Chemistry Reference
In-Depth Information
10
cESt and ParacESt agEntS for MolEcular
IMagIng
Osasere M. Evbuomwan
Department of Chemistry, University of Texas at Dallas, Richardson, TX, USA
Enzo Terreno and Silvio Aime
Departmento di Chimica I.F.M. and Centro di Imaging Moleculare, Universita di Torino, Torino, Italy
A. Dean Sherry
Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX, USA; Department of Chemistry,
University of Texas at Dallas, Richardson, TX, USA
10.1
IntroductIon
Magnetic resonance imaging (MRI) is a diagnostic technique that is well known for its ability to produce high spatial resolution
of soft tissue in clinical imaging [1]. The quality of anatomical information obtained in an MR image can be further
augmented by taking advantage of a paramagnetic contrast agent. Current clinically approved MRI contrast agents provide
little functional information about tissue other than information gained by dynamic contrast enhancement (DCE) measure-
ments [1]. To better understand specific physiological, biochemical, or metabolic abnormalities associated with disease, it
will be important to obtain information at the cellular and molecular level. This goal may be best accomplished by use of a
new class of contrast media referred to as chemical exchange saturation transfer (CEST) agents.
CEST agents offer some advantages over typical Gd
3+
-based MRI contrast agents because of the unique contrast mecha-
nism by which they operate. Typically, these agents possess one or more labile protons that have NMR frequencies chemi-
cally distinct from bulk water protons. Application of a radiofrequency (RF) pulse at this unique frequency causes selective
saturation of the CEST agent protons, and those saturated spins subsequently appear in the bulk water proton pool as a result
of chemical exchange (Figure 10.1). This leads to a partial reduction in solvent proton signal intensity, and the difference in
water intensity or contrast can be displayed as a dark signal, a bright signal (negative image intensity), or a colour map in an
MR image [2, 3]. CEST principles offer a fundamental advantage for MRI because contrast can be introduced only when a
frequency-selective RF pulse is applied at the resonance frequency of the labile protons. Hence, image contrast can be turned
on and off again at will, thus eliminating the need for pre- and post-contrast image acquisition.
The CEST signal is typically reported as the ratio of the bulk water magnetisation after application of a long pre-saturation
pulse (M
s
) relative to the water intensity without saturation (M
o
). A plot of M
s
/M
o
versus
pre-saturation frequency is now
commonly referred to as a CEST spectrum or a Z-spectrum [4, 5]. The magnitude of the CEST contrast is assessed by sub-
tracting the magnetisation ratio at a specific frequency of interest (on) from the effect at an equal frequency on the opposite
side of the water frequency (off).
