Biomedical Engineering Reference
In-Depth Information
Fluorine Nanoparticles
The major advantage of fluorine is the near-absence of this element in the human body, thus
providing contrast with no tissue background. The additional advantage of
19
F is the ability
to acquire both anatomical
1
H and
19
F “hot spot” scans, which then can be automatically
superimposed [68] and the fluorine signal quantified [69]. Since the signal-to-noise ratio
(SNR) of fluorine is almost the same as that of proton images, the contrast agents based on
fluorine necessitate a high load of
19
F nuclei, comparable to the presence of
1
H in tissues
[70]. Luckily, a method to achieve this high concentration has been known for years and
consists of a compound synthesis by the exchange of
1
H to
19
F nuclei [71]. Moreover, the
biocompatibility of fluorocarbons was tested in a clinical setting far before the advent of
MRI, and these compounds were employed as X-ray contrast agents [72], or blood substitutes
[73]. Thus, they are ideally suitable to be used as MRI contrast agents. For example, perfluo-
ropolyether nanoparticles have already been employed for the
in vivo
imaging of dendritic cells
[74], beta islets [75], and neural stem cells [76, 77]. Despite promising results, the application of
perfluorocarbons for “hot spot” MRI is cumbersome due to the requirement for labeling cells
with a high load of fluorine to reach an acceptable SNR [78], or the large amount of cells to
be transplanted for visualization
in vivo
[79].
PARACEST Nanoparticles
There is continuous search for noninvasive and clinically applicable novel contrast mecha-
nisms, especially for MRI. A newer method that has recently gained a wider use is chemical
exchange saturation transfer (CEST) MRI, termed as such because it depends on the
exchange of protons between compounds or their specific groups and bulk water as an effect
of saturation by an off-resonance pulse sequence. The same phenomenon has also been
observed for the rare earth metals, which are characterized by the paramagnetic shift in
the frequency of resonance (PARACEST). The benefit of CEST and PARACEST con-
trast agents is that this contrast is completely switchable, as the signal is present only as an
effect of the application of a frequency-specific saturation pulse, and is otherwise absent;
thus, there is no interference with regular MR imaging, such T1-weighted, T2-weighted,
or diffusion imaging. While proteins are relatively insensitive in providing CEST contrast,
the PARACEST nanoparticles have been shown to reveal a stronger signal. The superior
PARACEST signal has been achieved by imaging of europium and ytterbium chelates.
These chelates were then introduced to dendrimer nanoparticles to produce an
in vivo
applicable contrast agent [80]. Since the contrast is dependent on pulse frequency, this
enables the visualization of different cell populations by the application of PARACEST
nanoparticles [81]. However, given the issues mentioned above, it is unlikely that PARACEST
agents will enter the clinic any time soon. The CEST agents, on the other hand, are readily
clinically translatable as they consist of naturally occurring carbohydrates and proteins,
without the presence of metal ions.
Gold and Tantalum Nanoparticles
Heavy metals are characterized by a very high X-ray absorption rate, far better compared to
iodinated compounds, making them attractive cell-tracking agents that could be potentially
detectable by computed tomography (CT). Gold nanoparticles have been evaluated as a
contrast agent over recent years [82, 83]. An attractive feature of gold is that it is bioinert,
