Biomedical Engineering Reference
In-Depth Information
molecules placed in a magnetic fi eld after a pulse of radiofrequency has hit them.
Protons from different tissues relax at different rates, and this results in clearly
defi ned anatomical images. However, within a clinical setting, it is very diffi cult
to use MRI alone to differentiate healthy from diseased tissues, and the use of a
contrast agent is often necessary to make such a differentiation. Contrast agents
alter the relaxation time of the protons in their proximity, thus providing a better
contrast. In standard clinical MRI scans, the contrast agents are injected intrave-
nously, thus increasing the contrast systemically. Although the most commonly
used MRI contrast media are gadolinium chelates, these small- molecular - weight
contrast agents are rapidly cleared from the body, such that only a short time is
allowed for the imaging process [48]. Colloidal iron oxides may offer certain advan-
tages over gadolinium chelates as MRI contrast agents, including a long blood
circulating time, biocompatibility, and high relaxivity values [49]. Iron oxides are
generally imaged through T
2
- and T
2
-*weighted MRI. To date, a wide variety of
particles have been produced, which differ in their size (hydrodynamic particle
sizes varying from 10 to 500 nm) and type of coating material used (e.g., dextran,
starch, albumin, silicones, PEG) [50]. These particles are classifi ed according to
their size, as this infl uences both their physico-chemical and pharmacokinetic
properties. The fi rst particle type - the superparamagnetic iron oxides (SPIOs) - are
larger than 50 nm (coating included) in diameter, while the second type - the
ultrasmall superparamagnetic iron oxides (USPIOs) are smaller than 50 nm [51] .
An extensive review on the imaging applications of magnetic iron oxide nanopar-
ticles has recently been published [23, 47].
Several generations of iron oxide-based magnetic nanoparticles have been
developed:
•
First-generation MRI contrast agents tend to have a larger size (diameters
200 nm) and are polydisperse. When these agents are introduced into the body,
they are rapidly recognized as being “foreign” to the body, and are taken up by
the reticuloendothelial system (RES). Because they accumulate passively in the
liver and spleen, these agents are used to image liver diseases, especially liver
cancer.
•
Second - generation agents are mostly nanosized (diameters < 200 nm), and their
coatings are more extensive. These surface- modifi ed agents are designed to
prevent aggregation and avoid sequestration by the RES; consequently, they
have a narrow size distribution in solution and a long half-life in the blood
circulation. Materials such as dextran, PEG, and PVA have been used to coat
these nanoparticles.
•
Third-generation agents consist of magnetic cores coated with targeting ligands
such as antibodies, and are used for active targeting. These tend to be smaller in
size and have targeting units on their surface. These agents are designed to
actively target magnetic nanoparticles to the sites of disease.
>
Examples of the different generations of contrast agent are presented in the
following subsections.
