
Perfluorooctylbromide is an excellent compound for nanoparticle synthesis and multimo-
dality imaging. The presence of fluorine is detected by MRI, while bromide is visualized by
