Biomedical Engineering Reference
In-Depth Information
4.6.1
Improved Imaging Methods
Dynamic, or time-resolved, MRI imaging has already been explored to some
extent, for example in pH sensing using a lanthanide chemical exchange
saturation transfer (CEST) agent [314], and in the detection of apoptotic
cells (effectively detecting gene- expression) using protein - conjugated magnetic
nanoparticles [157]. The potential of dynamic MRI imaging using contrast agents
has been recently assessed [315]. By assuming a 5% change in signal to be suffi -
cient to detect an agent's response within a dynamic environment, simulations
were generated for the major types of agent currently undergoing evaluation. For
this, the Smoluchowski model was applied, using as inputs the inherent contrast
and known clearance properties. Among the conclusions drawn was that nanopar-
ticulate T
2
agents, because of their very low limits of detection [316], could be used
for dynamic imaging in humans at concentrations several orders of magnitude
lower than is possible with any of the alternatives, including gadolinium and the
new generation of CEST agents. However, as the temporal limit is probably
about 1 s this will limit the applications although, as in the case of conventional
static imaging, nanoparticulate agents occupy a separate part of the clinically
relevant parameter space and so have potential for as yet unidentifying
applications.
As discussed above, magnetic nanoparticle suspensions usually function
as either negative- or T
2
-contrast agents. The strong local fi eld generated by
the high susceptibility of these agents results in a shift in the resonance frequency,
as well as an easily detectable decrease in the (spin-spin) relaxation times,
of water molecules in close proximity to the nanoparticles. The downside of
these agents, arising from the large susceptibility artifacts, include diffi culties
in: the quantifi cation of particle concentrations; the detection of particles in
regions with intrinsically low signal-to-noise ratios; and distinguishing from
the susceptibility changes at tissue interfaces. The long echo times (TE values)
required limit the applications in dynamic imaging, as noted above. Signifi cant
efforts have been made, therefore, to develop techniques which generate
positive-contrast from magnetic nanoparticles, particularly with a view to quantify-
ing the nanoparticle concentration for tracking studies. In this respect,
three approaches have been attempted: (i) gradient- dephasing - based imaging;
(ii) off - resonance imaging ( ORI ); and (iii) off - resonance saturation. For the
purpose of illustration, ORI makes use of the induced resonance frequency shifts,
which can be in excess of 100 Hz at typical concentrations. It involves the use
of a spectrally shifted (“off-resonance”) RF pulse to selectively irradiate the shifted
water signals only. This has been shown to be effective, particularly at lower
end of the clinical fi eld range due to the narrower water resonance lines (15 Hz
at 4.7 T versus 45 Hz at 14 T), and for nanoparticle concentrations in excess
of 150
g Fe ml
- 1
[317], which was found to be suffi cient to detect the accumulation
of iron oxide nanoparticles in macrophages which had infi ltrated healing myocar-
dial infarcts.
μ
